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  • Female  (11)
  • American Association for the Advancement of Science (AAAS)  (11)
  • 2015-2019  (11)
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  • 1
    Publication Date: 2015-01-24
    Description: Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uhlen, Mathias -- Fagerberg, Linn -- Hallstrom, Bjorn M -- Lindskog, Cecilia -- Oksvold, Per -- Mardinoglu, Adil -- Sivertsson, Asa -- Kampf, Caroline -- Sjostedt, Evelina -- Asplund, Anna -- Olsson, IngMarie -- Edlund, Karolina -- Lundberg, Emma -- Navani, Sanjay -- Szigyarto, Cristina Al-Khalili -- Odeberg, Jacob -- Djureinovic, Dijana -- Takanen, Jenny Ottosson -- Hober, Sophia -- Alm, Tove -- Edqvist, Per-Henrik -- Berling, Holger -- Tegel, Hanna -- Mulder, Jan -- Rockberg, Johan -- Nilsson, Peter -- Schwenk, Jochen M -- Hamsten, Marica -- von Feilitzen, Kalle -- Forsberg, Mattias -- Persson, Lukas -- Johansson, Fredric -- Zwahlen, Martin -- von Heijne, Gunnar -- Nielsen, Jens -- Ponten, Fredrik -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):1260419. doi: 10.1126/science.1260419.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science for Life Laboratory, KTH-Royal Institute of Technology, SE-171 21 Stockholm, Sweden. Department of Proteomics, KTH-Royal Institute of Technology, SE-106 91 Stockholm, Sweden. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2970 Horsholm, Denmark. mathias.uhlen@scilifelab.se. ; Science for Life Laboratory, KTH-Royal Institute of Technology, SE-171 21 Stockholm, Sweden. ; Science for Life Laboratory, KTH-Royal Institute of Technology, SE-171 21 Stockholm, Sweden. Department of Proteomics, KTH-Royal Institute of Technology, SE-106 91 Stockholm, Sweden. ; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden. ; Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden. ; Science for Life Laboratory, KTH-Royal Institute of Technology, SE-171 21 Stockholm, Sweden. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden. ; Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, D-44139 Dortmund, Germany. ; Lab Surgpath, Mumbai, India. ; Department of Proteomics, KTH-Royal Institute of Technology, SE-106 91 Stockholm, Sweden. ; Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden. ; Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. ; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2970 Horsholm, Denmark. Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25613900" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Cell Line ; *Databases, Protein ; Female ; Genes ; Genetic Code ; Humans ; Internet ; Male ; Membrane Proteins/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Neoplasms/genetics/metabolism ; Protein Array Analysis ; Protein Isoforms/genetics/metabolism ; Proteome/genetics/*metabolism ; Tissue Distribution ; Transcription, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-04-25
    Description: Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4(+) T cells in the intestine and suggest that this process is dysregulated in human IBD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449822/" 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/PMC4449822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hepworth, Matthew R -- Fung, Thomas C -- Masur, Samuel H -- Kelsen, Judith R -- McConnell, Fiona M -- Dubrot, Juan -- Withers, David R -- Hugues, Stephanie -- Farrar, Michael A -- Reith, Walter -- Eberl, Gerard -- Baldassano, Robert N -- Laufer, Terri M -- Elson, Charles O -- Sonnenberg, Gregory F -- DK071176/DK/NIDDK NIH HHS/ -- DP5 OD012116/OD/NIH HHS/ -- DP5OD012116/OD/NIH HHS/ -- UL1-RR024134/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 May 29;348(6238):1031-5. doi: 10.1126/science.aaa4812. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. ; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA. ; Medical Research Council, Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. ; Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland. ; Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, MN, USA. ; Institut Pasteur, Microenvironment and Immunity Unit, Paris, France. ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA. ; Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA. ; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. gfsonnenberg@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908663" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/immunology ; Autoimmunity ; Bacteria/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Colon/*microbiology ; Female ; Flagellin/genetics/immunology ; Histocompatibility Antigens Class II/*immunology ; Humans ; *Immunity, Innate ; Inflammatory Bowel Diseases/immunology/*microbiology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred C57BL ; Symbiosis ; Thymus Gland/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-10-31
    Description: Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vacchelli, Erika -- Ma, Yuting -- Baracco, Elisa E -- Sistigu, Antonella -- Enot, David P -- Pietrocola, Federico -- Yang, Heng -- Adjemian, Sandy -- Chaba, Kariman -- Semeraro, Michaela -- Signore, Michele -- De Ninno, Adele -- Lucarini, Valeria -- Peschiaroli, Francesca -- Businaro, Luca -- Gerardino, Annamaria -- Manic, Gwenola -- Ulas, Thomas -- Gunther, Patrick -- Schultze, Joachim L -- Kepp, Oliver -- Stoll, Gautier -- Lefebvre, Celine -- Mulot, Claire -- Castoldi, Francesca -- Rusakiewicz, Sylvie -- Ladoire, Sylvain -- Apetoh, Lionel -- Bravo-San Pedro, Jose Manuel -- Lucattelli, Monica -- Delarasse, Cecile -- Boige, Valerie -- Ducreux, Michel -- Delaloge, Suzette -- Borg, Christophe -- Andre, Fabrice -- Schiavoni, Giovanna -- Vitale, Ilio -- Laurent-Puig, Pierre -- Mattei, Fabrizio -- Zitvogel, Laurence -- Kroemer, Guido -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):972-8. doi: 10.1126/science.aad0779. Epub 2015 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. ; Regina Elena National Cancer Institute, Rome, Italy. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. ; Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy. ; Italian National Research Council, Institute for Photonics and Nanotechnology, Rome, Italy. ; Genomics and Immunoregulation, Life and Medical Science Center Institute, University of Bonn, Germany. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. ; Universite Paris Sorbonne Cite, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. Sotio, Prague, Czech Republic. ; Department of Medical Oncology, Centre Georges-Francois Leclerc, Dijon, France. Universite Bourgogne Franche-Comte, Dijon, France. Centre Georges Francois Leclerc, Dijon, France. ; Department of Life Sciences, University of Siena, Siena, Italy. ; Institut du Cerveau et de la Moelle Epiniere, ICM CNRS UMR 7225 - INSERM U 1127 - UPMC-P6 UMR S 1127, Equipe Neurogenetique et Physiologie Hopital de la Pitie-Salpetriere, 47, Boulevard de l'Hopital, 75013 Paris, France. ; INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France. ; Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France. ; INSERM, U981, Villejuif, France. Department of Breast Oncology, Gustave Roussy Cancer Campus, Villejuif, France. ; University of Franche-Comte, INSERM 1098, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. Department of Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. ; Regina Elena National Cancer Institute, Rome, Italy. Department of Biology, University of Rome "Tor Vergata," Rome, Italy. ; Universite Paris Sorbonne Cite, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Pole de Biologie, Hopital Europeen Georges Pompidou, AP-HP, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Pole de Biologie, Hopital Europeen Georges Pompidou, AP-HP, Paris, France. Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, 17176 Stockholm, Sweden. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516201" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Annexin A1/metabolism/pharmacology ; Anthracyclines/*therapeutic use ; Breast Neoplasms/drug therapy/immunology ; Cell Line, Tumor ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/drug therapy/immunology ; Dendritic Cells/drug effects/immunology ; Female ; Humans ; Immunity, Innate/genetics ; Leukocytes/drug effects/immunology ; Mice ; Neoplasms/*drug therapy/*immunology ; Polymorphism, Single Nucleotide ; Receptors, Formyl Peptide/genetics/*physiology ; T-Lymphocytes/immunology
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  • 4
    Publication Date: 2015-01-13
    Description: Parasitic worms modulate host immune responses in ways that affect microbial co-infections. For this reason, anthelmintic therapy may be a potent tool for indirectly controlling microbial pathogens. However, the population-level consequences of this type of intervention on co-infecting microbes are unknown. We evaluated the effects of anthelmintic treatment on bovine tuberculosis (BTB) acquisition, mortality after infection, and pathogen fitness in free-ranging African buffalo. We found that treatment had no effect on the probability of BTB infection, but buffalo survival after infection was ninefold higher among treated individuals. These contrasting effects translated into an approximately eightfold increase in the reproductive number of BTB for anthelmintic-treated compared with untreated buffalo. Our results indicate that anthelmintic treatment can enhance the spread of microbial pathogens in some real-world situations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ezenwa, Vanessa O -- Jolles, Anna E -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):175-7. doi: 10.1126/science.1261714.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Odum School of Ecology and Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. vezenwa@uga.edu. ; College of Veterinary Medicine and Department of Integrative Biology, Oregon State University, Corvallis, OR 97331, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25574023" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antinematodal Agents/*therapeutic use ; Buffaloes/immunology/microbiology/parasitology ; Cattle ; Coinfection ; Communicable Diseases/immunology/*mortality/veterinary ; Female ; Fenbendazole/therapeutic use ; Genetic Fitness/*drug effects ; Helminthiasis, Animal/*drug therapy/immunology ; Host-Pathogen Interactions/*drug effects/immunology ; Incidence ; Mycobacterium bovis/*drug effects/genetics/physiology ; Th1 Cells/immunology ; Tuberculosis, Bovine/immunology/*mortality
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  • 5
    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
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  • 6
    Publication Date: 2015-09-19
    Description: The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fumagalli, Matteo -- Moltke, Ida -- Grarup, Niels -- Racimo, Fernando -- Bjerregaard, Peter -- Jorgensen, Marit E -- Korneliussen, Thorfinn S -- Gerbault, Pascale -- Skotte, Line -- Linneberg, Allan -- Christensen, Cramer -- Brandslund, Ivan -- Jorgensen, Torben -- Huerta-Sanchez, Emilia -- Schmidt, Erik B -- Pedersen, Oluf -- Hansen, Torben -- Albrechtsen, Anders -- Nielsen, Rasmus -- R01-HG003229/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1343-7. doi: 10.1126/science.aab2319.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. ; Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. ; National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Greenland Center for Health Research, University of Greenland, Nuuk, Greenland. ; National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Steno Diabetes Center, 2820 Gentofte, Denmark. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark. ; Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Anthropology, University College London, London WC1H 0BW, UK. ; Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ; Department of Medicine, Lillebaelt Hospital, Vejle, Denmark. ; Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. ; Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Faculty of Medicine, University of Aalborg, Aalborg, Denmark. ; School of Natural Sciences, University of California-Merced, Merced, CA 95343, USA. ; Faculty of Medicine, University of Aalborg, Aalborg, Denmark. Department of Cardiology, Aalborg University Hospital, 9100 Aalborg, Denmark. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu. ; Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. Department of Statistics, University of California-Berkeley, Berkeley, CA 94720, USA. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383953" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/*genetics ; Alleles ; Arctic Regions ; Body Height/genetics ; Body Weight/genetics ; Chromosomes, Human, Pair 11/genetics ; Climate ; *Diet, High-Fat ; Fatty Acids, Omega-3/*administration & dosage/analysis ; Female ; Genetic Loci ; Genome, Human/genetics ; Genome-Wide Association Study ; Greenland ; Humans ; Inuits/*genetics ; Linkage Disequilibrium ; Male ; Membrane Lipids/analysis/genetics ; Polymorphism, Single Nucleotide ; Selection, Genetic
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-08-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Margoliash, Daniel -- Tchernichovski, Ofer -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):688-9. doi: 10.1126/science.aac7860.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA. dan@bigbird.uchicago.edu. ; Department of Psychology, Hunter College, City University of New York, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26273040" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Callithrix/*growth & development ; Female ; Male ; *Vocalization, Animal
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  • 8
    Publication Date: 2015-06-20
    Description: Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-gamma-producing CD4 T cells. By contrast, we report that mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-) dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b(-)CD103(+) DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T cells, but only mucosal vaccination induced effector T cells that rapidly seeded uterine mucosa with resident memory T cells (T(RM) cells). Optimal Ct clearance required both T(RM) seeding and subsequent infection-induced recruitment of circulating memory T cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T cell subsets with distinct migratory properties.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605428/" 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/PMC4605428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stary, Georg -- Olive, Andrew -- Radovic-Moreno, Aleksandar F -- Gondek, David -- Alvarez, David -- Basto, Pamela A -- Perro, Mario -- Vrbanac, Vladimir D -- Tager, Andrew M -- Shi, Jinjun -- Yethon, Jeremy A -- Farokhzad, Omid C -- Langer, Robert -- Starnbach, Michael N -- von Andrian, Ulrich H -- 1 R01-EB015419-01/EB/NIBIB NIH HHS/ -- AI069259/AI/NIAID NIH HHS/ -- AI078897/AI/NIAID NIH HHS/ -- AI095261/AI/NIAID NIH HHS/ -- AI111595/AI/NIAID NIH HHS/ -- P01 AI078897/AI/NIAID NIH HHS/ -- P30-AI060354/AI/NIAID NIH HHS/ -- R00 CA160350/CA/NCI NIH HHS/ -- R01 AI039558/AI/NIAID NIH HHS/ -- R01 AI062827/AI/NIAID NIH HHS/ -- R01 AI069259/AI/NIAID NIH HHS/ -- R01 AI072252/AI/NIAID NIH HHS/ -- R01 AI111595/AI/NIAID NIH HHS/ -- R01 AI39558/AI/NIAID NIH HHS/ -- R37-EB000244/EB/NIBIB NIH HHS/ -- T32 HL066987/HL/NHLBI NIH HHS/ -- U19 AI095261/AI/NIAID NIH HHS/ -- U19 AI113187/AI/NIAID NIH HHS/ -- U54-CA119349/CA/NCI NIH HHS/ -- U54-CA151884/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 19;348(6241):aaa8205. doi: 10.1126/science.aaa8205.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. uva@hms.harvard.edu georg_stary@hms.harvard.edu. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Sanofi Pasteur, Cambridge, MA 02139, USA. ; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. King Abdulaziz University, Jeddah, Saudi Arabia. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. uva@hms.harvard.edu georg_stary@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089520" target="_blank"〉PubMed〈/a〉
    Keywords: Adjuvants, Immunologic/administration & dosage ; Animals ; Antigens, CD/immunology ; Antigens, CD11/immunology ; Bacterial Vaccines/administration & dosage/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Chlamydia Infections/*prevention & control ; Chlamydia trachomatis/*immunology/radiation effects ; Dendritic Cells/immunology ; Female ; *Immunologic Memory ; Integrin alpha Chains/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mucous Membrane/immunology ; Nanoparticles/administration & dosage ; T-Lymphocyte Subsets/immunology ; Th1 Cells/*immunology ; Ultraviolet Rays ; Uterus/*immunology ; Vaccination/methods ; Vaccines, Inactivated/administration & dosage/immunology
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  • 9
    Publication Date: 2015-11-07
    Description: More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impairs tumor growth in Apc/Kras(G12D) mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778961/" 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/PMC4778961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yun, Jihye -- Mullarky, Edouard -- Lu, Changyuan -- Bosch, Kaitlyn N -- Kavalier, Adam -- Rivera, Keith -- Roper, Jatin -- Chio, Iok In Christine -- Giannopoulou, Eugenia G -- Rago, Carlo -- Muley, Ashlesha -- Asara, John M -- Paik, Jihye -- Elemento, Olivier -- Chen, Zhengming -- Pappin, Darryl J -- Dow, Lukas E -- Papadopoulos, Nickolas -- Gross, Steven S -- Cantley, Lewis C -- KL2 TR000458/TR/NCATS NIH HHS/ -- P01 CA117969/CA/NCI NIH HHS/ -- P01 CA117969-09/CA/NCI NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P01 CA120964-07/CA/NCI NIH HHS/ -- S10 RR022615/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 11;350(6266):1391-6. doi: 10.1126/science.aaa5004. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. ; Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Biological and Biomedical Sciences Graduate Program, Harvard Medical School, Boston, MA 02115, USA. ; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. ; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. ; Molecular Oncology Research Institute and Division of Gastroenterology, Tufts Medical Center, Boston, MA 02111, USA. ; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA. ; Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA. ; Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, NY 10065, USA. ; Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. lcantley@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541605" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein/genetics ; Animals ; Ascorbic Acid/administration & dosage/pharmacology/*therapeutic use ; Cell Line, Tumor ; Colorectal Neoplasms/*drug therapy/*genetics ; Dehydroascorbic Acid/metabolism ; Female ; Glucose Transporter Type 1/metabolism ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/metabolism ; Glycolysis/drug effects ; Humans ; Mice ; Mice, Mutant Strains ; Mice, Nude ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins B-raf/*genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; Reactive Oxygen Species/metabolism ; Xenograft Model Antitumor Assays ; ras Proteins/*genetics
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  • 10
    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
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