ALBERT

Description: Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876960/" 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/PMC4876960/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruibal, Paula -- Oestereich, Lisa -- Ludtke, Anja -- Becker-Ziaja, Beate -- Wozniak, David M -- Kerber, Romy -- Korva, Misa -- Cabeza-Cabrerizo, Mar -- Bore, Joseph A -- Koundouno, Fara Raymond -- Duraffour, Sophie -- Weller, Romy -- Thorenz, Anja -- Cimini, Eleonora -- Viola, Domenico -- Agrati, Chiara -- Repits, Johanna -- Afrough, Babak -- Cowley, Lauren A -- Ngabo, Didier -- Hinzmann, Julia -- Mertens, Marc -- Vitoriano, Ines -- Logue, Christopher H -- Boettcher, Jan Peter -- Pallasch, Elisa -- Sachse, Andreas -- Bah, Amadou -- Nitzsche, Katja -- Kuisma, Eeva -- Michel, Janine -- Holm, Tobias -- Zekeng, Elsa-Gayle -- Garcia-Dorival, Isabel -- Wolfel, Roman -- Stoecker, Kilian -- Fleischmann, Erna -- Strecker, Thomas -- Di Caro, Antonino -- Avsic-Zupanc, Tatjana -- Kurth, Andreas -- Meschi, Silvia -- Mely, Stephane -- Newman, Edmund -- Bocquin, Anne -- Kis, Zoltan -- Kelterbaum, Anne -- Molkenthin, Peter -- Carletti, Fabrizio -- Portmann, Jasmine -- Wolff, Svenja -- Castilletti, Concetta -- Schudt, Gordian -- Fizet, Alexandra -- Ottowell, Lisa J -- Herker, Eva -- Jacobs, Thomas -- Kretschmer, Birte -- Severi, Ettore -- Ouedraogo, Nobila -- Lago, Mar -- Negredo, Anabel -- Franco, Leticia -- Anda, Pedro -- Schmiedel, Stefan -- Kreuels, Benno -- Wichmann, Dominic -- Addo, Marylyn M -- Lohse, Ansgar W -- De Clerck, Hilde -- Nanclares, Carolina -- Jonckheere, Sylvie -- Van Herp, Michel -- Sprecher, Armand -- Xiaojiang, Gao -- Carrington, Mary -- Miranda, Osvaldo -- Castro, Carlos M -- Gabriel, Martin -- Drury, Patrick -- Formenty, Pierre -- Diallo, Boubacar -- Koivogui, Lamine -- Magassouba, N'Faly -- Carroll, Miles W -- Gunther, Stephan -- Munoz-Fontela, Cesar -- HHSN261200800001E/PHS HHS/ -- Z01 BC010791-01/Intramural NIH HHS/ -- Z01 BC010791-02/Intramural NIH HHS/ -- Z01 BC010792-01/Intramural NIH HHS/ -- England -- Nature. 2016 May 5;533(7601):100-4. doi: 10.1038/nature17949.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany. ; Bernhard Nocht Institute for Tropical Medicine, World Health Organization Collaborating Center for Arbovirus and Hemorrhagic Fever Reference and Research, 20359 Hamburg, Germany. ; German Center for Infection Research (DZIF), Partner Sites Hamburg, Munich, and Marburg, Germany. ; European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. ; Institute of Experimental Virology, Twincore, Center for Experimental and Clinical Infection Research, 30625 Hannover, Germany. ; Hannover Medical School, 30625 Hannover, Germany. ; National Institute for Infectious Diseases 'Lazzaro Spallanzani', 00149 Rome, Italy. ; Public Health England, Porton Down, Salisbury SP4 0JG, UK. ; Public Health England, Colindale Ave, London NW9 5EQ, UK. ; Robert Koch Institute, 13353 Berlin, Germany. ; Friedrich Loeffler Institute, 17493 Greifswald-Island of Riems, Germany. ; Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland. ; Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. ; Bundeswehr Institute of Microbiology, 80937 Munich, Germany. ; Institute of Virology, Philipps University, 35043 Marburg, Germany. ; Laboratoire P4-Jean Merieux, US003 INSERM, 69365 Lyon, France. ; National Center for Epidemiology, Hungarian National Biosafety Laboratory, H1097 Budapest, Hungary. ; European Centre for Disease Prevention and Control, 171 65 Solna, Sweden. ; Federal Office for Civil Protection, CH-3700 Spiez, Switzerland. ; Unite de Biologie des Infections Virales Emergentes, Institut Pasteur, 69365 Lyon, France. ; Eurice, European Research and Project Office, 10115 Berlin, Germany. ; Infectious Diseases Unit, Internal Medicine Service, Hospital La Paz, 28046 Madrid, Spain. ; National Center of Microbiology, Institute of Health 'Carlos III', 28220 Madrid, Spain. ; University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. ; Medecins sans Frontieres, B-1050 Brussels, Belgium. ; Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA. ; Hospital Militar Central Dr. Carlos J. Finlay, 11400 Havana, Cuba. ; World Health Organization, 1211 Geneva 27, Switzerland. ; Institut National de Sante Publique, 2101 Conakry, Guinea. ; Universite Gamal Abdel Nasser de Conakry, CHU Donka, 2101 Conakry, Guinea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27147028" target="_blank"〉PubMed〈/a〉

Description: The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 x 10(-3) and 1.42 x 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quick, Joshua -- Loman, Nicholas J -- Duraffour, Sophie -- Simpson, Jared T -- Severi, Ettore -- Cowley, Lauren -- Bore, Joseph Akoi -- Koundouno, Raymond -- Dudas, Gytis -- Mikhail, Amy -- Ouedraogo, Nobila -- Afrough, Babak -- Bah, Amadou -- Baum, Jonathan H J -- Becker-Ziaja, Beate -- Boettcher, Jan Peter -- Cabeza-Cabrerizo, Mar -- Camino-Sanchez, Alvaro -- Carter, Lisa L -- Doerrbecker, Juliane -- Enkirch, Theresa -- Garcia-Dorival, Isabel -- Hetzelt, Nicole -- Hinzmann, Julia -- Holm, Tobias -- Kafetzopoulou, Liana Eleni -- Koropogui, Michel -- Kosgey, Abigael -- Kuisma, Eeva -- Logue, Christopher H -- Mazzarelli, Antonio -- Meisel, Sarah -- Mertens, Marc -- Michel, Janine -- Ngabo, Didier -- Nitzsche, Katja -- Pallasch, Elisa -- Patrono, Livia Victoria -- Portmann, Jasmine -- Repits, Johanna Gabriella -- Rickett, Natasha Y -- Sachse, Andreas -- Singethan, Katrin -- Vitoriano, Ines -- Yemanaberhan, Rahel L -- Zekeng, Elsa G -- Racine, Trina -- Bello, Alexander -- Sall, Amadou Alpha -- Faye, Ousmane -- Faye, Oumar -- Magassouba, N'Faly -- Williams, Cecelia V -- Amburgey, Victoria -- Winona, Linda -- Davis, Emily -- Gerlach, Jon -- Washington, Frank -- Monteil, Vanessa -- Jourdain, Marine -- Bererd, Marion -- Camara, Alimou -- Somlare, Hermann -- Camara, Abdoulaye -- Gerard, Marianne -- Bado, Guillaume -- Baillet, Bernard -- Delaune, Deborah -- Nebie, Koumpingnin Yacouba -- Diarra, Abdoulaye -- Savane, Yacouba -- Pallawo, Raymond Bernard -- Gutierrez, Giovanna Jaramillo -- Milhano, Natacha -- Roger, Isabelle -- Williams, Christopher J -- Yattara, Facinet -- Lewandowski, Kuiama -- Taylor, James -- Rachwal, Phillip -- Turner, Daniel J -- Pollakis, Georgios -- Hiscox, Julian A -- Matthews, David A -- O'Shea, Matthew K -- Johnston, Andrew McD -- Wilson, Duncan -- Hutley, Emma -- Smit, Erasmus -- Di Caro, Antonino -- Wolfel, Roman -- Stoecker, Kilian -- Fleischmann, Erna -- Gabriel, Martin -- Weller, Simon A -- Koivogui, Lamine -- Diallo, Boubacar -- Keita, Sakoba -- Rambaut, Andrew -- Formenty, Pierre -- Gunther, Stephan -- Carroll, Miles W -- Medical Research Council/United Kingdom -- England -- Nature. 2016 Feb 11;530(7589):228-32. doi: 10.1038/nature16996. Epub 2016 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK. ; The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Ontario Institute for Cancer Research, Toronto M5G 0A3, Canada. ; Department of Computer Science, University of Toronto, Toronto M5S 3G4, Canada. ; European Centre for Disease Prevention and Control (ECDC), 171 65 Solna, Sweden. ; National Infection Service, Public Health England, London NW9 5EQ, UK. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK. ; Postgraduate Training for Applied Epidemiology (PAE, German FETP), Robert Koch Institute, D-13302 Berlin, Germany. ; National Infection Service, Public Health England, Porton Down, Wiltshire SP4 0JG, UK. ; Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland. ; Robert Koch Institute, D-13302 Berlin, Germany. ; University College London, London WC1E 6BT, UK. ; Paul-Ehrlich-Institut, Division of Veterinary Medicine, D-63225 Langen, Germany. ; Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. ; Laboratory for Clinical and Epidemiological Virology, Department of Microbiology and Immunology, KU Leuven, Leuven B-3000, Belgium. ; Ministry of Health Guinea, Conakry BP 585, Guinea. ; Kenya Medical Research Institute, Nairobi P.O. BOX 54840 - 00200, Kenya. ; National Institute for Infectious Diseases L. Spallanzani, 00149 Rome, Italy. ; Friedrich-Loeffler-Institute, D-17493 Greifswald, Germany. ; Federal Office for Civil Protection, Spiez Laboratory, 3700 Spiez, Switzerland. ; Janssen-Cilag, Stockholm, Box 7073 - 19207, Sweden. ; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool L69 7BE, UK. ; Institute of Virology, Technische Universitat Munchen, D-81675 Munich, Germany. ; Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. ; Institut Pasteur Dakar, Dakar, DP 220 Senegal. ; Laboratoire de Fievres Hemorragiques de Guinee, Conakry BP 5680, Guinea. ; Sandia National Laboratories, PO Box 5800 MS1363, Albuquerque, New Mexico 87185-1363, USA. ; Ratoma Ebola Diagnostic Center, Conakry, Guinea. ; MRIGlobal, Kansas City, Missouri 64110-2241, USA. ; Expertise France, Laboratoire K-plan de Forecariah en Guinee, 75006 Paris, France. ; Federation des Laboratoires - HIA Begin, 94163 Saint-Mande cedex, France. ; Laboratoire de Biologie - Centre de Traitement des Soignants, Conakry, Guinea. ; World Health Organization, Conakry BP 817, Guinea. ; London School of Hygiene and Tropical Medicine, London EC1E 7HT, UK. ; Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. ; Public Health Wales, Cardiff CF11 9LJ, UK. ; Defence Science and Technology Laboratory (Dstl) Porton Down, Salisbury SP4 0JQ, UK. ; Oxford Nanopore Technologies, Oxford OX4 4GA, UK. ; Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. ; Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham B15 2TH, UK. ; Centre of Defence Pathology, Royal Centre for Defence Medicine, Birmingham B15 2TH, UK. ; Queen Elizabeth Hospital, Birmingham B12 2TH, UK. ; Bundeswehr Institute of Microbiology, D-80937 Munich, Germany. ; Institut National de Sante Publique, Conakry BP 1147, Guinea. ; Fogarty International Center, National Institutes of Health, Bethesda, MD 20892-2220, USA. ; Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 2FL, UK. ; University of Southampton, South General Hospital, Southampton SO16 6YD, UK. ; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, PHE Porton Down, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26840485" target="_blank"〉PubMed〈/a〉

Description: The IPCC Assessment Reports offer the scientific foundation for international climate negotiations and constitute an unmatched resource for climate change researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding across diverse climate change research communities, we have streamlined an annual process to identify and synthesise essential research advances. We collected input from experts on different fields using an online questionnaire and prioritised a set of ten key research insights with high policy relevance. This year we focus on: (1) looming overshoot of the 1.5°C warming limit, (2) urgency of phasing-out fossil fuels, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future of natural carbon sinks, (5) need for join governance of biodiversity loss and climate change, (6) advances in the science of compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. We first present a succinct account of these Insights, reflect on their policy implications, and offer an integrated set of policy relevant messages. This science synthesis and science communication effort is also the basis for a report targeted to policymakers as a contribution to elevate climate science every year, in time for the UNFCCC COP.