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  • 1
    Publication Date: 2015-12-18
    Description: Understanding how ecological communities are organized and how they change through time is critical to predicting the effects of climate change. Recent work documenting the co-occurrence structure of modern communities found that most significant species pairs co-occur less frequently than would be expected by chance. However, little is known about how co-occurrence structure changes through time. Here we evaluate changes in plant and animal community organization over geological time by quantifying the co-occurrence structure of 359,896 unique taxon pairs in 80 assemblages spanning the past 300 million years. Co-occurrences of most taxon pairs were statistically random, but a significant fraction were spatially aggregated or segregated. Aggregated pairs dominated from the Carboniferous period (307 million years ago) to the early Holocene epoch (11,700 years before present), when there was a pronounced shift to more segregated pairs, a trend that continues in modern assemblages. The shift began during the Holocene and coincided with increasing human population size and the spread of agriculture in North America. Before the shift, an average of 64% of significant pairs were aggregated; after the shift, the average dropped to 37%. The organization of modern and late Holocene plant and animal assemblages differs fundamentally from that of assemblages over the past 300 million years that predate the large-scale impacts of humans. Our results suggest that the rules governing the assembly of communities have recently been changed by human activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lyons, S Kathleen -- Amatangelo, Kathryn L -- Behrensmeyer, Anna K -- Bercovici, Antoine -- Blois, Jessica L -- Davis, Matt -- DiMichele, William A -- Du, Andrew -- Eronen, Jussi T -- Faith, J Tyler -- Graves, Gary R -- Jud, Nathan -- Labandeira, Conrad -- Looy, Cindy V -- McGill, Brian -- Miller, Joshua H -- Patterson, David -- Pineda-Munoz, Silvia -- Potts, Richard -- Riddle, Brett -- Terry, Rebecca -- Toth, Aniko -- Ulrich, Werner -- Villasenor, Amelia -- Wing, Scott -- Anderson, Heidi -- Anderson, John -- Waller, Donald -- Gotelli, Nicholas J -- England -- Nature. 2016 Jan 7;529(7584):80-3. doi: 10.1038/nature16447. Epub 2015 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Paleobiology, National Museum of Natural History, Smithsonian Institution, Washington DC 20013, USA. ; Department of Environmental Science and Biology, The College at Brockport - SUNY, Brockport, New York 14420, USA. ; School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, California 95343, USA. ; Department of Geology and Geophysics, Yale University, New Haven, Connecticut 06520, USA. ; Hominid Paleobiology Doctoral Program, Center for the Advanced Study of Hominid Paleobiology, Department of Anthropology, George Washington University, Washington DC 20052, USA. ; Department of Geosciences and Geography, University of Helsinki, PO Box 64, 00014 University of Helsinki, Finland. ; School of Social Science, The University of Queensland, Brisbane, Queensland 4072, Australia. ; Department of Vertebrate Zoology, National Museum of Natural History, Smithsonian Institution, Washington DC 20013, USA. ; Center for Macroecology, Evolution and Climate, University of Copenhagen, Copenhagen 2100, Denmark. ; Biological Sciences Graduate Program, University of Maryland, College Park, Maryland 20742, USA. ; Florida Museum of Natural History, University of Florida, Gainsville, Florida 32611, USA. ; Department of Entomology, University of Maryland College Park, College Park, Maryland 20742, USA. ; Key Lab of Insect Evolution and Environmental Changes, Capital Normal University, Beijing 100048, China. ; Department of Integrative Biology and Museum of Paleontology, University of California Berkeley, Berkeley, California 94720, USA. ; School Biology and Ecology &Sustainability Solutions Initiative, University of Maine, Orono, Maine 04469, USA. ; Department of Geology, University of Cincinnati, Cincinnati, Ohio 45221, USA. ; Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia. ; Department of Anthropology, Human Origins Program, National Museum of Natural History, Smithsonian Institution, Washington DC 20013, USA. ; School of Life Sciences, University of Nevada-Las Vegas, Las Vegas, Nevada 89154, USA. ; Department of Integrative Biology, Oregon State University, Corvallis, Oregon 97331, USA. ; Chair of Ecology and Biogeography, Nicolaus Copernicus University, Lwowska 1, 87-100 Torun, Poland. ; Evolutionary Studies Institute, University of the Witwatersrand, Jorissen Street, Braamfontein, Johannesburg 2001, South Africa. ; Department of Botany, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. ; Department of Biology, University of Vermont, Burlington, Vermont 05405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26675730" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*history ; Animals ; *Ecosystem ; History, Ancient ; Human Activities/*history ; Humans ; North America ; *Plant Physiological Phenomena ; Population Dynamics ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, Mark M -- U19 AI057229/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):371-2. doi: 10.1126/science.aaa5082.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Institute for Immunity, Transplantation and Infection, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. mmdavis@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25613876" target="_blank"〉PubMed〈/a〉
    Keywords: CD4-Positive T-Lymphocytes/*immunology ; Candida albicans/*immunology ; Host-Pathogen Interactions/*immunology ; Humans ; *Immunologic Memory ; Mycobacterium tuberculosis/*immunology ; T-Lymphocyte Subsets/*immunology ; Vaccines/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2016-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nardone, Roland M -- MacLeod, Roderick A F -- Capes-Davis, Amanda -- England -- Nature. 2016 Apr 21;532(7599):313.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27127813" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; DNA Contamination ; Databases, Factual ; *Disease Models, Animal ; Guidelines as Topic ; Heterografts/*standards ; Humans ; National Cancer Institute (U.S.) ; Neoplasms/*pathology ; Quality Control ; Reproducibility of Results ; United States ; Xenograft Model Antitumor Assays/*standards
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2016-02-04
    Description: The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 x 10(-3) and 1.42 x 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quick, Joshua -- Loman, Nicholas J -- Duraffour, Sophie -- Simpson, Jared T -- Severi, Ettore -- Cowley, Lauren -- Bore, Joseph Akoi -- Koundouno, Raymond -- Dudas, Gytis -- Mikhail, Amy -- Ouedraogo, Nobila -- Afrough, Babak -- Bah, Amadou -- Baum, Jonathan H J -- Becker-Ziaja, Beate -- Boettcher, Jan Peter -- Cabeza-Cabrerizo, Mar -- Camino-Sanchez, Alvaro -- Carter, Lisa L -- Doerrbecker, Juliane -- Enkirch, Theresa -- Garcia-Dorival, Isabel -- Hetzelt, Nicole -- Hinzmann, Julia -- Holm, Tobias -- Kafetzopoulou, Liana Eleni -- Koropogui, Michel -- Kosgey, Abigael -- Kuisma, Eeva -- Logue, Christopher H -- Mazzarelli, Antonio -- Meisel, Sarah -- Mertens, Marc -- Michel, Janine -- Ngabo, Didier -- Nitzsche, Katja -- Pallasch, Elisa -- Patrono, Livia Victoria -- Portmann, Jasmine -- Repits, Johanna Gabriella -- Rickett, Natasha Y -- Sachse, Andreas -- Singethan, Katrin -- Vitoriano, Ines -- Yemanaberhan, Rahel L -- Zekeng, Elsa G -- Racine, Trina -- Bello, Alexander -- Sall, Amadou Alpha -- Faye, Ousmane -- Faye, Oumar -- Magassouba, N'Faly -- Williams, Cecelia V -- Amburgey, Victoria -- Winona, Linda -- Davis, Emily -- Gerlach, Jon -- Washington, Frank -- Monteil, Vanessa -- Jourdain, Marine -- Bererd, Marion -- Camara, Alimou -- Somlare, Hermann -- Camara, Abdoulaye -- Gerard, Marianne -- Bado, Guillaume -- Baillet, Bernard -- Delaune, Deborah -- Nebie, Koumpingnin Yacouba -- Diarra, Abdoulaye -- Savane, Yacouba -- Pallawo, Raymond Bernard -- Gutierrez, Giovanna Jaramillo -- Milhano, Natacha -- Roger, Isabelle -- Williams, Christopher J -- Yattara, Facinet -- Lewandowski, Kuiama -- Taylor, James -- Rachwal, Phillip -- Turner, Daniel J -- Pollakis, Georgios -- Hiscox, Julian A -- Matthews, David A -- O'Shea, Matthew K -- Johnston, Andrew McD -- Wilson, Duncan -- Hutley, Emma -- Smit, Erasmus -- Di Caro, Antonino -- Wolfel, Roman -- Stoecker, Kilian -- Fleischmann, Erna -- Gabriel, Martin -- Weller, Simon A -- Koivogui, Lamine -- Diallo, Boubacar -- Keita, Sakoba -- Rambaut, Andrew -- Formenty, Pierre -- Gunther, Stephan -- Carroll, Miles W -- Medical Research Council/United Kingdom -- England -- Nature. 2016 Feb 11;530(7589):228-32. doi: 10.1038/nature16996. Epub 2016 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK. ; The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Ontario Institute for Cancer Research, Toronto M5G 0A3, Canada. ; Department of Computer Science, University of Toronto, Toronto M5S 3G4, Canada. ; European Centre for Disease Prevention and Control (ECDC), 171 65 Solna, Sweden. ; National Infection Service, Public Health England, London NW9 5EQ, UK. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK. ; Postgraduate Training for Applied Epidemiology (PAE, German FETP), Robert Koch Institute, D-13302 Berlin, Germany. ; National Infection Service, Public Health England, Porton Down, Wiltshire SP4 0JG, UK. ; Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland. ; Robert Koch Institute, D-13302 Berlin, Germany. ; University College London, London WC1E 6BT, UK. ; Paul-Ehrlich-Institut, Division of Veterinary Medicine, D-63225 Langen, Germany. ; Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. ; Laboratory for Clinical and Epidemiological Virology, Department of Microbiology and Immunology, KU Leuven, Leuven B-3000, Belgium. ; Ministry of Health Guinea, Conakry BP 585, Guinea. ; Kenya Medical Research Institute, Nairobi P.O. BOX 54840 - 00200, Kenya. ; National Institute for Infectious Diseases L. Spallanzani, 00149 Rome, Italy. ; Friedrich-Loeffler-Institute, D-17493 Greifswald, Germany. ; Federal Office for Civil Protection, Spiez Laboratory, 3700 Spiez, Switzerland. ; Janssen-Cilag, Stockholm, Box 7073 - 19207, Sweden. ; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool L69 7BE, UK. ; Institute of Virology, Technische Universitat Munchen, D-81675 Munich, Germany. ; Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. ; Institut Pasteur Dakar, Dakar, DP 220 Senegal. ; Laboratoire de Fievres Hemorragiques de Guinee, Conakry BP 5680, Guinea. ; Sandia National Laboratories, PO Box 5800 MS1363, Albuquerque, New Mexico 87185-1363, USA. ; Ratoma Ebola Diagnostic Center, Conakry, Guinea. ; MRIGlobal, Kansas City, Missouri 64110-2241, USA. ; Expertise France, Laboratoire K-plan de Forecariah en Guinee, 75006 Paris, France. ; Federation des Laboratoires - HIA Begin, 94163 Saint-Mande cedex, France. ; Laboratoire de Biologie - Centre de Traitement des Soignants, Conakry, Guinea. ; World Health Organization, Conakry BP 817, Guinea. ; London School of Hygiene and Tropical Medicine, London EC1E 7HT, UK. ; Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. ; Public Health Wales, Cardiff CF11 9LJ, UK. ; Defence Science and Technology Laboratory (Dstl) Porton Down, Salisbury SP4 0JQ, UK. ; Oxford Nanopore Technologies, Oxford OX4 4GA, UK. ; Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. ; Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham B15 2TH, UK. ; Centre of Defence Pathology, Royal Centre for Defence Medicine, Birmingham B15 2TH, UK. ; Queen Elizabeth Hospital, Birmingham B12 2TH, UK. ; Bundeswehr Institute of Microbiology, D-80937 Munich, Germany. ; Institut National de Sante Publique, Conakry BP 1147, Guinea. ; Fogarty International Center, National Institutes of Health, Bethesda, MD 20892-2220, USA. ; Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 2FL, UK. ; University of Southampton, South General Hospital, Southampton SO16 6YD, UK. ; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, PHE Porton Down, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26840485" target="_blank"〉PubMed〈/a〉
    Keywords: Aircraft ; Disease Outbreaks/statistics & numerical data ; Ebolavirus/classification/*genetics/pathogenicity ; *Epidemiological Monitoring ; Genome, Viral/*genetics ; Guinea/epidemiology ; Hemorrhagic Fever, Ebola/*epidemiology/*virology ; Humans ; Mutagenesis/genetics ; Mutation Rate ; Sequence Analysis, DNA/*instrumentation/*methods ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-01-28
    Description: Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752392/" 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/PMC4752392/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sekar, Aswin -- Bialas, Allison R -- de Rivera, Heather -- Davis, Avery -- Hammond, Timothy R -- Kamitaki, Nolan -- Tooley, Katherine -- Presumey, Jessy -- Baum, Matthew -- Van Doren, Vanessa -- Genovese, Giulio -- Rose, Samuel A -- Handsaker, Robert E -- Schizophrenia Working Group of the Psychiatric Genomics Consortium -- Daly, Mark J -- Carroll, Michael C -- Stevens, Beth -- McCarroll, Steven A -- R01 HG006855/HG/NHGRI NIH HHS/ -- R01 MH077139/MH/NIMH NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U01 MH105641/MH/NIMH NIH HHS/ -- England -- Nature. 2016 Feb 11;530(7589):177-83. doi: 10.1038/nature16549. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; MD-PhD Program, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA. ; Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814963" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Animals ; Axons/metabolism ; Base Sequence ; Brain/metabolism/pathology ; Complement C4/chemistry/*genetics ; Complement Pathway, Classical ; Dendrites/metabolism ; Gene Dosage/genetics ; Gene Expression Regulation/genetics ; Genetic Predisposition to Disease/*genetics ; Genetic Variation/*genetics ; Haplotypes/genetics ; Humans ; Major Histocompatibility Complex/genetics ; Mice ; Models, Animal ; Neuronal Plasticity/genetics/physiology ; Polymorphism, Single Nucleotide/genetics ; RNA, Messenger/analysis/genetics ; Risk Factors ; Schizophrenia/*genetics/pathology ; Synapses/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2016-01-29
    Description: Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Wei -- Emaminejad, Sam -- Nyein, Hnin Yin Yin -- Challa, Samyuktha -- Chen, Kevin -- Peck, Austin -- Fahad, Hossain M -- Ota, Hiroki -- Shiraki, Hiroshi -- Kiriya, Daisuke -- Lien, Der-Hsien -- Brooks, George A -- Davis, Ronald W -- Javey, Ali -- P01 HG000205/HG/NHGRI NIH HHS/ -- England -- Nature. 2016 Jan 28;529(7587):509-14. doi: 10.1038/nature16521.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, USA. ; Berkeley Sensor and Actuator Center, University of California, Berkeley, California 94720, USA. ; Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. ; Stanford Genome Technology Center, Stanford School of Medicine, Palo Alto, California 94304, USA. ; Integrative Biology, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819044" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Bicycling/physiology ; Body Water ; Calibration ; Electrolytes/analysis ; Female ; Glucose/analysis ; Healthy Volunteers ; Humans ; Lactic Acid/analysis ; Male ; Monitoring, Physiologic/*instrumentation/*methods ; Precision Medicine/instrumentation/methods ; Reproducibility of Results ; Running/physiology ; Skin ; Skin Temperature ; Sweat/*chemistry ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2015-05-02
    Description: Centrioles are ancient organelles that build centrosomes, the major microtubule-organizing centers of animal cells. Extra centrosomes are a common feature of cancer cells. To investigate the importance of centrosomes in the proliferation of normal and cancer cells, we developed centrinone, a reversible inhibitor of Polo-like kinase 4 (Plk4), a serine-threonine protein kinase that initiates centriole assembly. Centrinone treatment caused centrosome depletion in human and other vertebrate cells. Centrosome loss irreversibly arrested normal cells in a senescence-like G1 state by a p53-dependent mechanism that was independent of DNA damage, stress, Hippo signaling, extended mitotic duration, or segregation errors. In contrast, cancer cell lines with normal or amplified centrosome numbers could proliferate indefinitely after centrosome loss. Upon centrinone washout, each cancer cell line returned to an intrinsic centrosome number "set point." Thus, cells with cancer-associated mutations fundamentally differ from normal cells in their response to centrosome loss.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764081/" 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/PMC4764081/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, Yao Liang -- Anzola, John V -- Davis, Robert L -- Yoon, Michelle -- Motamedi, Amir -- Kroll, Ashley -- Seo, Chanmee P -- Hsia, Judy E -- Kim, Sun K -- Mitchell, Jennifer W -- Mitchell, Brian J -- Desai, Arshad -- Gahman, Timothy C -- Shiau, Andrew K -- Oegema, Karen -- GM074207/GM/NIGMS NIH HHS/ -- GM089970/GM/NIGMS NIH HHS/ -- GM103403/GM/NIGMS NIH HHS/ -- R01 GM089970/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1155-60. doi: 10.1126/science.aaa5111. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. ; Small Molecule Discovery Program, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. ; Department of Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. ; Small Molecule Discovery Program, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. koegema@ucsd.edu ashiau@ucsd.edu. ; Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. koegema@ucsd.edu ashiau@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931445" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Proliferation ; Centrioles/*drug effects ; Humans ; Mice ; Piperazines/pharmacology ; Protein Kinase Inhibitors/chemistry/*pharmacology ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors ; Pyrimidines/chemistry/*pharmacology ; Sulfones/chemistry/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2015-07-23
    Description: How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733658/" 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/PMC4733658/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raghavan, Maanasa -- Steinrucken, Matthias -- Harris, Kelley -- Schiffels, Stephan -- Rasmussen, Simon -- DeGiorgio, Michael -- Albrechtsen, Anders -- Valdiosera, Cristina -- Avila-Arcos, Maria C -- Malaspinas, Anna-Sapfo -- Eriksson, Anders -- Moltke, Ida -- Metspalu, Mait -- Homburger, Julian R -- Wall, Jeff -- Cornejo, Omar E -- Moreno-Mayar, J Victor -- Korneliussen, Thorfinn S -- Pierre, Tracey -- Rasmussen, Morten -- Campos, Paula F -- Damgaard, Peter de Barros -- Allentoft, Morten E -- Lindo, John -- Metspalu, Ene -- Rodriguez-Varela, Ricardo -- Mansilla, Josefina -- Henrickson, Celeste -- Seguin-Orlando, Andaine -- Malmstrom, Helena -- Stafford, Thomas Jr -- Shringarpure, Suyash S -- Moreno-Estrada, Andres -- Karmin, Monika -- Tambets, Kristiina -- Bergstrom, Anders -- Xue, Yali -- Warmuth, Vera -- Friend, Andrew D -- Singarayer, Joy -- Valdes, Paul -- Balloux, Francois -- Leboreiro, Ilan -- Vera, Jose Luis -- Rangel-Villalobos, Hector -- Pettener, Davide -- Luiselli, Donata -- Davis, Loren G -- Heyer, Evelyne -- Zollikofer, Christoph P E -- Ponce de Leon, Marcia S -- Smith, Colin I -- Grimes, Vaughan -- Pike, Kelly-Anne -- Deal, Michael -- Fuller, Benjamin T -- Arriaza, Bernardo -- Standen, Vivien -- Luz, Maria F -- Ricaut, Francois -- Guidon, Niede -- Osipova, Ludmila -- Voevoda, Mikhail I -- Posukh, Olga L -- Balanovsky, Oleg -- Lavryashina, Maria -- Bogunov, Yuri -- Khusnutdinova, Elza -- Gubina, Marina -- Balanovska, Elena -- Fedorova, Sardana -- Litvinov, Sergey -- Malyarchuk, Boris -- Derenko, Miroslava -- Mosher, M J -- Archer, David -- Cybulski, Jerome -- Petzelt, Barbara -- Mitchell, Joycelynn -- Worl, Rosita -- Norman, Paul J -- Parham, Peter -- Kemp, Brian M -- Kivisild, Toomas -- Tyler-Smith, Chris -- Sandhu, Manjinder S -- Crawford, Michael -- Villems, Richard -- Smith, David Glenn -- Waters, Michael R -- Goebel, Ted -- Johnson, John R -- Malhi, Ripan S -- Jakobsson, Mattias -- Meltzer, David J -- Manica, Andrea -- Durbin, Richard -- Bustamante, Carlos D -- Song, Yun S -- Nielsen, Rasmus -- Willerslev, Eske -- 098051/Wellcome Trust/United Kingdom -- 261213/European Research Council/International -- 2R01HG003229-09/HG/NHGRI NIH HHS/ -- BB/H005854/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- R01-AI17892/AI/NIAID NIH HHS/ -- R01-GM094402/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):aab3884. doi: 10.1126/science.aab3884. Epub 2015 Jul 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Computer Science Division, University of California, Berkeley, Berkeley, CA 94720, USA. Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA. Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA 01003, USA. ; Department of Mathematics, University of California, Berkeley, Berkeley, CA 94720, USA. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark. ; Departments of Biology and Statistics, Pennsylvania State University, 502 Wartik Laboratory, University Park, PA 16802, USA. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Department of Archaeology and History, La Trobe University, Melbourne, Victoria 3086, Australia. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Department of Genetics, School of Medicine, Stanford University, 300 Pasteur Drive, Lane Building, Room L331, Stanford, CA 94305, USA. ; Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. Integrative Systems Biology Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia. ; Department of Genetics, School of Medicine, Stanford University, 300 Pasteur Drive, Lane Building, Room L331, Stanford, CA 94305, USA. ; Institute for Human Genetics, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. ; School of Biological Sciences, Washington State University, Post Office Box 644236, Heald 429, Pullman, WA 99164, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Centro de Investigacion en Ciencias del Mar y Limnologia/Centro Interdisciplinar de Investigacao Marinha e Ambiental, Centro Interdisciplinar de Investigacao Marinha e Ambiental, Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal. ; Department of Anthropology, University of Illinois at Urbana-Champaign, 607 S. Mathews Avenue, Urbana, IL 61801, USA. ; Centro Mixto, Universidad Complutense de Madrid-Instituto de Salud Carlos III de Evolucion y Comportamiento Humano, Madrid, Spain. ; Instituto Nacional de Antropologia e Historia, Moneda 13, Centro, Cuauhtemoc, 06060 Mexico City, Mexico. ; University of Utah, Department of Anthropology, 270 S 1400 E, Salt Lake City, UT 84112, USA. ; Department of Evolutionary Biology and Science for Life Laboratory, Uppsala University, Norbyvagen 18D, SE-752 36 Uppsala, Sweden. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Acceleration Mass Spectrometry 14C Dating Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, 8000 Aarhus, Denmark. ; Department of Genetics, School of Medicine, Stanford University, 300 Pasteur Drive, Lane Building, Room L331, Stanford, CA 94305, USA. Laboratorio Nacional de Genomica para la Biodiversidad (LANGEBIO), Centro de Investigacion y de Estudios Avanzados, Irapuato, Guanajuato 36821, Mexico. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. ; Genetics Institute, University College London, Gower Street, London WC1E 6BT, UK. Evolutionsbiologiskt Centrum, Norbyvagen 18D, 75236 Uppsala, Sweden. ; Department of Geography, University of Cambridge, Downing Place, Cambridge CB2 3EN, UK. ; Centre for Past Climate Change and Department of Meteorology, University of Reading, Earley Gate, Post Office Box 243, Reading, UK. ; School of Geographical Sciences, University Road, Clifton, Bristol BS8 1SS, UK. ; Genetics Institute, University College London, Gower Street, London WC1E 6BT, UK. ; Escuela Nacional de AntropologIa e Historia, Periferico Sur y Zapote s/n Colonia Isidro Fabela, Tlalpan, Isidro Fabela, 14030 Mexico City, Mexico. ; Instituto de Investigacion en Genetica Molecular, Universidad de Guadalajara, Ocotlan, Mexico. ; Dipartimento di Scienze Biologiche, Geologiche e Ambientali (BiGeA), Universita di Bologna, Via Selmi 3, 40126 Bologna, Italy. ; Department of Anthropology, Oregon State University, 238 Waldo Hall, Corvallis, OR 97331 USA. ; Museum National d'Histoire Naturelle, CNRS, Universite Paris 7 Diderot, Sorbonne Paris Cite, Sorbonne Universites, Unite Eco-Anthropologie et Ethnobiologie (UMR7206), Paris, France. ; Anthropological Institute and Museum, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. ; Department of Archaeology and History, La Trobe University, Melbourne, Victoria 3086, Australia. ; Department of Archaeology, Memorial University, Queen's College, 210 Prince Philip Drive, St. John's, Newfoundland A1C 5S7, Canada. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig 04103, Germany. ; Department of Archaeology, Memorial University, Queen's College, 210 Prince Philip Drive, St. John's, Newfoundland A1C 5S7, Canada. ; Department of Earth System Science, University of California, Irvine, Keck Carbon Cycle Accelerator Mass Spectrometry Group, B321 Croul Hall, Irvine, CA 92697, USA. ; Instituto de Alta Investigacion, Universidad de Tarapaca, 18 de Septiembre 2222, Carsilla 6-D Arica, Chile. ; Departamento de Antropologia, Universidad de Tarapaca, 18 de Septiembre 2222, Carsilla 6-D Arica, Chile. ; Fundacao Museu do Homem Americano, Centro Cultural Sergio Motta, Campestre, 64770-000 Sao Raimundo Nonato, Brazil. ; Laboratoire d'Anthropologie Moleculaire et Imagerie de Synthese UMR-5288, CNRS, Universite de Toulouse, 31073 Toulouse, France. ; Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentyeva 10, 630090 Novosibirsk, Russia. Novosibirsk State University, 2 Pirogova Street, 630090 Novosibirsk, Russia. ; Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentyeva 10, 630090 Novosibirsk, Russia. Institute of Internal Medicine, Siberian Branch of RAS, 175/1 ul. B. Bogatkova, Novosibirsk 630089, Russia. Novosibirsk State University, Laboratory of Molecular Epidemiology and Bioinformatics, 630090 Novosibirsk, Russia. ; Vavilov Institute of General Genetics, Gubkina 3, 119333 Moscow, Russia. Research Centre for Medical Genetics, Moskvorechie 1, 115478 Moscow, Russia. ; Kemerovo State University, Krasnaya 3, 650000 Kemerovo, Russia. ; Vavilov Institute of General Genetics, Gubkina 3, 119333 Moscow, Russia. ; Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Prospekt Oktyabrya 71, 450054 Ufa, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Zaki Validi 32, 450076 Ufa, Russia. ; Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentyeva 10, 630090 Novosibirsk, Russia. ; Research Centre for Medical Genetics, Moskvorechie 1, 115478 Moscow, Russia. ; Department of Molecular Genetics, Yakut Scientific Centre of Complex Medical Problems, Sergelyahskoe Shosse 4, 677010 Yakutsk, Russia. Laboratory of Molecular Biology, Institute of Natural Sciences, M. K. Ammosov North-Eastern Federal University, 677000 Yakutsk, Russia. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Prospekt Oktyabrya 71, 450054 Ufa, Russia. ; Institute of Biological Problems of the North, Russian Academy of Sciences, Portovaya Street 18, Magadan 685000, Russia. ; Department of Anthropology, Western Washington University, Bellingham, WA 98225, USA. ; Department of Anthropology, Northwest Community College, 353 Fifth Street, Prince Rupert, British Columbia V8J 3L6, Canada. ; Canadian Museum of History, 100 Rue Laurier, Gatineau, Quebec K1A 0M8, Canada. University of Western Ontario, London, Ontario N6A 3K7, Canada. Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. ; Metlakatla Treaty Office, Post Office Box 224, Prince Rupert, BC V8J 3P6, Canada. ; Sealaska Heritage Institute, 105 S. Seward Street, Juneau, AK 99801, USA. ; Department of Structural Biology, Stanford University School of Medicine, D100 Fairchild Science Building, Stanford, CA 94305-5126, USA. ; School of Biological Sciences, Washington State University, Post Office Box 644236, Heald 429, Pullman, WA 99164, USA. Department of Anthropology, Washington State University, Pullman, WA 99163, USA. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Division of Biological Anthropology, University of Cambridge, Henry Wellcome Building, Fitzwilliam Street, Cambridge CB2 1QH, UK. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK. Department of Medicine, University of Cambridge, Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Laboratory of Biological Anthropology, University of Kansas, 1415 Jayhawk Boulevard, 622 Fraser Hall, Lawrence, KS 66045, USA. ; Molecular Anthropology Laboratory, 209 Young Hall, Department of Anthropology, University of California, One Shields Avenue, Davis, CA 95616, USA. ; Center for the Study of the First Americans, Texas A&M University, College Station, TX 77843-4352, USA. Department of Anthropology, Texas A&M University, College Station, TX 77843-4352, USA. Department of Geography, Texas A&M University, College Station, TX 77843-4352, USA. ; Center for the Study of the First Americans, Texas A&M University, College Station, TX 77843-4352, USA. ; Santa Barbara Museum of Natural History, 2559 Puesta del Sol, Santa Barbara, CA 93105, USA. ; Department of Anthropology, University of Illinois at Urbana-Champaign, 607 S. Mathews Avenue, Urbana, IL 61801, USA. Carle R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Department of Anthropology, Southern Methodist University, Dallas, TX 75275, USA. ; Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. ; Computer Science Division, University of California, Berkeley, Berkeley, CA 94720, USA. Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA. Department of Integrative Biology, University of California, 3060 Valley Life Sciences Building 3140, Berkeley, CA 94720, USA. ewillierslev@snm.ku.dk rasmus_nielsen@berkeley.edu yss@berkeley.edu. ; Department of Integrative Biology, University of California, 3060 Valley Life Sciences Building 3140, Berkeley, CA 94720, USA. ewillierslev@snm.ku.dk rasmus_nielsen@berkeley.edu yss@berkeley.edu. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ewillierslev@snm.ku.dk rasmus_nielsen@berkeley.edu yss@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26198033" target="_blank"〉PubMed〈/a〉
    Keywords: Americas ; Gene Flow ; Genomics ; History, Ancient ; Human Migration/*history ; Humans ; Indians, North American/genetics/*history ; Models, Genetic ; Siberia
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2015-02-28
    Description: Global sustainability challenges, from maintaining biodiversity to providing clean air and water, are closely interconnected yet often separately studied and managed. Systems integration-holistic approaches to integrating various components of coupled human and natural systems-is critical to understand socioeconomic and environmental interconnections and to create sustainability solutions. Recent advances include the development and quantification of integrated frameworks that incorporate ecosystem services, environmental footprints, planetary boundaries, human-nature nexuses, and telecoupling. Although systems integration has led to fundamental discoveries and practical applications, further efforts are needed to incorporate more human and natural components simultaneously, quantify spillover systems and feedbacks, integrate multiple spatial and temporal scales, develop new tools, and translate findings into policy and practice. Such efforts can help address important knowledge gaps, link seemingly unconnected challenges, and inform policy and management decisions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jianguo -- Mooney, Harold -- Hull, Vanessa -- Davis, Steven J -- Gaskell, Joanne -- Hertel, Thomas -- Lubchenco, Jane -- Seto, Karen C -- Gleick, Peter -- Kremen, Claire -- Li, Shuxin -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1258832. doi: 10.1126/science.1258832.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Integration and Sustainability, Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI, USA. liuji@msu.edu. ; Department of Biology, Stanford University, Stanford, CA, USA. ; Center for Systems Integration and Sustainability, Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI, USA. ; Department of Earth System Science, University of California, Irvine, CA, USA. ; World Bank, Washington, DC, USA. ; Department of Agricultural Economics, Purdue University, West Lafayette, IN, USA. ; Department of Integrative Biology, Oregon State University, Corvallis, OR, USA. ; School of Forestry and Environmental Studies, Yale University, New Haven, CT, USA. ; The Pacific Institute, Oakland, CA, USA. ; Department of Environmental Science, Policy and Management, University of California, Berkeley, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722418" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Biofuels ; *Conservation of Natural Resources ; Earth (Planet) ; Endangered Species ; *Environmental Pollution ; Humans ; Socioeconomic Factors ; *Systems Integration ; Ursidae
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-07-01
    Description: Patterns of amino acid conservation have served as a tool for understanding protein evolution. The same principles have also found broad application in human genomics, driven by the need to interpret the pathogenic potential of variants in patients. Here we performed a systematic comparative genomics analysis of human disease-causing missense variants. We found that an appreciable fraction of disease-causing alleles are fixed in the genomes of other species, suggesting a role for genomic context. We developed a model of genetic interactions that predicts most of these to be simple pairwise compensations. Functional testing of this model on two known human disease genes revealed discrete cis amino acid residues that, although benign on their own, could rescue the human mutations in vivo. This approach was also applied to ab initio gene discovery to support the identification of a de novo disease driver in BTG2 that is subject to protective cis-modification in more than 50 species. Finally, on the basis of our data and models, we developed a computational tool to predict candidate residues subject to compensation. Taken together, our data highlight the importance of cis-genomic context as a contributor to protein evolution; they provide an insight into the complexity of allele effect on phenotype; and they are likely to assist methods for predicting allele pathogenicity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537371/" 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/PMC4537371/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jordan, Daniel M -- Frangakis, Stephan G -- Golzio, Christelle -- Cassa, Christopher A -- Kurtzberg, Joanne -- Task Force for Neonatal Genomics -- Davis, Erica E -- Sunyaev, Shamil R -- Katsanis, Nicholas -- R01 DK072301/DK/NIDDK NIH HHS/ -- R01 DK075972/DK/NIDDK NIH HHS/ -- R01 DK095721/DK/NIDDK NIH HHS/ -- R01 EY021872/EY/NEI NIH HHS/ -- R01 GM078598/GM/NIGMS NIH HHS/ -- R01 HD042601/HD/NICHD NIH HHS/ -- R01 MH101244/MH/NIMH NIH HHS/ -- R01DK072301/DK/NIDDK NIH HHS/ -- R01DK075972/DK/NIDDK NIH HHS/ -- R01EY021872/EY/NEI NIH HHS/ -- R01HD04260/HD/NICHD NIH HHS/ -- U01 HG006500/HG/NHGRI NIH HHS/ -- England -- Nature. 2015 Aug 13;524(7564):225-9. doi: 10.1038/nature14497. Epub 2015 Jun 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Human Disease Modeling, Duke University, Durham, North Carolina 27701, USA. ; Department of Pediatrics, Division of Pediatric Blood and Marrow Transplantation, Duke University, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26123021" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics ; Alleles ; Animals ; Disease/*genetics ; Evolution, Molecular ; Genome, Human/genetics ; *Genomics ; Humans ; Immediate-Early Proteins/genetics ; Microcephaly/genetics ; Mutation, Missense/*genetics ; Phenotype ; Proteins/genetics ; Sequence Alignment ; Suppression, Genetic/*genetics ; Tumor Suppressor Proteins/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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