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  • American Association for the Advancement of Science (AAAS)  (1,005)
  • American Association of Petroleum Geologists (AAPG)
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  • 1
    Publication Date: 2014-05-17
    Description: A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinohara, Hisaaki -- Behar, Marcelo -- Inoue, Kentaro -- Hiroshima, Michio -- Yasuda, Tomoharu -- Nagashima, Takeshi -- Kimura, Shuhei -- Sanjo, Hideki -- Maeda, Shiori -- Yumoto, Noriko -- Ki, Sewon -- Akira, Shizuo -- Sako, Yasushi -- Hoffmann, Alexander -- Kurosaki, Tomohiro -- Okada-Hatakeyama, Mariko -- 5R01CA141722/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 May 16;344(6185):760-4. doi: 10.1126/science.1250020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ; Laboratory for Cell Signaling Dynamics, RIKEN Quantitative Biology Center (QBiC), 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan. Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Graduate School of Engineering, Tottori University 4-101, Koyama-minami, Tottori 680-8552, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ; Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; CARD Signaling Adaptor Proteins/genetics/*metabolism ; Cell Line ; Chickens ; Feedback, Physiological ; Guanylate Cyclase/genetics/*metabolism ; I-kappa B Kinase/*metabolism ; MAP Kinase Kinase Kinases/genetics/*metabolism ; Mice ; Mice, Knockout ; Mutation ; NF-kappa B/*agonists ; Phosphorylation ; Receptors, Antigen, B-Cell/genetics/*metabolism ; Serine/genetics/metabolism ; Signal Transduction
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):29. doi: 10.1126/science.344.6179.29.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700839" target="_blank"〉PubMed〈/a〉
    Keywords: *Administrative Personnel ; Biomedical Research/*economics/organization & administration ; Budgets ; Financing, Government ; Illinois ; National Institutes of Health (U.S.)/economics ; Research Support as Topic/*organization & administration ; United States ; Universities/*economics/organization & administration
    Print ISSN: 0036-8075
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  • 3
    Publication Date: 2014-03-29
    Description: The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl(-)-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wietek, Jonas -- Wiegert, J Simon -- Adeishvili, Nona -- Schneider, Franziska -- Watanabe, Hiroshi -- Tsunoda, Satoshi P -- Vogt, Arend -- Elstner, Marcus -- Oertner, Thomas G -- Hegemann, Peter -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):409-12. doi: 10.1126/science.1249375. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology, Experimental Biophysics, Humboldt Universitat zu Berlin, D-10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674867" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Binding Sites ; CA1 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Ion Channel Gating ; Light ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Patch-Clamp Techniques ; Protein Conformation ; Protein Engineering ; Pyramidal Cells/metabolism ; Rats ; Recombinant Fusion Proteins/chemistry ; Rhodopsin/*chemistry/genetics/*metabolism ; Transfection
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1460-1. doi: 10.1126/science.343.6178.1460.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675951" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; *Breast Neoplasms ; Female ; Humans ; *Patient Advocacy ; United States
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):26. doi: 10.1126/science.344.6179.26.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700836" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; Financing, Government ; Humans ; National Institutes of Health (U.S.)/*economics ; Parkinson Disease ; Research Personnel/*economics ; *Research Support as Topic ; United States
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arita, Isao -- Francis, Donald -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1010. doi: 10.1126/science.345.6200.1010-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Director Emeritus, National Hospital Organization, Kumamoto Medical Center, Kumamoto 861-8068, Japan. ; Executive Director, Global Solutions for Infectious Diseases, South San Francisco, CA 94080, USA. dfrancis@gsid.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170141" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Specimen Banks ; Biological Warfare Agents ; *Disease Eradication ; Humans ; Risk Assessment ; Russia ; Smallpox/epidemiology/*prevention & control/virology ; United States ; *Variola virus ; World Health Organization
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):238. doi: 10.1126/science.343.6168.238.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436398" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture ; Air Pollutants/*adverse effects/analysis ; Air Pollution/*adverse effects/prevention & control ; Ammonia/*adverse effects/analysis ; Animals ; Fertilizers/*adverse effects ; Health/*economics ; Heart Diseases/chemically induced ; Humans ; Livestock ; Models, Biological ; North Carolina ; Particulate Matter/*adverse effects/analysis ; Respiratory Tract Diseases/chemically induced ; United States ; United States Environmental Protection Agency
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 May 16;344(6185):679. doi: 10.1126/science.344.6185.679.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833367" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation/*standards ; Animals ; Biomedical Research/*standards ; Cells ; Female ; Male ; Mice ; National Institutes of Health (U.S.) ; Sex Factors ; United States ; X Chromosome ; Y Chromosome
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clery, Daniel -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):290-1. doi: 10.1126/science.346.6207.290.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324365" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chemistry ; Mice ; Microscopy, Fluorescence/*methods ; *Nobel Prize ; Organelles/ultrastructure ; United States
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNutt, Marcia -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):6. doi: 10.1126/science.1250035.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marcia McNutt is Editor-in-Chief of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385608" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Gross Domestic Product/trends ; Research/*economics/*trends ; United States
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNutt, Marcia -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):229. doi: 10.1126/science.1250475.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marcia McNutt is Editor-in-Chief of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436391" target="_blank"〉PubMed〈/a〉
    Keywords: Disclosure/*standards ; *Guidelines as Topic ; Humans ; National Institute of Neurological Disorders and Stroke ; *Peer Review, Research ; Reproducibility of Results ; Translational Medical Research/standards ; United States
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  • 12
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):24-5. doi: 10.1126/science.344.6179.24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700835" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; Budgets ; Financing, Government ; National Institutes of Health (U.S.)/*economics ; *Research Support as Topic/trends ; United States ; Universities/economics
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):15. doi: 10.1126/science.343.6166.15.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385614" target="_blank"〉PubMed〈/a〉
    Keywords: Research Report ; Social Control, Formal ; United States ; *United States Environmental Protection Agency ; *Wetlands
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  • 14
    Publication Date: 2014-11-15
    Description: Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Benyue -- Chassaing, Benoit -- Shi, Zhenda -- Uchiyama, Robin -- Zhang, Zhan -- Denning, Timothy L -- Crawford, Sue E -- Pruijssers, Andrea J -- Iskarpatyoti, Jason A -- Estes, Mary K -- Dermody, Terence S -- Ouyang, Wenjun -- Williams, Ifor R -- Vijay-Kumar, Matam -- Gewirtz, Andrew T -- AI038296/AI/NIAID NIH HHS/ -- AI080656/AI/NIAID NIH HHS/ -- AI107943/AI/NIAID NIH HHS/ -- DK061417/DK/NIDDK NIH HHS/ -- DK064730/DK/NIDDK NIH HHS/ -- DK56338/DK/NIDDK NIH HHS/ -- R01 AI038296/AI/NIAID NIH HHS/ -- R37 AI038296/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):861-5. doi: 10.1126/science.1256999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pediatrics, Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Department of Immunology, Genentech, South San Francisco, CA, USA. ; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Nutritional Sciences and Medicine, Pennsylvania State University, University Park, PA 16802, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. agewirtz@gsu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diarrhea/immunology/therapy/virology ; Disease Models, Animal ; Feces/virology ; Flagellin/*administration & dosage/immunology ; Homeodomain Proteins/genetics ; *Immunity, Innate ; Interleukin-18/administration & dosage/genetics/*immunology ; Interleukins/administration & dosage/genetics/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mutation ; Rotavirus Infections/immunology/*prevention & control/therapy ; Toll-Like Receptor 5/genetics/*physiology ; Virus Shedding
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  • 15
    Publication Date: 2014-09-13
    Description: In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431643/" 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/PMC4431643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gire, Stephen K -- Goba, Augustine -- Andersen, Kristian G -- Sealfon, Rachel S G -- Park, Daniel J -- Kanneh, Lansana -- Jalloh, Simbirie -- Momoh, Mambu -- Fullah, Mohamed -- Dudas, Gytis -- Wohl, Shirlee -- Moses, Lina M -- Yozwiak, Nathan L -- Winnicki, Sarah -- Matranga, Christian B -- Malboeuf, Christine M -- Qu, James -- Gladden, Adrianne D -- Schaffner, Stephen F -- Yang, Xiao -- Jiang, Pan-Pan -- Nekoui, Mahan -- Colubri, Andres -- Coomber, Moinya Ruth -- Fonnie, Mbalu -- Moigboi, Alex -- Gbakie, Michael -- Kamara, Fatima K -- Tucker, Veronica -- Konuwa, Edwin -- Saffa, Sidiki -- Sellu, Josephine -- Jalloh, Abdul Azziz -- Kovoma, Alice -- Koninga, James -- Mustapha, Ibrahim -- Kargbo, Kandeh -- Foday, Momoh -- Yillah, Mohamed -- Kanneh, Franklyn -- Robert, Willie -- Massally, James L B -- Chapman, Sinead B -- Bochicchio, James -- Murphy, Cheryl -- Nusbaum, Chad -- Young, Sarah -- Birren, Bruce W -- Grant, Donald S -- Scheiffelin, John S -- Lander, Eric S -- Happi, Christian -- Gevao, Sahr M -- Gnirke, Andreas -- Rambaut, Andrew -- Garry, Robert F -- Khan, S Humarr -- Sabeti, Pardis C -- 095831/Wellcome Trust/United Kingdom -- 1DP2OD006514-01/OD/NIH HHS/ -- 1U01HG007480-01/HG/NHGRI NIH HHS/ -- 260864/European Research Council/International -- DP2 OD006514/OD/NIH HHS/ -- GM080177/GM/NIGMS NIH HHS/ -- HHSN272200900049C/AI/NIAID NIH HHS/ -- HHSN272200900049C/PHS HHS/ -- T32 GM080177/GM/NIGMS NIH HHS/ -- U01 HG007480/HG/NHGRI NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U19 AI115589/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1369-72. doi: 10.1126/science.1259657. Epub 2014 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. ; Kenema Government Hospital, Kenema, Sierra Leone. Eastern Polytechnic College, Kenema, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Tulane University Medical Center, New Orleans, LA 70112, USA. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Redeemer's University, Ogun State, Nigeria. ; University of Sierra Leone, Freetown, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214632" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Disease Outbreaks ; Ebolavirus/*genetics/isolation & purification ; *Epidemiological Monitoring ; Genetic Variation ; Genome, Viral/genetics ; Genomics/methods ; Hemorrhagic Fever, Ebola/epidemiology/*transmission/*virology ; Humans ; Mutation ; Sequence Analysis, DNA ; Sierra Leone/epidemiology
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  • 16
    Publication Date: 2014-10-11
    Description: Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354858/" 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/PMC4354858/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jianjun -- Fujimoto, Junya -- Zhang, Jianhua -- Wedge, David C -- Song, Xingzhi -- Zhang, Jiexin -- Seth, Sahil -- Chow, Chi-Wan -- Cao, Yu -- Gumbs, Curtis -- Gold, Kathryn A -- Kalhor, Neda -- Little, Latasha -- Mahadeshwar, Harshad -- Moran, Cesar -- Protopopov, Alexei -- Sun, Huandong -- Tang, Jiabin -- Wu, Xifeng -- Ye, Yuanqing -- William, William N -- Lee, J Jack -- Heymach, John V -- Hong, Waun Ki -- Swisher, Stephen -- Wistuba, Ignacio I -- Futreal, P Andrew -- CA016672/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P50 CA070907/CA/NCI NIH HHS/ -- P50CA70907/CA/NCI NIH HHS/ -- T32 CA-009666/CA/NCI NIH HHS/ -- T32 CA009666/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):256-9. doi: 10.1126/science.1256930.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Applied Cancer Science Institute, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Honorary Faculty, Wellcome Trust Sanger Institute, Hinxton, UK CB10 1SA. afutreal@mdanderson.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301631" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/*genetics/pathology ; DNA Mutational Analysis ; Exome/genetics ; Genes, Neoplasm ; *Genetic Heterogeneity ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neoplasm Recurrence, Local/*genetics/pathology
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  • 17
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Eliot -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):359. doi: 10.1126/science.343.6169.359.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458618" target="_blank"〉PubMed〈/a〉
    Keywords: Consumer Organizations ; *Embryonic Stem Cells ; Humans ; *Patents as Topic ; Stem Cell Research/*legislation & jurisprudence ; Supreme Court Decisions ; United States
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  • 18
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kean, Sam -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1457-9. doi: 10.1126/science.343.6178.1457.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675950" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/*genetics ; Checkpoint Kinase 2/genetics ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; *Genetic Predisposition to Disease ; Humans ; Mutation ; Nuclear Proteins/genetics ; *Oncogenes ; Tumor Suppressor Proteins/genetics
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-11-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woolley, Mary -- Leshner, Alan I -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):791. doi: 10.1126/science.aaa2692.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mary Woolley is the president and chief executive officer of Research!America. mwoolley@researchamerica.org. ; Alan I. Leshner is the chief executive officer of the American Association for the Advancement of Science and executive publisher of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395507" target="_blank"〉PubMed〈/a〉
    Keywords: Earthquakes ; *Federal Government ; Floods ; Hemorrhagic Fever, Ebola ; Humans ; Petroleum Pollution ; Politics ; Science/*economics/*trends ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pringle, Heather -- New York, N.Y. -- Science. 2014 Feb 28;343(6174):961-3. doi: 10.1126/science.343.6174.961.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24578560" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Migration ; Animals ; Archaeology ; Arctic Regions ; Asian Continental Ancestry Group/*genetics ; *Cold Temperature ; DNA, Mitochondrial/genetics ; Deer/*genetics ; Genetic Variation ; *Human Migration ; Humans ; Ice Cover ; Indians, North American/*genetics ; Islands ; Mutation ; North America ; Rivers ; Siberia
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  • 21
    Publication Date: 2014-03-08
    Description: The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" 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/PMC3991565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Huixian -- Wang, Chong -- Gregory, Karen J -- Han, Gye Won -- Cho, Hyekyung P -- Xia, Yan -- Niswender, Colleen M -- Katritch, Vsevolod -- Meiler, Jens -- Cherezov, Vadim -- Conn, P Jeffrey -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK097376/DK/NIDDK NIH HHS/ -- R01 GM080403/GM/NIGMS NIH HHS/ -- R01 GM099842/GM/NIGMS NIH HHS/ -- R01 MH062646/MH/NIMH NIH HHS/ -- R01 MH090192/MH/NIMH NIH HHS/ -- R01 NS031373/NS/NINDS NIH HHS/ -- R21 NS078262/NS/NINDS NIH HHS/ -- R37 NS031373/NS/NINDS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24603153" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Allosteric Site ; Amino Acid Sequence ; Benzamides/*chemistry/*metabolism ; Binding Sites ; Cholesterol ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Metabotropic Glutamate/*chemistry/*metabolism ; Structure-Activity Relationship ; Thiazoles/*chemistry/*metabolism
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1441-2. doi: 10.1126/science.345.6203.1441.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237082" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Communicable Disease Control/*economics ; Disease Outbreaks/*prevention & control ; Drug Industry/*economics ; Drugs, Investigational/*economics ; Ebola Vaccines/*economics ; Hemorrhagic Fever, Ebola/*epidemiology/*prevention & control ; Humans ; United States
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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kennedy, Donald -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):13. doi: 10.1126/science.346.6205.13. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donald Kennedy is president emeritus at Stanford University, Stanford, CA, and a former editor-in-chief of Science. kennedyd@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278586" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/economics/*trends ; Research/economics/*trends ; United States ; United States Department of Agriculture
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharjee, Yudhijit -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):33. doi: 10.1126/science.344.6179.33.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700842" target="_blank"〉PubMed〈/a〉
    Keywords: BK Virus ; Biomedical Research/*economics ; Financing, Government ; National Institutes of Health (U.S.)/*economics ; *Research Support as Topic/economics/organization & administration ; Salaries and Fringe Benefits ; Travel/economics ; United States ; Virology
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharjee, Yudhijit -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1306-9. doi: 10.1126/science.343.6177.1306.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653017" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Evolution ; DNA, Intergenic/genetics ; Databases, Nucleic Acid ; *Genome, Human ; *Genomics ; History, 20th Century ; History, 21st Century ; Humans ; Molecular Sequence Annotation ; Mutation ; National Human Genome Research Institute (U.S.) ; Transcription Factors/metabolism ; Transcription, Genetic ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-07-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):247-8. doi: 10.1126/science.345.6194.247.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035464" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthrax ; Biohazard Release/*prevention & control ; Centers for Disease Control and Prevention (U.S.) ; Humans ; *Influenza, Human ; *Laboratories ; National Institutes of Health (U.S.) ; Public Health ; *Safety ; United States
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kerr, Richard A -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):138-9. doi: 10.1126/science.344.6180.138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24723588" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Research Personnel/*economics ; *Solar System ; Space Flight/*economics ; United States ; United States National Aeronautics and Space Administration/*economics
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  • 28
    Publication Date: 2014-05-24
    Description: Decisions take time if information gradually accumulates to a response threshold, but the neural mechanisms of integration and thresholding are unknown. We characterized a decision process in Drosophila that bears the behavioral signature of evidence accumulation. As stimulus contrast in trained odor discriminations decreased, reaction times increased and perceptual accuracy declined, in quantitative agreement with a drift-diffusion model. FoxP mutants took longer than wild-type flies to form decisions of similar or reduced accuracy, especially in difficult, low-contrast tasks. RNA interference with FoxP expression in alphabeta core Kenyon cells, or the overexpression of a potassium conductance in these neurons, recapitulated the FoxP mutant phenotype. A mushroom body subdomain whose development or function require the transcription factor FoxP thus supports the progression of a decision toward commitment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206523/" 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/PMC4206523/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DasGupta, Shamik -- Ferreira, Clara Howcroft -- Miesenbock, Gero -- 090309/Wellcome Trust/United Kingdom -- G0700888/Medical Research Council/United Kingdom -- G0701225/Medical Research Council/United Kingdom -- R01 DA030601/DA/NIDA NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 May 23;344(6186):901-4. doi: 10.1126/science.1252114.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, OX1 3SR, UK. ; Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, OX1 3SR, UK. gero.miesenboeck@cncb.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855268" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; Cell Line ; *Decision Making ; Drosophila Proteins/genetics/*physiology ; Drosophila melanogaster/genetics/*physiology ; Forkhead Transcription Factors/genetics/*physiology ; Mushroom Bodies/growth & development/metabolism ; Mutation ; Neurons/physiology ; Odors ; *Psychomotor Performance ; RNA Interference ; Reaction Time/genetics/*physiology ; Smell
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bloom, Barry R -- Marcuse, Edgar -- Mnookin, Seth -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):339. doi: 10.1126/science.1254834.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Barry R. Bloom is a professor at the Harvard School of Public Health, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763557" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Disease Outbreaks/*prevention & control ; *Health Knowledge, Attitudes, Practice ; Humans ; Infant ; Parents/*psychology ; *Research ; Research Design ; *Treatment Refusal/psychology ; United States ; *Vaccination/psychology/utilization
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  • 30
    Publication Date: 2014-07-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis S -- Wilder, Elizabeth L -- Zerhouni, Elias -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):274-6. doi: 10.1126/science.1255860. Epub 2014 Jun 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institutes of Health, Bethesda, MD 20892, USA. francis.collins@nih.gov. ; National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035478" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; *Financial Management ; Humans ; National Institutes of Health (U.S.)/*economics ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-09-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hand, Eric -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1233. doi: 10.1126/science.345.6202.1233.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214586" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollutants/analysis/*standards ; Air Pollution/analysis/*legislation & jurisprudence ; China ; Climate Change ; Ozone/analysis/*standards ; United States ; United States Environmental Protection Agency/economics/legislation & ; jurisprudence ; Wind
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1298. doi: 10.1126/science.343.6177.1298-b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653013" target="_blank"〉PubMed〈/a〉
    Keywords: *Budgets ; Financing, Government ; *Politics ; Public Policy ; *Research Support as Topic ; United States ; United States Government Agencies/economics/*legislation & ; jurisprudence/organization & administration
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 May 23;344(6186):836-7. doi: 10.1126/science.344.6186.836.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855257" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Policy Making ; Social Mobility/*statistics & numerical data/*trends ; Taxes ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1298-9. doi: 10.1126/science.343.6177.1298-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653012" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Financing, Government ; *Politics ; Public Policy ; *Research Support as Topic ; United States ; United States Government Agencies/*legislation & jurisprudence/organization & ; administration
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-02-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):830. doi: 10.1126/science.343.6173.830.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558139" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; *Federal Government ; Research/*economics ; United States
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  • 36
    Publication Date: 2014-07-26
    Description: Proteins that cap the ends of the actin filament are essential regulators of cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end. The lack of structural information severely limits our understanding of Tmod's capping mechanism. We describe crystal structures of actin complexes with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal domains of Tmod. The structures and biochemical analysis of structure-inspired mutants showed that one Tmod molecule interacts with three actin subunits at the pointed end, while also contacting two tropomyosin molecules on each side of the filament. We found that Tmod achieves high-affinity binding through several discrete low-affinity interactions, which suggests a mechanism for controlled subunit exchange at the pointed end.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367809/" 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/PMC4367809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rao, Jampani Nageswara -- Madasu, Yadaiah -- Dominguez, Roberto -- GM-0080/GM/NIGMS NIH HHS/ -- R01 GM073791/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):463-7. doi: 10.1126/science.1256159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. droberto@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061212" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*chemistry ; Actins/*chemistry ; Amino Acid Sequence ; Animals ; Crystallography, X-Ray ; Humans ; Molecular Sequence Data ; Mutation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rabbits ; Tropomodulin/*chemistry/genetics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-24
    Description: This Review presents basic facts regarding the long-run evolution of income and wealth inequality in Europe and the United States. Income and wealth inequality was very high a century ago, particularly in Europe, but dropped dramatically in the first half of the 20th century. Income inequality has surged back in the United States since the 1970s so that the United States is much more unequal than Europe today. We discuss possible interpretations and lessons for the future.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piketty, Thomas -- Saez, Emmanuel -- New York, N.Y. -- Science. 2014 May 23;344(6186):838-43. doi: 10.1126/science.1251936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Economics, Paris School of Economics, Paris, France. thomas.piketty@psemail.eu. ; Department of Economics, University of California at Berkeley, Berkeley, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855258" target="_blank"〉PubMed〈/a〉
    Keywords: *Economic Development ; Europe ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Income/history/*statistics & numerical data/*trends ; Socioeconomic Factors/history ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):357. doi: 10.1126/science.343.6169.357.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458616" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; *Budgets ; *Financing, Government ; National Institutes of Health (U.S.)/*economics ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):596-8. doi: 10.1126/science.343.6171.596.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503830" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/*trends ; Clinical Trials as Topic/economics/trends ; Financing, Organized ; Humans ; *National Institutes of Health (U.S.) ; *Peer Review, Research ; Publications/*statistics & numerical data ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):237. doi: 10.1126/science.343.6168.237.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436397" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/education ; *Budgets ; Physics/economics ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2014 May 2;344(6183):457-8. doi: 10.1126/science.344.6183.457.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786052" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Camels/virology ; Communicable Diseases, Emerging/*epidemiology/*transmission/virology ; Coronavirus/genetics/*isolation & purification ; *Disease Outbreaks ; Food Contamination ; Genome, Viral ; Humans ; Meat/virology ; Milk/virology ; Mutation ; Risk Assessment ; Saudi Arabia/epidemiology ; Severe Acute Respiratory Syndrome/*epidemiology/*transmission/virology ; Species Specificity
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 Jan 10;343(6167):125-6. doi: 10.1126/science.343.6167.125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24408407" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; Curriculum ; Science/*education ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cordova, France -- Mervis, Jeffrey -- New York, N.Y. -- Science. 2014 May 30;344(6187):959-61. doi: 10.1126/science.344.6187.959.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876473" target="_blank"〉PubMed〈/a〉
    Keywords: *Foundations ; Science/*economics ; United States
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  • 44
    Publication Date: 2014-05-24
    Description: Cushing's syndrome is caused by excess cortisol production from the adrenocortical gland. In corticotropin-independent Cushing's syndrome, the excess cortisol production is primarily attributed to an adrenocortical adenoma, in which the underlying molecular pathogenesis has been poorly understood. We report a hotspot mutation (L206R) in PRKACA, which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), in more than 50% of cases with adrenocortical adenomas associated with corticotropin-independent Cushing's syndrome. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of PRKACA, leading to constitutive, cAMP-independent PKA activation. These results highlight the major role of cAMP-independent activation of cAMP/PKA signaling by somatic mutations in corticotropin-independent Cushing's syndrome, providing insights into the diagnosis and therapeutics of this syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sato, Yusuke -- Maekawa, Shigekatsu -- Ishii, Ryohei -- Sanada, Masashi -- Morikawa, Teppei -- Shiraishi, Yuichi -- Yoshida, Kenichi -- Nagata, Yasunobu -- Sato-Otsubo, Aiko -- Yoshizato, Tetsuichi -- Suzuki, Hiromichi -- Shiozawa, Yusuke -- Kataoka, Keisuke -- Kon, Ayana -- Aoki, Kosuke -- Chiba, Kenichi -- Tanaka, Hiroko -- Kume, Haruki -- Miyano, Satoru -- Fukayama, Masashi -- Nureki, Osamu -- Homma, Yukio -- Ogawa, Seishi -- New York, N.Y. -- Science. 2014 May 23;344(6186):917-20. doi: 10.1126/science.1252328.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp. ; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. sogawa-tky@umin.ac.jp homma-uro@umin.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855271" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Cortex Neoplasms/*genetics ; Adrenocortical Adenoma/*genetics ; Adrenocorticotropic Hormone/metabolism ; Animals ; Catalytic Domain/genetics ; Cushing Syndrome/*genetics/metabolism ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/*genetics/metabolism ; DNA Mutational Analysis ; GTP-Binding Protein alpha Subunits/genetics ; HEK293 Cells ; Humans ; Mice ; Mutation ; NIH 3T3 Cells ; PC12 Cells ; Rats
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-07-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carney, Joanne Padron -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):243. doi: 10.1126/science.1258492.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joanne Padron Carney is the director of government relations at AAAS, Washington, DC. jcarney@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035462" target="_blank"〉PubMed〈/a〉
    Keywords: *Communication ; *Federal Government ; Policy ; *Policy Making ; *Science ; United States
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  • 46
    Publication Date: 2014-01-18
    Description: Transcription factors (TFs) are key players in evolution. Changes affecting their function can yield novel life forms but may also have deleterious effects. Consequently, gene duplication events that release one gene copy from selective pressure are thought to be the common mechanism by which TFs acquire new activities. Here, we show that LEAFY, a major regulator of flower development and cell division in land plants, underwent changes to its DNA binding specificity, even though plant genomes generally contain a single copy of the LEAFY gene. We examined how these changes occurred at the structural level and identify an intermediate LEAFY form in hornworts that appears to adopt all different specificities. This promiscuous intermediate could have smoothed the evolutionary transitions, thereby allowing LEAFY to evolve new binding specificities while remaining a single-copy gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sayou, Camille -- Monniaux, Marie -- Nanao, Max H -- Moyroud, Edwige -- Brockington, Samuel F -- Thevenon, Emmanuel -- Chahtane, Hicham -- Warthmann, Norman -- Melkonian, Michael -- Zhang, Yong -- Wong, Gane Ka-Shu -- Weigel, Detlef -- Parcy, Francois -- Dumas, Renaud -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):645-8. doi: 10.1126/science.1248229. Epub 2014 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, Laboratoire de Physiologie Cellulaire et Vegetale (LPCV), UMR 5168, 38054 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436181" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis Proteins/chemistry/classification/genetics ; DNA, Plant/*chemistry ; DNA-Binding Proteins/*chemistry/classification/*genetics ; Electrophoretic Mobility Shift Assay ; *Evolution, Molecular ; Gene Dosage ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Proteins/*chemistry/classification/*genetics ; Protein Binding/genetics ; Protein Structure, Tertiary ; Species Specificity ; Transcription Factors/chemistry/classification/genetics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carswell, Cally -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):154-6. doi: 10.1126/science.346.6206.154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cally Carswell is a freelance science and environment writer in Santa Fe.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301598" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Pinus/*parasitology ; Plant Bark/*parasitology ; Trees/*parasitology ; United States ; *Weevils
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  • 48
    Publication Date: 2014-08-30
    Description: Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. Similarly, an H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M-containing nucleosomes, and its misregulation in Drosophila results in changes of H3K9 methylation levels and heterochromatic silencing defects. We have established histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508193/" 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/PMC4508193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herz, Hans-Martin -- Morgan, Marc -- Gao, Xin -- Jackson, Jessica -- Rickels, Ryan -- Swanson, Selene K -- Florens, Laurence -- Washburn, Michael P -- Eissenberg, Joel C -- Shilatifard, Ali -- CA R01CA089455/CA/NCI NIH HHS/ -- R01 CA089455/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1065-70. doi: 10.1126/science.1255104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ; Saint Louis University School of Medicine, Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis, MO, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ash@northwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170156" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Chromatin/*metabolism ; Disease Models, Animal ; Drosophila Proteins/genetics ; Drosophila melanogaster ; Gene Silencing ; Glioma/genetics/metabolism ; Heterochromatin/metabolism ; Histone-Lysine N-Methyltransferase/genetics ; Histones/*genetics/metabolism ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Lysine/*genetics ; Methionine/*genetics ; Methylation ; Mutation ; Signal Transduction
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  • 49
    Publication Date: 2014-11-15
    Description: Lightning plays an important role in atmospheric chemistry and in the initiation of wildfires, but the impact of global warming on lightning rates is poorly constrained. Here we propose that the lightning flash rate is proportional to the convective available potential energy (CAPE) times the precipitation rate. Using observations, the product of CAPE and precipitation explains 77% of the variance in the time series of total cloud-to-ground lightning flashes over the contiguous United States (CONUS). Storms convert CAPE times precipitated water mass to discharged lightning energy with an efficiency of 1%. When this proxy is applied to 11 climate models, CONUS lightning strikes are predicted to increase 12 +/- 5% per degree Celsius of global warming and about 50% over this century.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Romps, David M -- Seeley, Jacob T -- Vollaro, David -- Molinari, John -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):851-4. doi: 10.1126/science.1259100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth and Planetary Science, University of California, Berkeley, and Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. romps@berkeley.edu. ; Department of Earth and Planetary Science, University of California, Berkeley, and Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. ; Department of Atmospheric and Environmental Sciences, State University of New York at Albany, Albany, NY, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395536" target="_blank"〉PubMed〈/a〉
    Keywords: *Convection ; *Global Warming ; *Lightning ; United States
    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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  • 50
    Publication Date: 2014-11-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Francis S -- Heimer, Hakon -- Giedd, Jay N -- Lein, Edward S -- Sestan, Nenad -- Weinberger, Daniel R -- Casey, B J -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):547-9. doi: 10.1126/science.1260497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sackler Institute, Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA. ; Schizophrenia Research Forum, Brain and Behavior Research Foundation, Providence, RI 02906, USA. Banbury Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. ; Division of Child and Adolescent Psychiatry, University of California, San Diego, CA 92123, USA. ; Allen Institute for Brain Science, Seattle, WA 98103, USA. ; Department of Neurobiology and Psychiatry, Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. ; Lieber Institute for Brain Development, Baltimore, MD 21205, USA. Department of Psychiatry, Neurology, Neuroscience, and the Institute of Genomic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 20215, USA. ; Sackler Institute, Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA. bjc2002@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359951" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; *Adolescent Behavior ; *Adolescent Development ; Age of Onset ; Brain/*growth & development/physiology ; *Early Medical Intervention ; Humans ; Mental Disorders/diagnosis/epidemiology/*prevention & control ; *Mental Health ; National Institutes of Health (U.S.)/economics ; Neuroimaging ; United States
    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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  • 51
    Publication Date: 2014-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazer, David -- Kennedy, Ryan -- King, Gary -- Vespignani, Alessandro -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1203-5. doi: 10.1126/science.1248506.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lazer Laboratory, Northeastern University, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626916" target="_blank"〉PubMed〈/a〉
    Keywords: Centers for Disease Control and Prevention (U.S.) ; Data Collection/statistics & numerical data ; Data Interpretation, Statistical ; *Disease Outbreaks ; Humans ; Influenza, Human/*epidemiology ; Office Visits/statistics & numerical data/*trends ; Prognosis ; Social Media/*utilization ; United States
    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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  • 52
    Publication Date: 2014-06-21
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138491/" 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/PMC4138491/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉H3Africa Consortium -- Rotimi, Charles -- Abayomi, Akin -- Abimiku, Alash'le -- Adabayeri, Victoria May -- Adebamowo, Clement -- Adebiyi, Ezekiel -- Ademola, Adebowale D -- Adeyemo, Adebowale -- Adu, Dwomoa -- Affolabi, Dissou -- Agongo, Godfred -- Ajayi, Samuel -- Akarolo-Anthony, Sally -- Akinyemi, Rufus -- Akpalu, Albert -- Alberts, Marianne -- Alonso Betancourt, Orlando -- Alzohairy, Ahmed Mansour -- Ameni, Gobena -- Amodu, Olukemi -- Anabwani, Gabriel -- Andersen, Kristian -- Arogundade, Fatiu -- Arulogun, Oyedunni -- Asogun, Danny -- Bakare, Rasheed -- Balde, Naby -- Baniecki, Mary Lynn -- Beiswanger, Christine -- Benkahla, Alia -- Bethke, Lara -- Boehnke, Micheal -- Boima, Vincent -- Brandful, James -- Brooks, Andrew I -- Brosius, Frank C -- Brown, Chester -- Bucheton, Bruno -- Burke, David T -- Burnett, Barrington G -- Carrington-Lawrence, Stacy -- Carstens, Nadia -- Chisi, John -- Christoffels, Alan -- Cooper, Richard -- Cordell, Heather -- Crowther, Nigel -- Croxton, Talishiea -- de Vries, Jantina -- Derr, Leslie -- Donkor, Peter -- Doumbia, Seydou -- Duncanson, Audrey -- Ekem, Ivy -- El Sayed, Ahmed -- Engel, Mark E -- Enyaru, John C K -- Everett, Dean -- Fadlelmola, Faisal M -- Fakunle, Eyitayo -- Fischbeck, Kenneth H -- Fischer, Anne -- Folarin, Onikepe -- Gamieldien, Junaid -- Garry, Robert F -- Gaseitsiwe, Simani -- Gbadegesin, Rasheed -- Ghansah, Anita -- Giovanni, Maria -- Goesbeck, Parham -- Gomez-Olive, F Xavier -- Grant, Donald S -- Grewal, Ravnit -- Guyer, Mark -- Hanchard, Neil A -- Happi, Christian T -- Hazelhurst, Scott -- Hennig, Branwen J -- Hertz-, Christiane -- Fowler -- Hide, Winston -- Hilderbrandt, Friedhelm -- Hugo-Hamman, Christopher -- Ibrahim, Muntaser E -- James, Regina -- Jaufeerally-Fakim, Yasmina -- Jenkins, Carolyn -- Jentsch, Ute -- Jiang, Pan-Pan -- Joloba, Moses -- Jongeneel, Victor -- Joubert, Fourie -- Kader, Mukthar -- Kahn, Kathleen -- Kaleebu, Pontiano -- Kapiga, Saidi H -- Kassim, Samar Kamal -- Kasvosve, Ishmael -- Kayondo, Jonathan -- Keavney, Bernard -- Kekitiinwa, Adeodata -- Khan, Sheik Humarr -- Kimmel, Paul -- King, Mary-Claire -- Kleta, Robert -- Koffi, Mathurin -- Kopp, Jeffrey -- Kretzler, Matthias -- Kumuthini, Judit -- Kyobe, Samuel -- Kyobutungi, Catherine -- Lackland, Daniel T -- Lacourciere, Karen A -- Landoure, Guida -- Lawlor, Rita -- Lehner, Thomas -- Lesosky, Maia -- Levitt, Naomi -- Littler, Katherine -- Lombard, Zane -- Loring, Jeanne F -- Lyantagaye, Sylvester -- Macleod, Annette -- Madden, Ebony B -- Mahomva, Chengetai R -- Makani, Julie -- Mamven, Manmak -- Marape, Marape -- Mardon, Graeme -- Marshall, Patricia -- Martin, Darren P -- Masiga, Daniel -- Mason, Robin -- Mate-Kole, Michael -- Matovu, Enock -- Mayige, Mary -- Mayosi, Bongani M -- Mbanya, Jean Claude -- McCurdy, Sheryl A -- McCarthy, Mark I -- McIlleron, Helen -- Mc'Ligeyo, S O -- Merle, Corrine -- Mocumbi, Ana Olga -- Mondo, Charles -- Moran, John V -- Motala, Ayesha -- Moxey-Mims, Marva -- Mpoloka, Wata Sununguko -- Msefula, Chisomo L -- Mthiyane, Thuli -- Mulder, Nicola -- Mulugeta, Gebregziab her -- Mumba, Dieuodonne -- Musuku, John -- Nagdee, Mo -- Nash, Oyekanmi -- Ndiaye, Daouda -- Nguyen, Anh Quynh -- Nicol, Mark -- Nkomazana, Oathokwa -- Norris, Shane -- Nsangi, Betty -- Nyarko, Alexander -- Nyirenda, Moffat -- Obe, Eileen -- Obiakor, Reginald -- Oduro, Abraham -- Ofori-Acquah, Solomon F -- Ogah, Okechukwu -- Ogendo, Stephen -- Ohene-Frempong, Kwaku -- Ojo, Akinlolu -- Olanrewaju, Timothy -- Oli, John -- Osafo, Charlotte -- Ouwe Missi Oukem-Boyer, Odile -- Ovbiagele, Bruce -- Owen, Andrew -- Owolabi, Mayowa Ojo -- Owolabi, Lukman -- Owusu-Dabo, Ellis -- Pare, Guillaume -- Parekh, Rulan -- Patterton, Hugh G -- Penno, Margaret B -- Peterson, Jane -- Pieper, Rembert -- Plange-Rhule, Jacob -- Pollak, Martin -- Puzak, Julia -- Ramesar, Rajkumar S -- Ramsay, Michele -- Rasooly, Rebekah -- Reddy, Shiksha -- Sabeti, Pardis C -- Sagoe, Kwamena -- Salako, Tunde -- Samassekou, Oumar -- Sandhu, Manjinder S -- Sankoh, Osman -- Sarfo, Fred Stephen -- Sarr, Marie -- Shaboodien, Gasnat -- Sidibe, Issa -- Simo, Gustave -- Simuunza, Martin -- Smeeth, Liam -- Sobngwi, Eugene -- Soodyall, Himla -- Sorgho, Hermann -- Sow Bah, Oumou -- Srinivasan, Sudha -- Stein, Dan J -- Susser, Ezra S -- Swanepoel, Carmen -- Tangwa, Godfred -- Tareila, Andrew -- Tastan Bishop, Ozlem -- Tayo, Bamidele -- Tiffin, Nicki -- Tinto, Halidou -- Tobin, Ekaete -- Tollman, Stephen Meir -- Traore, Mahamadou -- Treadwell, Marsha J -- Troyer, Jennifer -- Tsimako-Johnstone, Masego -- Tukei, Vincent -- Ulasi, Ifeoma -- Ulenga, Nzovu -- van Rooyen, Beverley -- Wachinou, Ablo Prudence -- Waddy, Salina P -- Wade, Alisha -- Wayengera, Misaki -- Whitworth, James -- Wideroff, Louise -- Winkler, Cheryl A -- Winnicki, Sarah -- Wonkam, Ambroise -- Yewondwos, Mengistu -- sen, Tadase -- Yozwiak, Nathan -- Zar, Heather -- 085349/Wellcome Trust/United Kingdom -- 095009/Wellcome Trust/United Kingdom -- 095201/Wellcome Trust/United Kingdom -- 098504/Wellcome Trust/United Kingdom -- 104111/Wellcome Trust/United Kingdom -- MC_U123292700/Medical Research Council/United Kingdom -- P20 MD006899/MD/NIMHD NIH HHS/ -- R01 AI104621/AI/NIAID NIH HHS/ -- RG/08/012/25941/British Heart Foundation/United Kingdom -- U01 HG007044/HG/NHGRI NIH HHS/ -- U41 HG006941/HG/NHGRI NIH HHS/ -- U54 AI110398/AI/NIAID NIH HHS/ -- U54 HG006938/HG/NHGRI NIH HHS/ -- U54 HG006939/HG/NHGRI NIH HHS/ -- U54 HG007479/HG/NHGRI NIH HHS/ -- UH2 HG007051/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1346-8. doi: 10.1126/science.1251546.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24948725" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Disease/*genetics ; England ; Genetics, Medical/trends ; Genome-Wide Association Study/*trends ; Genomics/*trends ; Health ; Humans ; National Institutes of Health (U.S.) ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 53
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murray, Thomas H -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1208-10. doi: 10.1126/science.1248080.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Hastings Center, Garrison, New York, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626919" target="_blank"〉PubMed〈/a〉
    Keywords: *Bioethical Issues ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Embryo, Mammalian ; Guidelines as Topic ; Humans ; Insemination, Artificial ; Mitochondria/*genetics ; Mitochondrial Diseases/*genetics/*prevention & control ; Ovum ; Reproductive Techniques, Assisted/*ethics/legislation & jurisprudence ; United States ; United States Food and Drug Administration
    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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  • 54
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2014 May 23;344(6186):820-1. doi: 10.1126/science.344.6186.820.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855250" target="_blank"〉PubMed〈/a〉
    Keywords: Developed Countries/*economics/statistics & numerical data ; Developing Countries/*economics/statistics & numerical data ; Income/*statistics & numerical data ; Socioeconomic Factors ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 55
    Publication Date: 2014-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carmona, Richard -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):589. doi: 10.1126/science.343.6171.589.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503826" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Inhalation ; Adult ; Child ; *Device Approval ; Humans ; Nicotine/*administration & dosage ; Smoking/*epidemiology/*prevention & control ; United States ; United States Food and Drug Administration
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 56
    Publication Date: 2014-10-04
    Description: Human mitochondrial ribosomes are highly divergent from all other known ribosomes and are specialized to exclusively translate membrane proteins. They are linked with hereditary mitochondrial diseases and are often the unintended targets of various clinically useful antibiotics. Using single-particle cryogenic electron microscopy, we have determined the structure of its large subunit to 3.4 angstrom resolution, revealing 48 proteins, 21 of which are specific to mitochondria. The structure unveils an adaptation of the exit tunnel for hydrophobic nascent peptides, extensive remodeling of the central protuberance, including recruitment of mitochondrial valine transfer RNA (tRNA(Val)) to play an integral structural role, and changes in the tRNA binding sites related to the unusual characteristics of mitochondrial tRNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246062/" 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/PMC4246062/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Alan -- Amunts, Alexey -- Bai, Xiao-chen -- Sugimoto, Yoichiro -- Edwards, Patricia C -- Murshudov, Garib -- Scheres, Sjors H W -- Ramakrishnan, V -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- MC_UP_A025_1012/Medical Research Council/United Kingdom -- MC_UP_A025_1013/Medical Research Council/United Kingdom -- WT096570/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):718-22. doi: 10.1126/science.1258026. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ramak@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278503" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Humans ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/chemistry/ultrastructure ; Mutation ; Nucleic Acid Conformation ; Protein Conformation ; RNA, Transfer, Val/analysis/*chemistry ; Ribosome Subunits/*chemistry/genetics/*ultrastructure
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  • 57
    Publication Date: 2014-05-31
    Description: Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kbeta (PI4KIIIbeta) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIbeta interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046302/" 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/PMC4046302/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, John E -- Inglis, Alison J -- Perisic, Olga -- Masson, Glenn R -- McLaughlin, Stephen H -- Rutaganira, Florentine -- Shokat, Kevan M -- Williams, Roger L -- MC_U105184308/Medical Research Council/United Kingdom -- PG/11/109/29247/British Heart Foundation/United Kingdom -- PG11/109/29247/British Heart Foundation/United Kingdom -- R01AI099245/AI/NIAID NIH HHS/ -- T32 GM064337/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. jeburke@uvic.ca rlw@mrc-lmb.cam.ac.uk. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876499" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antimalarials/chemistry/pharmacology ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Drug Design ; Humans ; I-kappa B Kinase/*chemistry ; Molecular Sequence Data ; Mutation ; Phosphotransferases (Alcohol Group Acceptor)/*chemistry/genetics ; Plasmodium/drug effects/growth & development ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; rab GTP-Binding Proteins/*chemistry
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  • 58
    Publication Date: 2014-01-25
    Description: Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918581/" 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/PMC3918581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murchison, Elizabeth P -- Wedge, David C -- Alexandrov, Ludmil B -- Fu, Beiyuan -- Martincorena, Inigo -- Ning, Zemin -- Tubio, Jose M C -- Werner, Emma I -- Allen, Jan -- De Nardi, Andrigo Barboza -- Donelan, Edward M -- Marino, Gabriele -- Fassati, Ariberto -- Campbell, Peter J -- Yang, Fengtang -- Burt, Austin -- Weiss, Robin A -- Stratton, Michael R -- 088340/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- G0501446/Medical Research Council/United Kingdom -- G0900950/Medical Research Council/United Kingdom -- G9721629/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):437-40. doi: 10.1126/science.1247167.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458646" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage/*genetics ; Dog Diseases/*genetics ; Dogs/*genetics ; Founder Effect ; Gene Dosage ; Genome ; Karyotype ; Mutation ; Retroelements ; Venereal Tumors, Veterinary/*epidemiology/*genetics
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Nicholas Z -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):873-4. doi: 10.1126/science.1253506.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Economics and Environmental Studies Program, Middlebury College, Middlebury, VT 05753 USA. Faculty Research Fellow, National Bureau of Economic Research, Cambridge, MA 02138 USA. nmuller@middlebury.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146270" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollution/*economics ; Environment ; Greenhouse Effect/*economics ; Gross Domestic Product/*trends ; United States
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 60
    Publication Date: 2014-04-05
    Description: Adrenal Cushing's syndrome is caused by excess production of glucocorticoid from adrenocortical tumors and hyperplasias, which leads to metabolic disorders. We performed whole-exome sequencing of 49 blood-tumor pairs and RNA sequencing of 44 tumors from cortisol-producing adrenocortical adenomas (ACAs), adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasias (AIMAHs), and adrenocortical oncocytomas (ADOs). We identified a hotspot in the PRKACA gene with a L205R mutation in 69.2% (27 out of 39) of ACAs and validated in 65.5% of a total of 87 ACAs. Our data revealed that the activating L205R mutation, which locates in the P+1 loop of the protein kinase A (PKA) catalytic subunit, promoted PKA substrate phosphorylation and target gene expression. Moreover, we discovered the recurrently mutated gene DOT1L in AIMAHs and CLASP2 in ADOs. Collectively, these data highlight potentially functional mutated genes in adrenal Cushing's syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, Yanan -- He, Minghui -- Gao, Zhibo -- Peng, Ying -- Li, Yanli -- Li, Lin -- Zhou, Weiwei -- Li, Xiangchun -- Zhong, Xu -- Lei, Yiming -- Su, Tingwei -- Wang, Hang -- Jiang, Yiran -- Yang, Lin -- Wei, Wei -- Yang, Xu -- Jiang, Xiuli -- Liu, Li -- He, Juan -- Ye, Junna -- Wei, Qing -- Li, Yingrui -- Wang, Weiqing -- Wang, Jun -- Ning, Guang -- New York, N.Y. -- Science. 2014 May 23;344(6186):913-7. doi: 10.1126/science.1249480. Epub 2014 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. ; BGI-Shanghai, BGI-Shenzhen, Shenzhen, China. ; Department of Pathology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. ; Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. guangning@medmail.com.cn wangj@genomics.org.cn wqingw@hotmail.com. ; BGI-Shanghai, BGI-Shenzhen, Shenzhen, China. Department of Biology, University of Copenhagen, Copenhagen, Denmark. King Abdulaziz University, Jeddah, Saudi Arabia. Macau University of Science and Technology, Macau, China. Department of Medicine, University of Hong Kong, Hong Kong. guangning@medmail.com.cn wangj@genomics.org.cn wqingw@hotmail.com. ; Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), and Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China. guangning@medmail.com.cn wangj@genomics.org.cn wqingw@hotmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700472" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Cortex Neoplasms/*genetics/*metabolism ; Adrenocortical Adenoma/*genetics/*metabolism ; Amino Acid Substitution ; Arginine/genetics ; Catalytic Domain/genetics ; Cells, Cultured ; Cushing Syndrome/*genetics ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/chemistry/*genetics ; Glucocorticoids/metabolism ; Humans ; Hydrocortisone/*metabolism ; Leucine/genetics ; Methyltransferases/genetics ; Microtubule-Associated Proteins/genetics ; Mutation
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):404. doi: 10.1126/science.346.6208.404.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342775" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Coronavirus ; Federal Government ; Humans ; Influenza A Virus, H5N1 Subtype ; Mice ; Risk ; Security Measures ; United States ; Virology/*economics/*trends ; Virus Diseases/*prevention & control/*transmission
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-09-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malakoff, David -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1115. doi: 10.1126/science.345.6201.1115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190776" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomedical Research ; Federal Government ; Humans ; Influenza A Virus, H5N1 Subtype/*pathogenicity ; Influenza A Virus, H7N9 Subtype/*pathogenicity ; Risk Management ; United States
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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):150-1. doi: 10.1126/science.346.6206.150.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301595" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Biomedical Research/*economics ; Humans ; National Institutes of Health (U.S.)/economics/legislation & jurisprudence ; Research Personnel/statistics & numerical data ; Research Support as Topic/*legislation & jurisprudence ; United States
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malakoff, David -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1464-7. doi: 10.1126/science.344.6191.1464.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970074" target="_blank"〉PubMed〈/a〉
    Keywords: Climate Change ; Ecosystem ; Environmental Pollution ; *Natural Gas/economics/toxicity ; *Oil and Gas Fields ; United States ; Water Quality
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  • 65
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-07-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):366-7. doi: 10.1126/science.345.6195.366.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061183" target="_blank"〉PubMed〈/a〉
    Keywords: *Awards and Prizes ; Financing, Organized ; Humans ; National Institute of General Medical Sciences (U.S.)/economics ; National Institutes of Health (U.S.)/*economics ; Research Personnel/*economics ; United States
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  • 66
    Publication Date: 2014-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malakoff, David -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1186-7. doi: 10.1126/science.343.6176.1186.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626907" target="_blank"〉PubMed〈/a〉
    Keywords: *Budgets ; Federal Government ; Science/*economics ; United States
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  • 67
    Publication Date: 2014-03-29
    Description: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATalpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033833/" 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/PMC4033833/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Annaluru, Narayana -- Muller, Heloise -- Mitchell, Leslie A -- Ramalingam, Sivaprakash -- Stracquadanio, Giovanni -- Richardson, Sarah M -- Dymond, Jessica S -- Kuang, Zheng -- Scheifele, Lisa Z -- Cooper, Eric M -- Cai, Yizhi -- Zeller, Karen -- Agmon, Neta -- Han, Jeffrey S -- Hadjithomas, Michalis -- Tullman, Jennifer -- Caravelli, Katrina -- Cirelli, Kimberly -- Guo, Zheyuan -- London, Viktoriya -- Yeluru, Apurva -- Murugan, Sindurathy -- Kandavelou, Karthikeyan -- Agier, Nicolas -- Fischer, Gilles -- Yang, Kun -- Martin, J Andrew -- Bilgel, Murat -- Bohutski, Pavlo -- Boulier, Kristin M -- Capaldo, Brian J -- Chang, Joy -- Charoen, Kristie -- Choi, Woo Jin -- Deng, Peter -- DiCarlo, James E -- Doong, Judy -- Dunn, Jessilyn -- Feinberg, Jason I -- Fernandez, Christopher -- Floria, Charlotte E -- Gladowski, David -- Hadidi, Pasha -- Ishizuka, Isabel -- Jabbari, Javaneh -- Lau, Calvin Y L -- Lee, Pablo A -- Li, Sean -- Lin, Denise -- Linder, Matthias E -- Ling, Jonathan -- Liu, Jaime -- Liu, Jonathan -- London, Mariya -- Ma, Henry -- Mao, Jessica -- McDade, Jessica E -- McMillan, Alexandra -- Moore, Aaron M -- Oh, Won Chan -- Ouyang, Yu -- Patel, Ruchi -- Paul, Marina -- Paulsen, Laura C -- Qiu, Judy -- Rhee, Alex -- Rubashkin, Matthew G -- Soh, Ina Y -- Sotuyo, Nathaniel E -- Srinivas, Venkatesh -- Suarez, Allison -- Wong, Andy -- Wong, Remus -- Xie, Wei Rose -- Xu, Yijie -- Yu, Allen T -- Koszul, Romain -- Bader, Joel S -- Boeke, Jef D -- Chandrasegaran, Srinivasan -- 092076/Wellcome Trust/United Kingdom -- GM077291/GM/NIGMS NIH HHS/ -- R01 GM077291/GM/NIGMS NIH HHS/ -- R01 GM090192/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):55-8. doi: 10.1126/science.1249252. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Health Sciences, Johns Hopkins University (JHU) School of Public Health, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674868" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Chromosomes, Fungal/genetics/metabolism ; DNA, Fungal/genetics ; Genes, Fungal ; Genetic Fitness ; Genome, Fungal ; Genomic Instability ; Introns ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; RNA, Fungal/genetics ; RNA, Transfer/genetics ; Saccharomyces cerevisiae/cytology/*genetics/physiology ; Sequence Analysis, DNA ; Sequence Deletion ; Synthetic Biology/*methods ; Transformation, Genetic
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1327. doi: 10.1126/science.344.6190.1327.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24948712" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; *Health Status ; Humans ; National Institute of Child Health and Human Development (U.S.)/*trends ; *Patient Selection ; United States
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  • 69
    Publication Date: 2014-02-22
    Description: Robustness, the maintenance of a character in the presence of genetic change, can help preserve adaptive traits but also may hinder evolvability, the ability to bring forth novel adaptations. We used genotype networks to analyze the binding site repertoires of 193 transcription factors from mice and yeast, providing empirical evidence that robustness and evolvability need not be conflicting properties. Network vertices represent binding sites where two sites are connected if they differ in a single nucleotide. We show that the binding sites of larger genotype networks are not only more robust, but the sequences adjacent to such networks can also bind more transcription factors, thus demonstrating that robustness can facilitate evolvability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payne, Joshua L -- Wagner, Andreas -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):875-7. doi: 10.1126/science.1249046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558158" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites/genetics ; Gene Regulatory Networks ; Mice ; Mutation ; Saccharomyces cerevisiae Proteins/chemistry ; Transcription Factors/*chemistry ; Transcription, Genetic
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 May 16;344(6185):687-9. doi: 10.1126/science.344.6185.687.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833372" target="_blank"〉PubMed〈/a〉
    Keywords: Actinin/genetics ; Animals ; Caspase 12/genetics ; *Gene Knockout Techniques ; *Genetic Association Studies ; Humans ; Mice ; *Molecular Targeted Therapy ; Muscular Dystrophies/genetics ; Mutation ; NAV1.7 Voltage-Gated Sodium Channel/genetics ; Proprotein Convertases/genetics ; Receptors, CCR5/genetics ; Serine Endopeptidases/genetics
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malakoff, David -- New York, N.Y. -- Science. 2014 Jan 3;343(6166):13. doi: 10.1126/science.343.6166.13.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385612" target="_blank"〉PubMed〈/a〉
    Keywords: Commerce/*economics ; Federal Government ; Investments/*legislation & jurisprudence ; Research/*economics ; Tax Exemption/*legislation & jurisprudence ; United States
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):350. doi: 10.1126/science.344.6182.350.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763564" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Financing, Government ; *National Institutes of Health (U.S.)/economics/organization & administration ; Peer Review, Research ; *Research Support as Topic ; United States
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kintisch, Eli -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1070-1. doi: 10.1126/science.344.6188.1070.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904132" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollutants/*standards ; Air Pollution/*prevention & control ; Carbon Dioxide/*standards ; Global Warming/*prevention & control ; Greenhouse Effect/*prevention & control ; United States ; United States Environmental Protection Agency/legislation & jurisprudence
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  • 74
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimm, David -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):988. doi: 10.1126/science.345.6200.988.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170127" target="_blank"〉PubMed〈/a〉
    Keywords: *Accreditation ; Animal Welfare/*standards ; Animals ; United States
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  • 75
    Publication Date: 2014-10-18
    Description: Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458378/" 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/PMC4458378/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baud, Matthias G J -- Lin-Shiao, Enrique -- Cardote, Teresa -- Tallant, Cynthia -- Pschibul, Annica -- Chan, Kwok-Ho -- Zengerle, Michael -- Garcia, Jordi R -- Kwan, Terence T-L -- Ferguson, Fleur M -- Ciulli, Alessio -- 097945/Z/11/Z/Wellcome Trust/United Kingdom -- 100476/Z/12/Z/Wellcome Trust/United Kingdom -- BB/G023123/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J001201/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. a.ciulli@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25323695" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Azepines/chemistry/pharmacology ; Cell Line, Tumor ; Chromatin/chemistry ; Crystallography, X-Ray ; Humans ; Leucine/genetics ; Models, Molecular ; Molecular Probes/*chemistry ; Mutation ; Nuclear Proteins/antagonists & inhibitors/*chemistry/genetics ; Protein Engineering/*methods ; Protein Structure, Tertiary ; Transcription Factors/antagonists & inhibitors/*chemistry/genetics ; Triazoles/chemistry/pharmacology
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  • 76
    Publication Date: 2014-03-29
    Description: The cloning of the breast cancer susceptibility genes BRCA1 and BRCA2 nearly two decades ago helped set in motion an avalanche of research exploring how genomic information can be optimally applied to identify and clinically care for individuals with a high risk of developing cancer. Genetic testing for mutations in BRCA1, BRCA2, and other breast cancer susceptibility genes has since proved to be a valuable tool for determining eligibility for enhanced screening and prevention strategies, as well as for identifying patients most likely to benefit from a targeted therapy. Here, we discuss the landscape of inherited mutations and sequence variants in BRCA1 and BRCA2, the complexities of determining disease risk when the pathogenicity of sequence variants is uncertain, and current strategies for clinical management of women who carry BRCA1/2 mutations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074902/" 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/PMC4074902/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couch, Fergus J -- Nathanson, Katherine L -- Offit, Kenneth -- 3P30CA008748-47/CA/NCI NIH HHS/ -- CA016520/CA/NCI NIH HHS/ -- CA116167/CA/NCI NIH HHS/ -- CA116201/CA/NCI NIH HHS/ -- CA128978/CA/NCI NIH HHS/ -- CA135509/CA/NCI NIH HHS/ -- P50 CA116201/CA/NCI NIH HHS/ -- R01 CA128978/CA/NCI NIH HHS/ -- R01 CA135509/CA/NCI NIH HHS/ -- U01 CA116167/CA/NCI NIH HHS/ -- U01 CA164947/CA/NCI NIH HHS/ -- U01CA164947/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1466-70. doi: 10.1126/science.1251827.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675953" target="_blank"〉PubMed〈/a〉
    Keywords: BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/*drug therapy/genetics/prevention & control ; Cloning, Molecular ; Female ; *Genetic Predisposition to Disease ; Humans ; Models, Genetic ; Mutation ; *Precision Medicine
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1167-70. doi: 10.1126/science.346.6214.1167.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477439" target="_blank"〉PubMed〈/a〉
    Keywords: BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Breast Neoplasms/genetics/prevention & control ; Female ; *Genes, Neoplasm ; *Genetic Counseling ; Genetic Predisposition to Disease/*genetics ; *Genetic Testing ; Humans ; Jews/*genetics ; Mutation ; Neoplasms/genetics/*prevention & control ; Ovarian Neoplasms/genetics/prevention & control ; *Uncertainty
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  • 78
    Publication Date: 2014-07-12
    Description: Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358808/" 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/PMC4358808/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Min -- Bardia, Aditya -- Aceto, Nicola -- Bersani, Francesca -- Madden, Marissa W -- Donaldson, Maria C -- Desai, Rushil -- Zhu, Huili -- Comaills, Valentine -- Zheng, Zongli -- Wittner, Ben S -- Stojanov, Petar -- Brachtel, Elena -- Sgroi, Dennis -- Kapur, Ravi -- Shioda, Toshihiro -- Ting, David T -- Ramaswamy, Sridhar -- Getz, Gad -- Iafrate, A John -- Benes, Cyril -- Toner, Mehmet -- Maheswaran, Shyamala -- Haber, Daniel A -- CA129933/CA/NCI NIH HHS/ -- EB008047/EB/NIBIB NIH HHS/ -- P41 EB002503/EB/NIBIB NIH HHS/ -- R01 CA129933/CA/NCI NIH HHS/ -- U01 EB012493/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):216-20. doi: 10.1126/science.1253533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medical Epidemiology and Biostatistics, Karolinska Insitutet, Stockholm, Sweden. ; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. ; Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. ; Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. ; Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Harvard Medical School, Charlestown, MA 02129, USA. maheswaran@helix.mgh.harvard.edu haber@helix.mgh.harvard.edu. ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA. maheswaran@helix.mgh.harvard.edu haber@helix.mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013076" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*pharmacology/therapeutic use ; Breast Neoplasms/*drug therapy/genetics ; Cell Culture Techniques ; Cell Separation ; Culture ; Drug Resistance, Neoplasm/*genetics ; Drug Screening Assays, Antitumor/methods ; Estrogen Receptor alpha/genetics ; Female ; Gene Frequency ; Humans ; Mice ; Microfluidics/methods ; *Molecular Targeted Therapy ; Mutation ; Neoplastic Cells, Circulating/*drug effects/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Sequence Analysis, DNA ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):24-7. doi: 10.1126/science.346.6205.24. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Genetic Engineering ; Humans ; *Mice ; Mice, Mutant Strains ; Mutation ; Neoplasms ; Neoplasms, Experimental/*drug therapy/genetics ; Pancreatic Neoplasms/*drug therapy/genetics ; Proto-Oncogene Proteins/genetics ; Tumor Suppressor Protein p53/genetics ; *Xenograft Model Antitumor Assays ; ras Proteins/genetics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1301. doi: 10.1126/science.343.6177.1301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653015" target="_blank"〉PubMed〈/a〉
    Keywords: Colorado ; *Ecosystem ; *Floods ; Groundwater ; Mexico ; *Rivers ; Salinity ; Trees/*growth & development ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gronewold, Andrew D -- Stow, Craig A -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1084-5. doi: 10.1126/science.1249978.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Oceanic and Atmospheric Administration (NOAA), Great Lakes Environmental Research Laboratory (GLERL), Ann Arbor, MI, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604186" target="_blank"〉PubMed〈/a〉
    Keywords: Canada ; *Climate Change ; *Environmental Monitoring ; *Lakes ; United States ; *Water Resources
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  • 82
    Publication Date: 2014-03-08
    Description: River networks evolve as migrating drainage divides reshape river basins and change network topology by capture of river channels. We demonstrate that a characteristic metric of river network geometry gauges the horizontal motion of drainage divides. Assessing this metric throughout a landscape maps the dynamic states of entire river networks, revealing diverse conditions: Drainage divides in the Loess Plateau of China appear stationary; the young topography of Taiwan has migrating divides driving adjustment of major basins; and rivers draining the ancient landscape of the southeastern United States are reorganizing in response to escarpment retreat and coastal advance. The ability to measure the dynamic reorganization of river basins presents opportunities to examine landscape-scale interactions among tectonics, erosion, and ecology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willett, Sean D -- McCoy, Scott W -- Perron, J Taylor -- Goren, Liran -- Chen, Chia-Yu -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1248765. doi: 10.1126/science.1248765.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geological Institute, Swiss Federal Institute of Technology, 8092 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604204" target="_blank"〉PubMed〈/a〉
    Keywords: Climate ; Geologic Sediments ; Models, Theoretical ; *Rivers ; Soil ; Taiwan ; United States ; *Water Movements
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 83
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):28-9. doi: 10.1126/science.344.6179.28.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700838" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*economics ; Brain/growth & development ; Faculty ; Financing, Government ; National Institutes of Health (U.S.)/economics ; *Research Personnel/economics/education ; *Research Support as Topic ; United States ; Zebrafish
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-02-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNutt, Marcia -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):815. doi: 10.1126/science.1251932.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marcia McNutt is Editor-in-Chief of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558130" target="_blank"〉PubMed〈/a〉
    Keywords: Canada ; *Conservation of Natural Resources ; *Extraction and Processing Industry ; *Fossil Fuels ; Petroleum ; *Renewable Energy ; United States
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  • 85
    Publication Date: 2014-04-20
    Description: Cytoplasmic plant immune receptors recognize specific pathogen effector proteins and initiate effector-triggered immunity. In Arabidopsis, the immune receptors RPS4 and RRS1 are both required to activate defense to three different pathogens. We show that RPS4 and RRS1 physically associate. Crystal structures of the N-terminal Toll-interleukin-1 receptor/resistance (TIR) domains of RPS4 and RRS1, individually and as a heterodimeric complex (respectively at 2.05, 1.75, and 2.65 angstrom resolution), reveal a conserved TIR/TIR interaction interface. We show that TIR domain heterodimerization is required to form a functional RRS1/RPS4 effector recognition complex. The RPS4 TIR domain activates effector-independent defense, which is inhibited by the RRS1 TIR domain through the heterodimerization interface. Thus, RPS4 and RRS1 function as a receptor complex in which the two components play distinct roles in recognition and signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Simon J -- Sohn, Kee Hoon -- Wan, Li -- Bernoux, Maud -- Sarris, Panagiotis F -- Segonzac, Cecile -- Ve, Thomas -- Ma, Yan -- Saucet, Simon B -- Ericsson, Daniel J -- Casey, Lachlan W -- Lonhienne, Thierry -- Winzor, Donald J -- Zhang, Xiaoxiao -- Coerdt, Anne -- Parker, Jane E -- Dodds, Peter N -- Kobe, Bostjan -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):299-303. doi: 10.1126/science.1247357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744375" target="_blank"〉PubMed〈/a〉
    Keywords: Agrobacterium/physiology ; Amino Acid Motifs ; Arabidopsis/chemistry/*immunology/microbiology ; Arabidopsis Proteins/*chemistry/genetics/metabolism ; Bacterial Proteins/immunology/metabolism ; Cell Death ; Crystallography, X-Ray ; Immunity, Innate ; Models, Molecular ; Mutation ; Plant Diseases/immunology/microbiology ; Plant Leaves/microbiology ; Plant Proteins/*chemistry/genetics/metabolism ; Plants, Genetically Modified ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Immunologic/*chemistry/genetics/metabolism ; Signal Transduction ; Tobacco/genetics/immunology/metabolism/microbiology
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  • 86
    Publication Date: 2014-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kalokairinou, Louiza -- Howard, Heidi Carmen -- Borry, Pascal -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):296-8. doi: 10.1126/science.1256396. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Public Health and Primary Care, University of Leuven, B-3000 Leuven, Belgium. ; Center for Research Ethics and Bioethics, Uppsala University, SE-751 22 Uppsala, Sweden. ; Department of Public Health and Primary Care, University of Leuven, B-3000 Leuven, Belgium. pascal.borry@med.kuleuven.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324369" target="_blank"〉PubMed〈/a〉
    Keywords: *Consumer Advocacy ; European Union ; Genetic Privacy/*legislation & jurisprudence ; Genetic Services/*legislation & jurisprudence ; Genetic Testing ; Genomics/*legislation & jurisprudence ; *Guidelines as Topic ; Humans ; Risk Assessment/classification ; United States ; United States Food and Drug Administration
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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Porter, John Edward -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1207. doi: 10.1126/science.1256929.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉John Edward Porter is a former U.S. congressman, a partner in the law firm of Hogan Lovells, and chair of Research!America.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24925988" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/*trends ; Budgets ; Capital Financing/*organization & administration/trends ; Humans ; *Information Dissemination ; National Institutes of Health (U.S.)/*economics ; United States
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  • 88
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- R01 CA154517/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):356-7. doi: 10.1126/science.343.6169.356.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458615" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*genetics ; Financing, Organized ; Genetic Research/economics/*ethics/legislation & jurisprudence ; Health Information Systems/*ethics/legislation & jurisprudence ; Humans ; Molecular Epidemiology ; Mutation ; Neoplasms/*genetics ; Patient Access to Records/*ethics/legislation & jurisprudence
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  • 89
    Publication Date: 2014-04-26
    Description: Extensive genomic diversity within coexisting members of a microbial species has been revealed through selected cultured isolates and metagenomic assemblies. Yet, the cell-by-cell genomic composition of wild uncultured populations of co-occurring cells is largely unknown. In this work, we applied large-scale single-cell genomics to study populations of the globally abundant marine cyanobacterium Prochlorococcus. We show that they are composed of hundreds of subpopulations with distinct "genomic backbones," each backbone consisting of a different set of core gene alleles linked to a small distinctive set of flexible genes. These subpopulations are estimated to have diverged at least a few million years ago, suggesting ancient, stable niche partitioning. Such a large set of coexisting subpopulations may be a general feature of free-living bacterial species with huge populations in highly mixed habitats.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kashtan, Nadav -- Roggensack, Sara E -- Rodrigue, Sebastien -- Thompson, Jessie W -- Biller, Steven J -- Coe, Allison -- Ding, Huiming -- Marttinen, Pekka -- Malmstrom, Rex R -- Stocker, Roman -- Follows, Michael J -- Stepanauskas, Ramunas -- Chisholm, Sallie W -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):416-20. doi: 10.1126/science.1248575.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763590" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Biological Evolution ; Ecosystem ; Genes, Bacterial ; *Genetic Variation ; *Genome, Bacterial ; Metagenomics ; Molecular Sequence Data ; Mutation ; Phylogeny ; Polymorphism, Single Nucleotide ; Prochlorococcus/classification/*genetics/*physiology ; Seasons ; Seawater/*microbiology ; Sequence Analysis, DNA ; Single-Cell Analysis
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  • 90
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glaeser, Edward L -- Shleifer, Andrei -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1233. doi: 10.1126/science.1256540.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University, Boston, MA, USA. ; Harvard University, Boston, MA, USA. shleifer@fas.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24926006" target="_blank"〉PubMed〈/a〉
    Keywords: *Behavior ; Economics/*history ; History, 20th Century ; History, 21st Century ; Humans ; Investments/history ; Nobel Prize ; Racism/history/psychology ; Sociology/*history ; Training Support/history ; United States
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  • 91
    Publication Date: 2014-11-22
    Description: Through their association with a kleisin subunit (Scc1), cohesin's Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two alpha helices, forming a four-helix bundle with the coiled coil emerging from Smc3's adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin's association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin's dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300515/" 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/PMC4300515/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gligoris, Thomas G -- Scheinost, Johanna C -- Burmann, Frank -- Petela, Naomi -- Chan, Kok-Lung -- Uluocak, Pelin -- Beckouet, Frederic -- Gruber, Stephan -- Nasmyth, Kim -- Lowe, Jan -- 091859/Z/10/Z/Wellcome Trust/United Kingdom -- 095514/Wellcome Trust/United Kingdom -- 095514/Z/11/Z/Wellcome Trust/United Kingdom -- C573/A 12386/Cancer Research UK/United Kingdom -- C573/A11625/Medical Research Council/United Kingdom -- MC_U105184326/Medical Research Council/United Kingdom -- U10518432/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):963-7. doi: 10.1126/science.1256917.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. ; Max-Planck-Institut fur Biochemie, 82152, Martinsried, Germany. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Medical Research Council (MRC) Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Dunn School of Pathology, University of Oxford, Oxford OX1 3RF, UK. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk. ; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25414305" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry ; Amino Acid Sequence ; Cell Cycle Proteins/*chemistry/genetics ; Chromosomal Proteins, Non-Histone/*chemistry/genetics ; Conserved Sequence ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; DNA/chemistry ; Mutation ; Protein Multimerization ; Protein Structure, Tertiary ; Saccharomyces cerevisiae Proteins/*chemistry/genetics
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Eliot -- New York, N.Y. -- Science. 2014 May 23;344(6186):826-7. doi: 10.1126/science.344.6186.826.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855253" target="_blank"〉PubMed〈/a〉
    Keywords: *Capitalism ; Databases, Factual ; France ; History, 18th Century ; History, 21st Century ; Income/history/statistics & numerical data/*trends ; Income Tax/history/statistics & numerical data/*trends ; Socioeconomic Factors/history ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Eliot -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):27. doi: 10.1126/science.344.6179.27.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700837" target="_blank"〉PubMed〈/a〉
    Keywords: Biochemistry ; Biomedical Research/*economics ; Financing, Government ; National Institutes of Health (U.S.)/economics ; Peer Review, Research ; Research Personnel/*economics ; *Research Support as Topic ; United States ; United States Government Agencies/economics
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  • 94
    Publication Date: 2014-11-15
    Description: Targeted cancer therapies have produced substantial clinical responses, but most tumors develop resistance to these drugs. Here, we describe a pharmacogenomic platform that facilitates rapid discovery of drug combinations that can overcome resistance. We established cell culture models derived from biopsy samples of lung cancer patients whose disease had progressed while on treatment with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors and then subjected these cells to genetic analyses and a pharmacological screen. Multiple effective drug combinations were identified. For example, the combination of ALK and MAPK kinase (MEK) inhibitors was active in an ALK-positive resistant tumor that had developed a MAP2K1 activating mutation, and the combination of EGFR and fibroblast growth factor receptor (FGFR) inhibitors was active in an EGFR mutant resistant cancer with a mutation in FGFR3. Combined ALK and SRC (pp60c-src) inhibition was effective in several ALK-driven patient-derived models, a result not predicted by genetic analysis alone. With further refinements, this strategy could help direct therapeutic choices for individual patients.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388482/" 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/PMC4388482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crystal, Adam S -- Shaw, Alice T -- Sequist, Lecia V -- Friboulet, Luc -- Niederst, Matthew J -- Lockerman, Elizabeth L -- Frias, Rosa L -- Gainor, Justin F -- Amzallag, Arnaud -- Greninger, Patricia -- Lee, Dana -- Kalsy, Anuj -- Gomez-Caraballo, Maria -- Elamine, Leila -- Howe, Emily -- Hur, Wooyoung -- Lifshits, Eugene -- Robinson, Hayley E -- Katayama, Ryohei -- Faber, Anthony C -- Awad, Mark M -- Ramaswamy, Sridhar -- Mino-Kenudson, Mari -- Iafrate, A John -- Benes, Cyril H -- Engelman, Jeffrey A -- 086357/Wellcome Trust/United Kingdom -- 102696/Wellcome Trust/United Kingdom -- 1U54HG006097-01/HG/NHGRI NIH HHS/ -- P50 CA090578/CA/NCI NIH HHS/ -- P50CA090578/CA/NCI NIH HHS/ -- R01 CA137008/CA/NCI NIH HHS/ -- R01 CA164273/CA/NCI NIH HHS/ -- R01CA137008/CA/NCI NIH HHS/ -- R01CA164273/CA/NCI NIH HHS/ -- U54 HG006097/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1480-6. doi: 10.1126/science.1254721. Epub 2014 Nov 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Department of Medicine and Harvard Medical School, Boston, MA 02114, USA. ; Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology and Harvard Medical School, Boston, MA 02115, USA. Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul, 136-791, South Korea. ; Massachusetts General Hospital Cancer Center, Department of Pathology and Harvard Medical School, Boston, MA 02114, USA. ; Massachusetts General Hospital Cancer Center, Department of Medicine and Harvard Medical School, Boston, MA 02114, USA. jengelman@partners.org cbenes@partners.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25394791" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/genetics ; DNA Mutational Analysis ; Drug Resistance, Neoplasm/*genetics ; Drug Screening Assays, Antitumor ; Enzyme Activation/genetics ; Humans ; Lung Neoplasms/*drug therapy/enzymology/genetics ; MAP Kinase Kinase 1/genetics/metabolism ; Molecular Targeted Therapy/*methods ; Mutation ; *Patient-Specific Modeling ; Protein Kinase Inhibitors/*therapeutic use ; Proto-Oncogene Proteins pp60(c-src)/antagonists & inhibitors ; Pyrimidines/therapeutic use ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptor, Fibroblast Growth Factor, Type 3/antagonists & inhibitors/genetics ; Sulfones/therapeutic use ; Tumor Cells, Cultured
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  • 95
    Publication Date: 2014-01-18
    Description: Ribosome biogenesis drives cell growth and proliferation, but mechanisms that modulate this process within specific lineages remain poorly understood. Here, we identify a Drosophila RNA polymerase I (Pol I) regulatory complex composed of Under-developed (Udd), TAF1B, and a TAF1C-like factor. Disruption of udd or TAF1B results in reduced ovarian germline stem cell (GSC) proliferation. Female GSCs display high levels of ribosomal RNA (rRNA) transcription, and Udd becomes enriched in GSCs relative to their differentiating daughters. Increasing Pol I transcription delays differentiation, whereas reducing rRNA production induces both morphological changes that accompany multicellular cyst formation and specific decreased expression of the bone morphogenetic protein (BMP) pathway component Mad. These findings demonstrate that modulating rRNA synthesis fosters changes in the cell fate, growth, and proliferation of female Drosophila GSCs and their daughters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084784/" 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/PMC4084784/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Qiao -- Shalaby, Nevine A -- Buszczak, Michael -- R01 GM086647/GM/NIGMS NIH HHS/ -- R01GM045820/GM/NIGMS NIH HHS/ -- R01GM086647/GM/NIGMS NIH HHS/ -- T32 DK007745/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):298-301. doi: 10.1126/science.1246384.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436420" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage/*genetics ; *Cell Proliferation ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*cytology/genetics ; Female ; *Genes, rRNA ; Histone Acetyltransferases/genetics/metabolism ; Mutation ; Nuclear Proteins/genetics/metabolism ; Ovary/cytology/*physiology ; RNA Polymerase I/genetics/*metabolism ; Stem Cells/cytology/*physiology ; TATA-Binding Protein Associated Factors ; Transcription Factor TFIID/genetics/metabolism ; Transcription Factors/genetics/metabolism ; *Transcription, Genetic
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  • 96
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-11-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):798. doi: 10.1126/science.346.6211.798.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395513" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; Engineering/manpower ; Faculty ; Female ; Humans ; Mathematics/manpower ; Physics/manpower ; Science/*manpower ; *Sexism ; United States ; Universities ; *Women
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pringle, Heather -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):364-7. doi: 10.1126/science.343.6169.364.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24458621" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Commerce ; Dinosaurs ; *Fossils ; Horses ; United States
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-24
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159256/" 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/PMC4159256/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xie, Yu -- R24 HD041028/HD/NICHD NIH HHS/ -- R24HD041028/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2014 May 23;344(6186):809-10. doi: 10.1126/science.1252743.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA. Center for Social Research, Peking University, Beijing 100871, China. yuxie@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855244" target="_blank"〉PubMed〈/a〉
    Keywords: Democracy ; Employment/*statistics & numerical data ; Internationality ; Reward ; Science/*economics/*trends ; Socioeconomic Factors ; United States
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  • 99
    Publication Date: 2014-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baillie, J Kenneth -- New York, N.Y. -- Science. 2014 May 23;344(6186):807-8. doi: 10.1126/science.1255074.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Roslin Institute, University of Edinburgh, Midlothian EH25 9RG, UK, and Intensive Care Unit, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK. j.k.baillie@ed.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855243" target="_blank"〉PubMed〈/a〉
    Keywords: Communicable Diseases/*drug therapy/*genetics ; Disease Resistance/drug effects/*genetics/immunology ; *Genetic Predisposition to Disease ; Genetic Variation ; Genomics/*methods ; Host-Pathogen Interactions/drug effects/*genetics/immunology ; Humans ; Immune System/*drug effects/*immunology ; Membrane Proteins/genetics ; Mutation ; RNA-Binding Proteins/genetics ; Translational Medical Research
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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kennel, Charles -- Dressler, Alan -- New York, N.Y. -- Science. 2014 Jan 10;343(6167):140-1. doi: 10.1126/science.1244231.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24408421" target="_blank"〉PubMed〈/a〉
    Keywords: Cost-Benefit Analysis ; Planning Techniques ; Space Flight/*economics/*statistics & numerical data ; *Uncertainty ; United States ; United States National Aeronautics and Space Administration/economics
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