ALBERT

Description: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified 〉300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" 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/PMC3235490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International HIV Controllers Study -- Pereyra, Florencia -- Jia, Xiaoming -- McLaren, Paul J -- Telenti, Amalio -- de Bakker, Paul I W -- Walker, Bruce D -- Ripke, Stephan -- Brumme, Chanson J -- Pulit, Sara L -- Carrington, Mary -- Kadie, Carl M -- Carlson, Jonathan M -- Heckerman, David -- Graham, Robert R -- Plenge, Robert M -- Deeks, Steven G -- Gianniny, Lauren -- Crawford, Gabriel -- Sullivan, Jordan -- Gonzalez, Elena -- Davies, Leela -- Camargo, Amy -- Moore, Jamie M -- Beattie, Nicole -- Gupta, Supriya -- Crenshaw, Andrew -- Burtt, Noel P -- Guiducci, Candace -- Gupta, Namrata -- Gao, Xiaojiang -- Qi, Ying -- Yuki, Yuko -- Piechocka-Trocha, Alicja -- Cutrell, Emily -- Rosenberg, Rachel -- Moss, Kristin L -- Lemay, Paul -- O'Leary, Jessica -- Schaefer, Todd -- Verma, Pranshu -- Toth, Ildiko -- Block, Brian -- Baker, Brett -- Rothchild, Alissa -- Lian, Jeffrey -- Proudfoot, Jacqueline -- Alvino, Donna Marie L -- Vine, Seanna -- Addo, Marylyn M -- Allen, Todd M -- Altfeld, Marcus -- Henn, Matthew R -- Le Gall, Sylvie -- Streeck, Hendrik -- Haas, David W -- Kuritzkes, Daniel R -- Robbins, Gregory K -- Shafer, Robert W -- Gulick, Roy M -- Shikuma, Cecilia M -- Haubrich, Richard -- Riddler, Sharon -- Sax, Paul E -- Daar, Eric S -- Ribaudo, Heather J -- Agan, Brian -- Agarwal, Shanu -- Ahern, Richard L -- Allen, Brady L -- Altidor, Sherly -- Altschuler, Eric L -- Ambardar, Sujata -- Anastos, Kathryn -- Anderson, Ben -- Anderson, Val -- Andrady, Ushan -- Antoniskis, Diana -- Bangsberg, David -- Barbaro, Daniel -- Barrie, William -- Bartczak, J -- Barton, Simon -- Basden, Patricia -- Basgoz, Nesli -- Bazner, Suzane -- Bellos, Nicholaos C -- Benson, Anne M -- Berger, Judith -- Bernard, Nicole F -- Bernard, Annette M -- Birch, Christopher -- Bodner, Stanley J -- Bolan, Robert K -- Boudreaux, Emilie T -- Bradley, Meg -- Braun, James F -- Brndjar, Jon E -- Brown, Stephen J -- Brown, Katherine -- Brown, Sheldon T -- Burack, Jedidiah -- Bush, Larry M -- Cafaro, Virginia -- Campbell, Omobolaji -- Campbell, John -- Carlson, Robert H -- Carmichael, J Kevin -- Casey, Kathleen K -- Cavacuiti, Chris -- Celestin, Gregory -- Chambers, Steven T -- Chez, Nancy -- Chirch, Lisa M -- Cimoch, Paul J -- Cohen, Daniel -- Cohn, Lillian E -- Conway, Brian -- Cooper, David A -- Cornelson, Brian -- Cox, David T -- Cristofano, Michael V -- Cuchural, George Jr -- Czartoski, Julie L -- Dahman, Joseph M -- Daly, Jennifer S -- Davis, Benjamin T -- Davis, Kristine -- Davod, Sheila M -- DeJesus, Edwin -- Dietz, Craig A -- Dunham, Eleanor -- Dunn, Michael E -- Ellerin, Todd B -- Eron, Joseph J -- Fangman, John J W -- Farel, Claire E -- Ferlazzo, Helen -- Fidler, Sarah -- Fleenor-Ford, Anita -- Frankel, Renee -- Freedberg, Kenneth A -- French, Neel K -- Fuchs, Jonathan D -- Fuller, Jon D -- Gaberman, Jonna -- Gallant, Joel E -- Gandhi, Rajesh T -- Garcia, Efrain -- Garmon, Donald -- Gathe, Joseph C Jr -- Gaultier, Cyril R -- Gebre, Wondwoosen -- Gilman, Frank D -- Gilson, Ian -- Goepfert, Paul A -- Gottlieb, Michael S -- Goulston, Claudia -- Groger, Richard K -- Gurley, T Douglas -- Haber, Stuart -- Hardwicke, Robin -- Hardy, W David -- Harrigan, P Richard -- Hawkins, Trevor N -- Heath, Sonya -- Hecht, Frederick M -- Henry, W Keith -- Hladek, Melissa -- Hoffman, Robert P -- Horton, James M -- Hsu, Ricky K -- Huhn, Gregory D -- Hunt, Peter -- Hupert, Mark J -- Illeman, Mark L -- Jaeger, Hans -- Jellinger, Robert M -- John, Mina -- Johnson, Jennifer A -- Johnson, Kristin L -- Johnson, Heather -- Johnson, Kay -- Joly, Jennifer -- Jordan, Wilbert C -- Kauffman, Carol A -- Khanlou, Homayoon -- Killian, Robert K -- Kim, Arthur Y -- Kim, David D -- Kinder, Clifford A -- Kirchner, Jeffrey T -- Kogelman, Laura -- Kojic, Erna Milunka -- Korthuis, P Todd -- Kurisu, Wayne -- Kwon, Douglas S -- LaMar, Melissa -- Lampiris, Harry -- Lanzafame, Massimiliano -- Lederman, Michael M -- Lee, David M -- Lee, Jean M L -- Lee, Marah J -- Lee, Edward T Y -- Lemoine, Janice -- Levy, Jay A -- Llibre, Josep M -- Liguori, Michael A -- Little, Susan J -- Liu, Anne Y -- Lopez, Alvaro J -- Loutfy, Mono R -- Loy, Dawn -- Mohammed, Debbie Y -- Man, Alan -- Mansour, Michael K -- Marconi, Vincent C -- Markowitz, Martin -- Marques, Rui -- Martin, Jeffrey N -- Martin, Harold L Jr -- Mayer, Kenneth Hugh -- McElrath, M Juliana -- McGhee, Theresa A -- McGovern, Barbara H -- McGowan, Katherine -- McIntyre, Dawn -- Mcleod, Gavin X -- Menezes, Prema -- Mesa, Greg -- Metroka, Craig E -- Meyer-Olson, Dirk -- Miller, Andy O -- Montgomery, Kate -- Mounzer, Karam C -- Nagami, Ellen H -- Nagin, Iris -- Nahass, Ronald G -- Nelson, Margret O -- Nielsen, Craig -- Norene, David L -- O'Connor, David H -- Ojikutu, Bisola O -- Okulicz, Jason -- Oladehin, Olakunle O -- Oldfield, Edward C 3rd -- Olender, Susan A -- Ostrowski, Mario -- Owen, William F Jr -- Pae, Eunice -- Parsonnet, Jeffrey -- Pavlatos, Andrew M -- Perlmutter, Aaron M -- Pierce, Michael N -- Pincus, Jonathan M -- Pisani, Leandro -- Price, Lawrence Jay -- Proia, Laurie -- Prokesch, Richard C -- Pujet, Heather Calderon -- Ramgopal, Moti -- Rathod, Almas -- Rausch, Michael -- Ravishankar, J -- Rhame, Frank S -- Richards, Constance Shamuyarira -- Richman, Douglas D -- Rodes, Berta -- Rodriguez, Milagros -- Rose, Richard C 3rd -- Rosenberg, Eric S -- Rosenthal, Daniel -- Ross, Polly E -- Rubin, David S -- Rumbaugh, Elease -- Saenz, Luis -- Salvaggio, Michelle R -- Sanchez, William C -- Sanjana, Veeraf M -- Santiago, Steven -- Schmidt, Wolfgang -- Schuitemaker, Hanneke -- Sestak, Philip M -- Shalit, Peter -- Shay, William -- Shirvani, Vivian N -- Silebi, Vanessa I -- Sizemore, James M Jr -- Skolnik, Paul R -- Sokol-Anderson, Marcia -- Sosman, James M -- Stabile, Paul -- Stapleton, Jack T -- Starrett, Sheree -- Stein, Francine -- Stellbrink, Hans-Jurgen -- Sterman, F Lisa -- Stone, Valerie E -- Stone, David R -- Tambussi, Giuseppe -- Taplitz, Randy A -- Tedaldi, Ellen M -- Theisen, William -- Torres, Richard -- Tosiello, Lorraine -- Tremblay, Cecile -- Tribble, Marc A -- Trinh, Phuong D -- Tsao, Alice -- Ueda, Peggy -- Vaccaro, Anthony -- Valadas, Emilia -- Vanig, Thanes J -- Vecino, Isabel -- Vega, Vilma M -- Veikley, Wenoah -- Wade, Barbara H -- Walworth, Charles -- Wanidworanun, Chingchai -- Ward, Douglas J -- Warner, Daniel A -- Weber, Robert D -- Webster, Duncan -- Weis, Steve -- Wheeler, David A -- White, David J -- Wilkins, Ed -- Winston, Alan -- Wlodaver, Clifford G -- van't Wout, Angelique -- Wright, David P -- Yang, Otto O -- Yurdin, David L -- Zabukovic, Brandon W -- Zachary, Kimon C -- Zeeman, Beth -- Zhao, Meng -- AI030914/AI/NIAID NIH HHS/ -- AI068636/AI/NIAID NIH HHS/ -- AI069415/AI/NIAID NIH HHS/ -- AI069419/AI/NIAID NIH HHS/ -- AI069423/AI/NIAID NIH HHS/ -- AI069424/AI/NIAID NIH HHS/ -- AI069428/AI/NIAID NIH HHS/ -- AI069432/AI/NIAID NIH HHS/ -- AI069434/AI/NIAID NIH HHS/ -- AI069450/AI/NIAID NIH HHS/ -- AI069452/AI/NIAID NIH HHS/ -- AI069465/AI/NIAID NIH HHS/ -- AI069471/AI/NIAID NIH HHS/ -- AI069472/AI/NIAID NIH HHS/ -- AI069474/AI/NIAID NIH HHS/ -- AI069477/AI/NIAID NIH HHS/ -- AI069484/AI/NIAID NIH HHS/ -- AI069495/AI/NIAID NIH HHS/ -- AI069501/AI/NIAID NIH HHS/ -- AI069502/AI/NIAID NIH HHS/ -- AI069511/AI/NIAID NIH HHS/ -- AI069513/AI/NIAID NIH HHS/ -- AI069532/AI/NIAID NIH HHS/ -- AI069556/AI/NIAID NIH HHS/ -- AI077505/AI/NIAID NIH HHS/ -- AI087145/AI/NIAID NIH HHS/ -- AI25859/AI/NIAID NIH HHS/ -- 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HHS/ -- U01 AI069484-06/AI/NIAID NIH HHS/ -- U01 AI069495/AI/NIAID NIH HHS/ -- U01 AI069495-05/AI/NIAID NIH HHS/ -- U01 AI069495-06/AI/NIAID NIH HHS/ -- U01 AI069501/AI/NIAID NIH HHS/ -- U01 AI069501-05/AI/NIAID NIH HHS/ -- U01 AI069501-06/AI/NIAID NIH HHS/ -- U01 AI069502/AI/NIAID NIH HHS/ -- U01 AI069502-05/AI/NIAID NIH HHS/ -- U01 AI069502-06/AI/NIAID NIH HHS/ -- U01 AI069511/AI/NIAID NIH HHS/ -- U01 AI069511-05/AI/NIAID NIH HHS/ -- U01 AI069511-06/AI/NIAID NIH HHS/ -- U01 AI069513-05/AI/NIAID NIH HHS/ -- U01 AI069513-06/AI/NIAID NIH HHS/ -- U01 AI069532/AI/NIAID NIH HHS/ -- U01 AI069532-05/AI/NIAID NIH HHS/ -- U01 AI069532-06/AI/NIAID NIH HHS/ -- U01 AI069556-05/AI/NIAID NIH HHS/ -- U01 AI069556-06/AI/NIAID NIH HHS/ -- U01 MH085520/MH/NIMH NIH HHS/ -- U01 MH085520-01/MH/NIMH NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- UL1 RR024131-06/RR/NCRR NIH HHS/ -- UL1 RR024131-07/RR/NCRR NIH HHS/ -- UL1 RR024975/RR/NCRR NIH HHS/ -- UL1 RR024975-04/RR/NCRR NIH HHS/ -- UL1 RR024975-05/RR/NCRR NIH HHS/ -- UM1 AI068634/AI/NIAID NIH HHS/ -- UM1 AI068634-06/AI/NIAID NIH HHS/ -- UM1 AI068634-07/AI/NIAID NIH HHS/ -- UM1 AI068636-06/AI/NIAID NIH HHS/ -- UM1 AI068636-07/AI/NIAID NIH HHS/ -- UM1 AI069477/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1551-7. doi: 10.1126/science.1195271. Epub 2010 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051598" target="_blank"〉PubMed〈/a〉

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〉

Description: A major goal of HIV-1 vaccine research is the design of immunogens capable of inducing broadly neutralizing antibodies (bnAbs) that bind to the viral envelope glycoprotein (Env). Poor binding of Env to unmutated precursors of bnAbs, including those of the VRC01 class, appears to be a major problem for bnAb induction. We engineered an immunogen that binds to VRC01-class bnAb precursors and immunized knock-in mice expressing germline-reverted VRC01 heavy chains. Induced antibodies showed characteristics of VRC01-class bnAbs, including a short CDRL3 (light-chain complementarity-determining region 3) and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate VRC01-class precursors. The results suggest that rational epitope design can prime rare B cell precursors for affinity maturation to desired targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669217/" 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/PMC4669217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph G -- Ota, Takayuki -- Sok, Devin -- Pauthner, Matthias -- Kulp, Daniel W -- Kalyuzhniy, Oleksandr -- Skog, Patrick D -- Thinnes, Theresa C -- Bhullar, Deepika -- Briney, Bryan -- Menis, Sergey -- Jones, Meaghan -- Kubitz, Mike -- Spencer, Skye -- Adachi, Yumiko -- Burton, Dennis R -- Schief, William R -- Nemazee, David -- 1UM1AI100663/AI/NIAID NIH HHS/ -- P01 AI094419/AI/NIAID NIH HHS/ -- P01AI081625/AI/NIAID NIH HHS/ -- R01 AI073148/AI/NIAID NIH HHS/ -- R01 AI081625/AI/NIAID NIH HHS/ -- R01-AI073148/AI/NIAID NIH HHS/ -- T32 AI007244/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):156-61. doi: 10.1126/science.aac5894. Epub 2015 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center (NAC), The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center (NAC), The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. nemazee@scripps.edu schief@scripps.edu burton@scripps.edu. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. nemazee@scripps.edu schief@scripps.edu burton@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089355" target="_blank"〉PubMed〈/a〉

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〉

Description: The pathogenesis of asthma reflects, in part, the activity of T cell cytokines. Murine models support participation of interleukin-4 (IL-4) and the IL-4 receptor in asthma. Selective neutralization of IL-13, a cytokine related to IL-4 that also binds to the alpha chain of the IL-4 receptor, ameliorated the asthma phenotype, including airway hyperresponsiveness, eosinophil recruitment, and mucus overproduction. Administration of either IL-13 or IL-4 conferred an asthma-like phenotype to nonimmunized T cell-deficient mice by an IL-4 receptor alpha chain-dependent pathway. This pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL-4 receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897229/" 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/PMC3897229/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grunig, G -- Warnock, M -- Wakil, A E -- Venkayya, R -- Brombacher, F -- Rennick, D M -- Sheppard, D -- Mohrs, M -- Donaldson, D D -- Locksley, R M -- Corry, D B -- 03344/PHS HHS/ -- 47412/PHS HHS/ -- K08 HL003344/HL/NHLBI NIH HHS/ -- T32 HL07185/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2261-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856950" target="_blank"〉PubMed〈/a〉

Description: Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis. Further, decreased mTORC1 signaling was sufficient to extend life span independently from changes in glucose homeostasis, as female mice heterozygous for both mTOR and mLST8 exhibited decreased mTORC1 activity and extended life span but had normal glucose tolerance and insulin sensitivity. Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324089/" 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/PMC3324089/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lamming, Dudley W -- Ye, Lan -- Katajisto, Pekka -- Goncalves, Marcus D -- Saitoh, Maki -- Stevens, Deanna M -- Davis, James G -- Salmon, Adam B -- Richardson, Arlan -- Ahima, Rexford S -- Guertin, David A -- Sabatini, David M -- Baur, Joseph A -- 1F32AG032833-01A1/AG/NIA NIH HHS/ -- CA129105/CA/NCI NIH HHS/ -- F32 AG032833/AG/NIA NIH HHS/ -- P30DK19525/DK/NIDDK NIH HHS/ -- R01 CA129105/CA/NCI NIH HHS/ -- R01 CA129105-05/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Mar 30;335(6076):1638-43. doi: 10.1126/science.1215135.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22461615" target="_blank"〉PubMed〈/a〉

Description: Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korin, Netanel -- Kanapathipillai, Mathumai -- Matthews, Benjamin D -- Crescente, Marilena -- Brill, Alexander -- Mammoto, Tadanori -- Ghosh, Kaustabh -- Jurek, Samuel -- Bencherif, Sidi A -- Bhatta, Deen -- Coskun, Ahmet U -- Feldman, Charles L -- Wagner, Denisa D -- Ingber, Donald E -- New York, N.Y. -- Science. 2012 Aug 10;337(6095):738-42. doi: 10.1126/science.1217815. Epub 2012 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22767894" target="_blank"〉PubMed〈/a〉

Description: The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432565/" 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/PMC3432565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iliev, Iliyan D -- Funari, Vincent A -- Taylor, Kent D -- Nguyen, Quoclinh -- Reyes, Christopher N -- Strom, Samuel P -- Brown, Jordan -- Becker, Courtney A -- Fleshner, Phillip R -- Dubinsky, Marla -- Rotter, Jerome I -- Wang, Hanlin L -- McGovern, Dermot P B -- Brown, Gordon D -- Underhill, David M -- 086558/Wellcome Trust/United Kingdom -- AI071116/AI/NIAID NIH HHS/ -- P01-DK046763/DK/NIDDK NIH HHS/ -- R01 DK093426/DK/NIDDK NIH HHS/ -- UL1 RR033176/RR/NCRR NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- UL1RR033176/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Jun 8;336(6086):1314-7. doi: 10.1126/science.1221789. Epub 2012 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22674328" target="_blank"〉PubMed〈/a〉

Description: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 in humans are unknown. We identified germline heterozygous mutations in CTLA4 in subjects with severe immune dysregulation from four unrelated families. Whereas Ctla4 heterozygous mice have no obvious phenotype, human CTLA4 haploinsufficiency caused dysregulation of FoxP3(+) regulatory T (Treg) cells, hyperactivation of effector T cells, and lymphocytic infiltration of target organs. Patients also exhibited progressive loss of circulating B cells, associated with an increase of predominantly autoreactive CD21(lo) B cells and accumulation of B cells in nonlymphoid organs. Inherited human CTLA4 haploinsufficiency demonstrates a critical quantitative role for CTLA-4 in governing T and B lymphocyte homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371526/" 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/PMC4371526/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuehn, Hye Sun -- Ouyang, Weiming -- Lo, Bernice -- Deenick, Elissa K -- Niemela, Julie E -- Avery, Danielle T -- Schickel, Jean-Nicolas -- Tran, Dat Q -- Stoddard, Jennifer -- Zhang, Yu -- Frucht, David M -- Dumitriu, Bogdan -- Scheinberg, Phillip -- Folio, Les R -- Frein, Cathleen A -- Price, Susan -- Koh, Christopher -- Heller, Theo -- Seroogy, Christine M -- Huttenlocher, Anna -- Rao, V Koneti -- Su, Helen C -- Kleiner, David -- Notarangelo, Luigi D -- Rampertaap, Yajesh -- Olivier, Kenneth N -- McElwee, Joshua -- Hughes, Jason -- Pittaluga, Stefania -- Oliveira, Joao B -- Meffre, Eric -- Fleisher, Thomas A -- Holland, Steven M -- Lenardo, Michael J -- Tangye, Stuart G -- Uzel, Gulbu -- 5R01HL113304-01/HL/NHLBI NIH HHS/ -- AI061093/AI/NIAID NIH HHS/ -- AI071087/AI/NIAID NIH HHS/ -- AI095848/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- P01 AI061093/AI/NIAID NIH HHS/ -- R01 AI071087/AI/NIAID NIH HHS/ -- R01 HL113304/HL/NHLBI NIH HHS/ -- R21 AI095848/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 26;345(6204):1623-7. doi: 10.1126/science.1255904. Epub 2014 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. tfleishe@cc.nih.gov lenardo@nih.gov guzel@niaid.nih.gov. ; Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA. tfleishe@cc.nih.gov lenardo@nih.gov guzel@niaid.nih.gov. ; Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. tfleishe@cc.nih.gov lenardo@nih.gov guzel@niaid.nih.gov. ; Immunology and Immunodeficiency Group, Immunology Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. St. Vincent's Clinical School Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia. ; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. ; Immunology and Immunodeficiency Group, Immunology Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. ; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA. ; Department of Pediatrics, University of Texas Medical School, Houston, TX 77030, USA. ; NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA. ; Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA. ; Radiology and Imaging and Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. ; Clinical Research Directorate, Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. ; Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. ; Department of Pediatrics, University of Wisconsin, Madison, WI 53706, USA. ; Department of Pediatrics, University of Wisconsin, Madison, WI 53706, USA. Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA. ; Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA. ; Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA 10217, USA. ; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; Merck Research Laboratories, Merck & Co., Boston, MA 02130, USA. ; Instituto de Medicina Integral Prof. Fernando Figueira-IMIP, 50070 Recife-PE, Brazil. ; NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. tfleishe@cc.nih.gov lenardo@nih.gov guzel@niaid.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25213377" target="_blank"〉PubMed〈/a〉

Description: Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, are too small, or occur too rapidly to see clearly with existing tools. We crafted ultrathin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at subsecond intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. The results provide a visceral reminder of the beauty and the complexity of living systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336192/" 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/PMC4336192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Bi-Chang -- Legant, Wesley R -- Wang, Kai -- Shao, Lin -- Milkie, Daniel E -- Davidson, Michael W -- Janetopoulos, Chris -- Wu, Xufeng S -- Hammer, John A 3rd -- Liu, Zhe -- English, Brian P -- Mimori-Kiyosue, Yuko -- Romero, Daniel P -- Ritter, Alex T -- Lippincott-Schwartz, Jennifer -- Fritz-Laylin, Lillian -- Mullins, R Dyche -- Mitchell, Diana M -- Bembenek, Joshua N -- Reymann, Anne-Cecile -- Bohme, Ralph -- Grill, Stephan W -- Wang, Jennifer T -- Seydoux, Geraldine -- Tulu, U Serdar -- Kiehart, Daniel P -- Betzig, Eric -- GM33830/GM/NIGMS NIH HHS/ -- R01 GM033830/GM/NIGMS NIH HHS/ -- R01GM080370/GM/NIGMS NIH HHS/ -- R01HD37047/HD/NICHD NIH HHS/ -- RM01-GM61010/GM/NIGMS NIH HHS/ -- T32 GM007445/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):1257998. doi: 10.1126/science.1257998. Epub 2014 Oct 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. ; Coleman Technologies, Incorporated, Newtown Square, PA 19073, USA. ; National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, FL 32310, USA. ; Department of Biological Sciences, University of the Sciences, Philadelphia, PA 19104, USA. ; Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Optical Image Analysis Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan. ; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA. ; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 0XY, England, UK. ; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA. ; Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Max Planck Institute for the Physics of Complex Systems, 01307 Dresden, Germany. ; Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. ; Department of Biology, Duke University, Durham, NC 27708, USA. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. betzige@janelia.hhmi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342811" target="_blank"〉PubMed〈/a〉