85 research outputs found

    Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

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    The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

    532 nm low-power laser irradiation recovers Ī³-secretase inhibitor-mediated cell growth suppression and promotes cell proliferation via Akt signaling.

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    The Ī³-secretase inhibitor (GSI) has been shown to inhibit expression of amyloid beta (AĪ²), but GSI also has a side effect of reducing cell survival. Since low-power laser irradiation (LLI) has been known to promote cell survival, we examined whether 532 nm LLI can rescue the GSI side effect or not.The human-derived glioblastoma cells (A-172) were cultured in 35 mm culture dishes or 96-well plate. The center of dish or selected wells was irradiated with 532 nm laser (Nd:YVO4, CW, 60 mW) for 20, 40 and 60 min, respectively. The irradiated cells were photographed at immediately after, 24 and 48 h later and counted. GSI was supplemented in medium 3 h before LLI. The MTT assay was also used to estimate viable cells at 48 h after irradiation. The expression of phosphorylated Akt (p-Akt) or phosphorylated PTEN (p-PTEN) was examined by immunofluorescent staining and measured by fluorescence intensity using the software (BZ-9000, KEYENCE, Japan).GSI application depressed cell proliferation as well as cell survival compared to control. GSI down-regulated AĪ² but up-regulated p-PTEN and suppressed p-Akt. Application of 532 nm LLI in the presence of GSI significantly recovered the GSI-mediated effects, i.e., LLI could decrease elevated p-PTEN, while increased p-Akt expression with keeping AĪ² suppression. The LLI effects had a dose-dependency.We confirmed that GSI potently suppressed intracellular AĪ² and decreased cell survival. We conclude that a combination of GSI application and 532 nm LLI can increase cell proliferation via Akt activation while keeping PTEN and AĪ² suppressed

    Effect of the decreased frequency of going out on the association between anxiety and sleep disorder during the COVID-19 pandemic: a mediation analysis

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    Abstract Purpose The objective of the present study was to examine the relationship between anxiety and sleep disorder during the COVID-19 pandemic and to evaluate whether sleep disorder is mediated by the decreased frequency of going out. Methods The data of a total of 1976 residents aged 18Ā years and over who had responded to a self-reported questionnaires at a health survey in 2020 were analyzed. The subjects were divided into four groups based on their response to the questionnaire on anxiety about the COVID-19 pandemic. Sleep disorder was measured using the Athens Insomnia Scale (AIS). A cross-sectional analysis was performed to examine the association between anxiety about the COVID-19 pandemic and AIS scores. Mediation analysis was used to calculate the association between anxiety and AIS scores during the COVID-19 pandemic, with decreased frequency of going out as a potential mediating variable. Results In the cross-sectional study, the level of anxiety about the COVID-19 pandemic was significantly associated with the AIS score (pā€‰<ā€‰0.001). On mediation analysis, the direct effect of the relationship showed that anxiety positively influenced AIS scores (Ī²ā€‰=ā€‰0.283, pā€‰<ā€‰0.01). The indirect effect of the relationship showed that the decreased frequency of going out positively mediated the relationship between anxiety and AIS scores (Ī²ā€‰=ā€‰0.342, pā€‰<ā€‰0.05). The decreased frequency of going out accounted for almost 10% of the AIS score. Conclusion The present study found that anxiety about the COVID-19 pandemic was significantly associated with sleep disorder, with the decreased frequency of going out mediating this association

    Education level and incident functional disability in elderly Japanese: The Ohsaki Cohort 2006 study.

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    As the factors that link education level with incident functional disability in elderly Japanese have never been investigated, the present study investigated this issue in an elderly Japanese population. A 9-year prospective cohort study (2006-2015) was conducted among 8,680 Japanese individuals (ā‰„65 years), Ohsaki city, Japan. In a baseline survey, we collected data on education level and potential mediators. Data on incident functional disability were retrieved from the Long-term Care Insurance database. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident functional disability by education level (below upper-secondary education (reference), and upper secondary education and above). Mediating effects were estimated using accelerated failure time model and a logistic regression model. During 9-year follow-up period, 2,742 cases (31.6%) of incident functional disability were observed, and education level showed an inverse association with functional disability (P for trend <0.01). Participation in community activities had the largest mediating effect (34.7%) on the relationship between education level and incident functional disability. This effect remained among those aged 65-74 years (19.9%) but became negligible among those aged ā‰„75 years. Other potential mediators (such as smoking and drinking status) were also tested, but these showed only small mediating effects. The inverse association between education level and the incident risk of functional disability appears to be largely mediated by participation in community activities among elderly Japanese, especially those aged 65-74 years
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