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  • Female  (14)
  • American Association for the Advancement of Science (AAAS)  (14)
  • American Meteorological Society
  • 2015-2019  (14)
  • 2010-2014
  • 1990-1994
  • 1955-1959
  • 2016  (14)
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  • 2015-2019  (14)
  • 2010-2014
  • 1990-1994
  • 1955-1959
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  • 1
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    Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-03-12
    Description: Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zanoni, Paolo -- Khetarpal, Sumeet A -- Larach, Daniel B -- Hancock-Cerutti, William F -- Millar, John S -- Cuchel, Marina -- DerOhannessian, Stephanie -- Kontush, Anatol -- Surendran, Praveen -- Saleheen, Danish -- Trompet, Stella -- Jukema, J Wouter -- De Craen, Anton -- Deloukas, Panos -- Sattar, Naveed -- Ford, Ian -- Packard, Chris -- Majumder, Abdullah al Shafi -- Alam, Dewan S -- Di Angelantonio, Emanuele -- Abecasis, Goncalo -- Chowdhury, Rajiv -- Erdmann, Jeanette -- Nordestgaard, Borge G -- Nielsen, Sune F -- Tybjaerg-Hansen, Anne -- Schmidt, Ruth Frikke -- Kuulasmaa, Kari -- Liu, Dajiang J -- Perola, Markus -- Blankenberg, Stefan -- Salomaa, Veikko -- Mannisto, Satu -- Amouyel, Philippe -- Arveiler, Dominique -- Ferrieres, Jean -- Muller-Nurasyid, Martina -- Ferrario, Marco -- Kee, Frank -- Willer, Cristen J -- Samani, Nilesh -- Schunkert, Heribert -- Butterworth, Adam S -- Howson, Joanna M M -- Peloso, Gina M -- Stitziel, Nathan O -- Danesh, John -- Kathiresan, Sekar -- Rader, Daniel J -- CHD Exome+ Consortium -- CARDIoGRAM Exome Consortium -- Global Lipids Genetics Consortium -- R01 DK089256/DK/NIDDK NIH HHS/ -- R01 HL117078/HL/NHLBI NIH HHS/ -- TL1 RR024133/RR/NCRR NIH HHS/ -- TL1R000138/PHS HHS/ -- TL1RR024133/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1166-71. doi: 10.1126/science.aad3517.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Departments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. INSERM UMR 1166 ICAN, Universite Pierre et Marie Curie Paris 6, Hopital de la Pitie, Paris, France. ; INSERM UMR 1166 ICAN, Universite Pierre et Marie Curie Paris 6, Hopital de la Pitie, Paris, France. ; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. ; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Centre for Non-Communicable Diseases, Karachi, Pakistan. ; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands. Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands. ; Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands. The Interuniversity Cardiology Institute of the Netherlands, Utrecht, Netherlands. ; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands. ; Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK. ; Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. ; Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK. ; Glasgow Clinical Research Facility, Western Infirmary, Glasgow, UK. ; National Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Dhaka, Bangladesh. ; International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh. ; Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. ; Institute for Integrative and Experimental Genomics, University of Lubeck, Lubeck 23562, Germany. ; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. ; Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark. ; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark. ; Department of Health, National Institute for Health and Welfare, Helsinki, Finland. ; Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA. ; Department of Health, National Institute for Health and Welfare, Helsinki, Finland. Institute of Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland. ; Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany. University Medical Center Hamburg-Eppendorf, Hamburg, Germany. ; Department of Epidemiology and Public Health, Institut Pasteur de Lille, Lille, France. ; Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, France. ; Department of Epidemiology, Toulouse University-CHU Toulouse, Toulouse, France. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, Germany. Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany. ; Research Centre in Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy. ; UKCRC Centre of Excellence for Public Health, Queens University, Belfast, Northern Ireland. ; Department of Computational Medicine and Bioinformatics, Department of Human Genetics, and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. ; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hotel, Leicester, UK. ; Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Munich, Germany. ; Broad Institute and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA. ; Department of Medicine, Division of Cardiology, Department of Genetics, and the McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK. ; Departments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. rader@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965621" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Amino Acid Substitution ; Animals ; Cholesterol, HDL/*blood ; Coronary Disease/*blood/*genetics ; DNA Mutational Analysis ; Female ; Genetic Variation ; Heterozygote ; Homozygote ; Humans ; Leucine/genetics ; Male ; Mice ; Middle Aged ; Proline/genetics ; Protein Processing, Post-Translational ; Risk ; Scavenger Receptors, Class B/*genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-03-05
    Description: As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy-induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGranahan, Nicholas -- Furness, Andrew J S -- Rosenthal, Rachel -- Ramskov, Sofie -- Lyngaa, Rikke -- Saini, Sunil Kumar -- Jamal-Hanjani, Mariam -- Wilson, Gareth A -- Birkbak, Nicolai J -- Hiley, Crispin T -- Watkins, Thomas B K -- Shafi, Seema -- Murugaesu, Nirupa -- Mitter, Richard -- Akarca, Ayse U -- Linares, Joseph -- Marafioti, Teresa -- Henry, Jake Y -- Van Allen, Eliezer M -- Miao, Diana -- Schilling, Bastian -- Schadendorf, Dirk -- Garraway, Levi A -- Makarov, Vladimir -- Rizvi, Naiyer A -- Snyder, Alexandra -- Hellmann, Matthew D -- Merghoub, Taha -- Wolchok, Jedd D -- Shukla, Sachet A -- Wu, Catherine J -- Peggs, Karl S -- Chan, Timothy A -- Hadrup, Sine R -- Quezada, Sergio A -- Swanton, Charles -- 12100/Cancer Research UK/United Kingdom -- 1R01CA155010-02/CA/NCI NIH HHS/ -- 1R01CA182461-01/CA/NCI NIH HHS/ -- 1R01CA184922-01/CA/NCI NIH HHS/ -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1463-9. doi: 10.1126/science.aaf1490. Epub 2016 Mar 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Francis Crick Institute, London WC2A 3LY, UK. Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London (UCL), London WC1E 6BT, UK. Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK. ; Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK. Cancer Immunology Unit, UCL Cancer Institute, UCL, London WC1E 6BT, UK. ; Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK. ; Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1970 Frederiksberg C, Denmark. ; The Francis Crick Institute, London WC2A 3LY, UK. Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK. ; The Francis Crick Institute, London WC2A 3LY, UK. ; Cancer Immunology Unit, UCL Cancer Institute, UCL, London WC1E 6BT, UK. Department of Cellular Pathology, UCL, London WC1E 6BT, UK. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Department of Dermatology, University Hospital, University Duisburg-Essen, 45147 Essen, Germany. German Cancer Consortium (DKTK), 69121 Heidelberg, Germany. ; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. ; Hematology/Oncology Division, 177 Fort Washington Avenue, Columbia University, New York, NY 10032, USA. ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY 10065, USA. Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Department of Internal Medicine, Brigham and Woman's Hospital, Boston, MA 02115, USA. ; Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK. Cancer Immunology Unit, UCL Cancer Institute, UCL, London WC1E 6BT, UK. s.quezada@ucl.ac.uk charles.swanton@crick.ac.uk. ; The Francis Crick Institute, London WC2A 3LY, UK. Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London WC1E 6BT, UK. s.quezada@ucl.ac.uk charles.swanton@crick.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26940869" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/drug therapy/genetics/*immunology ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/genetics/*immunology ; Antineoplastic Agents/therapeutic use ; CD4-Positive T-Lymphocytes/*immunology ; CTLA-4 Antigen/immunology ; Carcinoma, Non-Small-Cell Lung/genetics/immunology ; Cell Cycle Checkpoints/immunology ; Female ; Humans ; *Immunologic Surveillance ; Lung Neoplasms/drug therapy/genetics/*immunology ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Melanoma/immunology ; Middle Aged ; Mutation ; Programmed Cell Death 1 Receptor/immunology ; Skin Neoplasms/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Zika virus in the Americas: Early epidemiological and genetic findings (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-03-26
    Description: Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faria, Nuno Rodrigues -- Azevedo, Raimunda do Socorro da Silva -- Kraemer, Moritz U G -- Souza, Renato -- Cunha, Mariana Sequetin -- Hill, Sarah C -- Theze, Julien -- Bonsall, Michael B -- Bowden, Thomas A -- Rissanen, Ilona -- Rocco, Iray Maria -- Nogueira, Juliana Silva -- Maeda, Adriana Yurika -- Vasami, Fernanda Giseli da Silva -- Macedo, Fernando Luiz de Lima -- Suzuki, Akemi -- Rodrigues, Sueli Guerreiro -- Cruz, Ana Cecilia Ribeiro -- Nunes, Bruno Tardeli -- Medeiros, Daniele Barbosa de Almeida -- Rodrigues, Daniela Sueli Guerreiro -- Nunes Queiroz, Alice Louize -- da Silva, Eliana Vieira Pinto -- Henriques, Daniele Freitas -- Travassos da Rosa, Elisabeth Salbe -- de Oliveira, Consuelo Silva -- Martins, Livia Caricio -- Vasconcelos, Helena Baldez -- Casseb, Livia Medeiros Neves -- Simith, Darlene de Brito -- Messina, Jane P -- Abade, Leandro -- Lourenco, Jose -- Carlos Junior Alcantara, Luiz -- de Lima, Maricelia Maia -- Giovanetti, Marta -- Hay, Simon I -- de Oliveira, Rodrigo Santos -- Lemos, Poliana da Silva -- de Oliveira, Layanna Freitas -- de Lima, Clayton Pereira Silva -- da Silva, Sandro Patroca -- de Vasconcelos, Janaina Mota -- Franco, Luciano -- Cardoso, Jedson Ferreira -- Vianez-Junior, Joao Lidio da Silva Goncalves -- Mir, Daiana -- Bello, Gonzalo -- Delatorre, Edson -- Khan, Kamran -- Creatore, Marisa -- Coelho, Giovanini Evelim -- de Oliveira, Wanderson Kleber -- Tesh, Robert -- Pybus, Oliver G -- Nunes, Marcio R T -- Vasconcelos, Pedro F C -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095066/Wellcome Trust/United Kingdom -- 102427/Wellcome Trust/United Kingdom -- MR/L009528/1/Medical Research Council/United Kingdom -- R24 AT 120942/AT/NCCIH NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):345-9. doi: 10.1126/science.aaf5036. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Para State, Brazil. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Instituto Adolfo Lutz, University of Sao Paulo, Sao Paulo, Brazil. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. Metabiota, San Francisco, CA 94104, USA. ; Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil. ; Centre of Post Graduation in Collective Health, Department of Health, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil. ; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA 98121, USA. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. ; Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. ; Laboratorio de AIDS and Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. ; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Department of Medicine, Division of Infectious Diseases, University of Toronto, Toronto, Ontario, Canada. ; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. ; Brazilian Ministry of Health, Brasilia, Brazil. ; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. Metabiota, San Francisco, CA 94104, USA. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br. ; Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br. ; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Para State, Brazil. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013429" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/virology ; Americas/epidemiology ; Animals ; *Disease Outbreaks ; Female ; Genome, Viral/genetics ; Humans ; Incidence ; Insect Vectors/virology ; Microcephaly/*epidemiology/virology ; Molecular Epidemiology ; Molecular Sequence Data ; Mutation ; Pacific Islands/epidemiology ; Phylogeny ; Pregnancy ; RNA, Viral/genetics ; Sequence Analysis, RNA ; Travel ; Zika Virus/classification/*genetics/isolation & purification ; Zika Virus Infection/*epidemiology/transmission/*virology
    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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  • 4
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    Health and population effects of rare gene knockouts in adult humans with related parents (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-03-05
    Description: Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narasimhan, Vagheesh M -- Hunt, Karen A -- Mason, Dan -- Baker, Christopher L -- Karczewski, Konrad J -- Barnes, Michael R -- Barnett, Anthony H -- Bates, Chris -- Bellary, Srikanth -- Bockett, Nicholas A -- Giorda, Kristina -- Griffiths, Christopher J -- Hemingway, Harry -- Jia, Zhilong -- Kelly, M Ann -- Khawaja, Hajrah A -- Lek, Monkol -- McCarthy, Shane -- McEachan, Rosie -- O'Donnell-Luria, Anne -- Paigen, Kenneth -- Parisinos, Constantinos A -- Sheridan, Eamonn -- Southgate, Laura -- Tee, Louise -- Thomas, Mark -- Xue, Yali -- Schnall-Levin, Michael -- Petkov, Petko M -- Tyler-Smith, Chris -- Maher, Eamonn R -- Trembath, Richard C -- MacArthur, Daniel G -- Wright, John -- Durbin, Richard -- van Heel, David A -- GM 099640/GM/NIGMS NIH HHS/ -- MR/M009017/1/Medical Research Council/United Kingdom -- R01 GM104371/GM/NIGMS NIH HHS/ -- R01GM104371/GM/NIGMS NIH HHS/ -- WT098051/Wellcome Trust/United Kingdom -- WT099769/Wellcome Trust/United Kingdom -- WT101597/Wellcome Trust/United Kingdom -- WT102627/Wellcome Trust/United Kingdom -- British Heart Foundation/United Kingdom -- Arthritis Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- Department of Health/United Kingdom -- Chief Scientist Office/United Kingdom -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):474-7. doi: 10.1126/science.aac8624. Epub 2016 Mar 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. ; Bradford Institute for Health Research, Bradford Teaching Hospitals National Health Service (NHS) Foundation Trust, Bradford BD9 6RJ, UK. ; Center for Genome Dynamics, The Jackson Laboratory, Bar Harbor, ME 04609, USA. ; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. ; Diabetes and Endocrine Centre, Heart of England NHS Foundation Trust and University of Birmingham, Birmingham B9 5SS, UK. ; TPP, Mill House, Troy Road, Leeds LS18 5TN, UK. ; Aston Research Centre for Healthy Ageing, Aston University, Birmingham B4 7ET, UK. ; 10X Genomics, 7068 Koll Center Parkway, Suite 415, Pleasanton, CA 94566, USA. ; Farr Institute of Health Informatics Research, London NW1 2DA, UK. Institute of Health Informatics, University College London, London NW1 2DA, UK. ; School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK. ; Department of Medical Genetics, University of Cambridge and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Box 238, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. ; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. Faculty of Life Sciences and Medicine, King's College London, London SE1 1UL, UK. ; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. rd@sanger.ac.uk d.vanheel@qmul.ac.uk. ; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. rd@sanger.ac.uk d.vanheel@qmul.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26940866" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Consanguinity ; DNA Mutational Analysis ; Drug Prescriptions ; Exome/genetics ; Female ; Fertility ; Gene Knockout Techniques ; Genes, Lethal ; Genetic Loci ; Genome, Human ; Great Britain ; *Health ; Histone-Lysine N-Methyltransferase/*genetics ; Homologous Recombination ; Homozygote ; Humans ; Male ; Mothers ; Pakistan/ethnology ; Phenotype
    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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  • 5
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    Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-23
    Description: Influenza A virus (IAV) causes up to half a million deaths worldwide annually, 90% of which occur in older adults. We show that IAV-infected monocytes from older humans have impaired antiviral interferon production but retain intact inflammasome responses. To understand the in vivo consequence, we used mice expressing a functional Mx gene encoding a major interferon-induced effector against IAV in humans. In Mx1-intact mice with weakened resistance due to deficiencies in Mavs and Tlr7, we found an elevated respiratory bacterial burden. Notably, mortality in the absence of Mavs and Tlr7 was independent of viral load or MyD88-dependent signaling but dependent on bacterial burden, caspase-1/11, and neutrophil-dependent tissue damage. Therefore, in the context of weakened antiviral resistance, vulnerability to IAV disease is a function of caspase-dependent pathology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pillai, Padmini S -- Molony, Ryan D -- Martinod, Kimberly -- Dong, Huiping -- Pang, Iris K -- Tal, Michal C -- Solis, Angel G -- Bielecki, Piotr -- Mohanty, Subhasis -- Trentalange, Mark -- Homer, Robert J -- Flavell, Richard A -- Wagner, Denisa D -- Montgomery, Ruth R -- Shaw, Albert C -- Staeheli, Peter -- Iwasaki, Akiko -- 5T32HL066987-13/HL/NHLBI NIH HHS/ -- AI062428/AI/NIAID NIH HHS/ -- AI064705/AI/NIAID NIH HHS/ -- AI081884/AI/NIAID NIH HHS/ -- F31 AG039163/AG/NIA NIH HHS/ -- HHSN272201100019C/PHS HHS/ -- K24 AG02489/AG/NIA NIH HHS/ -- K24 AG042489/AG/NIA NIH HHS/ -- N01 AI500031/AI/NIAID NIH HHS/ -- P30 AG21342/AG/NIA NIH HHS/ -- R01HL102101/HL/NHLBI NIH HHS/ -- R01HL125501/HL/NHLBI NIH HHS/ -- T32 AI007019-36/AI/NIAID NIH HHS/ -- T32 AI007019-38/AI/NIAID NIH HHS/ -- T32 AI055403/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):463-6. doi: 10.1126/science.aaf3926.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA. ; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. ; Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. ; Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. ; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA. ; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA. Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06520, USA. ; Section of Rheumatology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA. ; Institut fur Medizinische Mikrobiologie und Hygiene, Institute of Virology, University Medical Center Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany. ; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA. Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06520, USA. akiko.iwasaki@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102485" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adult ; Aged ; Aged, 80 and over ; Animals ; Bacterial Infections/etiology/*immunology ; Caspase 1/metabolism ; Caspases/metabolism ; Female ; Humans ; Immunity, Innate/genetics/*immunology ; Influenza A virus/*immunology ; Influenza, Human/complications/*immunology ; Interferon-beta/immunology ; Male ; Membrane Glycoproteins/genetics/metabolism ; Mice ; Monocytes/immunology ; Myxovirus Resistance Proteins/genetics/*physiology ; Neutrophils/immunology ; Orthomyxoviridae Infections/*immunology ; Respiratory Tract Infections/*immunology/microbiology ; Toll-Like Receptor 7/genetics/metabolism ; Viral Load ; Young Adult
    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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  • 6
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    Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-27
    Description: Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corti, Davide -- Misasi, John -- Mulangu, Sabue -- Stanley, Daphne A -- Kanekiyo, Masaru -- Wollen, Suzanne -- Ploquin, Aurelie -- Doria-Rose, Nicole A -- Staupe, Ryan P -- Bailey, Michael -- Shi, Wei -- Choe, Misook -- Marcus, Hadar -- Thompson, Emily A -- Cagigi, Alberto -- Silacci, Chiara -- Fernandez-Rodriguez, Blanca -- Perez, Laurent -- Sallusto, Federica -- Vanzetta, Fabrizia -- Agatic, Gloria -- Cameroni, Elisabetta -- Kisalu, Neville -- Gordon, Ingelise -- Ledgerwood, Julie E -- Mascola, John R -- Graham, Barney S -- Muyembe-Tamfun, Jean-Jacques -- Trefry, John C -- Lanzavecchia, Antonio -- Sullivan, Nancy J -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. ; Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. njsull@mail.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917593" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Antibodies, Monoclonal/*administration & dosage/immunology/isolation & ; purification ; Antibodies, Neutralizing/*administration & dosage/immunology/isolation & ; purification ; Antibodies, Viral/*administration & dosage/immunology/isolation & purification ; Clinical Trials as Topic ; Disease Outbreaks ; Ebolavirus/*immunology ; Female ; Hemorrhagic Fever, Ebola/epidemiology/*prevention & control ; Humans ; Macaca ; Male ; Molecular Sequence Data ; Survivors
    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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    Long-read sequence assembly of the gorilla genome (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-02
    Description: Accurate sequence and assembly of genomes is a critical first step for studies of genetic variation. We generated a high-quality assembly of the gorilla genome using single-molecule, real-time sequence technology and a string graph de novo assembly algorithm. The new assembly improves contiguity by two to three orders of magnitude with respect to previously released assemblies, recovering 87% of missing reference exons and incomplete gene models. Although regions of large, high-identity segmental duplications remain largely unresolved, this comprehensive assembly provides new biological insight into genetic diversity, structural variation, gene loss, and representation of repeat structures within the gorilla genome. The approach provides a path forward for the routine assembly of mammalian genomes at a level approaching that of the current quality of the human genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gordon, David -- Huddleston, John -- Chaisson, Mark J P -- Hill, Christopher M -- Kronenberg, Zev N -- Munson, Katherine M -- Malig, Maika -- Raja, Archana -- Fiddes, Ian -- Hillier, LaDeana W -- Dunn, Christopher -- Baker, Carl -- Armstrong, Joel -- Diekhans, Mark -- Paten, Benedict -- Shendure, Jay -- Wilson, Richard K -- Haussler, David -- Chin, Chen-Shan -- Eichler, Evan E -- HG002385/HG/NHGRI NIH HHS/ -- HG003079/HG/NHGRI NIH HHS/ -- HG007234/HG/NHGRI NIH HHS/ -- HG007635/HG/NHGRI NIH HHS/ -- HG007990/HG/NHGRI NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- U41 HG007635/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):aae0344. doi: 10.1126/science.aae0344.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. ; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. ; Genomics Institute, University of California Santa Cruz and Howard Hughes Medical Institute, Santa Cruz, CA 95064, USA. ; McDonnell Genome Institute, Department of Medicine, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA. ; Pacific Biosciences of California, Menlo Park, CA 94025, USA. ; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. eee@gs.washington.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034376" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Contig Mapping ; Evolution, Molecular ; Expressed Sequence Tags ; Female ; Genetic Variation ; Genome, Human ; Genomics ; Gorilla gorilla/*genetics ; Humans ; Sequence Alignment ; Sequence Analysis, DNA/*methods
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    METABOLISM. Mitochondria shape cardiac metabolism (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gottlieb, Roberta A -- Bernstein, Daniel -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1162-3. doi: 10.1126/science.aad8222.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. roberta.gottlieb@cshs.org. ; Department of Pediatrics, Stanford University, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785456" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Heart/*embryology ; Heart Failure/*metabolism ; Male ; Mitochondria, Heart/*metabolism/*physiology ; Mitochondrial Degradation/*physiology ; *Mitochondrial Dynamics ; Myocardium/*metabolism ; Ubiquitin-Protein Ligases/*metabolism
    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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  • 9
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    Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex (2016)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2016-03-05
    Description: During corticogenesis, excitatory neurons are born from progenitors located in the ventricular zone (VZ), from where they migrate to assemble into circuits. How neuronal identity is dynamically specified upon progenitor division is unknown. Here, we study this process using a high-temporal-resolution technology allowing fluorescent tagging of isochronic cohorts of newborn VZ cells. By combining this in vivo approach with single-cell transcriptomics in mice, we identify and functionally characterize neuron-specific primordial transcriptional programs as they dynamically unfold. Our results reveal early transcriptional waves that instruct the sequence and pace of neuronal differentiation events, guiding newborn neurons toward their final fate, and contribute to a road map for the reverse engineering of specific classes of cortical neurons from undifferentiated cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Telley, Ludovic -- Govindan, Subashika -- Prados, Julien -- Stevant, Isabelle -- Nef, Serge -- Dermitzakis, Emmanouil -- Dayer, Alexandre -- Jabaudon, Denis -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1443-6. doi: 10.1126/science.aad8361. Epub 2016 Mar 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Neurosciences, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Genetic Medicine and Development, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Genetic Medicine and Development, University of Geneva, Switzerland. Biomedical Research Foundation Academy of Athens, Greece. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Saudi Arabia. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Basic Neurosciences, University of Geneva, Switzerland. Department of Psychiatry, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Basic Neurosciences, University of Geneva, Switzerland. Clinic of Neurology, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. denis.jabaudon@unige.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26940868" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cerebral Ventricles/cytology/embryology ; DNA-Binding Proteins/genetics ; Female ; GPI-Linked Proteins/genetics ; Green Fluorescent Proteins/genetics ; Male ; Mice ; Neocortex/cytology/*embryology ; Nerve Tissue Proteins/genetics ; Neural Stem Cells/cytology ; Neurogenesis/*genetics ; Neurons/*cytology ; Neuropeptides/genetics ; SOXB1 Transcription Factors/genetics ; *Transcription, Genetic ; Transcriptome
    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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    Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-01-02
    Description: Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772156/" 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/PMC4772156/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferenczi, Emily A -- Zalocusky, Kelly A -- Liston, Conor -- Grosenick, Logan -- Warden, Melissa R -- Amatya, Debha -- Katovich, Kiefer -- Mehta, Hershel -- Patenaude, Brian -- Ramakrishnan, Charu -- Kalanithi, Paul -- Etkin, Amit -- Knutson, Brian -- Glover, Gary H -- Deisseroth, Karl -- 1F31MH105151_01/MH/NIMH NIH HHS/ -- P41 EB015891/EB/NIBIB NIH HHS/ -- R00 MH097822/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Neurosciences Program, Stanford University, Stanford, CA 94305, USA. ; Brain Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. ; Department of Psychology, Stanford University, Stanford, CA 94305, USA. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. ; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA. ; Department of Radiology, Stanford University, Stanford, CA, 94305, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA. deissero@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26722001" target="_blank"〉PubMed〈/a〉
    Keywords: Anhedonia/*physiology ; Animals ; Brain Mapping ; Corpus Striatum/cytology/drug effects/*physiology ; Depressive Disorder/physiopathology ; Dopamine/pharmacology ; Dopaminergic Neurons/drug effects/*physiology ; Female ; Magnetic Resonance Imaging ; Male ; Mesencephalon/cytology/drug effects/physiology ; *Motivation ; Nerve Net/physiology ; Oxygen/blood ; Prefrontal Cortex/cytology/drug effects/*physiology ; Rats ; Rats, Inbred LEC ; Rats, Sprague-Dawley ; *Reward ; Schizophrenia/physiopathology
    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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