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  • 11
    Publication Date: 2016-03-05
    Description: Identifying key molecules that launch regeneration has been a long-sought goal. Multiple regenerative animals show an initial wound-associated proliferative response that transits into sustained proliferation if a considerable portion of the body part has been removed. In the axolotl, appendage amputation initiates a round of wound-associated cell cycle induction followed by continued proliferation that is dependent on nerve-derived signals. A wound-associated molecule that triggers the initial proliferative response to launch regeneration has remained obscure. Here, using an expression cloning strategy followed by in vivo gain- and loss-of-function assays, we identified axolotl MARCKS-like protein (MLP) as an extracellularly released factor that induces the initial cell cycle response during axolotl appendage regeneration. The identification of a regeneration-initiating molecule opens the possibility of understanding how to elicit regeneration in other animals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795554/" 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/PMC4795554/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sugiura, Takuji -- Wang, Heng -- Barsacchi, Rico -- Simon, Andras -- Tanaka, Elly M -- England -- Nature. 2016 Mar 10;531(7593):237-40. doi: 10.1038/nature16974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DFG Research Center for Regenerative Therapies (CRTD), Technische Universitat Dresden, Fetscherstrasse 105, 01307 Dresden, Germany. ; Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. ; Karolinska Institute, Department of Cell and Molecular Biology, Centre of Developmental Biology for Regenerative Medicine, SE-171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934225" target="_blank"〉PubMed〈/a〉
    Keywords: Ambystoma mexicanum/injuries/*physiology ; Amputation, Traumatic/metabolism ; Animals ; Cell Cycle/genetics ; Cell Proliferation/genetics ; Cloning, Molecular ; Extremities/injuries/*physiology ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism/secretion ; Membrane Proteins/genetics/*metabolism/secretion ; Mice ; Molecular Sequence Data ; Muscle Fibers, Skeletal/cytology/physiology ; Notophthalmus viridescens/genetics/injuries/physiology ; Regeneration/*physiology ; Tail/cytology/injuries/physiology ; Wound Healing/physiology ; Xenopus ; Zebrafish
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  • 12
    Publication Date: 2016-02-27
    Description: Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corti, Davide -- Misasi, John -- Mulangu, Sabue -- Stanley, Daphne A -- Kanekiyo, Masaru -- Wollen, Suzanne -- Ploquin, Aurelie -- Doria-Rose, Nicole A -- Staupe, Ryan P -- Bailey, Michael -- Shi, Wei -- Choe, Misook -- Marcus, Hadar -- Thompson, Emily A -- Cagigi, Alberto -- Silacci, Chiara -- Fernandez-Rodriguez, Blanca -- Perez, Laurent -- Sallusto, Federica -- Vanzetta, Fabrizia -- Agatic, Gloria -- Cameroni, Elisabetta -- Kisalu, Neville -- Gordon, Ingelise -- Ledgerwood, Julie E -- Mascola, John R -- Graham, Barney S -- Muyembe-Tamfun, Jean-Jacques -- Trefry, John C -- Lanzavecchia, Antonio -- Sullivan, Nancy J -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. ; Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. njsull@mail.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917593" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Antibodies, Monoclonal/*administration & dosage/immunology/isolation & ; purification ; Antibodies, Neutralizing/*administration & dosage/immunology/isolation & ; purification ; Antibodies, Viral/*administration & dosage/immunology/isolation & purification ; Clinical Trials as Topic ; Disease Outbreaks ; Ebolavirus/*immunology ; Female ; Hemorrhagic Fever, Ebola/epidemiology/*prevention & control ; Humans ; Macaca ; Male ; Molecular Sequence Data ; Survivors
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  • 13
    Publication Date: 2016-02-26
    Description: T cell-mediated destruction of insulin-producing beta cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in beta cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in beta cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in beta cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delong, Thomas -- Wiles, Timothy A -- Baker, Rocky L -- Bradley, Brenda -- Barbour, Gene -- Reisdorph, Richard -- Armstrong, Michael -- Powell, Roger L -- Reisdorph, Nichole -- Kumar, Nitesh -- Elso, Colleen M -- DeNicola, Megan -- Bottino, Rita -- Powers, Alvin C -- Harlan, David M -- Kent, Sally C -- Mannering, Stuart I -- Haskins, Kathryn -- 1K01DK094941/DK/NIDDK NIH HHS/ -- 1R01DK081166/DK/NIDDK NIH HHS/ -- 5U01DK89572/DK/NIDDK NIH HHS/ -- DK104211/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):711-4. doi: 10.1126/science.aad2791.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. thomas.delong@ucdenver.edu katie.haskins@ucdenver.edu. ; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. ; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. ; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA. ; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USA. ; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA. VA Tennessee Valley Healthcare System, Nashville, TN, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912858" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; C-Peptide/chemistry/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Clone Cells ; Diabetes Mellitus, Experimental/*immunology/pathology ; Diabetes Mellitus, Type 1/*immunology/pathology ; Epitopes/*immunology ; Immune Tolerance ; Insulin-Secreting Cells/*immunology/pathology ; Mice ; Mice, Inbred NOD ; Molecular Sequence Data ; Peptides/chemistry/immunology
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  • 14
    Publication Date: 2016-02-26
    Description: The oxidation of methane with sulfate is an important microbial metabolism in the global carbon cycle. In marine methane seeps, this process is mediated by consortia of anaerobic methanotrophic archaea (ANME) that live in syntrophy with sulfate-reducing bacteria (SRB). The underlying interdependencies within this uncultured symbiotic partnership are poorly understood. We used a combination of rate measurements and single-cell stable isotope probing to demonstrate that ANME in deep-sea sediments can be catabolically and anabolically decoupled from their syntrophic SRB partners using soluble artificial oxidants. The ANME still sustain high rates of methane oxidation in the absence of sulfate as the terminal oxidant, lending support to the hypothesis that interspecies extracellular electron transfer is the syntrophic mechanism for the anaerobic oxidation of methane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheller, Silvan -- Yu, Hang -- Chadwick, Grayson L -- McGlynn, Shawn E -- Orphan, Victoria J -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):703-7. doi: 10.1126/science.aad7154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912857" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; *Carbon Cycle ; Electron Transport ; Geologic Sediments/microbiology ; Methane/*metabolism ; Methanosarcinales/classification/genetics/*metabolism ; Molecular Sequence Data ; Oxidation-Reduction ; Phylogeny ; RNA, Archaeal/classification/genetics ; Seawater/microbiology ; Sulfates/*metabolism ; Sulfur-Reducing Bacteria/metabolism
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  • 15
    Publication Date: 2016-02-16
    Description: The vertebrate brain is highly complex, but its evolutionary origin remains elusive. Because of the absence of certain developmental domains generally marked by the expression of regulatory genes, the embryonic brain of the lamprey, a jawless vertebrate, had been regarded as representing a less complex, ancestral state of the vertebrate brain. Specifically, the absence of a Hedgehog- and Nkx2.1-positive domain in the lamprey subpallium was thought to be similar to mouse mutants in which the suppression of Nkx2-1 leads to a loss of the medial ganglionic eminence. Here we show that the brain of the inshore hagfish (Eptatretus burgeri), another cyclostome group, develops domains equivalent to the medial ganglionic eminence and rhombic lip, resembling the gnathostome brain. Moreover, further investigation of lamprey larvae revealed that these domains are also present, ruling out the possibility of convergent evolution between hagfish and gnathostomes. Thus, brain regionalization as seen in crown gnathostomes is not an evolutionary innovation of this group, but dates back to the latest vertebrate ancestor before the divergence of cyclostomes and gnathostomes more than 500 million years ago.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sugahara, Fumiaki -- Pascual-Anaya, Juan -- Oisi, Yasuhiro -- Kuraku, Shigehiro -- Aota, Shin-ichi -- Adachi, Noritaka -- Takagi, Wataru -- Hirai, Tamami -- Sato, Noboru -- Murakami, Yasunori -- Kuratani, Shigeru -- England -- Nature. 2016 Mar 3;531(7592):97-100. doi: 10.1038/nature16518. Epub 2016 Feb 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Evolutionary Morphology Laboratory, RIKEN, Kobe 650-0047, Japan. ; Division of Biology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan. ; Development and Function of Inhibitory Neural Circuits, Max Planck Florida Institute for Neuroscience, Jupiter, Florida 33458, USA. ; Phyloinformatics Unit, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan. ; Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA. ; Division of Gross Anatomy and Morphogenesis, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-8510, Japan. ; Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26878236" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*anatomy & histology/*embryology ; Female ; Hagfishes/*anatomy & histology/*embryology/genetics ; Humans ; Lampreys/*anatomy & histology/*embryology/genetics/growth & development ; Larva/anatomy & histology ; Male ; Mice ; Molecular Sequence Data ; *Phylogeny ; Synteny/genetics
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  • 16
    Publication Date: 2016-02-09
    Description: The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 A resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins, implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walls, Alexandra C -- Tortorici, M Alejandra -- Bosch, Berend-Jan -- Frenz, Brandon -- Rottier, Peter J M -- DiMaio, Frank -- Rey, Felix A -- Veesler, David -- GM103310/GM/NIGMS NIH HHS/ -- T32GM008268/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Mar 3;531(7592):114-7. doi: 10.1038/nature16988. Epub 2016 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA. ; Institut Pasteur, Unite de Virologie Structurale, 75015 Paris, France. ; CNRS UMR 3569 Virologie, 75015 Paris, France. ; Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26855426" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Cell Line ; Coronavirus Infections/immunology/virology ; *Cryoelectron Microscopy ; Drosophila melanogaster ; Mice ; Models, Molecular ; Molecular Sequence Data ; Murine hepatitis virus/*chemistry/immunology/*ultrastructure ; Protein Multimerization ; Protein Structure, Tertiary ; Spike Glycoprotein, Coronavirus/*chemistry/immunology/*ultrastructure ; Viral Vaccines/chemistry/immunology ; Virus Internalization
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  • 17
    Publication Date: 2016-02-06
    Description: SH3 and multiple ankyrin repeat domains 3 (SHANK3) haploinsufficiency is causative for the neurological features of Phelan-McDermid syndrome (PMDS), including a high risk of autism spectrum disorder (ASD). We used unbiased, quantitative proteomics to identify changes in the phosphoproteome of Shank3-deficient neurons. Down-regulation of protein kinase B (PKB/Akt)-mammalian target of rapamycin complex 1 (mTORC1) signaling resulted from enhanced phosphorylation and activation of serine/threonine protein phosphatase 2A (PP2A) regulatory subunit, B56beta, due to increased steady-state levels of its kinase, Cdc2-like kinase 2 (CLK2). Pharmacological and genetic activation of Akt or inhibition of CLK2 relieved synaptic deficits in Shank3-deficient and PMDS patient-derived neurons. CLK2 inhibition also restored normal sociability in a Shank3-deficient mouse model. Our study thereby provides a novel mechanistic and potentially therapeutic understanding of deregulated signaling downstream of Shank3 deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bidinosti, Michael -- Botta, Paolo -- Kruttner, Sebastian -- Proenca, Catia C -- Stoehr, Natacha -- Bernhard, Mario -- Fruh, Isabelle -- Mueller, Matthias -- Bonenfant, Debora -- Voshol, Hans -- Carbone, Walter -- Neal, Sarah J -- McTighe, Stephanie M -- Roma, Guglielmo -- Dolmetsch, Ricardo E -- Porter, Jeffrey A -- Caroni, Pico -- Bouwmeester, Tewis -- Luthi, Andreas -- Galimberti, Ivan -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1199-203. doi: 10.1126/science.aad5487. Epub 2016 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Friedrich Miescher Institute, Basel, Switzerland. ; Analytical Sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Neuroscience, Novartis Institutes for Biomedical Research, Cambridge, USA. ; Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ivan.galimberti@novartis.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26847545" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Autism Spectrum Disorder/*drug therapy/enzymology/genetics ; Chromosome Deletion ; Chromosome Disorders/genetics ; Chromosomes, Human, Pair 22/genetics ; Disease Models, Animal ; Down-Regulation ; Gene Knockdown Techniques ; Humans ; Insulin-Like Growth Factor I/metabolism ; Mice ; Molecular Sequence Data ; Multiprotein Complexes/metabolism ; Nerve Tissue Proteins/*genetics ; Neurons/enzymology ; Phosphorylation ; Protein Phosphatase 2/metabolism ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Proteomics ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; Rats ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
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  • 18
    Publication Date: 2016-01-28
    Description: Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA-linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP)-activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toyama, Erin Quan -- Herzig, Sebastien -- Courchet, Julien -- Lewis, Tommy L Jr -- Loson, Oliver C -- Hellberg, Kristina -- Young, Nathan P -- Chen, Hsiuchen -- Polleux, Franck -- Chan, David C -- Shaw, Reuben J -- K99 NS091526/NS/NINDS NIH HHS/ -- K99NS091526/NS/NINDS NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01CA172229/CA/NCI NIH HHS/ -- R01DK080425/DK/NIDDK NIH HHS/ -- R01GM062967/GM/NIGMS NIH HHS/ -- R01GM110039/GM/NIGMS NIH HHS/ -- R01NS089456/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):275-81. doi: 10.1126/science.aab4138.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ; Department of Neuroscience, Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. ; Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. shaw@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816379" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/chemistry/genetics/*metabolism ; Adenosine Monophosphate/metabolism ; Amino Acid Motifs ; Cell Line, Tumor ; Cytoplasm/enzymology ; Dactinomycin/analogs & derivatives/pharmacology ; *Energy Metabolism ; Enzyme Activation ; GTP Phosphohydrolases/genetics/metabolism ; Humans ; Microtubule-Associated Proteins/genetics/metabolism ; Mitochondria/drug effects/enzymology/*physiology ; *Mitochondrial Dynamics ; Mitochondrial Proteins/genetics/metabolism ; Molecular Sequence Data ; Rotenone/pharmacology ; *Stress, Physiological
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  • 19
    Publication Date: 2016-01-28
    Description: Seagrasses colonized the sea on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet. Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes, genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae and that is important for ion homoeostasis, nutrient uptake and O2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming, to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, Jeanine L -- Rouze, Pierre -- Verhelst, Bram -- Lin, Yao-Cheng -- Bayer, Till -- Collen, Jonas -- Dattolo, Emanuela -- De Paoli, Emanuele -- Dittami, Simon -- Maumus, Florian -- Michel, Gurvan -- Kersting, Anna -- Lauritano, Chiara -- Lohaus, Rolf -- Topel, Mats -- Tonon, Thierry -- Vanneste, Kevin -- Amirebrahimi, Mojgan -- Brakel, Janina -- Bostrom, Christoffer -- Chovatia, Mansi -- Grimwood, Jane -- Jenkins, Jerry W -- Jueterbock, Alexander -- Mraz, Amy -- Stam, Wytze T -- Tice, Hope -- Bornberg-Bauer, Erich -- Green, Pamela J -- Pearson, Gareth A -- Procaccini, Gabriele -- Duarte, Carlos M -- Schmutz, Jeremy -- Reusch, Thorsten B H -- Van de Peer, Yves -- England -- Nature. 2016 Feb 18;530(7590):331-5. doi: 10.1038/nature16548. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Groningen Institute of Evolutionary Life Sciences (GELIFES), University of Groningen, PO Box 11103, 9700 CC Groningen, The Netherlands. ; Department of Plant Systems Biology, VIB and Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 927, B-9052 Ghent, Belgium. ; GEOMAR Helmholtz Centre for Ocean Research-Kiel, Evolutionary Ecology, Dusternbrooker Weg 20, D-24105 Kiel, Germany. ; Sorbonne Universite, UPMC Univ Paris 06, CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, F-29688, Roscoff cedex, France. ; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. ; Dipartimento di Scienze Agrarie e Ambientali, University of Udine, Via delle Scienze 206, 33100 Udine, Italy. ; INRA, UR1164 URGI-Research Unit in Genomics-Info, INRA de Versailles-Grignon, Route de Saint-Cyr, Versailles 78026, France. ; Institute for Evolution and Biodiversity, Westfalische Wilhelms-University of Munster, Hufferstrasse 1, D-48149 Munster, Germany. ; Institute for Computer Science, Heinrich Heine University, D-40255 Duesseldorf, Germany. ; Department of Biological and Environmental Sciences, Bioinformatics Infrastructure for Life Sciences (BILS), University of Gothenburg, Medicinaregatan 18A, 40530 Gothenburg, Sweden. ; Department of Energy Joint Genome Institute, 2800 Mitchell Dr., #100, Walnut Creek, California 94598, USA. ; Environmental and Marine Biology, Faculty of Science and Engineering, Abo Akademi University, Artillerigatan 6, FI-20520 Turku/Abo, Finland. ; HudsonAlpha Institute for Biotechnology, 601 Genome Way NW, Huntsville, Alabama 35806, USA. ; Marine Ecology Group, Nord University, Postbox 1490, 8049 Bodo, Norway. ; Amplicon Express, 2345 NE Hopkins Ct., Pullman, Washington 99163, USA. ; School of Marine Science and Policy, Department of Plant and Soil Sciences, Delaware Biotechnology Institute, University of Delaware, 15-Innovation Way, Newark, Delaware 19711, USA. ; Marine Ecology and Evolution, Centre for Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal. ; King Abdullah University of Science and Technology (KAUST), Red Sea Research Center (RSRC), Thuwal 23955-6900, Saudi Arabia. ; University of Kiel, Faculty of Mathematics and Natural Sciences, Christian-Albrechts-Platz 4, 24118 Kiel, Germany. ; Genomics Research Institute, University of Pretoria, Hatfield Campus, Pretoria 0028, South Africa. ; Bioinformatics Institute Ghent, Ghent University, Ghent B-9000, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814964" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/genetics ; Adaptation, Physiological/*genetics ; Cell Wall/chemistry ; Ethylenes/biosynthesis ; *Evolution, Molecular ; Gene Duplication ; Genes, Plant/genetics ; Genome, Plant/*genetics ; Metabolic Networks and Pathways ; Molecular Sequence Data ; Oceans and Seas ; Osmoregulation/genetics ; Phylogeny ; Plant Leaves/metabolism ; Plant Stomata/genetics ; Pollen/metabolism ; Salinity ; Salt-Tolerance/genetics ; *Seawater ; Seaweed/genetics ; Terpenes/metabolism ; Zosteraceae/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 20
    Publication Date: 2016-01-28
    Description: Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorenzo-Redondo, Ramon -- Fryer, Helen R -- Bedford, Trevor -- Kim, Eun-Young -- Archer, John -- Kosakovsky Pond, Sergei L -- Chung, Yoon-Seok -- Penugonda, Sudhir -- Chipman, Jeffrey G -- Fletcher, Courtney V -- Schacker, Timothy W -- Malim, Michael H -- Rambaut, Andrew -- Haase, Ashley T -- McLean, Angela R -- Wolinsky, Steven M -- AI1074340/AI/NIAID NIH HHS/ -- DA033773/DA/NIDA NIH HHS/ -- G1000196/Medical Research Council/United Kingdom -- GM110749/GM/NIGMS NIH HHS/ -- R01 DA033773/DA/NIDA NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2016 Feb 4;530(7588):51-6. doi: 10.1038/nature16933. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60011, USA. ; Institute for Emerging Infections, Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK. ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; Centro de Investigacao em Biodiversidade e Recursos Geneticos Universidade do Porto, 4485-661 Vairao, Portugal. ; Department of Medicine, University of California, San Diego, California 92093, USA. ; Division of AIDS, Center for Immunology and Pathology, Korea National Institutes of Health, Chungju-si, Chungcheongbuk-do, 28159, South Korea. ; Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy, Omaha, Nebraska 68198, USA. ; Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Department of Infectious Diseases, King's College London, Guy's Hospital, London SE21 7DN, UK. ; Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK. ; Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814962" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/administration & dosage/pharmacology/therapeutic use ; Carrier State/blood/*drug therapy/*virology ; Drug Resistance, Viral/drug effects ; HIV Infections/blood/*drug therapy/*virology ; HIV-1/drug effects/genetics/*growth & development/isolation & purification ; Haplotypes/drug effects ; Humans ; Lymph Nodes/drug effects/virology ; Models, Biological ; Molecular Sequence Data ; Phylogeny ; Selection, Genetic/drug effects ; Sequence Analysis, DNA ; Spatio-Temporal Analysis ; Time Factors ; *Viral Load/drug effects ; *Virus Replication/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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