ALBERT

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: Author(s): L. Poudel, C. de la Cruz, E. A. Payzant, A. F. May, M. Koehler, V. O. Garlea, A. E. Taylor, D. S. Parker, H. B. Cao, M. A. McGuire, W. Tian, M. Matsuda, H. Jeen, H. N. Lee, T. Hong, S. Calder, H. D. Zhou, M. D. Lumsden, V. Keppens, D. Mandrus, and A. D. Christianson The structural and the magnetic properties of CeCu 6 − x Ag x ( 0 ≤ x ≤ 0.85 ) and CeCu 6 − x Pd x ( 0 ≤ x ≤ 0.4 ) have been studied using neutron diffraction, resonant ultrasound spectroscopy (RUS), x-ray diffraction measurements, and first principles calculations. The structural and magnetic phase diagrams of CeCu 6 − x Ag … [Phys. Rev. B 92, 214421] Published Tue Dec 15, 2015

Description: After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510871/" 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/PMC4510871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchell, Duane A -- Batich, Kristen A -- Gunn, Michael D -- Huang, Min-Nung -- Sanchez-Perez, Luis -- Nair, Smita K -- Congdon, Kendra L -- Reap, Elizabeth A -- Archer, Gary E -- Desjardins, Annick -- Friedman, Allan H -- Friedman, Henry S -- Herndon, James E 2nd -- Coan, April -- McLendon, Roger E -- Reardon, David A -- Vredenburgh, James J -- Bigner, Darell D -- Sampson, John H -- 1UL2 RR024128-01/RR/NCRR NIH HHS/ -- P01 CA154291/CA/NCI NIH HHS/ -- P01-CA154291-01A1/CA/NCI NIH HHS/ -- P50 CA108786/CA/NCI NIH HHS/ -- P50 NS020023/NS/NINDS NIH HHS/ -- P50-CA108786/CA/NCI NIH HHS/ -- P50-NS20023/NS/NINDS NIH HHS/ -- R01 CA134844/CA/NCI NIH HHS/ -- R01 CA177476/CA/NCI NIH HHS/ -- R01 NS067037/NS/NINDS NIH HHS/ -- R01-CA134844/CA/NCI NIH HHS/ -- R01-CA177476-01/CA/NCI NIH HHS/ -- R01-NS067037/NS/NINDS NIH HHS/ -- T32 AI052077/AI/NIAID NIH HHS/ -- T32 GM007171/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Mar 19;519(7543):366-9. doi: 10.1038/nature14320. Epub 2015 Mar 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA [3] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; 1] Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA [3] Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA [4] Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA [5] Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25762141" target="_blank"〉PubMed〈/a〉

Description: No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as 'South American native ungulates'. To Charles Darwin, who first collected their remains, they included perhaps the 'strangest animal[s] ever discovered'. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago, or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria. Morphology-based analyses have proved unconvincing because convergences are pervasive among unrelated ungulate-like placentals. Approaches using ancient DNA have also been unsuccessful, probably because of rapid DNA degradation in semitropical and temperate deposits. Here we apply proteomic analysis to screen bone samples of the Late Quaternary South American native ungulate taxa Toxodon (Notoungulata) and Macrauchenia (Litopterna) for phylogenetically informative protein sequences. For each ungulate, we obtain approximately 90% direct sequence coverage of type I collagen alpha1- and alpha2-chains, representing approximately 900 of 1,140 amino-acid residues for each subunit. A phylogeny is estimated from an alignment of these fossil sequences with collagen (I) gene transcripts from available mammalian genomes or mass spectrometrically derived sequence data obtained for this study. The resulting consensus tree agrees well with recent higher-level mammalian phylogenies. Toxodon and Macrauchenia form a monophyletic group whose sister taxon is not Afrotheria or any of its constituent clades as recently claimed, but instead crown Perissodactyla (horses, tapirs, and rhinoceroses). These results are consistent with the origin of at least some South American native ungulates from 'condylarths', a paraphyletic assembly of archaic placentals. With ongoing improvements in instrumentation and analytical procedures, proteomics may produce a revolution in systematics such as that achieved by genomics, but with the possibility of reaching much further back in time.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Welker, Frido -- Collins, Matthew J -- Thomas, Jessica A -- Wadsley, Marc -- Brace, Selina -- Cappellini, Enrico -- Turvey, Samuel T -- Reguero, Marcelo -- Gelfo, Javier N -- Kramarz, Alejandro -- Burger, Joachim -- Thomas-Oates, Jane -- Ashford, David A -- Ashton, Peter D -- Rowsell, Keri -- Porter, Duncan M -- Kessler, Benedikt -- Fischer, Roman -- Baessmann, Carsten -- Kaspar, Stephanie -- Olsen, Jesper V -- Kiley, Patrick -- Elliott, James A -- Kelstrup, Christian D -- Mullin, Victoria -- Hofreiter, Michael -- Willerslev, Eske -- Hublin, Jean-Jacques -- Orlando, Ludovic -- Barnes, Ian -- MacPhee, Ross D E -- England -- Nature. 2015 Jun 4;522(7554):81-4. doi: 10.1038/nature14249. Epub 2015 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] BioArCh, University of York, York YO10 5DD, UK [2] Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; BioArCh, University of York, York YO10 5DD, UK. ; Department of Earth Sciences, Natural History Museum, London SW7 5BD, UK. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen K, Denmark. ; Institute of Zoology, Zoological Society of London, London NW1 4RY, UK. ; CONICET- Division Paleontologia de Vertebrados, Museo de La Plata. Facultad de Ciencias Naturales y Museo de La Plata, Universidad Nacional de La Plata. Paseo del Bosque s/n, B1900FWA, La Plata, Argentina. ; Seccion Paleontologia de Vertebrados. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia", 470 Angel Gallardo Av., C1405DJR, Buenos Aires, Argentina. ; Institute of Anthropology, Johannes Gutenberg-University, Anselm-Franz-von-Bentzel-Weg 7, D-55128 Mainz, Germany. ; Department of Chemistry, University of York, York YO10 5DD, UK. ; Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK. ; Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA. ; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK. ; Applications Development, Bruker Daltonik GmbH, 28359 Bremen, Germany. ; Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark. ; Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, UK. ; Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. ; 1] BioArCh, University of York, York YO10 5DD, UK [2] Institute for Biochemistry and Biology, Karl-Liebknecht-Strasse 24-25, 14476 Potsdam OT Golm, Germany. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; Department of Mammalogy, American Museum of Natural History, New York, New York 10024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25799987" target="_blank"〉PubMed〈/a〉

Description: Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437632/" 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/PMC4437632/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cirulli, Elizabeth T -- Lasseigne, Brittany N -- Petrovski, Slave -- Sapp, Peter C -- Dion, Patrick A -- Leblond, Claire S -- Couthouis, Julien -- Lu, Yi-Fan -- Wang, Quanli -- Krueger, Brian J -- Ren, Zhong -- Keebler, Jonathan -- Han, Yujun -- Levy, Shawn E -- Boone, Braden E -- Wimbish, Jack R -- Waite, Lindsay L -- Jones, Angela L -- Carulli, John P -- Day-Williams, Aaron G -- Staropoli, John F -- Xin, Winnie W -- Chesi, Alessandra -- Raphael, Alya R -- McKenna-Yasek, Diane -- Cady, Janet -- Vianney de Jong, J M B -- Kenna, Kevin P -- Smith, Bradley N -- Topp, Simon -- Miller, Jack -- Gkazi, Athina -- FALS Sequencing Consortium -- Al-Chalabi, Ammar -- van den Berg, Leonard H -- Veldink, Jan -- Silani, Vincenzo -- Ticozzi, Nicola -- Shaw, Christopher E -- Baloh, Robert H -- Appel, Stanley -- Simpson, Ericka -- Lagier-Tourenne, Clotilde -- Pulst, Stefan M -- Gibson, Summer -- Trojanowski, John Q -- Elman, Lauren -- McCluskey, Leo -- Grossman, Murray -- Shneider, Neil A -- Chung, Wendy K -- Ravits, John M -- Glass, Jonathan D -- Sims, Katherine B -- Van Deerlin, Vivianna M -- Maniatis, Tom -- Hayes, Sebastian D -- Ordureau, Alban -- Swarup, Sharan -- Landers, John -- Baas, Frank -- Allen, Andrew S -- Bedlack, Richard S -- Harper, J Wade -- Gitler, Aaron D -- Rouleau, Guy A -- Brown, Robert -- Harms, Matthew B -- Cooper, Gregory M -- Harris, Tim -- Myers, Richard M -- Goldstein, David B -- 089701/Wellcome Trust/United Kingdom -- K08 NS075094/NS/NINDS NIH HHS/ -- P01 AG017586/AG/NIA NIH HHS/ -- P01 AG032953/AG/NIA NIH HHS/ -- P50 AG025688/AG/NIA NIH HHS/ -- R37 NS033123/NS/NINDS NIH HHS/ -- R37 NS083524/NS/NINDS NIH HHS/ -- T32 GM007754/GM/NIGMS NIH HHS/ -- TL1 TR001066/TR/NCATS NIH HHS/ -- UL1 TR001067/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1436-41. doi: 10.1126/science.aaa3650. Epub 2015 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27708, USA. ; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA. ; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA. ; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA. ; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada. ; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Duke University School of Medicine, Durham, NC 27708, USA. ; Biogen Idec, Cambridge, MA 02142, USA. ; Neurogenetics DNA Diagnostic Laboratory, Center for Human Genetics Research, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Genome Analysis, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, Netherlands. ; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Republic of Ireland. ; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK. ; Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, 3508 GA Utrecht, Netherlands. ; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy, and Department of Pathophysiology and Transplantation, Dino Ferrari Center, Universita degli Studi di Milano, Milan 20122, Italy. ; Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. ; Houston Methodist Hospital, Houston, TX 77030, USA, and Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. ; Ludwig Institute for Cancer Research and Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Penn ALS Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Penn Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA. ; Department of Pediatrics and Medicine, Columbia University, New York, NY 10032, USA. ; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Neurology, Emory University, Atlanta, GA 30322, USA. ; Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10027, USA. ; Biogen Idec, Cambridge, MA 02142, USA. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27708, USA. ; Duke ALS Clinic and Durham VA Medical Center, Durham, NC 27708, USA. ; Biogen Idec, Cambridge, MA 02142, USA. tim.harris@biogenidec.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700176" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684952/" 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/PMC4684952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Jieqi -- Wegener, Jan Eike -- Huang, Teng-Wei -- Sripathy, Smitha -- De Jesus-Cortes, Hector -- Xu, Pin -- Tran, Stephanie -- Knobbe, Whitney -- Leko, Vid -- Britt, Jeremiah -- Starwalt, Ruth -- McDaniel, Latisha -- Ward, Chris S -- Parra, Diana -- Newcomb, Benjamin -- Lao, Uyen -- Nourigat, Cynthia -- Flowers, David A -- Cullen, Sean -- Jorstad, Nikolas L -- Yang, Yue -- Glaskova, Lena -- Vingeau, Sebastien -- Kozlitina, Julia -- Yetman, Michael J -- Jankowsky, Joanna L -- Reichardt, Sybille D -- Reichardt, Holger M -- Gartner, Jutta -- Bartolomei, Marisa S -- Fang, Min -- Loeb, Keith -- Keene, C Dirk -- Bernstein, Irwin -- Goodell, Margaret -- Brat, Daniel J -- Huppke, Peter -- Neul, Jeffrey L -- Bedalov, Antonio -- Pieper, Andrew A -- P30 AI036211/AI/NIAID NIH HHS/ -- P30 CA138292/CA/NCI NIH HHS/ -- P30 ES005605/ES/NIEHS NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- R01 AG031892/AG/NIA NIH HHS/ -- R01 HD062553/HD/NICHD NIH HHS/ -- S10 RR024574/RR/NCRR NIH HHS/ -- T32 AG000183/AG/NIA NIH HHS/ -- T32 HL092332/HL/NHLBI NIH HHS/ -- U01 HL100395/HL/NHLBI NIH HHS/ -- U54 HD083092/HD/NICHD NIH HHS/ -- England -- Nature. 2015 May 21;521(7552):E1-4. doi: 10.1038/nature14444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Gottingen, Robert-Koch-Strasse 40, 37075 Gottingen, Germany. ; 1] Jan and Dan Duncan Neurological Research Institute (Texas Children's Hospital), Baylor College of Medicine, Houston, Texas 77030, USA [2] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; 1] Graduate Program of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Graduate Program of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Jan and Dan Duncan Neurological Research Institute (Texas Children's Hospital), Baylor College of Medicine, Houston, Texas 77030, USA. ; Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA. ; Department of Cell &Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA. ; Institute for Cellular and Molecular Immunology; University of Gottingen Medical School, Humboldtallee 34, 37073 Gottingen, Germany. ; 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA. ; 1] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA [3] Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA [4] Stem Cell and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA [5] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA [6] Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. ; 1] Jan and Dan Duncan Neurological Research Institute (Texas Children's Hospital), Baylor College of Medicine, Houston, Texas 77030, USA [2] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA [3] Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA [4] Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA [5] Stem Cell and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA [6] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98105, USA. ; 1] Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA [2] Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA [3] Veterans Affairs, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA [4] Weill Cornell Autism Research Program, Weill Cornell Medical College, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25993969" target="_blank"〉PubMed〈/a〉

Description: The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Travis K -- Jordan, Robert -- Lo, Michael K -- Ray, Adrian S -- Mackman, Richard L -- Soloveva, Veronica -- Siegel, Dustin -- Perron, Michel -- Bannister, Roy -- Hui, Hon C -- Larson, Nate -- Strickley, Robert -- Wells, Jay -- Stuthman, Kelly S -- Van Tongeren, Sean A -- Garza, Nicole L -- Donnelly, Ginger -- Shurtleff, Amy C -- Retterer, Cary J -- Gharaibeh, Dima -- Zamani, Rouzbeh -- Kenny, Tara -- Eaton, Brett P -- Grimes, Elizabeth -- Welch, Lisa S -- Gomba, Laura -- Wilhelmsen, Catherine L -- Nichols, Donald K -- Nuss, Jonathan E -- Nagle, Elyse R -- Kugelman, Jeffrey R -- Palacios, Gustavo -- Doerffler, Edward -- Neville, Sean -- Carra, Ernest -- Clarke, Michael O -- Zhang, Lijun -- Lew, Willard -- Ross, Bruce -- Wang, Queenie -- Chun, Kwon -- Wolfe, Lydia -- Babusis, Darius -- Park, Yeojin -- Stray, Kirsten M -- Trancheva, Iva -- Feng, Joy Y -- Barauskas, Ona -- Xu, Yili -- Wong, Pamela -- Braun, Molly R -- Flint, Mike -- McMullan, Laura K -- Chen, Shan-Shan -- Fearns, Rachel -- Swaminathan, Swami -- Mayers, Douglas L -- Spiropoulou, Christina F -- Lee, William A -- Nichol, Stuart T -- Cihlar, Tomas -- Bavari, Sina -- R01 AI113321/AI/NIAID NIH HHS/ -- R01AI113321/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Mar 17;531(7594):381-5. doi: 10.1038/nature17180. Epub 2016 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA. ; United States Army Medical Research Institute of Infectious Diseases, Therapeutic Development Center, Frederick, Maryland 21702, USA. ; Gilead Sciences, Foster City, California 94404, USA. ; Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. ; Boston University School of Medicine, Boston, Massachusetts 02118, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934220" target="_blank"〉PubMed〈/a〉

Description: Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery. Despite a clear heritable component, the genetic aetiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family. Morpholino knockdown of the zebrafish homologue dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 messenger RNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1(+/-) mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs, as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720389/" 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/PMC4720389/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Durst, Ronen -- Sauls, Kimberly -- Peal, David S -- deVlaming, Annemarieke -- Toomer, Katelynn -- Leyne, Maire -- Salani, Monica -- Talkowski, Michael E -- Brand, Harrison -- Perrocheau, Maelle -- Simpson, Charles -- Jett, Christopher -- Stone, Matthew R -- Charles, Florie -- Chiang, Colby -- Lynch, Stacey N -- Bouatia-Naji, Nabila -- Delling, Francesca N -- Freed, Lisa A -- Tribouilloy, Christophe -- Le Tourneau, Thierry -- LeMarec, Herve -- Fernandez-Friera, Leticia -- Solis, Jorge -- Trujillano, Daniel -- Ossowski, Stephan -- Estivill, Xavier -- Dina, Christian -- Bruneval, Patrick -- Chester, Adrian -- Schott, Jean-Jacques -- Irvine, Kenneth D -- Mao, Yaopan -- Wessels, Andy -- Motiwala, Tahirali -- Puceat, Michel -- Tsukasaki, Yoshikazu -- Menick, Donald R -- Kasiganesan, Harinath -- Nie, Xingju -- Broome, Ann-Marie -- Williams, Katherine -- Johnson, Amanda -- Markwald, Roger R -- Jeunemaitre, Xavier -- Hagege, Albert -- Levine, Robert A -- Milan, David J -- Norris, Russell A -- Slaugenhaupt, Susan A -- 1P30 GM103342/GM/NIGMS NIH HHS/ -- 8P20 GM103444-07/GM/NIGMS NIH HHS/ -- C06 RR018823/RR/NCRR NIH HHS/ -- I01 BX002327/BX/BLRD VA/ -- K24 HL67434/HL/NHLBI NIH HHS/ -- R00-MH095867/MH/NIMH NIH HHS/ -- R01 HL109004/HL/NHLBI NIH HHS/ -- R01 HL127692/HL/NHLBI NIH HHS/ -- R01-HL095696/HL/NHLBI NIH HHS/ -- R01-HL109004/HL/NHLBI NIH HHS/ -- R01-HL127692/HL/NHLBI NIH HHS/ -- R01-HL33756/HL/NHLBI NIH HHS/ -- R01HL109506/HL/NHLBI NIH HHS/ -- R01HL122906-01/HL/NHLBI NIH HHS/ -- R01HL72265/HL/NHLBI NIH HHS/ -- T32 HL007208/HL/NHLBI NIH HHS/ -- T32 HL007260/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Sep 3;525(7567):109-13. doi: 10.1038/nature14670. Epub 2015 Aug 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA. ; Cardiology Division, Hadassah Hebrew University Medical Center, POB 12000 Jerusalem, Israel. ; Cardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA. ; Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA. ; Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; INSERM, UMR-970, Paris Cardiovascular Research Center, 75015 Paris, France. ; Universite Paris Descartes, Sorbonne Paris Cite, Faculty of Medicine, 75006 Paris, France. ; Department of Medicine (Cardiovascular Division), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ; Yale-New Haven Hospital Heart and Vascular Center, Yale School of Medicine, 20 York Street, New Haven, Connecticut 06510, USA. ; Department of Cardiology, University Hospital Amiens; INSERM U-1088, Jules Verne University of Picardie, 80000 Amiens, France. ; Inserm U1087; Institut du Thorax; University Hospital, 44007 Nantes, France. ; Centro Nacional de Investigaciones Cardiovasculares, Carlos III (CNIC), 28029 Madrid, Spain. ; Hospital Universitario Monteprincipe, 28660 Madrid, Spain. ; Genetic Causes of Disease Group, Centre for Genomic Regulation (CRG), 08003 Barcelona, Catalonia, Spain. ; Universitat Pompeu Fabra (UPF), 08002 Barcelona, Catalonia, Spain. ; Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Catalonia, Spain. ; CIBER in Epidemiology and Public Health (CIBERESP), 08036 Barcelona, Catalonia, Spain. ; Genomic and Epigenomic Variation in Disease Group, Centre for Genomic Regulation (CRG), 08003 Barcelona, Catalonia, Spain. ; CNRS, UMR 6291, 44007 Nantes, France. ; Universite de Nantes, 44322 Nantes, France. ; CHU Nantes, l'Institut du Thorax, Service de Cardiologie, 44093 Nantes, France. ; Service d'Anatomie Pathologique, Hopital Europeen Georges Pompidou, 75015 Paris, France. ; National Heart and Lung Institute, Harefield, Heart Science Centre, Imperial College London, London SW7 2AZ, UK. ; Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854, USA. ; INSERM UMR_S910, Team physiopathology of cardiac development Aix-Marseille University, Medical School La Timone, 13885 Marseille, France. ; Department of Cellular and Molecular Biology, University of Texas Health Science Center Northeast Tyler, Texas75708, USA. ; Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA. ; Department of Radiology and Radiological Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA. ; Assistance Publique - Hopitaux de Paris, Departement de Genetique, Hopital Europeen Georges Pompidou, 75015 Paris, France. ; Assistance Publique - Hopitaux de Paris, Departement de Cardiologie, Hopital Europeen Georges Pompidou, 75015 Paris, France. ; Cardiac Ultrasound Laboratory, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26258302" target="_blank"〉PubMed〈/a〉

Description: Author(s): W. A. MacFarlane, Q. Song, N. J. C. Ingle, K. H. Chow, M. Egilmez, I. Fan, M. D. Hossain, R. F. Kiefl, C. D. P. Levy, G. D. Morris, T. J. Parolin, M. R. Pearson, H. Saadaoui, Z. Salman, and D. Wang We present β -detected NMR measurements of the spin-lattice relaxation of Li + 8 implanted into an epitaxial heterostructure based on a 100 nm thick film of ferromagnetic (FM) EuO as a function of temperature through its FM transition. In the FM state, the spin-lattice relaxation rate follows the same … [Phys. Rev. B 92, 064409] Published Thu Aug 06, 2015

Description: Author(s): D. T. Adroja, A. D. Hillier, C. Ritter, A. Bhattacharyya, D. D. Khalyavin, A. M. Strydom, P. Peratheepan, B. Fåk, M. M. Koza, J. Kawabata, Y. Yamada, Y. Okada, Y. Muro, T. Takabatake, and J. W. Taylor The opening of a spin gap in the orthorhombic compounds Ce T 2 Al 10 ( T = Ru and Os ) is followed by antiferromagnetic ordering at T N = 27 and 28.5 K, respectively, with a small ordered moment ( 0.29 – 0.34 μ B ) along the c axis, which is not an easy axis of the crystal field (CEF). In order to investigate how the … [Phys. Rev. B 92, 094425] Published Mon Sep 14, 2015