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  • Humans  (4,468)
  • Nature Publishing Group (NPG)  (4,468)
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  • 1
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bender, Eric -- England -- Nature. 2016 May 11;533(7602):S59. doi: 10.1038/533S59a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27167392" target="_blank"〉PubMed〈/a〉
    Keywords: Diffusion of Innovation ; Drug Discovery/*economics/*methods/organization & administration/trends ; Drug Industry/economics/*methods/organization & administration/*trends ; Humans ; Leadership ; Patient Advocacy
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibney, Elizabeth -- England -- Nature. 2016 Mar 17;531(7594):284-5. doi: 10.1038/531284a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26983517" target="_blank"〉PubMed〈/a〉
    Keywords: Artificial Intelligence/*trends ; Child ; Diagnosis ; *Games, Recreational/psychology ; Humans ; Language ; Learning ; Male ; Smartphone/trends
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2016-03-10
    Description: Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high conservation of the acetylcholine-binding pocket has spurred current research into targeting allosteric sites on these receptors. Here we report the crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium. Comparison of these structures with each other, as well as with the previously reported M2 and M3 receptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute to a role in drug selectivity at this important receptor family. We also report identification of a cluster of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new insight into how allosteric modulation may be transmitted between the two spatially distinct domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thal, David M -- Sun, Bingfa -- Feng, Dan -- Nawaratne, Vindhya -- Leach, Katie -- Felder, Christian C -- Bures, Mark G -- Evans, David A -- Weis, William I -- Bachhawat, Priti -- Kobilka, Tong Sun -- Sexton, Patrick M -- Kobilka, Brian K -- Christopoulos, Arthur -- U19 GM106990/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Mar 17;531(7594):335-40. doi: 10.1038/nature17188. Epub 2016 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, Victoria, Australia. ; ConfometRx, 3070 Kenneth Street, Santa Clara, California 95054, USA. ; Neuroscience, Eli Lilly, Indianapolis, Indiana 46285, USA. ; Computational Chemistry and Chemoinformatics, Eli Lilly, Indianapolis, Indiana 46285, USA. ; Computational Chemistry and Chemoinformatics, Eli Lilly, Sunninghill Road, Windlesham GU20 6PH, UK. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26958838" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Allosteric Regulation/drug effects ; Allosteric Site/drug effects ; Alzheimer Disease ; Crystallization ; Crystallography, X-Ray ; Drug Inverse Agonism ; Humans ; Models, Molecular ; Nicotinic Acids/metabolism/pharmacology ; Receptor, Muscarinic M1/*chemistry/metabolism ; Receptor, Muscarinic M4/*chemistry/metabolism ; Schizophrenia ; Static Electricity ; Substrate Specificity ; Surface Properties ; Thiophenes/metabolism/pharmacology ; Tiotropium Bromide/pharmacology
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maxmen, Amy -- England -- Nature. 2016 Mar 17;531(7594):S58-9. doi: 10.1038/531S58a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26981730" target="_blank"〉PubMed〈/a〉
    Keywords: Asthma/epidemiology/psychology/therapy ; California ; Cities/*statistics & numerical data ; Crime/psychology ; *Health Behavior ; Humans ; *Parks, Recreational ; Poverty/psychology ; Social Class ; Stress, Psychological/prevention & control/*psychology/therapy ; Uncertainty
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-01-26
    Description: Intracellular aggregation of the human amyloid protein alpha-synuclein is causally linked to Parkinson's disease. While the isolated protein is intrinsically disordered, its native structure in mammalian cells is not known. Here we use nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy to derive atomic-resolution insights into the structure and dynamics of alpha-synuclein in different mammalian cell types. We show that the disordered nature of monomeric alpha-synuclein is stably preserved in non-neuronal and neuronal cells. Under physiological cell conditions, alpha-synuclein is amino-terminally acetylated and adopts conformations that are more compact than when in buffer, with residues of the aggregation-prone non-amyloid-beta component (NAC) region shielded from exposure to the cytoplasm, which presumably counteracts spontaneous aggregation. These results establish that different types of crowded intracellular environments do not inherently promote alpha-synuclein oligomerization and, more generally, that intrinsic structural disorder is sustainable in mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theillet, Francois-Xavier -- Binolfi, Andres -- Bekei, Beata -- Martorana, Andrea -- Rose, Honor May -- Stuiver, Marchel -- Verzini, Silvia -- Lorenz, Dorothea -- van Rossum, Marleen -- Goldfarb, Daniella -- Selenko, Philipp -- England -- Nature. 2016 Feb 4;530(7588):45-50. doi: 10.1038/nature16531. Epub 2016 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉In-Cell NMR Laboratory, Department of NMR-supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rossle Strasse 10, 13125 Berlin, Germany. ; Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Molecular Physiology and Cell Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rossle Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26808899" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Cell Line ; Cytoplasm/chemistry/metabolism ; Electron Spin Resonance Spectroscopy ; HeLa Cells ; Humans ; Intracellular Space/*chemistry/*metabolism ; Neurons/cytology/metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; alpha-Synuclein/*chemistry/*metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGilvray, Annabel -- England -- Nature. 2016 Mar 3;531(7592):S4-5. doi: 10.1038/531S4a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934524" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates/pharmacology/therapeutic use ; Aging/blood/drug effects/pathology/*psychology ; Alzheimer Disease/blood/therapy ; Animals ; Anti-Asthmatic Agents/pharmacology/therapeutic use ; Cognition Disorders/pathology/physiopathology/*prevention & control/*therapy ; Estrogens/pharmacology ; Female ; Hippocampus/drug effects/pathology/physiology/physiopathology ; Humans ; Inflammation Mediators/immunology ; Leukotrienes/immunology ; Macaca mulatta ; Male ; Mice ; Neuronal Plasticity/drug effects ; Parkinson Disease/therapy ; Plasma/chemistry/physiology ; Prefrontal Cortex/drug effects/pathology/physiology/physiopathology ; Quinolines/pharmacology/therapeutic use ; Rats ; Rejuvenation/*physiology/*psychology ; Synapses/drug effects/metabolism/pathology
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKinlay, Roger -- England -- Nature. 2016 Mar 31;531(7596):573-5. doi: 10.1038/531573a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Royal Institute of Navigation, and a former head of engineering at Thales UK. He sits on the EPSRC Quantum Technology Strategic Advisory Board.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Facility Design and Construction ; Geographic Information Systems/instrumentation/*utilization ; Hippocampus/anatomy & histology/physiology ; Humans ; Maps as Topic ; Orientation/physiology ; Satellite Communications/utilization ; Smartphone/utilization ; Spatial Learning/*physiology ; Spatial Memory/physiology ; Spatial Navigation/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldacre, Ben -- England -- Nature. 2016 Feb 4;530(7588):7. doi: 10.1038/530007a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842021" target="_blank"〉PubMed〈/a〉
    Keywords: Bias (Epidemiology) ; Clinical Trials as Topic/*methods/*standards ; *Editorial Policies ; Evidence-Based Medicine/methods/standards ; Guidelines as Topic ; Humans ; Periodicals as Topic/*standards ; Reproducibility of Results ; Research Report/*standards ; Treatment Outcome
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2016-04-07
    Description: As the last habitable continent colonized by humans, the site of multiple domestication hotspots, and the location of the largest Pleistocene megafaunal extinction, South America is central to human prehistory. Yet remarkably little is known about human population dynamics during colonization, subsequent expansions, and domestication. Here we reconstruct the spatiotemporal patterns of human population growth in South America using a newly aggregated database of 1,147 archaeological sites and 5,464 calibrated radiocarbon dates spanning fourteen thousand to two thousand years ago (ka). We demonstrate that, rather than a steady exponential expansion, the demographic history of South Americans is characterized by two distinct phases. First, humans spread rapidly throughout the continent, but remained at low population sizes for 8,000 years, including a 4,000-year period of 'boom-and-bust' oscillations with no net growth. Supplementation of hunting with domesticated crops and animals had a minimal impact on population carrying capacity. Only with widespread sedentism, beginning ~5 ka, did a second demographic phase begin, with evidence for exponential population growth in cultural hotspots, characteristic of the Neolithic transition worldwide. The unique extent of humanity's ability to modify its environment to markedly increase carrying capacity in South America is therefore an unexpectedly recent phenomenon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldberg, Amy -- Mychajliw, Alexis M -- Hadly, Elizabeth A -- England -- Nature. 2016 Apr 14;532(7598):232-5. doi: 10.1038/nature17176. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Stanford University, Stanford, California 94305, USA. ; Woods Institute, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049941" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Archaeology ; Climate ; Geographic Mapping ; History, Ancient ; Human Migration/*history ; Humans ; Population Dynamics/*history ; Radiometric Dating ; Siberia/ethnology ; South America
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2016-03-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bolkan, Scott -- Gordon, Joshua A -- England -- Nature. 2016 Apr 7;532(7597):45-6. doi: 10.1038/nature17311. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Columbia University, New York, New York 10032, USA. ; Department of Psychiatry, Columbia University.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007842" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Attention Deficit Disorder with Hyperactivity/*physiopathology/*psychology ; Female ; *Gene Deletion ; Humans ; Male ; Membrane Proteins/*deficiency/*genetics ; Thalamic Nuclei/*physiopathology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 11
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Urnov, Fyodor -- England -- Nature. 2016 Jan 28;529(7587):468-9. doi: 10.1038/529468a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sangamo BioSciences, Richmond, California 94804, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819037" target="_blank"〉PubMed〈/a〉
    Keywords: CRISPR-Associated Proteins/*genetics/*metabolism ; CRISPR-Cas Systems/*physiology ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; Endonucleases/*metabolism ; *Genetic Engineering ; Genome, Human/*genetics ; Humans
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 12
    Publication Date: 2016-03-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2016 Mar 10;531(7593):153. doi: 10.1038/nature.2016.19502.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26961637" target="_blank"〉PubMed〈/a〉
    Keywords: Brazil/epidemiology ; Colombia/epidemiology ; Epidemiological Monitoring ; Female ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/*diagnosis/*epidemiology/virology ; Microcephaly/diagnosis/*epidemiology/*virology ; Pregnancy ; Zika Virus/*pathogenicity ; Zika Virus Infection/*complications/diagnosis/*epidemiology/virology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 13
    Publication Date: 2016-02-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Chunxin -- Youle, Richard -- England -- Nature. 2016 Feb 18;530(7590):288-9. doi: 10.1038/530288a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887490" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*metabolism ; *Energy Metabolism ; Humans ; Mitochondria/*physiology ; *Mitochondrial Dynamics ; *Stress, Physiological
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 14
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2016 Apr 14;532(7598):155-6. doi: 10.1038/532155a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075072" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/virology ; Angola/epidemiology ; Animals ; Asia/epidemiology ; Child ; Cities/epidemiology ; Disease Outbreaks/statistics & numerical data ; *Fear ; Haplorhini/virology ; Humans ; South America/epidemiology ; Strategic Stockpile/statistics & numerical data ; Vaccination/statistics & numerical data ; World Health Organization ; Yellow Fever/*epidemiology/*transmission/virology ; Yellow Fever Vaccine/administration & dosage/supply & distribution
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 15
    Publication Date: 2016-02-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heuckeroth, Robert O -- England -- Nature. 2016 Mar 3;531(7592):44-5. doi: 10.1038/nature16877. Epub 2016 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Children's Hospital of Philadelphia Research Institute and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863191" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage ; *Cell- and Tissue-Based Therapy ; Drug Discovery/*methods ; Enteric Nervous System/*pathology ; Female ; Hirschsprung Disease/*drug therapy/*pathology ; Humans ; Male ; Neurons/*pathology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 16
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2016 Jan 7;529(7584):10-1. doi: 10.1038/529010a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26738575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chad/epidemiology ; Disease Eradication ; Dog Diseases/*epidemiology/parasitology/prevention & control/*transmission ; Dogs ; Dracunculiasis/*epidemiology/prevention & control/transmission/*veterinary ; Dracunculus Nematode/*isolation & purification ; Drinking Water/parasitology/standards ; Humans ; Rivers/parasitology ; Zoonoses/*epidemiology/parasitology/prevention & control/*transmission
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 17
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hodson, Richard -- England -- Nature. 2016 May 11;533(7602):S53. doi: 10.1038/533S53a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27167389" target="_blank"〉PubMed〈/a〉
    Keywords: Azepines ; *Cooperative Behavior ; *Diffusion of Innovation ; *Drug Discovery ; Drug Industry ; Humans ; *Information Dissemination ; Neglected Diseases ; *Open Access Publishing ; Triazoles ; Tropical Medicine
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 18
    Publication Date: 2016-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2016 Jan 14;529(7585):138-9. doi: 10.1038/529138a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26762436" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Animals ; Cats ; Chiroptera/*virology ; Disease Outbreaks/prevention & control/statistics & numerical data/veterinary ; Dogs ; Ebolavirus/*isolation & purification ; Hemorrhagic Fever, Ebola/*epidemiology/prevention & control/*veterinary/virology ; *Host Specificity ; Humans ; Livestock/virology ; Pets/virology ; Rodentia/virology ; Zoonoses/epidemiology/prevention & control/transmission/virology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 19
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2016 Feb 4;530(7588):18. doi: 10.1038/nature.2016.19270.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842037" target="_blank"〉PubMed〈/a〉
    Keywords: CRISPR-Cas Systems/*genetics ; Developmental Biology/ethics/legislation & jurisprudence/methods ; Embryo Research/ethics/*legislation & jurisprudence ; Embryo, Mammalian/embryology/metabolism ; Genetic Engineering/ethics/*legislation & jurisprudence ; Genome, Human/genetics ; Great Britain ; Humans ; Reproductive Techniques, Assisted/legislation & jurisprudence ; Research Personnel/*legislation & jurisprudence
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 20
    Publication Date: 2016-01-21
    Description: Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westermann, Alexander J -- Forstner, Konrad U -- Amman, Fabian -- Barquist, Lars -- Chao, Yanjie -- Schulte, Leon N -- Muller, Lydia -- Reinhardt, Richard -- Stadler, Peter F -- Vogel, Jorg -- England -- Nature. 2016 Jan 28;529(7587):496-501. doi: 10.1038/nature16547. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Wurzburg, RNA Biology Group, Institute for Molecular Infection Biology, Josef-Schneider-Strasse 2/D15, D-97080 Wurzburg, Germany. ; University of Wurzburg, Core Unit Systems Medicine, Josef-Schneider-Strasse 2/D15, D-97080 Wurzburg, Germany. ; University of Leipzig, Department of Computer Science and Interdisciplinary Center for Bioinformatics, Hartelstrasse 16-18, D-04107 Leipzig, Germany. ; University of Vienna, Theoretical Biochemistry Group, Institute for Theoretical Chemistry, Wahringer Strasse 17, A-1090 Vienna, Austria. ; Max Planck Genome Centre Cologne, Max Planck Institute for Plant Breeding Research, Carl-von-Linne-Weg 10, D-50829 Cologne, Germany. ; Max Planck Institute for Mathematics in the Sciences, Inselstrasse 22, D-04103 Leipzig, Germany. ; Santa Fe Institute, 1399 Hyde Park Rd, Santa Fe, New Mexico 87501, USA. ; Research Centre for Infectious Diseases (ZINF), University of Wurzburg, D-97070 Wurzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26789254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/metabolism ; Female ; Gene Expression Regulation/*genetics ; Genes, Bacterial/genetics ; HeLa Cells ; Host-Pathogen Interactions/*genetics ; Humans ; Janus Kinases/metabolism ; Mice ; Microbial Viability/genetics ; RNA, Bacterial/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Untranslated/*genetics/metabolism ; STAT Transcription Factors/metabolism ; Salmonella typhimurium/cytology/*genetics/pathogenicity ; Signal Transduction/genetics ; Transcriptome/genetics ; Virulence/genetics
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  • 21
    Publication Date: 2016-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castelvecchi, Davide -- England -- Nature. 2016 May 11;533(7602):153-4. doi: 10.1038/533153a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27172022" target="_blank"〉PubMed〈/a〉
    Keywords: *Computer Simulation/economics ; Humans ; Laboratories/*economics ; Prejudice/prevention & control/psychology ; Research/*economics/*instrumentation/trends ; Research Subjects ; Software/economics ; *User-Computer Interface
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  • 22
    Publication Date: 2016-04-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penn, Bennett H -- Cox, Jeffery S -- England -- Nature. 2016 Apr 21;532(7599):321-2. doi: 10.1038/nature17882. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, California 94143, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720-3370, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049940" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Endoplasmic Reticulum Stress ; Female ; Humans ; Inflammation/*metabolism ; Male ; Nod1 Signaling Adaptor Protein/*metabolism ; Nod2 Signaling Adaptor Protein/*metabolism ; *Signal Transduction
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  • 23
    Publication Date: 2016-04-15
    Description: Promoters are DNA sequences that have an essential role in controlling gene expression. While recent whole cancer genome analyses have identified numerous hotspots of somatic point mutations within promoters, many have not yet been shown to perturb gene expression or drive cancer development. As such, positive selection alone may not adequately explain the frequency of promoter point mutations in cancer genomes. Here we show that increased mutation density at gene promoters can be linked to promoter activity and differential nucleotide excision repair (NER). By analysing 1,161 human cancer genomes across 14 cancer types, we find evidence for increased local density of somatic point mutations within the centres of DNase I-hypersensitive sites (DHSs) in gene promoters. Mutated DHSs were strongly associated with transcription initiation activity, in which active promoters but not enhancers of equal DNase I hypersensitivity were most mutated relative to their flanking regions. Notably, analysis of genome-wide maps of NER shows that NER is impaired within the DHS centre of active gene promoters, while XPC-deficient skin cancers do not show increased promoter mutation density, pinpointing differential NER as the underlying cause of these mutation hotspots. Consistent with this finding, we observe that melanomas with an ultraviolet-induced DNA damage mutation signature show greatest enrichment of promoter mutations, whereas cancers that are not highly dependent on NER, such as colon cancer, show no sign of such enrichment. Taken together, our analysis has uncovered the presence of a previously unknown mechanism linking transcription initiation and NER as a major contributor of somatic point mutation hotspots at active gene promoters in cancer genomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perera, Dilmi -- Poulos, Rebecca C -- Shah, Anushi -- Beck, Dominik -- Pimanda, John E -- Wong, Jason W H -- England -- Nature. 2016 Apr 14;532(7598):259-63. doi: 10.1038/nature17437.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Prince of Wales Clinical School and Lowy Cancer Research Centre, UNSW Australia, Sydney 2052, Australia. ; Department of Haematology, Prince of Wales Hospital, Sydney 2031, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075100" target="_blank"〉PubMed〈/a〉
    Keywords: Colonic Neoplasms/genetics ; DNA Damage/genetics ; DNA Repair/*genetics/radiation effects ; Deoxyribonuclease I/metabolism ; Enhancer Elements, Genetic/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Genome, Human/*genetics ; Humans ; Lung Neoplasms/genetics ; Melanoma/genetics ; Mutagenesis/*genetics ; *Mutation Rate ; Neoplasms/*genetics ; Point Mutation/genetics ; Promoter Regions, Genetic/*genetics ; *Transcription Initiation, Genetic ; Ultraviolet Rays
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  • 24
    Publication Date: 2016-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2016 Feb 11;530(7589):142-3. doi: 10.1038/530142a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863963" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/analysis/immunology ; Biomedical Research/*trends ; Brazil/epidemiology ; Case-Control Studies ; Disease Models, Animal ; *Evidence-Based Medicine ; Female ; Fetal Diseases/epidemiology/etiology/virology ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/epidemiology/etiology/virology ; Infectious Disease Transmission, Vertical ; Microcephaly/epidemiology/*etiology/pathology/*virology ; Pregnancy ; Time Factors ; Zika Virus/genetics/immunology/isolation & purification/*pathogenicity ; Zika Virus Infection/*complications/diagnosis/epidemiology/*virology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 25
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2016 Apr 28;532(7600):424-5. doi: 10.1038/532424a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121817" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/legislation & jurisprudence/*trends ; *Federal Government ; Financing, Government/economics/legislation & jurisprudence ; Humans ; Immunotherapy/economics ; Information Dissemination ; Leadership ; Neoplasms/economics/genetics/immunology/*therapy ; *Private Sector/economics ; *Public-Private Sector Partnerships/economics ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 26
    Publication Date: 2016-03-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2016 Mar 24;531(7595):422-3. doi: 10.1038/531422a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008946" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Mobile Applications ; Monitoring, Physiologic/*methods/trends ; *Smartphone ; Telemedicine/*trends
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 27
    Publication Date: 2016-05-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamada, Tadataka -- Ogawa, V Ayano -- Freire, Maria -- England -- Nature. 2016 May 5;533(7601):29-31. doi: 10.1038/533029a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Global Health Risk Framework Commission, and venture partner at Frazier Healthcare Partners, Seattle, Washington, USA. ; Global Health Risk Framework Commission at the US National Academy of Medicine, Washington DC, USA. ; Global Health Risk Framework Commission, and president and executive director of the Foundation for the National Institutes of Health, Bethesda, Maryland, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27147017" target="_blank"〉PubMed〈/a〉
    Keywords: Communicable Diseases, Emerging/economics/epidemiology/mortality/prevention & ; control ; Disaster Planning/*economics/trends ; Disease Outbreaks/*economics/prevention & control ; Global Health/economics/trends ; *Health Expenditures ; Humans ; Infection/*economics/*epidemiology/mortality ; International Cooperation ; Pandemics/economics/prevention & control ; Public Policy ; Public-Private Sector Partnerships/economics ; Security Measures/*economics/trends ; Zika Virus
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pollock, Kevin -- England -- Nature. 2016 Mar 17;531(7594):S64-6. doi: 10.1038/531S64a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26981733" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cities ; *City Planning ; Feedback ; Humans ; *Physics ; Plague/epidemiology ; Rats ; *Urbanization ; Vietnam/epidemiology
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khurana, Ekta -- England -- Nature. 2016 Apr 14;532(7598):181-2. doi: 10.1038/532181a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Meyer Cancer Center and Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075092" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*genetics/*metabolism ; DNA Repair/*genetics ; DNA-Binding Proteins/*metabolism ; Genome, Human/*genetics ; Humans ; Melanoma/*genetics ; Mutagenesis/*genetics ; *Mutation Rate ; Neoplasms/*genetics ; Promoter Regions, Genetic/*genetics ; Transcription Factors/*metabolism ; *Transcription Initiation, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chi, Kelly Rae -- England -- Nature. 2016 Apr 14;532(7598):269-71. doi: 10.1038/532269a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075102" target="_blank"〉PubMed〈/a〉
    Keywords: Aged, 80 and over ; Biopsy/economics/*methods ; Blood Platelets/cytology ; DNA Mutational Analysis/economics/methods ; DNA, Neoplasm/*blood/genetics ; Drug Resistance, Neoplasm/genetics ; Exosomes/genetics ; Female ; Humans ; Neoplasm Metastasis/diagnosis/genetics ; Neoplasm Recurrence, Local/blood/diagnosis/genetics ; Neoplasms/*blood/*diagnosis/drug therapy/genetics ; Neoplastic Cells, Circulating/metabolism ; Phagocytosis ; Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity
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  • 31
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chi, Kelly Rae -- England -- Nature. 2016 Mar 3;531(7592):S16-7. doi: 10.1038/531S16a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*anatomy & histology/*physiology ; Cognition/*physiology ; Computer Simulation ; Humans ; Models, Anatomic ; *Models, Neurological ; Neocortex/physiology ; Neurons/physiology ; Rats
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  • 32
    Publication Date: 2016-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chu, Derrick M -- Aagaard, Kjersti M -- England -- Nature. 2016 Apr 21;532(7599):316-7. doi: 10.1038/nature17887. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Departments of Molecular and Human Genetics, Molecular and Cell Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074514" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Child, Preschool ; Chronic Disease ; Clostridium symbiosum/isolation & purification/physiology ; Diet/adverse effects/methods ; Feces/microbiology ; Female ; Germ-Free Life ; Growth Disorders/*diet therapy/etiology/*microbiology ; Healthy Volunteers ; Humans ; Infant ; Intestines/drug effects/*microbiology ; Liver/metabolism ; Malawi ; Malnutrition/complications/*diet therapy/*microbiology ; Mice ; Microbiota/drug effects/genetics/*physiology ; Milk, Human/chemistry/microbiology ; Mothers ; Oligosaccharides/analysis/pharmacology/therapeutic use ; Ruminococcus/isolation & purification/physiology ; Somatomedins/biosynthesis ; Weight Gain/drug effects
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  • 33
    Publication Date: 2016-05-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cherp, Aleh -- Jewell, Jessica -- England -- Nature. 2016 May 5;533(7601):36. doi: 10.1038/533036b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Central European University, Budapest, Hungary. ; International Institute for Applied Systems Analysis, Laxenburg, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27147023" target="_blank"〉PubMed〈/a〉
    Keywords: *Fukushima Nuclear Accident ; Humans ; Research/*trends
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  • 34
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qiu, Jane -- England -- Nature. 2016 Apr 28;532(7600):428-31. doi: 10.1038/532428a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121822" target="_blank"〉PubMed〈/a〉
    Keywords: Altitude ; Disasters/*prevention & control/*statistics & numerical data ; Earthquakes/mortality/*statistics & numerical data ; *Forecasting ; Humans ; Landslides/mortality/*statistics & numerical data ; Nepal ; Rain
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  • 35
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2016 Feb 18;530(7590):264. doi: 10.1038/nature.2016.19335.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887470" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Feed/*analysis/standards ; Animal Nutritional Physiological Phenomena ; Animals ; *Animals, Laboratory/genetics/microbiology ; Confounding Factors (Epidemiology) ; Diet/standards/veterinary ; *Environment ; Female ; Gastrointestinal Microbiome ; *Housing, Animal ; Humans ; Lighting ; Male ; Mice ; Mice, Inbred Strains ; Models, Animal ; Reproducibility of Results ; *Research Design/standards
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 36
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Jan 14;529(7585):127. doi: 10.1038/529127a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26762420" target="_blank"〉PubMed〈/a〉
    Keywords: Alcohol Drinking/epidemiology/*legislation & jurisprudence/psychology ; Evidence-Based Practice ; Female ; Great Britain/epidemiology ; Guidelines as Topic ; Health Behavior ; Health Policy/*legislation & jurisprudence ; Humans ; Male ; *Policy Making
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  • 37
    Publication Date: 2016-03-17
    Description: The integrated stress response (ISR) is a homeostatic mechanism by which eukaryotic cells sense and respond to stress-inducing signals, such as amino acid starvation. General controlled non-repressed (GCN2) kinase is a key orchestrator of the ISR, and modulates protein synthesis in response to amino acid starvation. Here we demonstrate in mice that GCN2 controls intestinal inflammation by suppressing inflammasome activation. Enhanced activation of ISR was observed in intestinal antigen presenting cells (APCs) and epithelial cells during amino acid starvation, or intestinal inflammation. Genetic deletion of Gcn2 (also known as Eif2ka4) in CD11c(+) APCs or intestinal epithelial cells resulted in enhanced intestinal inflammation and T helper 17 cell (TH17) responses, owing to enhanced inflammasome activation and interleukin (IL)-1beta production. This was caused by reduced autophagy in Gcn2(-/-) intestinal APCs and epithelial cells, leading to increased reactive oxygen species (ROS), a potent activator of inflammasomes. Thus, conditional ablation of Atg5 or Atg7 in intestinal APCs resulted in enhanced ROS and TH17 responses. Furthermore, in vivo blockade of ROS and IL-1beta resulted in inhibition of TH17 responses and reduced inflammation in Gcn2(-/-) mice. Importantly, acute amino acid starvation suppressed intestinal inflammation via a mechanism dependent on GCN2. These results reveal a mechanism that couples amino acid sensing with control of intestinal inflammation via GCN2.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854628/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854628/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ravindran, Rajesh -- Loebbermann, Jens -- Nakaya, Helder I -- Khan, Nooruddin -- Ma, Hualing -- Gama, Leonardo -- Machiah, Deepa K -- Lawson, Benton -- Hakimpour, Paul -- Wang, Yi-chong -- Li, Shuzhao -- Sharma, Prachi -- Kaufman, Randal J -- Martinez, Jennifer -- Pulendran, Bali -- R01 DK088227/DK/NIDDK NIH HHS/ -- R01 DK103185/DK/NIDDK NIH HHS/ -- R37 AI048638/AI/NIAID NIH HHS/ -- R37 DK042394/DK/NIDDK NIH HHS/ -- R37 DK057665/DK/NIDDK NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19 AI090023/AI/NIAID NIH HHS/ -- ZIA ES103286-01/Intramural NIH HHS/ -- England -- Nature. 2016 Mar 24;531(7595):523-7. doi: 10.1038/nature17186. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. ; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508, Brazil. ; Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India. ; Division of Pathology, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. ; Virology Core, Emory Vaccine Center and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. ; Degenerative Disease Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037 USA. ; National Institute of Environmental Health Sciences, Mail Drop D2-01 Research Triangle Park, North Carolina 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982722" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/administration & dosage/deficiency/*metabolism/pharmacology ; Animals ; Antigen-Presenting Cells/immunology/metabolism ; Autophagy ; Colitis/etiology/*metabolism/pathology/prevention & control ; Disease Models, Animal ; Epithelial Cells/metabolism ; Female ; Humans ; Inflammasomes/*antagonists & inhibitors/metabolism ; Inflammation/etiology/*metabolism/pathology/prevention & control ; Interleukin-1beta/immunology ; Intestines/*metabolism/*pathology ; Male ; Mice ; Microtubule-Associated Proteins/deficiency/metabolism ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Stress, Physiological ; Th17 Cells/immunology ; Ubiquitin-Activating Enzymes/deficiency/metabolism
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  • 38
    Publication Date: 2016-02-04
    Description: The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans. Prdm9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized the DNA-binding domain of PRDM9 in C57BL/6 mice. This change repositions DSB hotspots and completely restores fertility in male hybrids. Here we show that alteration of one Prdm9 allele impacts the behaviour of DSBs controlled by the other allele at chromosome-wide scales. These effects correlate strongly with the degree to which each PRDM9 variant binds both homologues at the DSB sites it controls. Furthermore, higher genome-wide levels of such 'symmetric' PRDM9 binding associate with increasing fertility measures, and comparisons of individual hotspots suggest binding symmetry plays a downstream role in the recombination process. These findings reveal that subspecies-specific degradation of PRDM9 binding sites by meiotic drive, which steadily increases asymmetric PRDM9 binding, has impacts beyond simply changing hotspot positions, and strongly support a direct involvement in hybrid infertility. Because such meiotic drive occurs across mammals, PRDM9 may play a wider, yet transient, role in the early stages of speciation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756437/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756437/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davies, Benjamin -- Hatton, Edouard -- Altemose, Nicolas -- Hussin, Julie G -- Pratto, Florencia -- Zhang, Gang -- Hinch, Anjali Gupta -- Moralli, Daniela -- Biggs, Daniel -- Diaz, Rebeca -- Preece, Chris -- Li, Ran -- Bitoun, Emmanuelle -- Brick, Kevin -- Green, Catherine M -- Camerini-Otero, R Daniel -- Myers, Simon R -- Donnelly, Peter -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095552/Z/11/Z/Wellcome Trust/United Kingdom -- 098387/Z/12/Z/Wellcome Trust/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2016 Feb 11;530(7589):171-6. doi: 10.1038/nature16931. Epub 2016 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford OX3 7BN, UK. ; Department of Statistics, University of Oxford, 24-29 St. Giles', Oxford OX1 3LB, UK. ; Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26840484" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Binding Sites ; Chromosome Pairing/genetics ; Chromosomes, Mammalian/genetics/metabolism ; DNA Breaks, Double-Stranded ; Female ; *Genetic Speciation ; Histone-Lysine N-Methyltransferase/*chemistry/genetics/*metabolism ; Humans ; Hybridization, Genetic/*genetics ; Infertility/*genetics ; Male ; Meiosis/genetics ; Mice ; Mice, Inbred C57BL ; Protein Binding ; *Protein Engineering ; Protein Structure, Tertiary/genetics ; Recombination, Genetic/genetics ; Zinc Fingers/*genetics
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  • 39
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Jan 28;529(7587):446-7. doi: 10.1038/529446a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819022" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; *Disease Models, Animal ; Dog Diseases/*genetics ; Dogs/*genetics/*psychology ; Female ; Humans ; Male ; Obsessive-Compulsive Disorder/genetics ; Surveys and Questionnaires
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  • 40
    Publication Date: 2016-03-18
    Description: Chronic hepatitis B virus infection is a leading cause of cirrhosis and liver cancer. Hepatitis B virus encodes the regulatory HBx protein whose primary role is to promote transcription of the viral genome, which persists as an extrachromosomal DNA circle in infected cells. HBx accomplishes this task by an unusual mechanism, enhancing transcription only from extrachromosomal DNA templates. Here we show that HBx achieves this by hijacking the cellular DDB1-containing E3 ubiquitin ligase to target the 'structural maintenance of chromosomes' (Smc) complex Smc5/6 for degradation. Blocking this event inhibits the stimulatory effect of HBx both on extrachromosomal reporter genes and on hepatitis B virus transcription. Conversely, silencing the Smc5/6 complex enhances extrachromosomal reporter gene transcription in the absence of HBx, restores replication of an HBx-deficient hepatitis B virus, and rescues wild-type hepatitis B virus in a DDB1-knockdown background. The Smc5/6 complex associates with extrachromosomal reporters and the hepatitis B virus genome, suggesting a direct mechanism of transcriptional inhibition. These results uncover a novel role for the Smc5/6 complex as a restriction factor selectively blocking extrachromosomal DNA transcription. By destroying this complex, HBx relieves the inhibition to allow productive hepatitis B virus gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Decorsiere, Adrien -- Mueller, Henrik -- van Breugel, Pieter C -- Abdul, Fabien -- Gerossier, Laetitia -- Beran, Rudolf K -- Livingston, Christine M -- Niu, Congrong -- Fletcher, Simon P -- Hantz, Olivier -- Strubin, Michel -- England -- Nature. 2016 Mar 17;531(7594):386-9. doi: 10.1038/nature17170.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Medicine, University Medical Centre (C.M.U.), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. ; CRCL, INSERM U1052, CNRS 5286, Universite de Lyon, 151, Cours A Thomas, 69424 Lyon Cedex, France. ; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, California 94404, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26983541" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/*metabolism ; Cell Line, Tumor ; DNA, Viral/genetics/metabolism ; Genes, Reporter ; Genome, Viral/genetics ; Hepatitis B/virology ; Hepatitis B virus/genetics/*physiology ; Hepatocytes/virology ; *Host Specificity ; Humans ; Liver/metabolism/virology ; Male ; Mice ; Plasmids/genetics/metabolism ; Protein Binding ; Proteolysis ; Trans-Activators/*metabolism ; Transcription, Genetic ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Virus Replication
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Feb 4;530(7588):17. doi: 10.1038/530017a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842036" target="_blank"〉PubMed〈/a〉
    Keywords: Attention/drug effects ; Cognition Disorders/*complications/*drug therapy/psychology ; Depression/*complications/drug therapy/*psychology ; *Drug Discovery ; *Drug Industry/legislation & jurisprudence ; Humans ; Memory/drug effects ; Schizophrenia/drug therapy ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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  • 42
    Publication Date: 2016-03-17
    Description: Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to ensure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but haploid human ES cells have yet to be reported. Here we generated and analysed a collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics, such as self-renewal capacity and a pluripotency-specific molecular signature. Moreover, we demonstrated the utility of these cells as a platform for loss-of-function genetic screening. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and of genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Surprisingly, we found that a haploid human genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers both in vitro and in vivo, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics and development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sagi, Ido -- Chia, Gloryn -- Golan-Lev, Tamar -- Peretz, Mordecai -- Weissbein, Uri -- Sui, Lina -- Sauer, Mark V -- Yanuka, Ofra -- Egli, Dieter -- Benvenisty, Nissim -- England -- Nature. 2016 Apr 7;532(7597):107-11. doi: 10.1038/nature17408. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. ; Department of Pediatrics, Columbia University, New York, New York 10032, USA. ; Center for Women's Reproductive Care, College of Physicians and Surgeons, Columbia University, New York, New York 10019, USA. ; The New York Stem Cell Foundation Research Institute, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982723" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Differentiation ; Cell Self Renewal ; Cell Separation ; Cell Size ; Chromosomes, Human, X/genetics ; Diploidy ; Down-Regulation/genetics ; Gene Deletion ; Genetic Association Studies/*methods ; Germ Layers/cytology ; *Haploidy ; Human Embryonic Stem Cells/*cytology/*metabolism ; Humans ; Karyotyping ; Oocytes/metabolism ; Oxidative Phosphorylation ; Parthenogenesis ; Pluripotent Stem Cells/cytology/metabolism ; X Chromosome Inactivation/genetics
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  • 43
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Apr 28;532(7600):414. doi: 10.1038/532414a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121803" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/economics/manpower/*organization & administration/*trends ; *Federal Government ; Humans ; International Cooperation ; National Cancer Institute (U.S.) ; Neoplasms/*therapy ; Research Personnel/organization & administration ; United States
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeClerck, Fabrice -- England -- Nature. 2016 Mar 17;531(7594):305. doi: 10.1038/531305e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioversity International - CGIAR, Montpellier, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26983528" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*trends ; *Biodiversity ; Conservation of Natural Resources ; *Food Supply ; Goals ; Humans ; United Nations
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  • 45
    Publication Date: 2016-05-07
    Description: Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876960/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876960/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruibal, Paula -- Oestereich, Lisa -- Ludtke, Anja -- Becker-Ziaja, Beate -- Wozniak, David M -- Kerber, Romy -- Korva, Misa -- Cabeza-Cabrerizo, Mar -- Bore, Joseph A -- Koundouno, Fara Raymond -- Duraffour, Sophie -- Weller, Romy -- Thorenz, Anja -- Cimini, Eleonora -- Viola, Domenico -- Agrati, Chiara -- Repits, Johanna -- Afrough, Babak -- Cowley, Lauren A -- Ngabo, Didier -- Hinzmann, Julia -- Mertens, Marc -- Vitoriano, Ines -- Logue, Christopher H -- Boettcher, Jan Peter -- Pallasch, Elisa -- Sachse, Andreas -- Bah, Amadou -- Nitzsche, Katja -- Kuisma, Eeva -- Michel, Janine -- Holm, Tobias -- Zekeng, Elsa-Gayle -- Garcia-Dorival, Isabel -- Wolfel, Roman -- Stoecker, Kilian -- Fleischmann, Erna -- Strecker, Thomas -- Di Caro, Antonino -- Avsic-Zupanc, Tatjana -- Kurth, Andreas -- Meschi, Silvia -- Mely, Stephane -- Newman, Edmund -- Bocquin, Anne -- Kis, Zoltan -- Kelterbaum, Anne -- Molkenthin, Peter -- Carletti, Fabrizio -- Portmann, Jasmine -- Wolff, Svenja -- Castilletti, Concetta -- Schudt, Gordian -- Fizet, Alexandra -- Ottowell, Lisa J -- Herker, Eva -- Jacobs, Thomas -- Kretschmer, Birte -- Severi, Ettore -- Ouedraogo, Nobila -- Lago, Mar -- Negredo, Anabel -- Franco, Leticia -- Anda, Pedro -- Schmiedel, Stefan -- Kreuels, Benno -- Wichmann, Dominic -- Addo, Marylyn M -- Lohse, Ansgar W -- De Clerck, Hilde -- Nanclares, Carolina -- Jonckheere, Sylvie -- Van Herp, Michel -- Sprecher, Armand -- Xiaojiang, Gao -- Carrington, Mary -- Miranda, Osvaldo -- Castro, Carlos M -- Gabriel, Martin -- Drury, Patrick -- Formenty, Pierre -- Diallo, Boubacar -- Koivogui, Lamine -- Magassouba, N'Faly -- Carroll, Miles W -- Gunther, Stephan -- Munoz-Fontela, Cesar -- HHSN261200800001E/PHS HHS/ -- Z01 BC010791-01/Intramural NIH HHS/ -- Z01 BC010791-02/Intramural NIH HHS/ -- Z01 BC010792-01/Intramural NIH HHS/ -- England -- Nature. 2016 May 5;533(7601):100-4. doi: 10.1038/nature17949.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany. ; Bernhard Nocht Institute for Tropical Medicine, World Health Organization Collaborating Center for Arbovirus and Hemorrhagic Fever Reference and Research, 20359 Hamburg, Germany. ; German Center for Infection Research (DZIF), Partner Sites Hamburg, Munich, and Marburg, Germany. ; European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. ; Institute of Experimental Virology, Twincore, Center for Experimental and Clinical Infection Research, 30625 Hannover, Germany. ; Hannover Medical School, 30625 Hannover, Germany. ; National Institute for Infectious Diseases 'Lazzaro Spallanzani', 00149 Rome, Italy. ; Public Health England, Porton Down, Salisbury SP4 0JG, UK. ; Public Health England, Colindale Ave, London NW9 5EQ, UK. ; Robert Koch Institute, 13353 Berlin, Germany. ; Friedrich Loeffler Institute, 17493 Greifswald-Island of Riems, Germany. ; Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland. ; Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. ; Bundeswehr Institute of Microbiology, 80937 Munich, Germany. ; Institute of Virology, Philipps University, 35043 Marburg, Germany. ; Laboratoire P4-Jean Merieux, US003 INSERM, 69365 Lyon, France. ; National Center for Epidemiology, Hungarian National Biosafety Laboratory, H1097 Budapest, Hungary. ; European Centre for Disease Prevention and Control, 171 65 Solna, Sweden. ; Federal Office for Civil Protection, CH-3700 Spiez, Switzerland. ; Unite de Biologie des Infections Virales Emergentes, Institut Pasteur, 69365 Lyon, France. ; Eurice, European Research and Project Office, 10115 Berlin, Germany. ; Infectious Diseases Unit, Internal Medicine Service, Hospital La Paz, 28046 Madrid, Spain. ; National Center of Microbiology, Institute of Health 'Carlos III', 28220 Madrid, Spain. ; University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. ; Medecins sans Frontieres, B-1050 Brussels, Belgium. ; Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA. ; Hospital Militar Central Dr. Carlos J. Finlay, 11400 Havana, Cuba. ; World Health Organization, 1211 Geneva 27, Switzerland. ; Institut National de Sante Publique, 2101 Conakry, Guinea. ; Universite Gamal Abdel Nasser de Conakry, CHU Donka, 2101 Conakry, Guinea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27147028" target="_blank"〉PubMed〈/a〉
    Keywords: CTLA-4 Antigen/metabolism ; Ebolavirus/*immunology ; Female ; Flow Cytometry ; Guinea/epidemiology ; Hemorrhagic Fever, Ebola/*immunology/mortality/*physiopathology ; Humans ; Inflammation Mediators/immunology ; Longitudinal Studies ; Lymphocyte Activation ; Male ; Patient Discharge ; Programmed Cell Death 1 Receptor/metabolism ; Survivors ; T-Lymphocytes/*immunology/metabolism ; Viral Load
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  • 46
    Publication Date: 2016-04-15
    Description: Somatic mutations are the driving force of cancer genome evolution. The rate of somatic mutations appears to be greatly variable across the genome due to variations in chromatin organization, DNA accessibility and replication timing. However, other variables that may influence the mutation rate locally are unknown, such as a role for DNA-binding proteins, for example. Here we demonstrate that the rate of somatic mutations in melanomas is highly increased at active transcription factor binding sites and nucleosome embedded DNA, compared to their flanking regions. Using recently available excision-repair sequencing (XR-seq) data, we show that the higher mutation rate at these sites is caused by a decrease of the levels of nucleotide excision repair (NER) activity. Our work demonstrates that DNA-bound proteins interfere with the NER machinery, which results in an increased rate of DNA mutations at the protein binding sites. This finding has important implications for our understanding of mutational and DNA repair processes and in the identification of cancer driver mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sabarinathan, Radhakrishnan -- Mularoni, Loris -- Deu-Pons, Jordi -- Gonzalez-Perez, Abel -- Lopez-Bigas, Nuria -- England -- Nature. 2016 Apr 14;532(7598):264-7. doi: 10.1038/nature17661.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain. ; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075101" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; DNA/*genetics/*metabolism ; *DNA Repair ; DNA, Neoplasm/genetics/metabolism ; DNA-Binding Proteins/*metabolism ; Gene Expression Regulation, Neoplastic/genetics ; Genome, Human/genetics ; Humans ; Lung Neoplasms/genetics ; Melanoma/*genetics ; Mutagenesis/*genetics ; *Mutation Rate ; Nucleosomes/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding ; Transcription Factors/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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