ALBERT

Description: Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, Peter -- Chang, David K -- Nones, Katia -- Johns, Amber L -- Patch, Ann-Marie -- Gingras, Marie-Claude -- Miller, David K -- Christ, Angelika N -- Bruxner, Tim J C -- Quinn, Michael C -- Nourse, Craig -- Murtaugh, L Charles -- Harliwong, Ivon -- Idrisoglu, Senel -- Manning, Suzanne -- Nourbakhsh, Ehsan -- Wani, Shivangi -- Fink, Lynn -- Holmes, Oliver -- Chin, Venessa -- Anderson, Matthew J -- Kazakoff, Stephen -- Leonard, Conrad -- Newell, Felicity -- Waddell, Nick -- Wood, Scott -- Xu, Qinying -- Wilson, Peter J -- Cloonan, Nicole -- Kassahn, Karin S -- Taylor, Darrin -- Quek, Kelly -- Robertson, Alan -- Pantano, Lorena -- Mincarelli, Laura -- Sanchez, Luis N -- Evers, Lisa -- Wu, Jianmin -- Pinese, Mark -- Cowley, Mark J -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chantrill, Lorraine A -- Mawson, Amanda -- Humphris, Jeremy -- Chou, Angela -- Pajic, Marina -- Scarlett, Christopher J -- Pinho, Andreia V -- Giry-Laterriere, Marc -- Rooman, Ilse -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Merrett, Neil D -- Toon, Christopher W -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Moran-Jones, Kim -- Jamieson, Nigel B -- Graham, Janet S -- Duthie, Fraser -- Oien, Karin -- Hair, Jane -- Grutzmann, Robert -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Corbo, Vincenzo -- Bassi, Claudio -- Rusev, Borislav -- Capelli, Paola -- Salvia, Roberto -- Tortora, Giampaolo -- Mukhopadhyay, Debabrata -- Petersen, Gloria M -- Australian Pancreatic Cancer Genome Initiative -- Munzy, Donna M -- Fisher, William E -- Karim, Saadia A -- Eshleman, James R -- Hruban, Ralph H -- Pilarsky, Christian -- Morton, Jennifer P -- Sansom, Owen J -- Scarpa, Aldo -- Musgrove, Elizabeth A -- Bailey, Ulla-Maja Hagbo -- Hofmann, Oliver -- Sutherland, Robert L -- Wheeler, David A -- Gill, Anthony J -- Gibbs, Richard A -- Pearson, John V -- Waddell, Nicola -- Biankin, Andrew V -- Grimmond, Sean M -- 103721/Z/14/Z/Wellcome Trust/United Kingdom -- A12481/Cancer Research UK/United Kingdom -- A18076/Cancer Research UK/United Kingdom -- C29717/A17263/Cancer Research UK/United Kingdom -- England -- Nature. 2016 Mar 3;531(7592):47-52. doi: 10.1038/nature16965. Epub 2016 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. ; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. ; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. ; QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. ; Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. ; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA. ; Genetic and Molecular Pathology, SA Pathology, Adelaide, South Australia 5000, Australia. ; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia 5000, Australia. ; Harvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA. ; Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales 2560, Australia. ; Department of Pathology. SydPath, St Vincent's Hospital, Sydney, NSW 2010, Australia. ; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2052, Australia. ; School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. ; Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia. ; University of Sydney, Sydney, New South Wales 2006, Australia. ; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown New South Wales 2050, Australia. ; School of Medicine, University of Western Sydney, Penrith, New South Wales 2175, Australia. ; Fiona Stanley Hospital, Robin Warren Drive, Murdoch, Western Australia 6150, Australia. ; Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. ; Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. ; School of Surgery M507, University of Western Australia, 35 Stirling Hwy, Nedlands 6009, Australia and St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia. ; Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. ; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. ; Department of Medical Oncology, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. ; Department of Pathology, Southern General Hospital, Greater Glasgow &Clyde NHS, Glasgow G51 4TF, UK. ; GGC Bio-repository, Pathology Department, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TY, UK. ; Department of Surgery, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. ; Departments of Pathology and Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston Texas 77030, USA. ; The David M. Rubenstein Pancreatic Cancer Research Center and Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy. ; Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Medical Oncology, Comprehensive Cancer Centre, University and Hospital Trust of Verona, Verona 37134, Italy. ; Mayo Clinic, Rochester, Minnesota 55905, USA. ; Elkins Pancreas Center, Baylor College of Medicine, One Baylor Plaza, MS226, Houston, Texas 77030-3411, USA. ; Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK. ; Institute for Cancer Science, University of Glasgow, Glasgow G12 8QQ, UK. ; University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26909576" target="_blank"〉PubMed〈/a〉

Description: Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523082/" 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/PMC4523082/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waddell, Nicola -- Pajic, Marina -- Patch, Ann-Marie -- Chang, David K -- Kassahn, Karin S -- Bailey, Peter -- Johns, Amber L -- Miller, David -- Nones, Katia -- Quek, Kelly -- Quinn, Michael C J -- Robertson, Alan J -- Fadlullah, Muhammad Z H -- Bruxner, Tim J C -- Christ, Angelika N -- Harliwong, Ivon -- Idrisoglu, Senel -- Manning, Suzanne -- Nourse, Craig -- Nourbakhsh, Ehsan -- Wani, Shivangi -- Wilson, Peter J -- Markham, Emma -- Cloonan, Nicole -- Anderson, Matthew J -- Fink, J Lynn -- Holmes, Oliver -- Kazakoff, Stephen H -- Leonard, Conrad -- Newell, Felicity -- Poudel, Barsha -- Song, Sarah -- Taylor, Darrin -- Waddell, Nick -- Wood, Scott -- Xu, Qinying -- Wu, Jianmin -- Pinese, Mark -- Cowley, Mark J -- Lee, Hong C -- Jones, Marc D -- Nagrial, Adnan M -- Humphris, Jeremy -- Chantrill, Lorraine A -- Chin, Venessa -- Steinmann, Angela M -- Mawson, Amanda -- Humphrey, Emily S -- Colvin, Emily K -- Chou, Angela -- Scarlett, Christopher J -- Pinho, Andreia V -- Giry-Laterriere, Marc -- Rooman, Ilse -- Samra, Jaswinder S -- Kench, James G -- Pettitt, Jessica A -- Merrett, Neil D -- Toon, Christopher -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Jamieson, Nigel B -- Graham, Janet S -- Niclou, Simone P -- Bjerkvig, Rolf -- Grutzmann, Robert -- Aust, Daniela -- Hruban, Ralph H -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Corbo, Vincenzo -- Bassi, Claudio -- Falconi, Massimo -- Zamboni, Giuseppe -- Tortora, Giampaolo -- Tempero, Margaret A -- Australian Pancreatic Cancer Genome Initiative -- Gill, Anthony J -- Eshleman, James R -- Pilarsky, Christian -- Scarpa, Aldo -- Musgrove, Elizabeth A -- Pearson, John V -- Biankin, Andrew V -- Grimmond, Sean M -- 103721/Wellcome Trust/United Kingdom -- C29717/A17263/Cancer Research UK/United Kingdom -- C596/A18076/Cancer Research UK/United Kingdom -- P30 CA006973/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P50 CA062924/CA/NCI NIH HHS/ -- P50 CA62924/CA/NCI NIH HHS/ -- England -- Nature. 2015 Feb 26;518(7540):495-501. doi: 10.1038/nature14169.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Herston Road, Brisbane 4006, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2010, Australia. ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia [3] South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia [4] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; 1] Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia [2] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] Department of Anatomical Pathology, St Vincent's Hospital, Sydney, New South Wales 2010, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. ; 1] Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia [2] University of Sydney, Sydney, New South Wales 2006, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] University of Sydney, Sydney, New South Wales 2006, Australia [3] Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. ; 1] Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia [2] School of Medicine, University of Western Sydney, Penrith, New South Wales 2175, Australia. ; Department of Surgery, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia. ; Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. ; Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. ; 1] School of Surgery M507, University of Western Australia, 35 Stirling Highway, Nedlands 6009, Australia [2] St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia [3] Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, Subiaco, Western Australia 6008, Australia. ; 1] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK [2] Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK [3] West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. ; 1] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK [2] Department of Medical Oncology, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. ; Norlux Neuro-Oncology Laboratory, CRP-Sante Luxembourg, 84 Val Fleuri, L-1526, Luxembourg. ; Norlux Neuro-Oncology, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5019 Bergen, Norway. ; Departments of Surgery and Pathology, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. ; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston Texas 77030, USA. ; The David M. Rubenstein Pancreatic Cancer Research Center and Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; 1] ARC-NET Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy [2] Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy. ; ARC-NET Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Surgery and Oncology, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. ; 1] Department of Surgery and Oncology, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy [2] Departments of Surgery and Pathology, Ospedale Sacro Cuore Don Calabria Negrar, Verona 37024, Italy. ; 1] Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy [2] Departments of Surgery and Pathology, Ospedale Sacro Cuore Don Calabria Negrar, Verona 37024, Italy. ; Department of Oncology, University and Hospital Trust of Verona, Verona 37134, Italy. ; Division of Hematology and Oncology, University of California, San Francisco, California 94122, USA. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] University of Sydney, Sydney, New South Wales 2006, Australia. ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25719666" target="_blank"〉PubMed〈/a〉

Description: The Protoaurignacian culture is pivotal to the debate about the timing of the arrival of modern humans in western Europe and the demise of Neandertals. However, which group is responsible for this culture remains uncertain. We investigated dental remains associated with the Protoaurignacian. The lower deciduous incisor from Riparo Bombrini is modern human, based on its morphology. The upper deciduous incisor from Grotta di Fumane contains ancient mitochondrial DNA of a modern human type. These teeth are the oldest human remains in an Aurignacian-related archaeological context, confirming that by 41,000 calendar years before the present, modern humans bearing Protoaurignacian culture spread into southern Europe. Because the last Neandertals date to 41,030 to 39,260 calendar years before the present, we suggest that the Protoaurignacian triggered the demise of Neandertals in this area.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benazzi, S -- Slon, V -- Talamo, S -- Negrino, F -- Peresani, M -- Bailey, S E -- Sawyer, S -- Panetta, D -- Vicino, G -- Starnini, E -- Mannino, M A -- Salvadori, P A -- Meyer, M -- Paabo, S -- Hublin, J-J -- New York, N.Y. -- Science. 2015 May 15;348(6236):793-6. doi: 10.1126/science.aaa2773. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. stefano.benazzi@unibo.it. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Dipartimento di Antichita, Filosofia, Storia e Geografia, Universita di Genova, Via Balbi 2, 16126 Genova, Italy. ; Sezione di Scienze Preistoriche e Antropologiche, Dipartimento di Studi Umanistici, Corso Ercole I d'Este 32, Universita di Ferrara, 44100 Ferrara, Italy. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. Center for the Study of Human Origins, Department of Anthropology, New York University, 25 Waverly Place, New York, NY 10003, USA. ; CNR Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy. ; Museo Archeologico del Finale, Chiostri di Santa Caterina, 17024 Finale Ligure Borgo, Italy. ; Scuola di Scienze Umanistiche, Dipartimento di Studi Storici, Universita di Torino, via S. Ottavio 20, 10124 Torino, Italy. Museo Preistorico Nazionale dei Balzi Rossi, Via Balzi Rossi 9, 18039 Ventimiglia, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908660" target="_blank"〉PubMed〈/a〉

Description: Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corti, Davide -- Misasi, John -- Mulangu, Sabue -- Stanley, Daphne A -- Kanekiyo, Masaru -- Wollen, Suzanne -- Ploquin, Aurelie -- Doria-Rose, Nicole A -- Staupe, Ryan P -- Bailey, Michael -- Shi, Wei -- Choe, Misook -- Marcus, Hadar -- Thompson, Emily A -- Cagigi, Alberto -- Silacci, Chiara -- Fernandez-Rodriguez, Blanca -- Perez, Laurent -- Sallusto, Federica -- Vanzetta, Fabrizia -- Agatic, Gloria -- Cameroni, Elisabetta -- Kisalu, Neville -- Gordon, Ingelise -- Ledgerwood, Julie E -- Mascola, John R -- Graham, Barney S -- Muyembe-Tamfun, Jean-Jacques -- Trefry, John C -- Lanzavecchia, Antonio -- Sullivan, Nancy J -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. ; Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. njsull@mail.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917593" target="_blank"〉PubMed〈/a〉

Description: Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fourgeaud, Lawrence -- Traves, Paqui G -- Tufail, Yusuf -- Leal-Bailey, Humberto -- Lew, Erin D -- Burrola, Patrick G -- Callaway, Perri -- Zagorska, Anna -- Rothlin, Carla V -- Nimmerjahn, Axel -- Lemke, Greg -- DP2 NS083038/DP/NCCDPHP CDC HHS/ -- DP2 NS083038/NS/NINDS NIH HHS/ -- P30CA014195/CA/NCI NIH HHS/ -- R01 AI089824/AI/NIAID NIH HHS/ -- R01 AI101400/AI/NIAID NIH HHS/ -- R01 NS085296/NS/NINDS NIH HHS/ -- R01 NS085938/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Apr 14;532(7598):240-4. doi: 10.1038/nature17630. Epub 2016 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Instituto de Investigaciones Biomedicas Alberto Sols (CSIC-UAM), Madrid 28029, Spain. ; Waitt Advanced Biophotonics Center, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Joint Master in Neuroscience Program, University of Strasbourg, Strasbourg 67081, France. ; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27049947" target="_blank"〉PubMed〈/a〉

Description: Two strains of St. Louis encephalitis virus were isolated from overwintering mosquitoes collected in Maryland and Pennsylvania during January and February 1977. There isolations from Culex pipiens constitute evidence that a mosquito-borne flavivirus can persist in a vector mosquito in temperate climates during the winter season.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, C L -- Eldridge, B F -- Hayes, D E -- Watts, D M -- Tammariello, R F -- Dalrymple, J M -- New York, N.Y. -- Science. 1978 Mar 24;199(4335):1346-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/628843" target="_blank"〉PubMed〈/a〉

Description: Long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs). However, even the best bNAbs neutralize 10-50% of HIV-1 isolates inefficiently (80% inhibitory concentration (IC80) 〉 5 mug ml(-1)), suggesting that high concentrations of these antibodies would be necessary to achieve general protection. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean half-maximum inhibitory concentration (IC50) 〈 0.05 mug ml(-1)). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2 and simian immunodeficiency virus isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46 and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17-77 mug ml(-1) of fully functional rhesus eCD4-Ig for more than 40 weeks, and these macaques were protected from several infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well-characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352131/" 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/PMC4352131/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gardner, Matthew R -- Kattenhorn, Lisa M -- Kondur, Hema R -- von Schaewen, Markus -- Dorfman, Tatyana -- Chiang, Jessica J -- Haworth, Kevin G -- Decker, Julie M -- Alpert, Michael D -- Bailey, Charles C -- Neale, Ernest S Jr -- Fellinger, Christoph H -- Joshi, Vinita R -- Fuchs, Sebastian P -- Martinez-Navio, Jose M -- Quinlan, Brian D -- Yao, Annie Y -- Mouquet, Hugo -- Gorman, Jason -- Zhang, Baoshan -- Poignard, Pascal -- Nussenzweig, Michel C -- Burton, Dennis R -- Kwong, Peter D -- Piatak, Michael Jr -- Lifson, Jeffrey D -- Gao, Guangping -- Desrosiers, Ronald C -- Evans, David T -- Hahn, Beatrice H -- Ploss, Alexander -- Cannon, Paula M -- Seaman, Michael S -- Farzan, Michael -- HHSN261200800001E/PHS HHS/ -- P01 AI100263/AI/NIAID NIH HHS/ -- P30 AI045008/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI080324/AI/NIAID NIH HHS/ -- R01 AI091476/AI/NIAID NIH HHS/ -- R01 AI095098/AI/NIAID NIH HHS/ -- R01 AI098485/AI/NIAID NIH HHS/ -- RR000168/RR/NCRR NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2015 Mar 5;519(7541):87-91. doi: 10.1038/nature14264. Epub 2015 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Infectious Diseases, The Scripps Research Institute, Jupiter, Florida 33458, USA. ; Department of Comparative Pathology, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA. ; Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. ; Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. ; Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Department of Comparative Pathology, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA [2] Immunathon Inc., Cambridge, Massachusetts 02141, USA. ; Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. ; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Department of Immunology, Institut Pasteur, Paris, 75015, France. ; Vaccine Research Center, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, New York, New York 10065, USA. ; 1] Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [2] Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Incorporated, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. ; 1] Department of Comparative Pathology, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA [2] Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. ; Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53711, USA. ; Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25707797" target="_blank"〉PubMed〈/a〉

Description: Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knowles, B -- Silveira, C B -- Bailey, B A -- Barott, K -- Cantu, V A -- Cobian-Guemes, A G -- Coutinho, F H -- Dinsdale, E A -- Felts, B -- Furby, K A -- George, E E -- Green, K T -- Gregoracci, G B -- Haas, A F -- Haggerty, J M -- Hester, E R -- Hisakawa, N -- Kelly, L W -- Lim, Y W -- Little, M -- Luque, A -- McDole-Somera, T -- McNair, K -- de Oliveira, L S -- Quistad, S D -- Robinett, N L -- Sala, E -- Salamon, P -- Sanchez, S E -- Sandin, S -- Silva, G G Z -- Smith, J -- Sullivan, C -- Thompson, C -- Vermeij, M J A -- Youle, M -- Young, C -- Zgliczynski, B -- Brainard, R -- Edwards, R A -- Nulton, J -- Thompson, F -- Rohwer, F -- England -- Nature. 2016 Mar 24;531(7595):466-70. doi: 10.1038/nature17193. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Biology Institute, Rio de Janeiro Federal University, Av. Carlos Chagas Filho 373, Rio de Janeiro, Rio de Janeiro 21941-599, Brazil. ; Department of Mathematics and Statistics, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Hawaii Institute of Marine Biology, University of Hawaii at Manoa, 46-007 Lilipuna Road, Kaneohe, Hawaii 96744, USA. ; Computational Science Research Center, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Rainbow Rock, Ocean View, Hawaii 96737, USA. ; Radboud University Medical Centre, Radboud Institute for Molecular Life Sciences, Centre for Molecular and Biomolecular Informatics, 6525HP Nijmegen, The Netherlands. ; Viral Information Institute, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Scripps Institution of Oceanography, 8622 Kennel Way, La Jolla, California 92037, USA. ; Department of Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Marine Sciences Department, Sao Paulo Federal University - Baixada Santista, Av. Alm. Saldanha da Gama, 89, Santos, Sao Paulo 11030-400, Brazil. ; National Geographic Society, 1145 17th St NW, Washington D.C. 20036, USA. ; CARMABI Foundation, Piscaderabaai z/n, Willemstad, Curacao, Netherlands Antilles. ; Aquatic Microbiology, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, 1098XH Amsterdam, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982729" target="_blank"〉PubMed〈/a〉

Description: A system of equine lymphocyte alloantigens designated ELA, is identified, and it is shown that the locus or loci controlling these markers must be closely linked to the locus controlling markers in the A system of horse blood groups. Among 29 offspring in two stallion families there was evidence for one recombinant. Lod scores for linkage between the A and ELA loci in the two families were 3.61 and 3.33, respectively, for theta equal to 0.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, E -- Stormont, C -- Suzuki, Y -- Trommershausen Smith, A -- New York, N.Y. -- Science. 1979 Jun 22;204(4399):1317-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/451540" target="_blank"〉PubMed〈/a〉