ALBERT

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: Observing marine mammal (MM) populations continuously in time and space over the immense ocean areas they inhabit is challenging but essential for gathering an unambiguous record of their distribution, as well as understanding their behaviour and interaction with prey species. Here we use passive ocean acoustic waveguide remote sensing (POAWRS) in an important North Atlantic feeding ground to instantaneously detect, localize and classify MM vocalizations from diverse species over an approximately 100,000 km(2) region. More than eight species of vocal MMs are found to spatially converge on fish spawning areas containing massive densely populated herring shoals at night-time and diffuse herring distributions during daytime. We find the vocal MMs divide the enormous fish prey field into species-specific foraging areas with varying degrees of spatial overlap, maintained for at least two weeks of the herring spawning period. The recorded vocalization rates are diel (24 h)-dependent for all MM species, with some significantly more vocal at night and others more vocal during the day. The four key baleen whale species of the region: fin, humpback, blue and minke have vocalization rate trends that are highly correlated to trends in fish shoaling density and to each other over the diel cycle. These results reveal the temporospatial dynamics of combined multi-species MM foraging activities in the vicinity of an extensive fish prey field that forms a massive ecological hotspot, and would be unattainable with conventional methodologies. Understanding MM behaviour and distributions is essential for management of marine ecosystems and for accessing anthropogenic impacts on these protected marine species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Delin -- Garcia, Heriberto -- Huang, Wei -- Tran, Duong D -- Jain, Ankita D -- Yi, Dong Hoon -- Gong, Zheng -- Jech, J Michael -- Godo, Olav Rune -- Makris, Nicholas C -- Ratilal, Purnima -- England -- Nature. 2016 Mar 17;531(7594):366-70. doi: 10.1038/nature16960. Epub 2016 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Ocean Acoustics and Ecosystem Sensing, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA. ; Laboratory for Undersea Remote Sensing, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. ; Northeast Fisheries Science Center, 166 Water Street, Woods Hole, Massachusetts 02543, USA. ; Institute of Marine Research, Post Office Box 1870, Nordnes, N-5817 Bergen, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934221" 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

Description: Author(s): A. Bhattacharyya, D. D. Khalyavin, F. Krüger, D. T. Adroja, A. M. Strydom, W. A. Kockelmann, and A. D. Hillier The newly discovered Ising-type ferromagnet CeRu 2 Al 2 B exhibits an additional phase transition at T N = 14.2  K before entering the ferromagnetic ground state at T C = 12.8  K. We clarify the nature of this transition through high resolution neutron diffraction measurements. The data reveal the presence of a… [Phys. Rev. B 93, 060410(R)] Published Mon Feb 29, 2016

Description: Author(s): M. G. Kim, M. Wang, G. S. Tucker, P. N. Valdivia, D. L. Abernathy, Songxue Chi, A. D. Christianson, A. A. Aczel, T. Hong, T. W. Heitmann, S. Ran, P. C. Canfield, E. D. Bourret-Courchesne, A. Kreyssig, D. H. Lee, A. I. Goldman, R. J. McQueeney, and R. J. Birgeneau We present the results of elastic and inelastic neutron scattering measurements on nonsuperconducting Ba ( Fe 0.957 Cu 0.043 ) 2 As 2 , a composition close to a quantum critical point between antiferromagnetic (AFM) ordered and paramagnetic phases. By comparing these results with the spin fluctuations in the … [Phys. Rev. B 92, 214404] Published Wed Dec 02, 2015

Description: The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Ling -- Chen, Xiang-Jun -- Zhu, Jie -- Xi, Yi-Bo -- Yang, Xu -- Hu, Li-Dan -- Ouyang, Hong -- Patel, Sherrina H -- Jin, Xin -- Lin, Danni -- Wu, Frances -- Flagg, Ken -- Cai, Huimin -- Li, Gen -- Cao, Guiqun -- Lin, Ying -- Chen, Daniel -- Wen, Cindy -- Chung, Christopher -- Wang, Yandong -- Qiu, Austin -- Yeh, Emily -- Wang, Wenqiu -- Hu, Xun -- Grob, Seanna -- Abagyan, Ruben -- Su, Zhiguang -- Tjondro, Harry Christianto -- Zhao, Xi-Juan -- Luo, Hongrong -- Hou, Rui -- Perry, J Jefferson P -- Gao, Weiwei -- Kozak, Igor -- Granet, David -- Li, Yingrui -- Sun, Xiaodong -- Wang, Jun -- Zhang, Liangfang -- Liu, Yizhi -- Yan, Yong-Bin -- Zhang, Kang -- England -- Nature. 2015 Jul 30;523(7562):607-11. doi: 10.1038/nature14650. Epub 2015 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. ; BGI-Shenzhen, Shenzhen 518083, China. ; 1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. ; Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. ; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] CapitalBio Genomics Co., Ltd., Dongguan 523808, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA. ; Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. ; Department of Biochemistry, University of California Riverside, Riverside, California 92521, USA. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA. ; King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. ; Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. ; Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [4] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26200341" target="_blank"〉PubMed〈/a〉

Description: Cancers emerge from an ongoing Darwinian evolutionary process, often leading to multiple competing subclones within a single primary tumour. This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths. However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported, recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and interclonal cooperation between multiple subclones. Here we sought definitive evidence for the existence of polyclonal seeding in human malignancy and to establish the clonal relationship among different metastases in the context of androgen-deprived metastatic prostate cancer. Using whole-genome sequencing, we characterized multiple metastases arising from prostate tumours in ten patients. Integrated analyses of subclonal architecture revealed the patterns of metastatic spread in unprecedented detail. Metastasis-to-metastasis spread was found to be common, either through de novo monoclonal seeding of daughter metastases or, in five cases, through the transfer of multiple tumour clones between metastatic sites. Lesions affecting tumour suppressor genes usually occur as single events, whereas mutations in genes involved in androgen receptor signalling commonly involve multiple, convergent events in different metastases. Our results elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413032/" 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/PMC4413032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gundem, Gunes -- Van Loo, Peter -- Kremeyer, Barbara -- Alexandrov, Ludmil B -- Tubio, Jose M C -- Papaemmanuil, Elli -- Brewer, Daniel S -- Kallio, Heini M L -- Hognas, Gunilla -- Annala, Matti -- Kivinummi, Kati -- Goody, Victoria -- Latimer, Calli -- O'Meara, Sarah -- Dawson, Kevin J -- Isaacs, William -- Emmert-Buck, Michael R -- Nykter, Matti -- Foster, Christopher -- Kote-Jarai, Zsofia -- Easton, Douglas -- Whitaker, Hayley C -- ICGC Prostate UK Group -- Neal, David E -- Cooper, Colin S -- Eeles, Rosalind A -- Visakorpi, Tapio -- Campbell, Peter J -- McDermott, Ultan -- Wedge, David C -- Bova, G Steven -- 077012/Wellcome Trust/United Kingdom -- A12758/Cancer Research UK/United Kingdom -- A14835/Cancer Research UK/United Kingdom -- CA92234/CA/NCI NIH HHS/ -- Cancer Research UK/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2015 Apr 16;520(7547):353-7. doi: 10.1038/nature14347. Epub 2015 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ; 1] Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Department of Human Genetics, KU Leuven, Herestraat 49 Box 602, B-3000 Leuven, Belgium [3] Cancer Research UK London Research Institute, London WC2A 3LY, UK. ; 1] Norwich Medical School and Department of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK [2] The Genome Analysis Centre, Norwich NR4 7UH, UK. ; Institute of Biosciences and Medical Technology, BioMediTech, University of Tampere and Fimlab Laboratories, Tampere University Hospital, Tampere FI-33520, Finland. ; The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA. ; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Maryland 20892, USA. ; University of Liverpool and HCA Pathology Laboratories, London WC1E 6JA, UK. ; Division of Genetics and Epidemiology, The Institute Of Cancer Research, London SW7 3RP, UK. ; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK. ; Uro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK. ; 1] Uro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK [2] Department of Surgical Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. ; 1] Norwich Medical School and Department of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK [2] Division of Genetics and Epidemiology, The Institute Of Cancer Research, London SW7 3RP, UK. ; 1] Division of Genetics and Epidemiology, The Institute Of Cancer Research, London SW7 3RP, UK [2] Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; and Sutton SM2 5PT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25830880" target="_blank"〉PubMed〈/a〉