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  • Articles  (226)
  • Mice  (131)
  • Male  (123)
  • Cell & Developmental Biology
  • American Association for the Advancement of Science (AAAS)  (226)
  • 2015-2019  (153)
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  • 1
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    Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-02-24
    Description: Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437632/" 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/PMC4437632/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cirulli, Elizabeth T -- Lasseigne, Brittany N -- Petrovski, Slave -- Sapp, Peter C -- Dion, Patrick A -- Leblond, Claire S -- Couthouis, Julien -- Lu, Yi-Fan -- Wang, Quanli -- Krueger, Brian J -- Ren, Zhong -- Keebler, Jonathan -- Han, Yujun -- Levy, Shawn E -- Boone, Braden E -- Wimbish, Jack R -- Waite, Lindsay L -- Jones, Angela L -- Carulli, John P -- Day-Williams, Aaron G -- Staropoli, John F -- Xin, Winnie W -- Chesi, Alessandra -- Raphael, Alya R -- McKenna-Yasek, Diane -- Cady, Janet -- Vianney de Jong, J M B -- Kenna, Kevin P -- Smith, Bradley N -- Topp, Simon -- Miller, Jack -- Gkazi, Athina -- FALS Sequencing Consortium -- Al-Chalabi, Ammar -- van den Berg, Leonard H -- Veldink, Jan -- Silani, Vincenzo -- Ticozzi, Nicola -- Shaw, Christopher E -- Baloh, Robert H -- Appel, Stanley -- Simpson, Ericka -- Lagier-Tourenne, Clotilde -- Pulst, Stefan M -- Gibson, Summer -- Trojanowski, John Q -- Elman, Lauren -- McCluskey, Leo -- Grossman, Murray -- Shneider, Neil A -- Chung, Wendy K -- Ravits, John M -- Glass, Jonathan D -- Sims, Katherine B -- Van Deerlin, Vivianna M -- Maniatis, Tom -- Hayes, Sebastian D -- Ordureau, Alban -- Swarup, Sharan -- Landers, John -- Baas, Frank -- Allen, Andrew S -- Bedlack, Richard S -- Harper, J Wade -- Gitler, Aaron D -- Rouleau, Guy A -- Brown, Robert -- Harms, Matthew B -- Cooper, Gregory M -- Harris, Tim -- Myers, Richard M -- Goldstein, David B -- 089701/Wellcome Trust/United Kingdom -- K08 NS075094/NS/NINDS NIH HHS/ -- P01 AG017586/AG/NIA NIH HHS/ -- P01 AG032953/AG/NIA NIH HHS/ -- P50 AG025688/AG/NIA NIH HHS/ -- R37 NS033123/NS/NINDS NIH HHS/ -- R37 NS083524/NS/NINDS NIH HHS/ -- T32 GM007754/GM/NIGMS NIH HHS/ -- TL1 TR001066/TR/NCATS NIH HHS/ -- UL1 TR001067/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1436-41. doi: 10.1126/science.aaa3650. Epub 2015 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27708, USA. ; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA. ; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA. ; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA. ; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada. ; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Duke University School of Medicine, Durham, NC 27708, USA. ; Biogen Idec, Cambridge, MA 02142, USA. ; Neurogenetics DNA Diagnostic Laboratory, Center for Human Genetics Research, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Genome Analysis, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, Netherlands. ; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Republic of Ireland. ; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK. ; Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, 3508 GA Utrecht, Netherlands. ; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy, and Department of Pathophysiology and Transplantation, Dino Ferrari Center, Universita degli Studi di Milano, Milan 20122, Italy. ; Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. ; Houston Methodist Hospital, Houston, TX 77030, USA, and Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. ; Ludwig Institute for Cancer Research and Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Penn ALS Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Penn Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA. ; Department of Pediatrics and Medicine, Columbia University, New York, NY 10032, USA. ; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Neurology, Emory University, Atlanta, GA 30322, USA. ; Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10027, USA. ; Biogen Idec, Cambridge, MA 02142, USA. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27708, USA. ; Duke ALS Clinic and Durham VA Medical Center, Durham, NC 27708, USA. ; Biogen Idec, Cambridge, MA 02142, USA. tim.harris@biogenidec.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700176" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*genetics ; Autophagy/*genetics ; Exome/*genetics ; Female ; Genes ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Protein Binding ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Risk ; Sequence Analysis, DNA ; Transcription Factor TFIIIA/genetics/metabolism ; Young Adult
    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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    Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-02-14
    Description: Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681433/" 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/PMC4681433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arner, Erik -- Daub, Carsten O -- Vitting-Seerup, Kristoffer -- Andersson, Robin -- Lilje, Berit -- Drablos, Finn -- Lennartsson, Andreas -- Ronnerblad, Michelle -- Hrydziuszko, Olga -- Vitezic, Morana -- Freeman, Tom C -- Alhendi, Ahmad M N -- Arner, Peter -- Axton, Richard -- Baillie, J Kenneth -- Beckhouse, Anthony -- Bodega, Beatrice -- Briggs, James -- Brombacher, Frank -- Davis, Margaret -- Detmar, Michael -- Ehrlund, Anna -- Endoh, Mitsuhiro -- Eslami, Afsaneh -- Fagiolini, Michela -- Fairbairn, Lynsey -- Faulkner, Geoffrey J -- Ferrai, Carmelo -- Fisher, Malcolm E -- Forrester, Lesley -- Goldowitz, Daniel -- Guler, Reto -- Ha, Thomas -- Hara, Mitsuko -- Herlyn, Meenhard -- Ikawa, Tomokatsu -- Kai, Chieko -- Kawamoto, Hiroshi -- Khachigian, Levon M -- Klinken, S Peter -- Kojima, Soichi -- Koseki, Haruhiko -- Klein, Sarah -- Mejhert, Niklas -- Miyaguchi, Ken -- Mizuno, Yosuke -- Morimoto, Mitsuru -- Morris, Kelly J -- Mummery, Christine -- Nakachi, Yutaka -- Ogishima, Soichi -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry -- Passier, Robert -- Patrikakis, Margaret -- Pombo, Ana -- Qin, Xian-Yang -- Roy, Sugata -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schwegmann, Anita -- Sugiyama, Daisuke -- Swoboda, Rolf -- Tanaka, Hiroshi -- Tomoiu, Andru -- Winteringham, Louise N -- Wolvetang, Ernst -- Yanagi-Mizuochi, Chiyo -- Yoneda, Misako -- Zabierowski, Susan -- Zhang, Peter -- Abugessaisa, Imad -- Bertin, Nicolas -- Diehl, Alexander D -- Fukuda, Shiro -- Furuno, Masaaki -- Harshbarger, Jayson -- Hasegawa, Akira -- Hori, Fumi -- Ishikawa-Kato, Sachi -- Ishizu, Yuri -- Itoh, Masayoshi -- Kawashima, Tsugumi -- Kojima, Miki -- Kondo, Naoto -- Lizio, Marina -- Meehan, Terrence F -- Mungall, Christopher J -- Murata, Mitsuyoshi -- Nishiyori-Sueki, Hiromi -- Sahin, Serkan -- Nagao-Sato, Sayaka -- Severin, Jessica -- de Hoon, Michiel J L -- Kawai, Jun -- Kasukawa, Takeya -- Lassmann, Timo -- Suzuki, Harukazu -- Kawaji, Hideya -- Summers, Kim M -- Wells, Christine -- FANTOM Consortium -- Hume, David A -- Forrest, Alistair R R -- Sandelin, Albin -- Carninci, Piero -- Hayashizaki, Yoshihide -- P30 CA010815/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1010-4. doi: 10.1126/science.1259418. Epub 2015 Feb 12.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678556" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cattle ; Cell Differentiation/*genetics ; Dogs ; *Enhancer Elements, Genetic ; *Gene Expression Regulation, Developmental ; Mice ; RNA, Messenger/genetics/metabolism ; Rats ; Stem Cells/*cytology/metabolism ; Transcription Factors/*metabolism ; *Transcription, Genetic
    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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    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
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  • 4
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    IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-07-15
    Description: Human inborn errors of immunity mediated by the cytokines interleukin-17A and interleukin-17F (IL-17A/F) underlie mucocutaneous candidiasis, whereas inborn errors of interferon-gamma (IFN-gamma) immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORgamma and RORgammaT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displayed an impaired IFN-gamma response to Mycobacterium. This principally reflected profoundly defective IFN-gamma production by circulating gammadelta T cells and CD4(+)CCR6(+)CXCR3(+) alphabeta T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORgamma, RORgammaT, or both.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668938/" 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/PMC4668938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Satoshi -- Markle, Janet G -- Deenick, Elissa K -- Mele, Federico -- Averbuch, Dina -- Lagos, Macarena -- Alzahrani, Mohammed -- Al-Muhsen, Saleh -- Halwani, Rabih -- Ma, Cindy S -- Wong, Natalie -- Soudais, Claire -- Henderson, Lauren A -- Marzouqa, Hiyam -- Shamma, Jamal -- Gonzalez, Marcela -- Martinez-Barricarte, Ruben -- Okada, Chizuru -- Avery, Danielle T -- Latorre, Daniela -- Deswarte, Caroline -- Jabot-Hanin, Fabienne -- Torrado, Egidio -- Fountain, Jeffrey -- Belkadi, Aziz -- Itan, Yuval -- Boisson, Bertrand -- Migaud, Melanie -- Arlehamn, Cecilia S Lindestam -- Sette, Alessandro -- Breton, Sylvain -- McCluskey, James -- Rossjohn, Jamie -- de Villartay, Jean-Pierre -- Moshous, Despina -- Hambleton, Sophie -- Latour, Sylvain -- Arkwright, Peter D -- Picard, Capucine -- Lantz, Olivier -- Engelhard, Dan -- Kobayashi, Masao -- Abel, Laurent -- Cooper, Andrea M -- Notarangelo, Luigi D -- Boisson-Dupuis, Stephanie -- Puel, Anne -- Sallusto, Federica -- Bustamante, Jacinta -- Tangye, Stuart G -- Casanova, Jean-Laurent -- 8UL1TR000043/TR/NCATS NIH HHS/ -- HHSN272200900044C/AI/NIAID NIH HHS/ -- HHSN272200900044C/PHS HHS/ -- R37 AI095983/AI/NIAID NIH HHS/ -- R37AI095983/AI/NIAID NIH HHS/ -- T32 AI007512/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):606-13. doi: 10.1126/science.aaa4282. Epub 2015 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. jmarkle@rockefeller.edu jean-laurent.casanova@rockefeller.edu. ; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia. ; Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland. ; Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel. ; Department of Immunology, School of Medicine, Universidad de Valparaiso, Santiago, Chile. Department of Pediatrics, Padre Hurtado Hospital and Clinica Alemana, Santiago, Chile. ; Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. ; Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Department of Pediatrics, Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia. ; Department of Pediatrics, Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia. ; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. ; Institut Curie, INSERM U932, Paris, France. ; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA. ; Caritas Baby Hospital, Post Office Box 11535, Jerusalem, Israel. ; Department of Immunology, School of Medicine, Universidad de Valparaiso, Santiago, Chile. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. ; Trudeau Institute, Saranac Lake, NY 12983, USA. ; La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; Department of Radiology, Assistance Publique-Hopitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France. ; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. ; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK. ; Laboratoire Dynamique du Genome et Systeme Immunitaire, INSERM UMR 1163, Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France. ; Laboratoire Dynamique du Genome et Systeme Immunitaire, INSERM UMR 1163, Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France. Pediatric Hematology-Immunology Unit, AP-HP, Necker Hospital for Sick Children, Paris, France. ; Institute of Cellular Medicine, Newcastle University and Great North Children's Hospital, Newcastle upon Tyne NE4 6BE, UK. ; Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France. ; Department of Paediatric Allergy Immunology, University of Manchester, Royal Manchester Children's Hospital, Manchester, UK. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. Pediatric Hematology-Immunology Unit, AP-HP, Necker Hospital for Sick Children, Paris, France. Center for the Study of Primary Immunodeficiencies, AP-HP, Necker Hospital for Sick Children, Paris, France. ; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. ; Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA. Manton Center for Orphan Disease Research, Children's Hospital, Boston, MA 02115, USA. ; Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland. Center of Medical Immunology, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. Center for the Study of Primary Immunodeficiencies, AP-HP, Necker Hospital for Sick Children, Paris, France. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France. Paris Descartes University, Imagine Institute, Paris, France. Pediatric Hematology-Immunology Unit, AP-HP, Necker Hospital for Sick Children, Paris, France. Howard Hughes Medical Institute, New York, NY 10065, USA. jmarkle@rockefeller.edu jean-laurent.casanova@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160376" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Candida albicans/*immunology ; Candidiasis, Chronic Mucocutaneous/complications/*genetics/immunology ; Cattle ; Child ; Child, Preschool ; DNA Mutational Analysis ; Exome/genetics ; Female ; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor ; Humans ; Immunity/*genetics ; Interferon-gamma/immunology ; Interleukin-17/immunology ; Mice ; Mutation ; Mycobacterium bovis/immunology/isolation & purification ; Mycobacterium tuberculosis/immunology/isolation & purification ; Nuclear Receptor Subfamily 1, Group F, Member 3/*genetics ; Pedigree ; Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology ; Receptors, Antigen, T-Cell, gamma-delta/genetics/immunology ; Severe Combined Immunodeficiency/*genetics ; T-Lymphocytes/immunology ; Thymus Gland/abnormalities/immunology ; Tuberculosis, Bovine/*genetics/immunology ; Tuberculosis, Pulmonary/*genetics/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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  • 5
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    TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-06-13
    Description: Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" 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/PMC4481126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yongyou -- Desai, Amar -- Yang, Sung Yeun -- Bae, Ki Beom -- Antczak, Monika I -- Fink, Stephen P -- Tiwari, Shruti -- Willis, Joseph E -- Williams, Noelle S -- Dawson, Dawn M -- Wald, David -- Chen, Wei-Dong -- Wang, Zhenghe -- Kasturi, Lakshmi -- Larusch, Gretchen A -- He, Lucy -- Cominelli, Fabio -- Di Martino, Luca -- Djuric, Zora -- Milne, Ginger L -- Chance, Mark -- Sanabria, Juan -- Dealwis, Chris -- Mikkola, Debra -- Naidoo, Jacinth -- Wei, Shuguang -- Tai, Hsin-Hsiung -- Gerson, Stanton L -- Ready, Joseph M -- Posner, Bruce -- Willson, James K V -- Markowitz, Sanford D -- 1P01CA95471-09/CA/NCI NIH HHS/ -- 5P30 CA142543-03/CA/NCI NIH HHS/ -- P01 CA095471/CA/NCI NIH HHS/ -- P30 CA043703/CA/NCI NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK097948/DK/NIDDK NIH HHS/ -- P50 CA130810/CA/NCI NIH HHS/ -- P50 CA150964/CA/NCI NIH HHS/ -- R01 CA127590/CA/NCI NIH HHS/ -- R25 CA148052/CA/NCI NIH HHS/ -- R25CA148052/CA/NCI NIH HHS/ -- U54 HL119810/HL/NHLBI NIH HHS/ -- U54HL119810/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Gastroenterology, Haeundae Paik Hospital, Inje University, Busan 612896, South Korea. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Surgery, Busan Paik Hospital, and Paik Institute of Clinical Research and Ocular Neovascular Research Center, Inje University, Busan, South Korea. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Family Medicine, University of Michigan, Ann Arbor MI 48109, USA. ; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. ; Proteomics Center, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA. ; College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068857" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Transplantation ; Colitis/enzymology/prevention & control ; Dinoprostone/metabolism ; Enzyme Inhibitors/chemistry/pharmacology ; Hematopoiesis/drug effects ; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/genetics/*physiology ; Liver Regeneration/drug effects ; Mice ; Mice, Knockout ; Prostaglandins/*metabolism ; Pyridines/chemistry/pharmacology ; Regeneration/drug effects/genetics/*physiology ; Thiophenes/chemistry/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Stem cells. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-01-09
    Description: Naive and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naive pluripotency. Mettl3 knockout preimplantation epiblasts and naive embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable. However, they fail to adequately terminate their naive state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m(6)A predominantly and directly reduces mRNA stability, including that of key naive pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naive and primed pluripotency in an opposing manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geula, Shay -- Moshitch-Moshkovitz, Sharon -- Dominissini, Dan -- Mansour, Abed AlFatah -- Kol, Nitzan -- Salmon-Divon, Mali -- Hershkovitz, Vera -- Peer, Eyal -- Mor, Nofar -- Manor, Yair S -- Ben-Haim, Moshe Shay -- Eyal, Eran -- Yunger, Sharon -- Pinto, Yishay -- Jaitin, Diego Adhemar -- Viukov, Sergey -- Rais, Yoach -- Krupalnik, Vladislav -- Chomsky, Elad -- Zerbib, Mirie -- Maza, Itay -- Rechavi, Yoav -- Massarwa, Rada -- Hanna, Suhair -- Amit, Ido -- Levanon, Erez Y -- Amariglio, Ninette -- Stern-Ginossar, Noam -- Novershtern, Noa -- Rechavi, Gideon -- Hanna, Jacob H -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1002-6. doi: 10.1126/science.1261417. Epub 2015 Jan 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. ; Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. ; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. ; Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. ; The Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. ; The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. The Department of Pediatrics and the Pediatric Immunology Unit, Rambam Medical Center, and the B. Rappaport Faculty of Medicine, Technion, Haifa, Israel. ; Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. ; The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. jacob.hanna@weizmann.ac.il noa.novershtern@weizmann.ac.il gidi.rechavi@sheba.health.gov.il. ; Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. jacob.hanna@weizmann.ac.il noa.novershtern@weizmann.ac.il gidi.rechavi@sheba.health.gov.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25569111" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*analogs & derivatives/metabolism ; Animals ; Blastocyst/enzymology ; Cell Differentiation/genetics/*physiology ; Cell Line ; Embryo Loss/genetics ; Epigenesis, Genetic ; Female ; Gene Knockout Techniques ; Male ; Methylation ; Methyltransferases/genetics/*physiology ; Mice ; Mice, Knockout ; Pluripotent Stem Cells/*cytology/enzymology ; RNA, Messenger/*metabolism
    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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  • 7
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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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  • 8
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    Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-11-07
    Description: Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721659/" 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/PMC4721659/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vetizou, Marie -- Pitt, Jonathan M -- Daillere, Romain -- Lepage, Patricia -- Waldschmitt, Nadine -- Flament, Caroline -- Rusakiewicz, Sylvie -- Routy, Bertrand -- Roberti, Maria P -- Duong, Connie P M -- Poirier-Colame, Vichnou -- Roux, Antoine -- Becharef, Sonia -- Formenti, Silvia -- Golden, Encouse -- Cording, Sascha -- Eberl, Gerard -- Schlitzer, Andreas -- Ginhoux, Florent -- Mani, Sridhar -- Yamazaki, Takahiro -- Jacquelot, Nicolas -- Enot, David P -- Berard, Marion -- Nigou, Jerome -- Opolon, Paule -- Eggermont, Alexander -- Woerther, Paul-Louis -- Chachaty, Elisabeth -- Chaput, Nathalie -- Robert, Caroline -- Mateus, Christina -- Kroemer, Guido -- Raoult, Didier -- Boneca, Ivo Gomperts -- Carbonnel, Franck -- Chamaillard, Mathias -- Zitvogel, Laurence -- R01 CA161879/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1079-84. doi: 10.1126/science.aad1329. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. University of Paris Sud XI, Kremlin-Bicetre, France. ; Institut National de la Recherche Agronomique (INRA), Micalis-UMR1319, 78360 Jouy-en-Josas, France. ; University of Lille, CNRS, INSERM, Centre Hospitalier Regional Universitaire de Lille, Institut Pasteur de Lille, U1019, UMR 8204, Centre d'Infection et d'Immunite de Lille (CIIL), F-59000 Lille, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. University of Paris Sud XI, Kremlin-Bicetre, France. Center of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Department of Radiation Oncology, New York University, New York, NY, USA. ; Microenvironment and Immunity Unit, Institut Pasteur, Paris, France. ; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. ; Department of Genetics and Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Metabolomics Platform, GRCC, Villejuif, France. ; Animalerie Centrale, Institut Pasteur, Paris, France. ; Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France. Universite de Toulouse, Universite Paul Sabatier, IPBS, F-31077 Toulouse, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. ; Service de microbiologie, GRCC, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, GRCC, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. INSERM U981, GRCC, Villejuif, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. ; Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Metabolomics Platform, GRCC, Villejuif, France. INSERM U848, Villejuif, France. Equipe 11 Labellisee-Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France. Pole de Biologie, Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France. ; Unite des Rickettsies, Faculte de Medecine, Universite de la Mediterranee, Marseille, France. ; Institut Pasteur, Unit of Biology and Genetics of the Bacterial Cell Wall, Paris, France. INSERM, Equipe Avenir, Paris, France. ; University of Paris Sud XI, Kremlin-Bicetre, France. Gastroenterology Department, Hopital Bicetre, Assistance Publique-Hopitaux de Paris, Paris, France. ; Institut de Cancerologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, Villejuif, France. University of Paris Sud XI, Kremlin-Bicetre, France. Center of Clinical Investigations in Biotherapies of Cancer 1428, Villejuif, France. laurence.zitvogel@gustaveroussy.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541610" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; Animals ; Anti-Bacterial Agents/pharmacology ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Bacteroides/*immunology ; CTLA-4 Antigen/*antagonists & inhibitors/immunology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/*immunology ; Germ-Free Life/immunology ; Humans ; Immunologic Memory ; Immunotherapy ; Intestines/immunology/microbiology ; Male ; Melanoma/*therapy ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Skin Neoplasms/*therapy ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-03-15
    Description: Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we showed that innate response activator B cells produce IL-3, which induces myelopoiesis of Ly-6C(high) monocytes and neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high mortality even after adjusting for prognostic indicators. This study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376966/" 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/PMC4376966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weber, Georg F -- Chousterman, Benjamin G -- He, Shun -- Fenn, Ashley M -- Nairz, Manfred -- Anzai, Atsushi -- Brenner, Thorsten -- Uhle, Florian -- Iwamoto, Yoshiko -- Robbins, Clinton S -- Noiret, Lorette -- Maier, Sarah L -- Zonnchen, Tina -- Rahbari, Nuh N -- Scholch, Sebastian -- Klotzsche-von Ameln, Anne -- Chavakis, Triantafyllos -- Weitz, Jurgen -- Hofer, Stefan -- Weigand, Markus A -- Nahrendorf, Matthias -- Weissleder, Ralph -- Swirski, Filip K -- 5R01HL095612/HL/NHLBI NIH HHS/ -- R01 HL095612/HL/NHLBI NIH HHS/ -- R56 AI104695/AI/NIAID NIH HHS/ -- R56-AI104695/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1260-5. doi: 10.1126/science.aaa4268.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Department of Visceral, Thoracic and Vascular Surgery, Technische Universitat Dresden, Dresden, Germany. fswirski@mgh.harvard.edu georg.weber@uniklinikum-dresden.de. ; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ; Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany. ; Department of Visceral, Thoracic and Vascular Surgery, Technische Universitat Dresden, Dresden, Germany. ; Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Technische Universitat Dresden, Dresden, Germany. ; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. fswirski@mgh.harvard.edu georg.weber@uniklinikum-dresden.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766237" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocyte Subsets/immunology ; Cytokines/immunology/metabolism ; Disease Models, Animal ; Humans ; Inflammation ; Interleukin-3/blood/*immunology/metabolism ; Lipopolysaccharides/immunology ; Lymphoid Tissue/immunology ; Mice ; Mice, Inbred BALB C ; Monocytes/immunology ; Myelopoiesis ; Neutrophils/immunology ; Peritonitis/immunology/pathology ; Prognosis ; Sepsis/*immunology/mortality/pathology/therapy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53 (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-08-01
    Description: The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1alpha (DD1alpha), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1alpha appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1alpha-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1alpha thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoon, Kyoung Wan -- Byun, Sanguine -- Kwon, Eunjeong -- Hwang, So-Young -- Chu, Kiki -- Hiraki, Masatsugu -- Jo, Seung-Hee -- Weins, Astrid -- Hakroush, Samy -- Cebulla, Angelika -- Sykes, David B -- Greka, Anna -- Mundel, Peter -- Fisher, David E -- Mandinova, Anna -- Lee, Sam W -- CA142805/CA/NCI NIH HHS/ -- CA149477/CA/NCI NIH HHS/ -- CA80058/CA/NCI NIH HHS/ -- DK062472/DK/NIDDK NIH HHS/ -- DK091218/DK/NIDDK NIH HHS/ -- DK093378/DK/NIDDK NIH HHS/ -- DK57683/DK/NIDDK NIH HHS/ -- S10RR027673/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):1261669. doi: 10.1126/science.1261669.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. ; Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. ; Center for Regenerative Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ; Department of Medicine, Glom-NExT Center for Glomerular Kidney Disease and Novel Experimental Therapeutics, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. swlee@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228159" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis/genetics/*immunology ; Autoimmune Diseases/genetics/immunology ; Cell Line, Tumor ; Female ; Humans ; Inflammation/genetics/immunology ; Macrophages/immunology ; Male ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Phagocytosis/*immunology ; Phosphatidylserines/*metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/*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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