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  • 1
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    KEGG as a reference resource for gene and protein annotation (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-07
    Description: KEGG ( http://www.kegg.jp/ or http://www.genome.jp/kegg/ ) is an integrated database resource for biological interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 complete genomes are annotated with KOs in the KEGG GENES database, which can be used as a reference data set for KO assignment and subsequent reconstruction of KEGG pathways and other molecular networks. As an annotation resource, the following improvements have been made. First, each KO record is re-examined and associated with protein sequence data used in experiments of functional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for antimicrobial resistance and drug interaction networks.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Data, information, knowledge and principle: back to metabolism in KEGG (2013)
    Oxford University Press
    Details
    Publication Date: 2013-12-29
    Description: In the hierarchy of data, information and knowledge, computational methods play a major role in the initial processing of data to extract information, but they alone become less effective to compile knowledge from information. The Kyoto Encyclopedia of Genes and Genomes (KEGG) resource ( http://www.kegg.jp/ or http://www.genome.jp/kegg/ ) has been developed as a reference knowledge base to assist this latter process. In particular, the KEGG pathway maps are widely used for biological interpretation of genome sequences and other high-throughput data. The link from genomes to pathways is made through the KEGG Orthology system, a collection of manually defined ortholog groups identified by K numbers. To better automate this interpretation process the KEGG modules defined by Boolean expressions of K numbers have been expanded and improved. Once genes in a genome are annotated with K numbers, the KEGG modules can be computationally evaluated revealing metabolic capacities and other phenotypic features. The reaction modules, which represent chemical units of reactions, have been used to analyze design principles of metabolic networks and also to improve the definition of K numbers and associated annotations. For translational bioinformatics, the KEGG MEDICUS resource has been developed by integrating drug labels (package inserts) used in society.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    KEGG: new perspectives on genomes, pathways, diseases and drugs (2017)
    Oxford University Press
    Details
    Publication Date: 2017-01-05
    Description: KEGG ( http://www.kegg.jp/ or http://www.genome.jp/kegg/ ) is an encyclopedia of genes and genomes. Assigning functional meanings to genes and genomes both at the molecular and higher levels is the primary objective of the KEGG database project. Molecular-level functions are stored in the KO (KEGG Orthology) database, where each KO is defined as a functional ortholog of genes and proteins. Higher-level functions are represented by networks of molecular interactions, reactions and relations in the forms of KEGG pathway maps, BRITE hierarchies and KEGG modules. In the past the KO database was developed for the purpose of defining nodes of molecular networks, but now the content has been expanded and the quality improved irrespective of whether or not the KOs appear in the three molecular network databases. The newly introduced addendum category of the GENES database is a collection of individual proteins whose functions are experimentally characterized and from which an increasing number of KOs are defined. Furthermore, the DISEASE and DRUG databases have been improved by systematic analysis of drug labels for better integration of diseases and drugs with the KEGG molecular networks. KEGG is moving towards becoming a comprehensive knowledge base for both functional interpretation and practical application of genomic information.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling (2015)
    Springer Nature
    Details
    Publication Date: 2015-04-17
    Description: Article Matriptase, a transmembrane serine protease, has been implicated in breast cancer since its discovery, but the mechanisms of this implication have not been elucidated. Here the authors show that matriptase abrogation in vivo affects c-Met signalling and the growth of breast cancer cells. Nature Communications doi: 10.1038/ncomms7776 Authors: Gina L. Zoratti, Lauren M. Tanabe, Fausto A. Varela, Andrew S. Murray, Christopher Bergum, Éloïc Colombo, Julie E. Lang, Alfredo A. Molinolo, Richard Leduc, Eric Marsault, Julie Boerner, Karin List
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 5
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    The Plasmodium Apicoplast Genome: Conserved Structure and Close Relationship of P. ovale to Rodent Malaria Parasites (2012)
    Oxford University Press
    Details
    Publication Date: 2012-08-23
    Description: Apicoplast, a nonphotosynthetic plastid derived from secondary symbiotic origin, is essential for the survival of malaria parasites of the genus Plasmodium . Elucidation of the evolution of the apicoplast genome in Plasmodium species is important to better understand the functions of the organelle. However, the complete apicoplast genome is available for only the most virulent human malaria parasite, Plasmodium falciparum . Here, we obtained the near-complete apicoplast genome sequences from eight Plasmodium species that infect a wide variety of vertebrate hosts and performed structural and phylogenetic analyses. We found that gene repertoire, gene arrangement, and other structural attributes were highly conserved. Phylogenetic reconstruction using 30 protein-coding genes of the apicoplast genome inferred, for the first time, a close relationship between P. ovale and rodent parasites. This close relatedness was robustly supported using multiple evolutionary assumptions and models. The finding suggests that an ancestral host switch occurred between rodent and human Plasmodium parasites.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Cerebellothalamocortical pathway abnormalities in torsinA DYT1 knock-in mice [Neuroscience] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-04-20
    Description: The factors that determine symptom penetrance in inherited disease are poorly understood. Increasingly, magnetic resonance diffusion tensor imaging (DTI) and PET are used to separate alterations in brain structure and function that are linked to disease symptomatology from those linked to gene carrier status. One example is DYT1 dystonia, a dominantly inherited movement disorder characterized by sustained muscle contractions, postures, and/or involuntary movements. This form of dystonia is caused by a 3-bp deletion (i.e., ΔE) in the TOR1A gene that encodes torsinA. Carriers of the DYT1 dystonia mutation, even if clinically nonpenetrant, exhibit abnormalities in cerebellothalamocortical (CbTC) motor pathways. However, observations in human gene carriers may be confounded by variability in genetic background and age. To address this problem, we implemented a unique multimodal imaging strategy in a congenic line of DYT1 mutant mice that contain the ΔE mutation in the endogenous mouse torsinA allele (i.e., DYT1 knock-in). Heterozygous knock-in mice and littermate controls underwent microPET followed by ex vivo high-field DTI and tractographic analysis. Mutant mice, which do not display abnormal movements, exhibited significant CbTC tract changes as well as abnormalities in brainstem regions linking cerebellar and basal ganglia motor circuits highly similar to those identified in human nonmanifesting gene carriers. Moreover, metabolic activity in the sensorimotor cortex of these animals was closely correlated with individual measures of CbTC pathway integrity. These findings further link a selective brain circuit abnormality to gene carrier status and demonstrate that DYT1 mutant torsinA has similar effects in mice and humans.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    Role of HERV-H during reprogramming [Cell Biology] (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-08-27
    Description: Pluripotency can be induced in somatic cells by overexpressing transcription factors, including POU class 5 homeobox 1 (OCT3/4), sex determining region Y-box 2 (SOX2), Krüppel-like factor 4 (KLF4), and myelocytomatosis oncogene (c-MYC). However, some induced pluripotent stem cells (iPSCs) exhibit defective differentiation and inappropriate maintenance of pluripotency features. Here we...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Spatiotemporal dynamics of inositol 1,4,5-trisphosphate that underlies complex Ca2+ mobilization patterns (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-05-29
    Description: Inositol 1,4,5-trisphosphate (IP3) is a second messenger that elicits complex spatiotemporal patterns of calcium ion (Ca2+) mobilization and has essential roles in the regulation of many cellular functions. In Madin-Darby canine kidney epithelial cells, green fluorescent protein-tagged pleckstrin homology domain translocated from the plasma membrane to the cytoplasm in response to increased concentration of IP3. The detection of translocation enabled monitoring of IP3 concentration changes within single cells and revealed spatiotemporal dynamics in the concentration of IP3 synchronous with Ca2+ oscillations and intracellular and intercellular IP3 waves that accompanied Ca2+ waves. Such changes in IP3 concentration may be fundamental to Ca2+ signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hirose, K -- Kadowaki, S -- Tanabe, M -- Takeshima, H -- Iino, M -- New York, N.Y. -- Science. 1999 May 28;284(5419):1527-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Faculty of Medicine, University of Tokyo and CREST, Japan Science and Technology Corporation, Tokyo 113-8654, Japan. hirose@calcium.cmp.m.u-tokyo.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10348740" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/pharmacology ; Animals ; Calcium/*metabolism ; *Calcium Signaling ; Cell Line ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Dogs ; Green Fluorescent Proteins ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol Phosphates/metabolism ; Isoenzymes/chemistry/metabolism ; Ligands ; Luminescent Proteins ; Microscopy, Confocal ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phospholipase C delta ; Recombinant Fusion Proteins/metabolism ; Time Factors ; Type C Phospholipases/chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Mechanical rotation of the c subunit oligomer in ATP synthase (F0F1): direct observation (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-11-27
    Description: F0F1, found in mitochondria or bacterial membranes, synthesizes adenosine 5'-triphosphate (ATP) coupling with an electrochemical proton gradient and also reversibly hydrolyzes ATP to form the gradient. An actin filament connected to a c subunit oligomer of F0 was able to rotate by using the energy of ATP hydrolysis. The rotary torque produced by the c subunit oligomer reached about 40 piconewton-nanometers, which is similar to that generated by the gamma subunit in the F1 motor. These results suggest that the gamma and c subunits rotate together during ATP hydrolysis and synthesis. Thus, coupled rotation may be essential for energy coupling between proton transport through F0 and ATP hydrolysis or synthesis in F1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sambongi, Y -- Iko, Y -- Tanabe, M -- Omote, H -- Iwamoto-Kihara, A -- Ueda, I -- Yanagida, T -- Wada, Y -- Futai, M -- New York, N.Y. -- Science. 1999 Nov 26;286(5445):1722-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University, CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation, Ibaraki, Osaka 567-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10576736" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry/metabolism ; Adenosine Triphosphate/*metabolism ; Binding Sites ; Biotinylation ; Energy Transfer ; Enzymes, Immobilized ; Escherichia coli/enzymology ; Hydrolysis ; Molecular Motor Proteins/*chemistry/*metabolism ; Proton-Motive Force ; Proton-Translocating ATPases/*chemistry/*metabolism ; Uncoupling Agents/metabolism/pharmacology ; Venturicidins/pharmacology ; Video Recording
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-22
    Description: Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors and lymphoid tissue inducer cells. These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells. Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection. After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moro, Kazuyo -- Yamada, Taketo -- Tanabe, Masanobu -- Takeuchi, Tsutomu -- Ikawa, Tomokatsu -- Kawamoto, Hiroshi -- Furusawa, Jun-Ichi -- Ohtani, Masashi -- Fujii, Hideki -- Koyasu, Shigeo -- England -- Nature. 2010 Jan 28;463(7280):540-4. doi: 10.1038/nature08636. Epub 2009 Dec 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20023630" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/*cytology/*immunology ; Animals ; Antigens, Ly/genetics/*immunology/metabolism ; B-Lymphocytes/cytology/immunology ; Cell Proliferation ; Cytokines/*immunology ; *Gene Expression Regulation ; Humans ; Lymphocytes/*immunology ; Membrane Proteins/genetics/*immunology ; Mesentery/immunology ; Mice ; Mice, Inbred C57BL ; Nematoda/physiology ; Nematode Infections/immunology ; Proto-Oncogene Proteins c-kit/genetics/*immunology ; Th2 Cells/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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