ALBERT

Description: Proteins are inherently plastic molecules, whose function often critically depends on excursions between different molecular conformations (conformers). However, a rigorous understanding of the relation between a protein's structure, dynamics and function remains elusive. This is because many of the conformers on its energy landscape are only transiently formed and marginally populated (less than a few per cent of the total number of molecules), so that they cannot be individually characterized by most biophysical tools. Here we study a lysozyme mutant from phage T4 that binds hydrophobic molecules and populates an excited state transiently (about 1 ms) to about 3% at 25 degrees C (ref. 5). We show that such binding occurs only via the ground state, and present the atomic-level model of the 'invisible', excited state obtained using a combined strategy of relaxation-dispersion NMR (ref. 6) and CS-Rosetta model building that rationalizes this observation. The model was tested using structure-based design calculations identifying point mutants predicted to stabilize the excited state relative to the ground state. In this way a pair of mutations were introduced, inverting the relative populations of the ground and excited states and altering function. Our results suggest a mechanism for the evolution of a protein's function by changing the delicate balance between the states on its energy landscape. More generally, they show that our approach can generate and validate models of excited protein states.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706084/" 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/PMC3706084/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bouvignies, Guillaume -- Vallurupalli, Pramodh -- Hansen, D Flemming -- Correia, Bruno E -- Lange, Oliver -- Bah, Alaji -- Vernon, Robert M -- Dahlquist, Frederick W -- Baker, David -- Kay, Lewis E -- R01 GM092802/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Aug 21;477(7362):111-4. doi: 10.1038/nature10349.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, The University of Toronto, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21857680" target="_blank"〉PubMed〈/a〉

Description: Intrinsically disordered proteins play important roles in cell signalling, transcription, translation and cell cycle regulation. Although they lack stable tertiary structure, many intrinsically disordered proteins undergo disorder-to-order transitions upon binding to partners. Similarly, several folded proteins use regulated order-to-disorder transitions to mediate biological function. In principle, the function of intrinsically disordered proteins may be controlled by post-translational modifications that lead to structural changes such as folding, although this has not been observed. Here we show that multisite phosphorylation induces folding of the intrinsically disordered 4E-BP2, the major neural isoform of the family of three mammalian proteins that bind eIF4E and suppress cap-dependent translation initiation. In its non-phosphorylated state, 4E-BP2 interacts tightly with eIF4E using both a canonical YXXXXLPhi motif (starting at Y54) that undergoes a disorder-to-helix transition upon binding and a dynamic secondary binding site. We demonstrate that phosphorylation at T37 and T46 induces folding of residues P18-R62 of 4E-BP2 into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking its accessibility to eIF4E. The folded state of pT37pT46 4E-BP2 is weakly stable, decreasing affinity by 100-fold and leading to an order-to-disorder transition upon binding to eIF4E, whereas fully phosphorylated 4E-BP2 is more stable, decreasing affinity by a factor of approximately 4,000. These results highlight stabilization of a phosphorylation-induced fold as the essential mechanism for phospho-regulation of the 4E-BP:eIF4E interaction and exemplify a new mode of biological regulation mediated by intrinsically disordered proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bah, Alaji -- Vernon, Robert M -- Siddiqui, Zeba -- Krzeminski, Mickael -- Muhandiram, Ranjith -- Zhao, Charlie -- Sonenberg, Nahum -- Kay, Lewis E -- Forman-Kay, Julie D -- MOP-114985/Canadian Institutes of Health Research/Canada -- MOP-119579/Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Mar 5;519(7541):106-9. doi: 10.1038/nature13999. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada [2] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada. ; 1] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada. ; 1] Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada [2] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4] Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533957" target="_blank"〉PubMed〈/a〉

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: West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carroll, Miles W -- Matthews, David A -- Hiscox, Julian A -- Elmore, Michael J -- Pollakis, Georgios -- Rambaut, Andrew -- Hewson, Roger -- Garcia-Dorival, Isabel -- Bore, Joseph Akoi -- Koundouno, Raymond -- Abdellati, Said -- Afrough, Babak -- Aiyepada, John -- Akhilomen, Patience -- Asogun, Danny -- Atkinson, Barry -- Badusche, Marlis -- Bah, Amadou -- Bate, Simon -- Baumann, Jan -- Becker, Dirk -- Becker-Ziaja, Beate -- Bocquin, Anne -- Borremans, Benny -- Bosworth, Andrew -- Boettcher, Jan Peter -- Cannas, Angela -- Carletti, Fabrizio -- Castilletti, Concetta -- Clark, Simon -- Colavita, Francesca -- Diederich, Sandra -- Donatus, Adomeh -- Duraffour, Sophie -- Ehichioya, Deborah -- Ellerbrok, Heinz -- Fernandez-Garcia, Maria Dolores -- Fizet, Alexandra -- Fleischmann, Erna -- Gryseels, Sophie -- Hermelink, Antje -- Hinzmann, Julia -- Hopf-Guevara, Ute -- Ighodalo, Yemisi -- Jameson, Lisa -- Kelterbaum, Anne -- Kis, Zoltan -- Kloth, Stefan -- Kohl, Claudia -- Korva, Misa -- Kraus, Annette -- Kuisma, Eeva -- Kurth, Andreas -- Liedigk, Britta -- Logue, Christopher H -- Ludtke, Anja -- Maes, Piet -- McCowen, James -- Mely, Stephane -- Mertens, Marc -- Meschi, Silvia -- Meyer, Benjamin -- Michel, Janine -- Molkenthin, Peter -- Munoz-Fontela, Cesar -- Muth, Doreen -- Newman, Edmund N C -- Ngabo, Didier -- Oestereich, Lisa -- Okosun, Jennifer -- Olokor, Thomas -- Omiunu, Racheal -- Omomoh, Emmanuel -- Pallasch, Elisa -- Palyi, Bernadett -- Portmann, Jasmine -- Pottage, Thomas -- Pratt, Catherine -- Priesnitz, Simone -- Quartu, Serena -- Rappe, Julie -- Repits, Johanna -- Richter, Martin -- Rudolf, Martin -- Sachse, Andreas -- Schmidt, Kristina Maria -- Schudt, Gordian -- Strecker, Thomas -- Thom, Ruth -- Thomas, Stephen -- Tobin, Ekaete -- Tolley, Howard -- Trautner, Jochen -- Vermoesen, Tine -- Vitoriano, Ines -- Wagner, Matthias -- Wolff, Svenja -- Yue, Constanze -- Capobianchi, Maria Rosaria -- Kretschmer, Birte -- Hall, Yper -- Kenny, John G -- Rickett, Natasha Y -- Dudas, Gytis -- Coltart, Cordelia E M -- Kerber, Romy -- Steer, Damien -- Wright, Callum -- Senyah, Francis -- Keita, Sakoba -- Drury, Patrick -- Diallo, Boubacar -- de Clerck, Hilde -- Van Herp, Michel -- Sprecher, Armand -- Traore, Alexis -- Diakite, Mandiou -- Konde, Mandy Kader -- Koivogui, Lamine -- Magassouba, N'Faly -- Avsic-Zupanc, Tatjana -- Nitsche, Andreas -- Strasser, Marc -- Ippolito, Giuseppe -- Becker, Stephan -- Stoecker, Kilian -- Gabriel, Martin -- Raoul, Herve -- Di Caro, Antonino -- Wolfel, Roman -- Formenty, Pierre -- Gunther, Stephan -- 095831/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Aug 6;524(7563):97-101. doi: 10.1038/nature14594. Epub 2015 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] University of Southampton, South General Hospital, Southampton SO16 6YD, UK. ; Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. ; Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, UK. ; Public Health England, Porton Down, Wiltshire SP4 0JG, UK. ; 1] Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK [2] Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA [3] Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 2FL, UK. ; 1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Universite Gamal Abdel Nasser de Conakry, Laboratoire des Fievres Hemorragiques en Guinee, Conakry, Guinea [3] Institut National de Sante Publique, Conakry, Guinea. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Tropical Medicine, B-2000 Antwerp, Belgium. ; 1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Swiss Tropical and Public Health Institute, University of Basel, CH-4002 Basel, Switzerland. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Institute of Virology, Philipps University Marburg, 35043 Marburg, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Reference Center for Viral Hemorrhagic Fevers, 69365 Lyon, France [3] Laboratoire P4 Inserm-Jean Merieux, US003 Inserm, 69365 Lyon, France. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Department of Biology, University of Antwerp, B-2020 Antwerp, Belgium. ; 1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, UK. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Robert Koch Institute, 13353 Berlin, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Institute for Infectious Diseases (INMI) Lazzaro Spallanzani, 00149 Rome, Italy. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Friedrich Loeffler Institute, Federal Research Institute for Animal Health, 17493 Greifswald, Insel Riems, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] KU Leuven Rega institute, B-3000 Leuven, Belgium. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] Redeemer's University, Osun State, Nigeria. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28029 Madrid, Spain. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Reference Center for Viral Hemorrhagic Fevers, 69365 Lyon, France [3] Unite de Biologie des Infections Virales Emergentes, Institut Pasteur, 69365 Lyon, France. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Bundeswehr Institute of Microbiology, 80937 Munich, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Center for Epidemiology, National Biosafety Laboratory, H-1097 Budapest, Hungary. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Public Health Agency of Sweden, 171 82 Solna, Sweden. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] KU Leuven Rega institute, B-3000 Leuven, Belgium. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Institute of Virology, University of Bonn, 53127 Bonn, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Federal Office for Civil Protection, Spiez Laboratory, CH-3700 Spiez, Switzerland. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bundeswehr Hospital, 22049 Hamburg, Germany. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Virology and Immunology, CH-3147 Mittelhausern, Switzerland. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Janssen-Cilag, SE-192 07 Sollentuna, Sweden. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Thunen Institute, D-22767 Hamburg, Germany. ; Eurice - European Research and Project Office GmbH, 10115 Berlin, Germany. ; Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK. ; Department of Infection and Population Health, University College London, London WC1E 6JB, UK. ; Research IT, University of Bristol, Bristol BS8 1HH, UK. ; Advanced Computing Research Centre, University of Bristol, Bristol BS8 1HH, UK. ; Ministry of Health Guinea, Conakry, Guinea. ; World Health Organization, 1211 Geneva 27, Switzerland. ; World Health Organization, Conakry, Guinea. ; Medecins Sans Frontieres, B-1050 Brussels, Belgium. ; Section Prevention et Lutte contre la Maladie a la Direction Prefectorale de la Sante de Gueckedou, Gueckedou, Guinea. ; Universite Gamal Abdel Nasser de Conakry, CHU Donka, Conakry, Guinea. ; Health and Sustainable Development Foundation, Conakry, Guinea. ; Institut National de Sante Publique, Conakry, Guinea. ; Universite Gamal Abdel Nasser de Conakry, Laboratoire des Fievres Hemorragiques en Guinee, Conakry, Guinea. ; 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Laboratoire P4 Inserm-Jean Merieux, US003 Inserm, 69365 Lyon, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26083749" target="_blank"〉PubMed〈/a〉

Description: 〈p〉Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin P P 〈/p〉

Description: Eukaryotic telomeres are transcribed into telomeric repeat-containing RNA (TERRA). Telomeric transcription has been documented in mammals, birds, zebra fish, plants and budding yeast. Here we show that the chromosome ends of Schizosaccharomyces pombe produce distinct RNA species. As with budding yeast and mammals, S. pombe contains G-rich TERRA molecules and subtelomeric RNA species transcribed in the opposite direction of TERRA (ARRET). Moreover, fission yeast chromosome ends produce two novel RNA species: C-rich telomeric repeat-containing transcripts (ARIA) and subtelomeric transcripts complementary to ARRET (αARRET). RNA polymerase II (RNAPII) associates with pombe chromosome ends in vivo and the telomeric factor Rap1 negatively regulates this association, as well as the cellular accumulation of RNA emanating from chromosome ends. We also show that the RNAPII subunit Rpb7 and the non-canonical poly(A) polymerases Cid12 and Cid14 are involved in the regulation of TERRA, ARIA, ARRET and αARRET transcripts. We confirm the evolutionary conservation of telomere transcription, and reveal intriguing similarities and differences in the composition and regulation of telomeric transcripts among model organisms.