96 research outputs found
The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts
No full textHere we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein–protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group
Drug target gene-based analyses of drug repositionability in rare and intractable diseases
No full textAbstract Drug development for rare and intractable diseases has been challenging for decades due to the low prevalence and insufficient information on these diseases. Drug repositioning is increasingly being used as a promising option in drug development. We aimed to analyze the trend of drug repositioning and inter-disease drug repositionability among rare and intractable diseases. We created a list of rare and intractable diseases based on the designated diseases in Japan. Drug information extracted from clinical trial data were integrated with information of drug target genes, which represent the mechanism of drug action. We obtained 753 drugs and 551 drug target genes from 8307 clinical trials for 189 diseases or disease groups. Trend analysis of drug sharing between a disease pair revealed that 1676 drug repositioning events occurred in 4401 disease pairs. A score, R gene, was invented to investigate the proportion of drug target genes shared between a disease pair. Annual changes of R gene corresponded to the trend of drug repositioning and predicted drug repositioning events occurring within a year or two. Drug target gene-based analyses well visualized the drug repositioning landscape. This approach facilitates drug development for rare and intractable diseases
Chemical and Biological Aspects of Water-Soluble Heterocyclic Marine Natural Products
No full textWater-soluble marine natural products are interesting as they generally do not penetrate into the cells but exhibit biological activities through cell surface receptors, ion channels, and glycans. Some molecules, however, interact with cell membrane and disrupt it. In this review, discovery, structures, and biological activities of water-soluble marine natural heterocyclic molecules are summarized with special emphasis on their biological activity and functions
New perspective on the clinical and laboratory characteristics of rheumatoid pleural effusion: A 29-case series
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in Modern Rheumatology following peer review. The version of record Minoda Saki Sada, Sada Ryuichi Minoda, Akebo Hiroyuki, et al. New perspective on the clinical and laboratory characteristics of rheumatoid pleural effusion: A 29-case series. Modern Rheumatology, (2024) is available online at: https://doi.org/10.1093/mr/roae082.Objective: Rheumatoid pleural effusion (RPE) usually occurs in middle-aged men. Pleural fluid analyses have revealed high lactate dehydrogenase (LDH) levels and low pH and glucose levels in RPE. We aimed to investigate the clinical and laboratory features of patients with RPE since the beginning of the 21st century. Methods: Medical records of patients with RPE were reviewed between May 2006 and October 2021. The patients were divided into <60 year (younger) and ≥60 year (older) groups. Results: The younger group comprised 6 patients (median age 53.5 years, female 33%) and older group comprised 23 patients (median age 76 years, female 52.2%). Compared to the younger group, the older group had fewer cases of fever (83.3 versus 18.2%, P = .007) and chest pain (66.7 versus 8.7%, P = .008). In pleural fluid analysis, the older group presented higher pH (P = .004) and lower LDH levels (P = .044). Seven patients died during the follow-up period. Conclusion: Most patients with RPE were over 60 years of age, and approximately half of them were female. The pleural fluid analysis showed milder inflammation in older patients than in middle-aged patients. The mortality rate of patients with RPE was distinctly higher than that previously reported
Improvement of Production and Isolation of Human Neuraminidase-1 in Cellulo Crystals
No full textIn cellulo crystallization is a developing technique to provide crystals for protein structure determination, particularly for proteins that are difficult to prepare by in vitro crystallization. This method has a key advantage: It requires neither a protein purification step nor a crystallization step. However, there is still no systematic strategy for improving the technique of in cellulo crystallization because the process occurs spontaneously. Here we report a protocol to produce and extract in cellulo crystals of human lysosomal neuraminidase-1 (NEU1) in human cultured cells. Overexpression of NEU1 protein by the retransfection of cells pretransfected with neu1-overexpressing plasmid improved the efficiency of NEU1 crystallization. Microscopic analysis revealed that NEU1 proteins were not crystallized in the lysosome but in the endoplasmic reticulum (ER). Screening of the buffer conditions used to extract crystals from cells further improved the crystal yield. The optimal pH was 7.0, which corresponds to the pH in the ER. Use of a high-yield flask with a large surface area also yielded more crystals. These optimizations enabled us to execute a serial femtosecond crystallography experiment with a sufficient number of crystals to generate a complete data set. Optimization of the in cellulo crystallization method was thus shown to be possible.Accepted Author ManuscriptBN/Arjen Jakobi La
Nature of the possible magnetic phases in a frustrated hyperkagome iridate
No full textBased on the Kitaev-Heisenberg model with Dzyaloshinskii-Moriya (DM) interactions, we studied the nature of possible magnetic phases in the frustrated hyperkagome iridate, Na4Ir3O8 (Na-438). Using Monte Carlo simulation, we showed that the phase diagram is mostly covered by two competing magnetic ordered phases, the Z(2) symmetry breaking (SB) phase and the Z(6) SB phase, latter of which is stabilized by the classical order by disorder. These two phases are intervened by a first-order phase-transition line with Z(8)-like symmetry. The critical nature at the Z(6) SB ordering temperature is characterized by the three-dimensional XY universality class, below which U(1) to Z(6) crossover phenomenon appears: the Z(6) spin anisotropy becomes irrelevant in a length scale shorter than a crossover length A,, while it becomes relevant otherwise. A possible phenomenology of polycrystalline Na-438 is discussed based on this crossover phenomenon.SCI(E)[email protected]
Reflection of cross-disciplinary research at Creative Research Institution (Hokkaido University) in the Web of Science database: appraisal and visualization using bibliometry
No full textThis study describes the results of a preliminary bibliometric analysis of 611 research items, published between 1996 and 2011 by researchers affiliated with Creative Research Institution (CRIS) and the Center for Advanced Science and Technology (CAST), Hokkaido University (HU), retrieved from the Web of Science (WoS) database. CRIS has a primary mission to promote cutting-edge, world-class, trans-departmental research within HU, and it conducts fundamental, commercialization-related, cross-disciplinary research and nurtures young in-house/recruited researchers through targeted, innovative tenure-track programs in multiple disciplines. Its research output derives from 3- to 7-year-long time-bound projects funded strategically by HU, external grants [e.g., MEXT Super-COE HU Research and Business Park Project (FY2003-7)], industryuniversity collaboration with regional businesses, and endowments (e.g., Meiji Dairies). Analyses using co-words, bibliographic coupling, overlay map aided with visualization, etc., lead to the following inferences: (i) The published items comprise a dozen welldefined (inter-)disciplinary clusters, dominated by 3 macro-disciplines (biomedical science, 33%; chemistry, 21%; agricultural science, ca. 10%) that constitute 18 clusters used for mapping; (ii) research conducted by externally funded or endowed projects in the biomedical, physical and environmental science and technology fields (3 broad areas of aggregation derived from the Science Overlay Map) is interdisciplinary; and (iii) there is an apparently low visibility of publications from projects jointly executed with industries to an almost complete absence of output from CRIS in the fields of social sciences in the WoS database
We\u27ve Only Just Begun: The Law of Sexual Harassment in Japan
No full textDiscussions about sexual harassment in Japan first began a decade ago. However, Japan\u27s Equal Employment Opportunity Law did not directly address sexual harassment until it was amended in 1997. Instead, Japanese courts responded with a jurisprudence that has distinctive characteristics regarding the nature of liability for sexual harassment. First, Japanese courts created a doctrine that sexual harassment constitutes a tort because it infringes on women\u27s personal rights or on her rights to the dignity of her personality regarding sexuality. Second, Japanese courts held employers liable for sexual harassment by supervisory employees of subordinates. The 1997 amendment to the Equal Employment Opportunity Law strengthened the regulation to a considerable degree. However, it remains to be seen how this provision will influence the civil liability of employers.
This article compares the Japanese law of sexual harassment with U.S. jurisprudence. Part II briefly describes the present situation regarding sexual harassment in Japan. In Part III, the author focuses on the legal bases of liability for sexual harassment under Japanese law and compares them with U.S. law. Lastly, in Part IV the author discusses Japanese law of employer liability for sexual harassment, including the new provision in the Equal Employment Opportunity Law, and compares employer liability in Japanese and U.S. law. This article concludes with a summary of the features of Japanese sexual harassment law and comments on future prospects
We\u27ve Only Just Begun: The Law of Sexual Harassment in Japan
No full textDiscussions about sexual harassment in Japan first began a decade ago. However, Japan\u27s Equal Employment Opportunity Law did not directly address sexual harassment until it was amended in 1997. Instead, Japanese courts responded with a jurisprudence that has distinctive characteristics regarding the nature of liability for sexual harassment. First, Japanese courts created a doctrine that sexual harassment constitutes a tort because it infringes on women\u27s personal rights or on her rights to the dignity of her personality regarding sexuality. Second, Japanese courts held employers liable for sexual harassment by supervisory employees of subordinates. The 1997 amendment to the Equal Employment Opportunity Law strengthened the regulation to a considerable degree. However, it remains to be seen how this provision will influence the civil liability of employers.
This article compares the Japanese law of sexual harassment with U.S. jurisprudence. Part II briefly describes the present situation regarding sexual harassment in Japan. In Part III, the author focuses on the legal bases of liability for sexual harassment under Japanese law and compares them with U.S. law. Lastly, in Part IV the author discusses Japanese law of employer liability for sexual harassment, including the new provision in the Equal Employment Opportunity Law, and compares employer liability in Japanese and U.S. law. This article concludes with a summary of the features of Japanese sexual harassment law and comments on future prospects
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