ALBERT

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ott, Edward -- England -- Nature. 2008 May 15;453(7193):300. doi: 10.1038/453300a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Edward Ott is in the Departments of Physics, and of Electrical and Computer Engineering, University of Maryland, College Park, Maryland 20742, USA.edott@umd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480808" target="_blank"〉PubMed〈/a〉

Description: Osmoregulated transporters sense intracellular osmotic pressure and respond to hyperosmotic stress by accumulation of osmolytes to restore normal hydration levels. Here we report the determination of the X-ray structure of a member of the family of betaine/choline/carnitine transporters, the Na(+)-coupled symporter BetP from Corynebacterium glutamicum, which is a highly effective osmoregulated uptake system for glycine betaine. Glycine betaine is bound in a tryptophan box occluded from both sides of the membrane with aromatic side chains lining the transport pathway. BetP has the same overall fold as three unrelated Na(+)-coupled symporters. Whereas these are crystallized in either the outward-facing or the inward-facing conformation, the BetP structure reveals a unique intermediate conformation in the Na(+)-coupled transport cycle. The trimeric architecture of BetP and the break in three-fold symmetry by the osmosensing C-terminal helices suggest a regulatory mechanism of Na(+)-coupled osmolyte transport to counteract osmotic stress.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ressl, Susanne -- Terwisscha van Scheltinga, Anke C -- Vonrhein, Clemens -- Ott, Vera -- Ziegler, Christine -- England -- Nature. 2009 Mar 5;458(7234):47-52. doi: 10.1038/nature07819.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Biophysics, Department of Structural Biology, 60438 Frankfurt am Main, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262666" target="_blank"〉PubMed〈/a〉

Description: Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies. To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheid, Johannes F -- Mouquet, Hugo -- Feldhahn, Niklas -- Seaman, Michael S -- Velinzon, Klara -- Pietzsch, John -- Ott, Rene G -- Anthony, Robert M -- Zebroski, Henry -- Hurley, Arlene -- Phogat, Adhuna -- Chakrabarti, Bimal -- Li, Yuxing -- Connors, Mark -- Pereyra, Florencia -- Walker, Bruce D -- Wardemann, Hedda -- Ho, David -- Wyatt, Richard T -- Mascola, John R -- Ravetch, Jeffrey V -- Nussenzweig, Michel C -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2009 Apr 2;458(7238):636-40. doi: 10.1038/nature07930. Epub 2009 Mar 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19287373" target="_blank"〉PubMed〈/a〉

Description: A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required for constitutive NF-kappaB pathway activity and survival in ABC DLBCL. Roughly 10% of ABC DLBCLs have mutant CARD11 isoforms that activate NF-kappaB, but the mechanism that engages wild-type CARD11 in other ABC DLBCLs was unknown. An RNA interference genetic screen revealed that a BCR signalling component, Bruton's tyrosine kinase, is essential for the survival of ABC DLBCLs with wild-type CARD11. In addition, knockdown of proximal BCR subunits (IgM, Ig-kappa, CD79A and CD79B) killed ABC DLBCLs with wild-type CARD11 but not other lymphomas. The BCRs in these ABC DLBCLs formed prominent clusters in the plasma membrane with low diffusion, similarly to BCRs in antigen-stimulated normal B cells. Somatic mutations affecting the immunoreceptor tyrosine-based activation motif (ITAM) signalling modules of CD79B and CD79A were detected frequently in ABC DLBCL biopsy samples but rarely in other DLBCLs and never in Burkitt's lymphoma or mucosa-associated lymphoid tissue lymphoma. In 18% of ABC DLBCLs, one functionally critical residue of CD79B, the first ITAM tyrosine, was mutated. These mutations increased surface BCR expression and attenuated Lyn kinase, a feedback inhibitor of BCR signalling. These findings establish chronic active BCR signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845535/" 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/PMC2845535/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, R Eric -- Ngo, Vu N -- Lenz, Georg -- Tolar, Pavel -- Young, Ryan M -- Romesser, Paul B -- Kohlhammer, Holger -- Lamy, Laurence -- Zhao, Hong -- Yang, Yandan -- Xu, Weihong -- Shaffer, Arthur L -- Wright, George -- Xiao, Wenming -- Powell, John -- Jiang, Jian-Kang -- Thomas, Craig J -- Rosenwald, Andreas -- Ott, German -- Muller-Hermelink, Hans Konrad -- Gascoyne, Randy D -- Connors, Joseph M -- Johnson, Nathalie A -- Rimsza, Lisa M -- Campo, Elias -- Jaffe, Elaine S -- Wilson, Wyndham H -- Delabie, Jan -- Smeland, Erlend B -- Fisher, Richard I -- Braziel, Rita M -- Tubbs, Raymond R -- Cook, J R -- Weisenburger, Dennis D -- Chan, Wing C -- Pierce, Susan K -- Staudt, Louis M -- NIH0011349228/PHS HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):88-92. doi: 10.1038/nature08638.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054396" target="_blank"〉PubMed〈/a〉

Description: Cell biology: Choreography of protein synthesis Nature 533, 7604 (2016). doi:10.1038/nature18436 Authors: Martin Ott Both nuclear genes and genes in organelles called mitochondria are involved in the assembly of the cellular energy-producing machinery. RNA-translation programs that coordinate the two systems have now been identified. See Article p.499

Description: Almost a decade after methane was first reported in the atmosphere of Mars there is an intensive discussion about both the reliability of the observations--particularly the suggested seasonal and latitudinal variations--and the sources of methane on Mars. Given that the lifetime of methane in the Martian atmosphere is limited, a process on or below the planet's surface would need to be continuously producing methane. A biological source would provide support for the potential existence of life on Mars, whereas a chemical origin would imply that there are unexpected geological processes. Methane release from carbonaceous meteorites associated with ablation during atmospheric entry is considered negligible. Here we show that methane is produced in much larger quantities from the Murchison meteorite (a type CM2 carbonaceous chondrite) when exposed to ultraviolet radiation under conditions similar to those expected at the Martian surface. Meteorites containing several per cent of intact organic matter reach the Martian surface at high rates, and our experiments suggest that a significant fraction of the organic matter accessible to ultraviolet radiation is converted to methane. Ultraviolet-radiation-induced methane formation from meteorites could explain a substantial fraction of the most recently estimated atmospheric methane mixing ratios. Stable hydrogen isotope analysis unambiguously confirms that the methane released from Murchison is of extraterrestrial origin. The stable carbon isotope composition, in contrast, is similar to that of terrestrial microbial origin; hence, measurements of this signature in future Mars missions may not enable an unambiguous identification of biogenic methane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keppler, Frank -- Vigano, Ivan -- McLeod, Andy -- Ott, Ulrich -- Fruchtl, Marion -- Rockmann, Thomas -- England -- Nature. 2012 May 30;486(7401):93-6. doi: 10.1038/nature11203.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atmospheric Chemistry, Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, 55128 Mainz, Germany. frank.keppler@mpic.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678286" target="_blank"〉PubMed〈/a〉

Description: Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the alpha1 subunit of soluble guanylyl cyclase (alpha1-sGC), and CCT7 encodes CCTeta, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce alpha1-sGC as well as beta1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in alpha1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erdmann, Jeanette -- Stark, Klaus -- Esslinger, Ulrike B -- Rumpf, Philipp Moritz -- Koesling, Doris -- de Wit, Cor -- Kaiser, Frank J -- Braunholz, Diana -- Medack, Anja -- Fischer, Marcus -- Zimmermann, Martina E -- Tennstedt, Stephanie -- Graf, Elisabeth -- Eck, Sebastian -- Aherrahrou, Zouhair -- Nahrstaedt, Janja -- Willenborg, Christina -- Bruse, Petra -- Braenne, Ingrid -- Nothen, Markus M -- Hofmann, Per -- Braund, Peter S -- Mergia, Evanthia -- Reinhard, Wibke -- Burgdorf, Christof -- Schreiber, Stefan -- Balmforth, Anthony J -- Hall, Alistair S -- Bertram, Lars -- Steinhagen-Thiessen, Elisabeth -- Li, Shu-Chen -- Marz, Winfried -- Reilly, Muredach -- Kathiresan, Sekar -- McPherson, Ruth -- Walter, Ulrich -- CARDIoGRAM -- Ott, Jurg -- Samani, Nilesh J -- Strom, Tim M -- Meitinger, Thomas -- Hengstenberg, Christian -- Schunkert, Heribert -- British Heart Foundation/United Kingdom -- England -- Nature. 2013 Dec 19;504(7480):432-6. doi: 10.1038/nature12722. Epub 2013 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut fur Integrative und Experimentelle Genomik, Universitat zu Lubeck, 23562 Lubeck, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany [3]. ; 1] Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg, 93053 Regensburg, Germany [2] Department of Genetic Epidemiology, University of Regensburg, 93053 Regensburg, Germany [3]. ; 1] Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg, 93053 Regensburg, Germany [2] Institut National de la Sante et de la Recherche Medicale (INSERM), UMR-S937 Paris, France [3]. ; 1] Deutsches Herzzentrum Munchen and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, 80636 Munchen, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, 80636 Munich, Germany [3]. ; Department of Pharmacology and Toxicology, Ruhr-University Bochum, 44801 Bochum, Germany. ; 1] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany [2] Institut fur Physiologie, Universitat zu Lubeck, 23562 Lubeck, Germany. ; 1] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany [2] Institut fur Humangenetik, Universitat zu Lubeck, 23562 Lubeck, Germany. ; Institut fur Humangenetik, Universitat zu Lubeck, 23562 Lubeck, Germany. ; Institut fur Integrative und Experimentelle Genomik, Universitat zu Lubeck, 23562 Lubeck, Germany. ; Klinik und Poliklinik fur Innere Medizin II, Universitatsklinikum Regensburg, 93053 Regensburg, Germany. ; 1] Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany [2] Institute of Human Genetics, Technische Universitat Munchen, 81675 Munchen, Germany. ; 1] Institut fur Integrative und Experimentelle Genomik, Universitat zu Lubeck, 23562 Lubeck, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany. ; 1] Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany [2] Department of Genomics, Research Center Life & Brain, University of Bonn, 53127 Bonn, Germany. ; 1] Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany [2] Division of Medical Genetics, University Hospital Basel and Department of Biomedicine, University of Basel, 4003 Basel, Switzerland. ; 1] Department of Cardiovascular Sciences, University of Leicester, Leicester LE1 7RH, UK [2] Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE1 7RH, UK. ; 1] Deutsches Herzzentrum Munchen and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, 80636 Munchen, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, 80636 Munich, Germany. ; Deutsches Herzzentrum Munchen and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, 80636 Munchen, Germany. ; Institute of Clinical Molecular Biology, Christian-Albrecht-Universitat, 24105 Kiel, Germany. ; Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK. ; Division of Cardiovascular and Neuronal Remodelling, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK. ; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany. ; Charite Research Group on Geriatrics, Charite-Universitatsmedizin, 10117 Berlin, Germany. ; 1] Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany [2] Department of Psychology, TU Dresden, 01062 Dresden, Germany. ; 1] Synlab Academy and Business Development, synlab Services GmbH, 68165 Mannheim, Germany [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria [3] Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany. ; The Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02215, USA [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02215, USA [3] Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02215, USA. ; University of Ottawa, Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. ; 1] Centrum fur Thrombose und Hamostase (CTH), Universitatsmedizin Mainz, 55131 Mainz, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site RheinMain, 55131 Mainz, Germany. ; 1] Institute of Psychology, Chinese Academy of Sciences, Beijing 100864, China [2] Laboratory of Statistical Genetics, Rockefeller University, New York 10065, USA. ; 1] Deutsches Herzzentrum Munchen and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, 80636 Munchen, Germany [2] Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany [3] Institute of Human Genetics, Technische Universitat Munchen, 81675 Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24213632" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ott, Sascha -- Hebenstreit, Daniel -- England -- Nature. 2014 Feb 20;506(7488):295. doi: 10.1038/506295b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Warwick, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553233" target="_blank"〉PubMed〈/a〉