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  • 101
    Publication Date: 2014-08-15
    Description: The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs. Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development, glucose metabolism and tissue regeneration. Overexpression of Lin28 is correlated with the onset of numerous cancers, whereas let-7, a tumour suppressor, silences several human oncogenes. Lin28 binds to precursor let-7 (pre-let-7) hairpins, triggering the 3' oligo-uridylation activity of TUT4 and TUT7 (refs 10-12). The oligoU tail added to pre-let-7 serves as a decay signal, as it is rapidly degraded by Dis3l2 (refs 13, 14), a homologue of the catalytic subunit of the RNA exosome. The molecular basis of Lin28-mediated recruitment of TUT4 and TUT7 to pre-let-7 and its subsequent degradation by Dis3l2 is largely unknown. To examine the mechanism of Dis3l2 substrate recognition we determined the structure of mouse Dis3l2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA-binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from that of its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first 12 nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3l2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28-let-7 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192074/" 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/PMC4192074/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faehnle, Christopher R -- Walleshauser, Jack -- Joshua-Tor, Leemor -- P30 CA045508/CA/NCI NIH HHS/ -- P41 GM111244/GM/NIGMS NIH HHS/ -- T32 GM065094/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Oct 9;514(7521):252-6. doi: 10.1038/nature13553. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] W. M. Keck Structural Biology Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [2] Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [3]. ; 1] W. M. Keck Structural Biology Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [2] Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [3] Watson School of Biological Science, Cold Spring Harbor, 1 Bungtown Road, New York 11724, USA [4]. ; 1] W. M. Keck Structural Biology Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [2] Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [3] Watson School of Biological Science, Cold Spring Harbor, 1 Bungtown Road, New York 11724, USA [4] Howard Hughes Medical Institute, Cold Spring Harbor, 1 Bungtown Road, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119025" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Exoribonucleases/*chemistry/*metabolism ; Exosome Multienzyme Ribonuclease Complex/chemistry ; Mice ; MicroRNAs/chemistry/genetics/*metabolism ; Models, Molecular ; Oligoribonucleotides/chemistry/metabolism ; RNA-Binding Proteins/chemistry/*metabolism ; Schizosaccharomyces pombe Proteins/chemistry ; Substrate Specificity ; Uracil Nucleotides/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 102
    Publication Date: 2014-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayden, Erika Check -- England -- Nature. 2014 Jun 5;510(7503):18. doi: 10.1038/510018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899284" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biotechnology/*economics/trends ; California ; Clinical Trials as Topic/*economics ; Embryonic Stem Cells/*transplantation ; Humans ; Models, Animal ; *Research Support as Topic ; Spinal Cord Injuries/pathology/*therapy ; *Stem Cell Transplantation/economics
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  • 103
    Publication Date: 2014-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woolhouse, Mark -- Farrar, Jeremy -- England -- Nature. 2014 May 29;509(7502):555-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24877180" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees/*organization & administration ; Animals ; Anti-Bacterial Agents/administration & dosage/*pharmacology/*supply & ; distribution/therapeutic use ; Drug Discovery/*organization & administration/statistics & numerical data/trends ; *Drug Resistance, Microbial/drug effects ; Drug Resistance, Multiple, Bacterial/drug effects ; Epidemiological Monitoring ; Global Health/statistics & numerical data ; Goals ; *Health Policy/economics/trends ; Humans ; Inappropriate Prescribing/prevention & control/veterinary ; *International Cooperation ; Leadership ; Methicillin-Resistant Staphylococcus aureus ; United States ; United States Food and Drug Administration ; World Health Organization
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 104
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2014 Apr 10;508(7495):158-9. doi: 10.1038/508158a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717486" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/therapeutic use ; Citric Acid Cycle/genetics ; Clinical Trials as Topic ; Glucose/metabolism ; Glutarates/metabolism ; Humans ; Isocitrate Dehydrogenase/antagonists & inhibitors/genetics/metabolism ; *Metabolic Networks and Pathways/genetics ; Mice ; Neoplasms/*drug therapy/enzymology/genetics/*metabolism ; Pyruvate Kinase/antagonists & inhibitors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 105
    Publication Date: 2014-02-07
    Description: Although it is generally agreed that the Arctic flora is among the youngest and least diverse on Earth, the processes that shaped it are poorly understood. Here we present 50 thousand years (kyr) of Arctic vegetation history, derived from the first large-scale ancient DNA metabarcoding study of circumpolar plant diversity. For this interval we also explore nematode diversity as a proxy for modelling vegetation cover and soil quality, and diets of herbivorous megafaunal mammals, many of which became extinct around 10 kyr bp (before present). For much of the period investigated, Arctic vegetation consisted of dry steppe-tundra dominated by forbs (non-graminoid herbaceous vascular plants). During the Last Glacial Maximum (25-15 kyr bp), diversity declined markedly, although forbs remained dominant. Much changed after 10 kyr bp, with the appearance of moist tundra dominated by woody plants and graminoids. Our analyses indicate that both graminoids and forbs would have featured in megafaunal diets. As such, our findings question the predominance of a Late Quaternary graminoid-dominated Arctic mammoth steppe.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willerslev, Eske -- Davison, John -- Moora, Mari -- Zobel, Martin -- Coissac, Eric -- Edwards, Mary E -- Lorenzen, Eline D -- Vestergard, Mette -- Gussarova, Galina -- Haile, James -- Craine, Joseph -- Gielly, Ludovic -- Boessenkool, Sanne -- Epp, Laura S -- Pearman, Peter B -- Cheddadi, Rachid -- Murray, David -- Brathen, Kari Anne -- Yoccoz, Nigel -- Binney, Heather -- Cruaud, Corinne -- Wincker, Patrick -- Goslar, Tomasz -- Alsos, Inger Greve -- Bellemain, Eva -- Brysting, Anne Krag -- Elven, Reidar -- Sonstebo, Jorn Henrik -- Murton, Julian -- Sher, Andrei -- Rasmussen, Morten -- Ronn, Regin -- Mourier, Tobias -- Cooper, Alan -- Austin, Jeremy -- Moller, Per -- Froese, Duane -- Zazula, Grant -- Pompanon, Francois -- Rioux, Delphine -- Niderkorn, Vincent -- Tikhonov, Alexei -- Savvinov, Grigoriy -- Roberts, Richard G -- MacPhee, Ross D E -- Gilbert, M Thomas P -- Kjaer, Kurt H -- Orlando, Ludovic -- Brochmann, Christian -- Taberlet, Pierre -- England -- Nature. 2014 Feb 6;506(7486):47-51. doi: 10.1038/nature12921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2]. ; 1] Department of Botany, Institute of Ecology and Earth Sciences, University of Tartu, 40 Lai Street, 51005 Tartu, Estonia [2]. ; 1] Laboratoire d'Ecologie Alpine (LECA) CNRS UMR 5553, University Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France [2]. ; 1] Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK [2]. ; 1] Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] Department of Integrative Biology, University of California Berkeley, 1005 Valley Life Sciences Building, Berkeley, 94720 California, USA [3]. ; 1] National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway [2] Department of Botany, Saint Petersburg State University, Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia [3]. ; 1] Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] Ancient DNA Laboratory, Veterinary and Life Sciences School, Murdoch University, 90 South Street, Perth, 6150 Western Australia, Australia [3]. ; Division of Biology, Kansas State University, Manhattan, 66506-4901 Kansas, USA. ; Laboratoire d'Ecologie Alpine (LECA) CNRS UMR 5553, University Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France. ; 1] National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway [2] Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, PO Box 1066, Blindern, NO-0318 Oslo, Norway (S.B.); Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, Research Unit Potsdam, Telegrafenberg A 43, 14473 Potsdam, Germany (L.S.E.); SpyGen, Savoie Technolac, 17 allee du lac Saint Andre, BP 274, 73375 Le Bourget-du-Lac Cedex, France (E.B.). ; Landscape Dynamics Unit, Swiss Federal Research Institute WSL, Zurcherstrasse 111, CH-8903 Birmensdorf, Switzerland. ; Institut des Sciences de l'Evolution de Montpellier, UMR 5554 Universite Montpellier 2, Bat.22, CC061, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France. ; University of Alaska Museum of the North, Fairbanks, 99775-6960 Alaska, USA. ; Department of Arctic and Marine Biology, UiT, The Arctic University of Norway, NO-9037 Tromso, Norway. ; Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK. ; Genoscope, Institut de Genomique du Commissariat a l'Energie Atomique (CEA), 91000 Evry, France. ; 1] Adam Mickiewicz University, Faculty of Physics, Umultowska 85, 61-614 Poznan, Poland [2] Poznan Radiocarbon Laboratory, Poznan Science and Technology Park, Rubiez 46, 61-612 Poznan, Poland. ; Tromso University Museum, NO-9037 Tromso, Norway. ; Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, P.O. Box 1066, Blindern, NO-0316 Oslo, Norway. ; National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway. ; Permafrost Laboratory, Department of Geography, University of Sussex, Brighton BN1 9QJ, UK. ; 1] Institute of Ecology and Evolution, Russian Academy of Sciences, 33 Leninsky Prospect, 119071 Moscow, Russia [2]. ; Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark. ; Department of Biology, Terrestrial Ecology, Universitetsparken 15, DK- 2100 Copenhagen O, Denmark. ; Australian Centre for Ancient DNA, School of Earth & Environmental Sciences, University of Adelaide, Adelaide, 5005 South Australia, Australia. ; Department of Geology/Quaternary Sciences, Lund University Solvegatan 12, SE-223 62 Lund, Sweden. ; Department of Earth and Atmospheric Sciences, University of Alberta, T6G 2E3 Edmonton, Alberta, Canada. ; Government of Yukon, Department of Tourism and Culture, Yukon Palaeontology Program, PO Box 2703 L2A, Y1A 2C6 Whitehorse, Yukon Territory, Canada. ; INRA, UMR1213 Herbivores, F-63122 Saint-Genes-Champanelle, France. ; Zoological Institute of Russian Academy of Sciences, Universitetskaya nab. 1, 199034 Saint-Petersburg, Russia. ; Institute of Applied Ecology of the North of North-Eastern Federal University, Belinskogo Street 58, 677000 Yakutsk, Republic of Sakha (Yakutia), Russia. ; Centre for Archaeological Science, School of Earth and Environmental Sciences, University of Wollongong, Wollongong, 2522 New South Wales, Australia. ; Division of Vertebrate Zoology/Mammalogy, American Museum of Natural History, New York, 10024 New York, USA. ; 1] National Centre for Biosystematics, Natural History Museum, University of Oslo, PO Box 1172, Blindern, NO-0318 Oslo, Norway [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arctic Regions ; *Biodiversity ; Bison/physiology ; Cold Climate ; *Diet ; Freezing ; *Herbivory ; High-Throughput Nucleotide Sequencing ; Horses/physiology ; Mammoths/physiology ; *Nematoda/classification/genetics/isolation & purification ; *Plants/classification/genetics ; Poaceae/genetics/growth & development ; Soil ; Time Factors ; Yukon Territory
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  • 106
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subramanian, Meera -- England -- Nature. 2014 May 29;509(7502):548-51. doi: 10.1038/509548a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870526" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollution, Indoor/*adverse effects/*prevention & control/statistics & ; numerical data ; Animals ; Atmosphere/chemistry ; *Biomass ; Cattle ; Cooking/economics/*instrumentation ; Developing Countries/statistics & numerical data ; Electricity ; Environmental Health/statistics & numerical data/trends ; Feces ; Female ; *Fires ; Global Health/*statistics & numerical data/trends ; Global Warming ; *Housing ; Humans ; India/epidemiology ; Meals ; Renewable Energy/economics ; Soot/adverse effects/analysis ; Wood
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  • 107
    Publication Date: 2014-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayden, Erika Check -- England -- Nature. 2014 May 8;509(7499):146. doi: 10.1038/509146a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805325" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Drug Industry/economics/organization & administration ; Humans ; Mice ; *Technology Transfer ; Translational Medical Research/economics/organization & administration ; Universities/*economics/*organization & administration
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  • 108
    Publication Date: 2014-01-07
    Description: Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 x 10(-13); odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 x 10(-4); OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ~50% frequency in Native American samples and ~10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127086/" 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/PMC4127086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉SIGMA Type 2 Diabetes Consortium -- Williams, Amy L -- Jacobs, Suzanne B R -- Moreno-Macias, Hortensia -- Huerta-Chagoya, Alicia -- Churchhouse, Claire -- Marquez-Luna, Carla -- Garcia-Ortiz, Humberto -- Gomez-Vazquez, Maria Jose -- Burtt, Noel P -- Aguilar-Salinas, Carlos A -- Gonzalez-Villalpando, Clicerio -- Florez, Jose C -- Orozco, Lorena -- Haiman, Christopher A -- Tusie-Luna, Teresa -- Altshuler, David -- F32 HG005944/HG/NHGRI NIH HHS/ -- P01 HL045522/HL/NHLBI NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 CA144034/CA/NCI NIH HHS/ -- R01 CA55069/CA/NCI NIH HHS/ -- R01 CA80205/CA/NCI NIH HHS/ -- R01 DK042273/DK/NIDDK NIH HHS/ -- R01 DK047482/DK/NIDDK NIH HHS/ -- R01 DK057295/DK/NIDDK NIH HHS/ -- R01 HG006399/HG/NHGRI NIH HHS/ -- R01DK053889/DK/NIDDK NIH HHS/ -- R01HL24799/HL/NHLBI NIH HHS/ -- R35 CA53890/CA/NCI NIH HHS/ -- U01DK085526/DK/NIDDK NIH HHS/ -- England -- Nature. 2014 Feb 6;506(7486):97-101. doi: 10.1038/nature12828. Epub 2013 Dec 25.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390345" target="_blank"〉PubMed〈/a〉
    Keywords: African Continental Ancestry Group/genetics ; Alleles ; Animals ; Asian Continental Ancestry Group/genetics ; Cohort Studies ; Diabetes Mellitus, Type 2/*genetics ; Endoplasmic Reticulum/genetics ; European Continental Ancestry Group/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Haplotypes/genetics ; HeLa Cells ; Humans ; Indians, North American/genetics ; Lipid Metabolism/genetics ; Liver/cytology/metabolism ; Male ; Mexico ; Monocarboxylic Acid Transporters/*genetics ; Neanderthals/genetics ; Polymorphism, Single Nucleotide/*genetics ; RNA, Messenger/genetics/metabolism ; Triglycerides/metabolism
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  • 109
    Publication Date: 2014-11-28
    Description: The immune system influences the fate of developing cancers by not only functioning as a tumour promoter that facilitates cellular transformation, promotes tumour growth and sculpts tumour cell immunogenicity, but also as an extrinsic tumour suppressor that either destroys developing tumours or restrains their expansion. Yet, clinically apparent cancers still arise in immunocompetent individuals in part as a consequence of cancer-induced immunosuppression. In many individuals, immunosuppression is mediated by cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), two immunomodulatory receptors expressed on T cells. Monoclonal-antibody-based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits-including durable responses--to patients with different malignancies. However, little is known about the identity of the tumour antigens that function as the targets of T cells activated by checkpoint blockade immunotherapy and whether these antigens can be used to generate vaccines that are highly tumour-specific. Here we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and we show that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Although mutant tumour-antigen-specific T cells are present in progressively growing tumours, they are reactivated following treatment with anti-PD-1 and/or anti-CTLA-4 and display some overlapping but mostly treatment-specific transcriptional profiles, rendering them capable of mediating tumour rejection. These results reveal that tumour-specific mutant antigens are not only important targets of checkpoint blockade therapy, but they can also be used to develop personalized cancer-specific vaccines and to probe the mechanistic underpinnings of different checkpoint blockade treatments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279952/" 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/PMC4279952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gubin, Matthew M -- Zhang, Xiuli -- Schuster, Heiko -- Caron, Etienne -- Ward, Jeffrey P -- Noguchi, Takuro -- Ivanova, Yulia -- Hundal, Jasreet -- Arthur, Cora D -- Krebber, Willem-Jan -- Mulder, Gwenn E -- Toebes, Mireille -- Vesely, Matthew D -- Lam, Samuel S K -- Korman, Alan J -- Allison, James P -- Freeman, Gordon J -- Sharpe, Arlene H -- Pearce, Erika L -- Schumacher, Ton N -- Aebersold, Ruedi -- Rammensee, Hans-Georg -- Melief, Cornelis J M -- Mardis, Elaine R -- Gillanders, William E -- Artyomov, Maxim N -- Schreiber, Robert D -- P01 AI054456/AI/NIAID NIH HHS/ -- P30 AR048335/AR/NIAMS NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P30 CA091842/CA/NCI NIH HHS/ -- P50 CA101942/CA/NCI NIH HHS/ -- R01 AI091965/AI/NIAID NIH HHS/ -- R01 CA043059/CA/NCI NIH HHS/ -- R01 CA190700/CA/NCI NIH HHS/ -- R37 CA043059/CA/NCI NIH HHS/ -- T32 CA009547/CA/NCI NIH HHS/ -- T32 CA00954729/CA/NCI NIH HHS/ -- U01 CA141541/CA/NCI NIH HHS/ -- England -- Nature. 2014 Nov 27;515(7528):577-81. doi: 10.1038/nature13988.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA. ; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA. ; Department of Immunology, Institute of Cell Biology, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Partner Site Tubingen, Auf der Morgenstelle 15, 72076 Tubingen, Germany. ; Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland. ; 1] Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA [2] Department of Medicine, Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA. ; The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; ISA Therapeutics B.V., 2333 CH Leiden, The Netherlands. ; Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. ; Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, USA. ; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland [2] Faculty of Science, University of Zurich, Zurich, 8093 Zurich, Switzerland. ; 1] ISA Therapeutics B.V., 2333 CH Leiden, The Netherlands [2] Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. ; 1] The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA [2] Department of Genetics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25428507" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/*therapeutic use ; Antigens, Neoplasm/*genetics/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/*therapeutic use ; Cell Cycle Checkpoints/*immunology ; Epitopes/genetics ; *Immunotherapy ; Male ; Mice ; Sarcoma/immunology/*therapy ; Vaccines, Synthetic/therapeutic use
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  • 110
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuhl, Inge -- Kukat, Christian -- Ruzzenente, Benedetta -- Milenkovic, Dusanka -- Mourier, Arnaud -- Miranda, Maria -- Koolmeister, Camilla -- Falkenberg, Maria -- Larsson, Nils-Goran -- England -- Nature. 2014 Oct 9;514(7521):E7-11. doi: 10.1038/nature13690.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany. ; Department of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden. ; 1] Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany [2] Department of Medical Biochemistry and Cell Biology, Goteborgs Universitet, 40530 Goteborg, Sweden. ; 1] Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany [2] Department of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297440" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/*enzymology ; DNA-Directed RNA Polymerases/*genetics/*metabolism ; Humans ; Mitochondria/*enzymology/*genetics ; RNA, Messenger/*biosynthesis ; *Transcription, Genetic
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  • 111
    Publication Date: 2014-07-18
    Description: Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far. Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5) marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated human or murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC-deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs in mice and p63alpha-positive LSCs in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246512/" 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/PMC4246512/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ksander, Bruce R -- Kolovou, Paraskevi E -- Wilson, Brian J -- Saab, Karim R -- Guo, Qin -- Ma, Jie -- McGuire, Sean P -- Gregory, Meredith S -- Vincent, William J B -- Perez, Victor L -- Cruz-Guilloty, Fernando -- Kao, Winston W Y -- Call, Mindy K -- Tucker, Budd A -- Zhan, Qian -- Murphy, George F -- Lathrop, Kira L -- Alt, Clemens -- Mortensen, Luke J -- Lin, Charles P -- Zieske, James D -- Frank, Markus H -- Frank, Natasha Y -- DP2 OD007483/OD/NIH HHS/ -- DP2OD007483/OD/NIH HHS/ -- EY08098/EY/NEI NIH HHS/ -- I01 BX000516/BX/BLRD VA/ -- I01 RX000989/RX/RRD VA/ -- K08 NS051349/NS/NINDS NIH HHS/ -- K08NS051349/NS/NINDS NIH HHS/ -- P30 EY014801/EY/NEI NIH HHS/ -- P30EY014801/EY/NEI NIH HHS/ -- P41EB015903/EB/NIBIB NIH HHS/ -- R01 CA113796/CA/NCI NIH HHS/ -- R01 CA138231/CA/NCI NIH HHS/ -- R01 CA158467/CA/NCI NIH HHS/ -- R01 EB017274/EB/NIBIB NIH HHS/ -- R01CA113796/CA/NCI NIH HHS/ -- R01CA138231/CA/NCI NIH HHS/ -- R01CA158467/CA/NCI NIH HHS/ -- R01EY018624/EY/NEI NIH HHS/ -- R01EY021768/EY/NEI NIH HHS/ -- U01HL100402/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 17;511(7509):353-7. doi: 10.1038/nature13426. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary and Harvard Medical School, Boston, Massachusetts 02114, USA [2]. ; 1] Transplant Research Program, Division of Nephrology, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Department of Medicine, VA Boston Healthcare System, Boston, Massachusetts 02130, USA. ; 1] Transplant Research Program, Division of Nephrology, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; 1] Department of Medicine, VA Boston Healthcare System, Boston, Massachusetts 02130, USA [2] Transplant Research Program, Division of Nephrology, Boston Children's Hospital, Boston, Massachusetts 02115, USA [3] Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Bascom Palmer Eye Institute and the Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. ; Department of Ophthalmology, University of Cincinnati Medical Center, Cincinnati, Ohio 45229, USA. ; Stephen A Wynn Institute for Vision Research, Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa 52242, USA. ; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Department of Ophthalmology, University of Pittsburgh School of Medicine & Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, Pennsylvania 15213, USA. ; Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] Transplant Research Program, Division of Nephrology, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02138, USA [4]. ; 1] Department of Medicine, VA Boston Healthcare System, Boston, Massachusetts 02130, USA [2] Transplant Research Program, Division of Nephrology, Boston Children's Hospital, Boston, Massachusetts 02115, USA [3] Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02138, USA [4] Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [5].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030174" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/deficiency/*metabolism ; Animals ; Apoptosis ; Biomarkers/metabolism ; Cell Differentiation ; Cell Proliferation ; Female ; Humans ; Limbus Corneae/*cytology/*physiology ; Male ; Mice ; Mice, Knockout ; Molecular Sequence Data ; P-Glycoprotein/deficiency/*metabolism ; *Regeneration ; Stem Cell Transplantation ; Stem Cells/cytology/*metabolism ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/metabolism ; *Wound Healing
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  • 112
    Publication Date: 2014-05-09
    Description: During immune responses, B lymphocytes clonally expand and undergo secondary diversification of their immunoglobulin genes in germinal centres (GCs). High-affinity B cells are expanded through iterative interzonal cycles of division and hypermutation in the GC dark zone followed by migration to the GC light zone, where they are selected on the basis of affinity to return to the dark zone. Here we combine a transgenic strategy to measure cell division and a photoactivatable fluorescent reporter to examine whether the extent of clonal expansion and hypermutation are regulated during interzonal GC cycles. We find that both cell division and hypermutation are directly proportional to the amount of antigen captured and presented by GC B cells to follicular helper T cells in the light zone. Our data explain how GC B cells with the highest affinity for antigen are selectively expanded and diversified.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271732/" 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/PMC4271732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gitlin, Alexander D -- Shulman, Ziv -- Nussenzweig, Michel C -- 1UM1 AI100663-01/AI/NIAID NIH HHS/ -- AI037526-19/AI/NIAID NIH HHS/ -- AI072529-06/AI/NIAID NIH HHS/ -- R01 AI037526/AI/NIAID NIH HHS/ -- R01 AI072529/AI/NIAID NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 29;509(7502):637-40. doi: 10.1038/nature13300. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA. ; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, 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/24805232" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Affinity/immunology ; Antigen Presentation/immunology ; Antigens/immunology ; B-Lymphocytes/*cytology/immunology/*metabolism ; Cell Movement ; Cell Proliferation ; *Clonal Selection, Antigen-Mediated/immunology ; Clone Cells/cytology/immunology/metabolism ; Genes, Reporter/genetics ; Germinal Center/*cytology/*immunology ; Male ; Mice ; S Phase ; Somatic Hypermutation, Immunoglobulin/*genetics ; T-Lymphocytes, Helper-Inducer/cytology/immunology ; Time Factors
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  • 113
    Publication Date: 2014-07-06
    Description: Tuberculosis remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent. Despite chemotherapy, the global tuberculosis epidemic has intensified because of HIV co-infection, the lack of an effective vaccine and the emergence of multi-drug-resistant bacteria. Alternative host-directed strategies could be exploited to improve treatment efficacy and outcome, contain drug-resistant strains and reduce disease severity and mortality. The innate inflammatory response elicited by Mycobacterium tuberculosis (Mtb) represents a logical host target. Here we demonstrate that interleukin-1 (IL-1) confers host resistance through the induction of eicosanoids that limit excessive type I interferon (IFN) production and foster bacterial containment. We further show that, in infected mice and patients, reduced IL-1 responses and/or excessive type I IFN induction are linked to an eicosanoid imbalance associated with disease exacerbation. Host-directed immunotherapy with clinically approved drugs that augment prostaglandin E2 levels in these settings prevented acute mortality of Mtb-infected mice. Thus, IL-1 and type I IFNs represent two major counter-regulatory classes of inflammatory cytokines that control the outcome of Mtb infection and are functionally linked via eicosanoids. Our findings establish proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network and represent feasible alternatives to conventional chemotherapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayer-Barber, Katrin D -- Andrade, Bruno B -- Oland, Sandra D -- Amaral, Eduardo P -- Barber, Daniel L -- Gonzales, Jacqueline -- Derrick, Steven C -- Shi, Ruiru -- Kumar, Nathella Pavan -- Wei, Wang -- Yuan, Xing -- Zhang, Guolong -- Cai, Ying -- Babu, Subash -- Catalfamo, Marta -- Salazar, Andres M -- Via, Laura E -- Barry, Clifton E 3rd -- Sher, Alan -- Intramural NIH HHS/ -- England -- Nature. 2014 Jul 3;511(7507):99-103. doi: 10.1038/nature13489. Epub 2014 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. ; 1] Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA [2] Department of Immunology, Biomedical Sciences Institutes, University of Sao Paulo, 05508-900 Sao Paulo, Brazil. ; T Lymphocyte Biology Unit, LPD, NIAID, NIH, Bethesda, Maryland 20892, USA. ; Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, Bethesda, Maryland 20892, USA. ; Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. ; Henan Chest Hospital, 450003 Zhengzhou, China. ; 1] NIH, International Center for Excellence in Research, 600 031 Chennai, India [2] National Institute for Research in Tuberculosis (NIRT), 600 031 Chennai, India. ; Sino-US International Research Center for Tuberculosis, and Henan Public Health Center, 450003 Zhengzhou, China. ; 1] NIH, International Center for Excellence in Research, 600 031 Chennai, India [2] Helminth Immunology Section, LPD, NIAID, NIH, Bethesda, Maryland 20892, USA. ; Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland 20892, USA. ; Oncovir Inc., Washington, Washington DC 20008, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24990750" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dinoprostone/antagonists & inhibitors/biosynthesis/metabolism ; Disease Models, Animal ; Female ; Humans ; Immunity, Innate/immunology ; *Immunotherapy ; Interferon Type I/antagonists & inhibitors/biosynthesis/*immunology ; Interleukin-1/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/*immunology ; Tuberculosis, Pulmonary/*immunology/microbiology/*therapy
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  • 114
    Publication Date: 2014-07-11
    Description: N-methyl-d-aspartate (NMDA) receptors are Hebbian-like coincidence detectors, requiring binding of glycine and glutamate in combination with the relief of voltage-dependent magnesium block to open an ion conductive pore across the membrane bilayer. Despite the importance of the NMDA receptor in the development and function of the brain, a molecular structure of an intact receptor has remained elusive. Here we present X-ray crystal structures of the Xenopus laevis GluN1-GluN2B NMDA receptor with the allosteric inhibitor, Ro25-6981, partial agonists and the ion channel blocker, MK-801. Receptor subunits are arranged in a 1-2-1-2 fashion, demonstrating extensive interactions between the amino-terminal and ligand-binding domains. The transmembrane domains harbour a closed-blocked ion channel, a pyramidal central vestibule lined by residues implicated in binding ion channel blockers and magnesium, and a approximately twofold symmetric arrangement of ion channel pore loops. These structures provide new insights into the architecture, allosteric coupling and ion channel function of NMDA receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263351/" 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/PMC4263351/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Chia-Hsueh -- Lu, Wei -- Michel, Jennifer Carlisle -- Goehring, April -- Du, Juan -- Song, Xianqiang -- Gouaux, Eric -- R37 NS038631/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 10;511(7508):191-7. doi: 10.1038/nature13548. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2]. ; 1] Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2] Howard Hughes Medical Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. ; Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dizocilpine Maleate/chemistry ; Ion Channels/chemistry ; Ligands ; *Models, Molecular ; Phenols ; Piperidines/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Receptors, N-Methyl-D-Aspartate/*chemistry ; Xenopus laevis/*physiology
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  • 115
    Publication Date: 2014-04-30
    Description: Replication fork stalling can promote genomic instability, predisposing to cancer and other diseases. Stalled replication forks may be processed by sister chromatid recombination (SCR), generating error-free or error-prone homologous recombination (HR) outcomes. In mammalian cells, a long-standing hypothesis proposes that the major hereditary breast/ovarian cancer predisposition gene products, BRCA1 and BRCA2, control HR/SCR at stalled replication forks. Although BRCA1 and BRCA2 affect replication fork processing, direct evidence that BRCA gene products regulate homologous recombination at stalled chromosomal replication forks is lacking, due to a dearth of tools for studying this process. Here we report that the Escherichia coli Tus/Ter complex can be engineered to induce site-specific replication fork stalling and chromosomal HR/SCR in mouse cells. Tus/Ter-induced homologous recombination entails processing of bidirectionally arrested forks. We find that the Brca1 carboxy (C)-terminal tandem BRCT repeat and regions of Brca1 encoded by exon 11-two Brca1 elements implicated in tumour suppression-control Tus/Ter-induced homologous recombination. Inactivation of either Brca1 or Brca2 increases the absolute frequency of 'long-tract' gene conversions at Tus/Ter-stalled forks, an outcome not observed in response to a site-specific endonuclease-mediated chromosomal double-strand break. Therefore, homologous recombination at stalled forks is regulated differently from homologous recombination at double-strand breaks arising independently of a replication fork. We propose that aberrant long-tract homologous recombination at stalled replication forks contributes to genomic instability and breast/ovarian cancer predisposition in BRCA mutant cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118467/" 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/PMC4118467/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willis, Nicholas A -- Chandramouly, Gurushankar -- Huang, Bin -- Kwok, Amy -- Follonier, Cindy -- Deng, Chuxia -- Scully, Ralph -- 5T32CA081156/CA/NCI NIH HHS/ -- R01 CA095175/CA/NCI NIH HHS/ -- R01 GM026938/GM/NIGMS NIH HHS/ -- R01 GM043265/GM/NIGMS NIH HHS/ -- R01 GM073894/GM/NIGMS NIH HHS/ -- R01CA095175/CA/NCI NIH HHS/ -- R01GM073894/GM/NIGMS NIH HHS/ -- R21 CA144017/CA/NCI NIH HHS/ -- R21CA144017/CA/NCI NIH HHS/ -- R37 GM026938/GM/NIGMS NIH HHS/ -- R37GM26938/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 26;510(7506):556-9. doi: 10.1038/nature13295. Epub 2014 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. ; 1] Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA [2] Temple University, 1801 North Broad Street, Philadelphia, Pennsylvania 19122, USA (G.C.); Brandeis University, 415 South Street, Waltham, Massachusetts 02453, USA (B.H.); University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA (A.K.). ; Princeton University, 101 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA. ; NIDDK, National Institutes of Health, Building 10, Room 9N105, 10 Center Drive, Bethesda, Maryland 20814, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24776801" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; BRCA1 Protein/chemistry/genetics/*metabolism ; BRCA2 Protein/genetics/metabolism ; DNA Breaks, Double-Stranded ; *DNA Replication ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics/*metabolism ; Exons/genetics ; Gene Conversion/genetics ; Genomic Instability/genetics ; Hereditary Breast and Ovarian Cancer Syndrome/genetics ; *Homologous Recombination ; Mice
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  • 116
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-03-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Feb 27;506(7489):407.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24579097" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Welfare/ethics/*standards ; Animals ; Animals, Laboratory/*physiology/*psychology ; *Emotions ; Euthanasia, Animal/*ethics/methods ; Mice ; Zebrafish/embryology/genetics/*physiology
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  • 117
    Publication Date: 2014-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Dec 18;516(7531):297. doi: 10.1038/516297a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519109" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/*classification/genetics ; Genome/genetics ; International Cooperation ; *Phylogeny
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  • 118
    Publication Date: 2014-02-14
    Description: Extant vertebrates form two clades, the jawless Cyclostomata (lampreys and hagfishes) and the jawed Gnathostomata (all other vertebrates), with contrasting facial architectures. These arise during development from just a few key differences in the growth patterns of the cranial primordia: notably, the nasal sacs and hypophysis originate from a single placode in cyclostomes but from separate placodes in gnathostomes, and infraoptic ectomesenchyme migrates forward either side of the single placode in cyclostomes but between the placodes in gnathostomes. Fossil stem gnathostomes preserve cranial anatomies rich in landmarks that provide proxies for developmental processes and allow the transition from jawless to jawed vertebrates to be broken down into evolutionary steps. Here we use propagation phase contrast synchrotron microtomography to image the cranial anatomy of the primitive placoderm (jawed stem gnathostome) Romundina, and show that it combines jawed vertebrate architecture with cranial and cerebral proportions resembling those of cyclostomes and the galeaspid (jawless stem gnathostome) Shuyu. This combination seems to be primitive for jawed vertebrates, and suggests a decoupling between ectomesenchymal growth trajectory, ectomesenchymal proliferation, and cerebral shape change during the origin of gnathostomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dupret, Vincent -- Sanchez, Sophie -- Goujet, Daniel -- Tafforeau, Paul -- Ahlberg, Per E -- England -- Nature. 2014 Mar 27;507(7493):500-3. doi: 10.1038/nature12980. Epub 2014 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Uppsala University, Department of Organismal Biology, Subdepartment of Evolution and Development, Norbyvagen 18A, SE-752 36, Uppsala, Sweden. ; 1] Uppsala University, Department of Organismal Biology, Subdepartment of Evolution and Development, Norbyvagen 18A, SE-752 36, Uppsala, Sweden [2] European Synchrotron Radiation Facility, 6 rue Jules Horowitz, 38043 Grenoble Cedex, France. ; Museum national d'Histoire naturelle, UMR 7207 CR2P CNRS/MNHN/UPMC, 8 rue Buffon, CP 38,75231 Paris Cedex 05, France. ; European Synchrotron Radiation Facility, 6 rue Jules Horowitz, 38043 Grenoble Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522530" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Brain/anatomy & histology ; Face/anatomy & histology ; Fishes/*anatomy & histology/classification ; *Fossils ; *Jaw/anatomy & histology ; Lampreys/anatomy & histology ; Neural Crest/anatomy & histology ; Phylogeny
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  • 119
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willyard, Cassandra -- England -- Nature. 2014 Nov 27;515(7528):S168-9. doi: 10.1038/515S168a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25427209" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Clinical Trials as Topic ; Drug Discovery/*trends ; Fibrin/genetics ; Gene Expression Regulation/drug effects ; Hemophilia A/*therapy ; Humans ; RNA Interference ; Recombinant Proteins/therapeutic use ; Thrombophilia/genetics ; *Thrombosis
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  • 120
    Publication Date: 2014-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pope, Benjamin D -- Gilbert, David M -- F31 CA165863/CA/NCI NIH HHS/ -- R01 GM083337/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Apr 17;508(7496):323-4. doi: 10.1038/508323a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Science, Florida State University, Tallahassee, Florida 32306, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740061" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Down Syndrome/*genetics ; Female ; Gene Expression Regulation/*genetics ; Genome/*genetics ; Humans ; Male ; Transcriptome/*genetics
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  • 121
    Publication Date: 2014-05-09
    Description: How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074887/" 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/PMC4074887/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jinseop S -- Greene, Matthew J -- Zlateski, Aleksandar -- Lee, Kisuk -- Richardson, Mark -- Turaga, Srinivas C -- Purcaro, Michael -- Balkam, Matthew -- Robinson, Amy -- Behabadi, Bardia F -- Campos, Michael -- Denk, Winfried -- Seung, H Sebastian -- EyeWirers -- R01 NS076467/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 15;509(7500):331-6. doi: 10.1038/nature13240. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2]. ; Electrical Engineering and Computer Science Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] 601 N 42nd Street, Seattle, Washington 98103, USA (M.R.); Princeton Neuroscience Institute and Computer Science Deptartment, Princeton, New Jersey 08544, USA (H.S.S.); Gatsby Computational Neuroscience Unit, London WC1N 3AR, UK (S.C.T.). ; Qualcomm Research, 5775 Morehouse Drive, San Diego, California 92121, USA. ; Max-Planck Institute for Medical Research, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805243" target="_blank"〉PubMed〈/a〉
    Keywords: Amacrine Cells/cytology/physiology/ultrastructure ; Animals ; Artificial Intelligence ; *Brain Mapping ; Crowdsourcing ; Dendrites/metabolism ; Mice ; *Models, Neurological ; Motion ; Neural Pathways/*physiology ; Presynaptic Terminals/metabolism ; Retina/*cytology/*physiology ; Retinal Bipolar Cells/cytology/physiology/ultrastructure ; *Spatio-Temporal Analysis
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  • 122
    Publication Date: 2014-05-23
    Description: Deregulation of lysine methylation signalling has emerged as a common aetiological factor in cancer pathogenesis, with inhibitors of several histone lysine methyltransferases (KMTs) being developed as chemotherapeutics. The largely cytoplasmic KMT SMYD3 (SET and MYND domain containing protein 3) is overexpressed in numerous human tumours. However, the molecular mechanism by which SMYD3 regulates cancer pathways and its relationship to tumorigenesis in vivo are largely unknown. Here we show that methylation of MAP3K2 by SMYD3 increases MAP kinase signalling and promotes the formation of Ras-driven carcinomas. Using mouse models for pancreatic ductal adenocarcinoma and lung adenocarcinoma, we found that abrogating SMYD3 catalytic activity inhibits tumour development in response to oncogenic Ras. We used protein array technology to identify the MAP3K2 kinase as a target of SMYD3. In cancer cell lines, SMYD3-mediated methylation of MAP3K2 at lysine 260 potentiates activation of the Ras/Raf/MEK/ERK signalling module and SMYD3 depletion synergizes with a MEK inhibitor to block Ras-driven tumorigenesis. Finally, the PP2A phosphatase complex, a key negative regulator of the MAP kinase pathway, binds to MAP3K2 and this interaction is blocked by methylation. Together, our results elucidate a new role for lysine methylation in integrating cytoplasmic kinase-signalling cascades and establish a pivotal role for SMYD3 in the regulation of oncogenic Ras signalling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122675/" 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/PMC4122675/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mazur, Pawel K -- Reynoird, Nicolas -- Khatri, Purvesh -- Jansen, Pascal W T C -- Wilkinson, Alex W -- Liu, Shichong -- Barbash, Olena -- Van Aller, Glenn S -- Huddleston, Michael -- Dhanak, Dashyant -- Tummino, Peter J -- Kruger, Ryan G -- Garcia, Benjamin A -- Butte, Atul J -- Vermeulen, Michiel -- Sage, Julien -- Gozani, Or -- DP2 OD007447/OD/NIH HHS/ -- R01 CA172560/CA/NCI NIH HHS/ -- T32 GM007276/GM/NIGMS NIH HHS/ -- U19 AI109662/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Jun 12;510(7504):283-7. doi: 10.1038/nature13320. Epub 2014 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Pediatrics, Stanford University School of Medicine, California 94305, USA [2] Department of Genetics, Stanford University School of Medicine, California 94305, USA [3]. ; 1] Department of Biology, Stanford University, California 94305, USA [2]. ; Institute for Immunity, Transplantation and Infection, and Department of Medicine, Stanford University School of Medicine, California 94305, USA. ; Department of Molecular Cancer Research and Department of Medical Oncology, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands. ; Department of Biology, Stanford University, California 94305, USA. ; Epigenetics Program and Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Cancer Epigenetics DPU, Oncology R&D, GlaxoSmithKline, Collegeville, Pennsylvania 19426 USA. ; 1] Cancer Epigenetics DPU, Oncology R&D, GlaxoSmithKline, Collegeville, Pennsylvania 19426 USA [2] Janssen Research and Development, 1400 McKean Road, Spring House, Pennsylvania 19477, USA (D.D.); Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, 6525GA Nijmegen, The Netherlands (M.V.). ; 1] Department of Pediatrics, Stanford University School of Medicine, California 94305, USA [2] Department of Genetics, Stanford University School of Medicine, California 94305, USA. ; 1] Department of Molecular Cancer Research and Department of Medical Oncology, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands [2] Janssen Research and Development, 1400 McKean Road, Spring House, Pennsylvania 19477, USA (D.D.); Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, 6525GA Nijmegen, The Netherlands (M.V.).〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24847881" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/enzymology/genetics/metabolism/pathology ; Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/*metabolism/pathology ; Disease Models, Animal ; Histone-Lysine N-Methyltransferase/*metabolism ; Humans ; Lung Neoplasms/enzymology/genetics/metabolism/pathology ; Lysine/*metabolism ; MAP Kinase Kinase Kinase 2/chemistry/*metabolism ; MAP Kinase Kinase Kinases/chemistry/*metabolism ; Methylation ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Oncogene Protein p21(ras)/genetics/*metabolism ; Pancreatic Neoplasms/enzymology/genetics/metabolism/pathology ; Protein Phosphatase 2/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins A-raf/metabolism ; Signal Transduction
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  • 123
    Publication Date: 2014-09-19
    Description: Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suez, Jotham -- Korem, Tal -- Zeevi, David -- Zilberman-Schapira, Gili -- Thaiss, Christoph A -- Maza, Ori -- Israeli, David -- Zmora, Niv -- Gilad, Shlomit -- Weinberger, Adina -- Kuperman, Yael -- Harmelin, Alon -- Kolodkin-Gal, Ilana -- Shapiro, Hagit -- Halpern, Zamir -- Segal, Eran -- Elinav, Eran -- England -- Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. ; 1] Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel [2]. ; 1] Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel [2]. ; Day Care Unit and the Laboratory of Imaging and Brain Stimulation, Kfar Shaul hospital, Jerusalem Center for Mental Health, Jerusalem 91060, Israel. ; 1] Internal Medicine Department, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel [2] Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel [3] Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel. ; The Nancy and Stephen Grand Israel National Center for Personalized Medicine (INCPM), Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; 1] Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel [2] Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25231862" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Aspartame/adverse effects ; Body Weight/drug effects ; Diet, High-Fat ; Dietary Fats/pharmacology ; Feces/microbiology ; Female ; Gastrointestinal Tract/*drug effects/*microbiology ; Germ-Free Life ; Glucose/metabolism ; Glucose Intolerance/*chemically induced/metabolism/*microbiology ; Humans ; Male ; Metabolic Syndrome X/chemically induced/metabolism/microbiology ; Mice ; Mice, Inbred C57BL ; Microbiota/*drug effects ; Saccharin/administration & dosage/adverse effects ; Sucrose/adverse effects/analogs & derivatives ; Sweetening Agents/*adverse effects ; Waist-Hip Ratio
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  • 124
    Publication Date: 2014-04-18
    Description: Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1(+) (but not Esr1(-)) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1(+) neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1(+) neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098836/" 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/PMC4098836/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Hyosang -- Kim, Dong-Wook -- Remedios, Ryan -- Anthony, Todd E -- Chang, Angela -- Madisen, Linda -- Zeng, Hongkui -- Anderson, David J -- 1F32HD055198-01/HD/NICHD NIH HHS/ -- 1K99NS074077/NS/NINDS NIH HHS/ -- R01 MH085082/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 29;509(7502):627-32. doi: 10.1038/nature13169. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Biology and Biological Engineering 156-29, California Institute of Technology, Pasadena, California 91125, USA [2] Howard Hughes Medical Institute, Pasadena, California 91125, USA. ; Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA. ; Division of Biology and Biological Engineering 156-29, California Institute of Technology, Pasadena, California 91125, USA. ; Allen Institute for Brain Science, Seattle, Washington 98103, USA. ; 1] Division of Biology and Biological Engineering 156-29, California Institute of Technology, Pasadena, California 91125, USA [2] Howard Hughes Medical Institute, Pasadena, California 91125, USA [3] Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739975" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression/*physiology ; Animals ; Estrogen Receptor alpha/*metabolism ; Female ; Integrases/genetics/metabolism ; Male ; Mice ; Neurons/*metabolism ; Optogenetics ; Sexual Behavior, Animal/*physiology ; Ventromedial Hypothalamic Nucleus/*cytology/*physiology
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  • 125
    Publication Date: 2014-04-04
    Description: The formation of precise connections between retina and lateral geniculate nucleus (LGN) involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the major histocompatibility complex (MHC) class I molecule H2-D(b) is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-K(b) and H2-D(b) (K(b)D(b)(-/-)), despite intact retinal activity and basal synaptic transmission, the developmentally regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-D(b) in K(b)D(b)(-/-) mice rescues both synapse elimination and eye-specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, long-term potentiation (LTP) is intact but long-term depression (LTD) is impaired in K(b)D(b)(-/-) mice. This change is due to an increase in Ca(2+)-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-D(b) to K(b)D(b)(-/-) neurons renders AMPA receptors Ca(2+) impermeable and rescues LTD. These observations reveal an MHC-class-I-mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-D(b) in functional and structural synapse pruning in CNS neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016165/" 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/PMC4016165/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Hanmi -- Brott, Barbara K -- Kirkby, Lowry A -- Adelson, Jaimie D -- Cheng, Sarah -- Feller, Marla B -- Datwani, Akash -- Shatz, Carla J -- EY02858/EY/NEI NIH HHS/ -- R01 EY002858/EY/NEI NIH HHS/ -- R01 EY013528/EY/NEI NIH HHS/ -- R01 EY13528/EY/NEI NIH HHS/ -- R01 MH071666/MH/NIMH NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- England -- Nature. 2014 May 8;509(7499):195-200. doi: 10.1038/nature13154. Epub 2014 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biology and Neurobiology and Bio-X, James H. Clark Center, 318 Campus Drive, Stanford, California 94305, USA. ; Department of Molecular and Cell Biology & Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA. ; 1] Departments of Biology and Neurobiology and Bio-X, James H. Clark Center, 318 Campus Drive, Stanford, California 94305, USA [2] Sage Bionetworks, 1100 Fairview Avenue N., Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695230" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Geniculate Bodies/*cytology/*physiology ; H-2 Antigens/genetics/immunology/metabolism ; Histocompatibility Antigen H-2D/genetics/immunology/*metabolism ; Long-Term Potentiation/physiology ; Long-Term Synaptic Depression ; Mice ; *Neural Pathways ; Receptors, N-Methyl-D-Aspartate/metabolism ; Retina/*cytology/*physiology ; Retinal Ganglion Cells/cytology/physiology ; Synapses/*metabolism ; Synaptic Transmission
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  • 126
    Publication Date: 2014-09-19
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449731/" 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/PMC4449731/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feehley, Taylor -- Nagler, Cathryn R -- R01 AI106302/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Oct 9;514(7521):176-7. doi: 10.1038/nature13752. Epub 2014 Sep 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25231865" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Gastrointestinal Tract/*drug effects/*microbiology ; Glucose Intolerance/*chemically induced/*microbiology ; Humans ; Male ; Microbiota/*drug effects ; Sweetening Agents/*adverse effects
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  • 127
    Publication Date: 2014-03-05
    Description: Epithelial folding mediated by apical constriction converts flat epithelial sheets into multilayered, complex tissue structures and is used throughout development in most animals. Little is known, however, about how forces produced near the apical surface of the tissue are transmitted within individual cells to generate the global changes in cell shape that characterize tissue deformation. Here we apply particle tracking velocimetry in gastrulating Drosophila embryos to measure the movement of cytoplasm and plasma membrane during ventral furrow formation. We find that cytoplasmic redistribution during the lengthening phase of ventral furrow formation can be precisely described by viscous flows that quantitatively match the predictions of hydrodynamics. Cell membranes move with the ambient cytoplasm, with little resistance to, or driving force on, the flow. Strikingly, apical constriction produces similar flow patterns in mutant embryos that fail to form cells before gastrulation ('acellular' embryos), such that the global redistribution of cytoplasm mirrors the summed redistribution occurring in individual cells of wild-type embryos. Our results indicate that during the lengthening phase of ventral furrow formation, hydrodynamic behaviour of the cytoplasm provides the predominant mechanism transmitting apically generated forces deep into the tissue and that cell individualization is dispensable.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111109/" 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/PMC4111109/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Bing -- Doubrovinski, Konstantin -- Polyakov, Oleg -- Wieschaus, Eric -- 5R37HD15587/HD/NICHD NIH HHS/ -- P50 GM 071508/GM/NIGMS NIH HHS/ -- R01 HD015587/HD/NICHD NIH HHS/ -- R37 HD015587/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 17;508(7496):392-6. doi: 10.1038/nature13070. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2]. ; Department of Physics, Princeton University, Princeton, New Jersey 08544, USA. ; 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Howard Hughes Medical Institute, Princeton University, Princeton, New Jersey 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590071" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/metabolism ; *Cell Polarity ; *Cell Shape ; Cytoplasm/metabolism ; Drosophila melanogaster/*cytology/*embryology ; Female ; Gastrulation ; Hydrodynamics ; Male ; Mesoderm/cytology/metabolism ; *Morphogenesis ; Movement
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  • 128
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glausiusz, Josie -- England -- Nature. 2014 Apr 17;508(7496):306-8. doi: 10.1038/508306a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzhydryl Compounds/adverse effects/analysis/*supply & distribution/*toxicity ; Environmental Exposure/*analysis ; Estrogens, Non-Steroidal/adverse effects/analysis/supply & distribution/toxicity ; Humans ; Phenols/adverse effects/analysis/*supply & distribution/*toxicity ; Plastics/chemistry/*supply & distribution/*toxicity ; Polycarboxylate Cement/chemistry ; Sulfones/adverse effects/analysis/supply & distribution/toxicity
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  • 129
    Publication Date: 2014-08-15
    Description: The connection between an altered gut microbiota and metabolic disorders such as obesity, diabetes, and cardiovascular disease is well established. Defects in preserving the integrity of the mucosal barriers can result in systemic endotoxaemia that contributes to chronic low-grade inflammation, which further promotes the development of metabolic syndrome. Interleukin (IL)-22 exerts essential roles in eliciting antimicrobial immunity and maintaining mucosal barrier integrity within the intestine. Here we investigate the connection between IL-22 and metabolic disorders. We find that the induction of IL-22 from innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various immune challenges, especially in the colon during infection with Citrobacter rodentium. While innate lymphoid cell populations are largely intact in obese mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised during the infection. Consequently, these mice are susceptible to C. rodentium infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal host defence. Importantly, we further unveil unexpected functions of IL-22 in regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat diet are prone to developing metabolic disorders. Strikingly, administration of exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and mice fed with high-fat diet reverses many of the metabolic symptoms, including hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as it improves insulin sensitivity, preserves gut mucosal barrier and endocrine functions, decreases endotoxaemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. In summary, we identify the IL-22 pathway as a novel target for therapeutic intervention in metabolic diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiaoting -- Ota, Naruhisa -- Manzanillo, Paolo -- Kates, Lance -- Zavala-Solorio, Jose -- Eidenschenk, Celine -- Zhang, Juan -- Lesch, Justin -- Lee, Wyne P -- Ross, Jed -- Diehl, Lauri -- van Bruggen, Nicholas -- Kolumam, Ganesh -- Ouyang, Wenjun -- England -- Nature. 2014 Oct 9;514(7521):237-41. doi: 10.1038/nature13564. Epub 2014 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Immunology, Genentech, South San Francisco, California 94080, USA [2]. ; Department of Immunology, Genentech, South San Francisco, California 94080, USA. ; Department of Biomedical Imaging, Genentech, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech, South San Francisco, California 94080, USA. ; 1] Department of Biomedical Imaging, Genentech, South San Francisco, California 94080, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119041" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue, White/drug effects/metabolism ; Animals ; CD4-Positive T-Lymphocytes/immunology/secretion ; Chronic Disease ; Citrobacter rodentium/drug effects/immunology/physiology ; Colon/drug effects/immunology/microbiology ; Diabetes Mellitus/*immunology/*metabolism/pathology ; Diet, High-Fat ; Female ; Hyperglycemia/diet therapy/drug therapy/metabolism ; *Immunity, Mucosal/drug effects ; Inflammation/drug therapy/metabolism/pathology ; Insulin/metabolism ; Insulin Resistance ; Interleukin-23/immunology/metabolism/pharmacology ; Interleukins/*immunology/*metabolism/pharmacology/therapeutic use ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Male ; Metabolic Diseases/diet therapy/drug therapy/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/metabolism ; Receptors, Interleukin/deficiency/metabolism ; Receptors, Leptin/deficiency/metabolism
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  • 130
    Publication Date: 2014-12-05
    Description: The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380172/" 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/PMC4380172/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ranade, Sanjeev S -- Woo, Seung-Hyun -- Dubin, Adrienne E -- Moshourab, Rabih A -- Wetzel, Christiane -- Petrus, Matt -- Mathur, Jayanti -- Begay, Valerie -- Coste, Bertrand -- Mainquist, James -- Wilson, A J -- Francisco, Allain G -- Reddy, Kritika -- Qiu, Zhaozhu -- Wood, John N -- Lewin, Gary R -- Patapoutian, Ardem -- 101054/Wellcome Trust/United Kingdom -- R01 DE022358/DE/NIDCR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 4;516(7529):121-5. doi: 10.1038/nature13980.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] Department of Neuroscience, Max-Delbruck Center for Molecular Medicine, Robert-Rossle Strasse 10, D-13092 Berlin, Germany [2] Klinik fur Anasthesiologie mit Schwerpunkt Operative Intensivmedizin, Campus Charite Mitte and Virchow-Klinikum Charite, Universitatsmedizin Berlin, Augustburgerplatz 1, 13353 Berlin, Germany. ; Department of Neuroscience, Max-Delbruck Center for Molecular Medicine, Robert-Rossle Strasse 10, D-13092 Berlin, Germany. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; 1] Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA [2] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25471886" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ion Channels/genetics/*metabolism ; Mechanoreceptors/metabolism ; Mechanotransduction, Cellular/genetics/*physiology ; Merkel Cells/physiology ; Mice ; Mice, Knockout ; Sensory Receptor Cells/physiology ; Skin/*innervation ; Touch/genetics/*physiology
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  • 131
    Publication Date: 2014-09-12
    Description: To prime reverse transcription, retroviruses require annealing of a transfer RNA molecule to the U5 primer binding site (U5-PBS) region of the viral genome. The residues essential for primer annealing are initially locked in intramolecular interactions; hence, annealing requires the chaperone activity of the retroviral nucleocapsid (NC) protein to facilitate structural rearrangements. Here we show that, unlike classical chaperones, the Moloney murine leukaemia virus NC uses a unique mechanism for remodelling: it specifically targets multiple structured regions in both the U5-PBS and tRNA(Pro) primer that otherwise sequester residues necessary for annealing. This high-specificity and high-affinity binding by NC consequently liberates these sequestered residues--which are exactly complementary--for intermolecular interactions. Furthermore, NC utilizes a step-wise, entropy-driven mechanism to trigger both residue-specific destabilization and residue-specific release. Our structures of NC bound to U5-PBS and tRNA(Pro) reveal the structure-based mechanism for retroviral primer annealing and provide insights as to how ATP-independent chaperones can target specific RNAs amidst the cellular milieu of non-target RNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Sarah B -- Yildiz, F Zehra -- Lo, Jennifer A -- Wang, Bo -- D'Souza, Victoria M -- England -- Nature. 2014 Nov 27;515(7528):591-5. doi: 10.1038/nature13709. Epub 2014 Sep 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Biology, Georgetown University, Washington DC 20057, USA. [3]. ; 1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2]. ; Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209668" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Genome, Viral/genetics ; Humans ; *Models, Molecular ; *Moloney murine leukemia virus/chemistry/genetics ; Nuclear Magnetic Resonance, Biomolecular ; *Nucleocapsid Proteins/chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary ; *RNA, Transfer/chemistry/metabolism ; RNA, Viral/*chemistry/*metabolism ; Reverse Transcription/genetics/*physiology
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  • 132
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Feb 13;506(7487):132.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24527498" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Endangered Species/*statistics & numerical data ; Female ; *Islands ; Male ; Wolves/*physiology
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  • 133
    Publication Date: 2014-08-19
    Description: The Palaeozoic form-taxon Lobopodia encompasses a diverse range of soft-bodied 'legged worms' known from exceptional fossil deposits. Although lobopodians occupy a deep phylogenetic position within Panarthropoda, a shortage of derived characters obscures their evolutionary relationships with extant phyla (Onychophora, Tardigrada and Euarthropoda). Here we describe a complex feature in the terminal claws of the mid-Cambrian lobopodian Hallucigenia sparsa--their construction from a stack of constituent elements--and demonstrate that equivalent elements make up the jaws and claws of extant Onychophora. A cladistic analysis, informed by developmental data on panarthropod head segmentation, indicates that the stacked sclerite components in these two taxa are homologous-resolving hallucigeniid lobopodians as stem-group onychophorans. The results indicate a sister-group relationship between Tardigrada and Euarthropoda, adding palaeontological support to the neurological and musculoskeletal evidence uniting these disparate clades. These findings elucidate the evolutionary transformations that gave rise to the panarthropod phyla, and expound the lobopodian-like morphology of the ancestral panarthropod.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Martin R -- Ortega-Hernandez, Javier -- England -- Nature. 2014 Oct 16;514(7522):363-6. doi: 10.1038/nature13576. Epub 2014 Aug 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth Sciences, Downing Site, University of Cambridge, Cambridge CB2 3EQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25132546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthropods/*anatomy & histology/*classification ; *Fossils ; Hoof and Claw/*anatomy & histology ; *Phylogeny
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  • 134
    Publication Date: 2014-08-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kundu, Parag -- Pettersson, Sven -- England -- Nature. 2014 Aug 28;512(7515):377-8. doi: 10.1038/nature13741. Epub 2014 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lee Kong Chian School of Medicine and the Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551. ; 1] Lee Kong Chian School of Medicine and the Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551. [2] National Cancer Center, Singapore General Hospital, Singapore and in the Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119031" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Humans ; Mycobacterium tuberculosis/*immunology ; Pigments, Biological/*metabolism ; Pseudomonas aeruginosa/*immunology ; Receptors, Aryl Hydrocarbon/*metabolism ; Receptors, Pattern Recognition/*metabolism
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  • 135
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eberl, Gerard -- England -- Nature. 2014 Apr 3;508(7494):47-8. doi: 10.1038/nature13216. Epub 2014 Mar 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphoid Tissue Development Unit, Institut Pasteur, 75724 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670655" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Fetus/*immunology ; Immunity, Innate/*immunology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology ; Tretinoin/*immunology/*pharmacology
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  • 136
    Publication Date: 2014-08-01
    Description: In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell-type-specific regulation directed by DNA binding factors. This comparatively static landscape is in marked contrast with the events of fertilization, during which the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, although methylation remains detectable at several notable features. These dynamics have been extensively characterized in the mouse, with only limited observations available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of residual maintenance are primarily restricted to gene bodies. Although most features share similar dynamics to those in mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island promoters that extend beyond known imprint control regions. Retrotransposon regulation is also highly diverse, and transitions from maternally to embryonically expressed elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178976/" 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/PMC4178976/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Zachary D -- Chan, Michelle M -- Humm, Kathryn C -- Karnik, Rahul -- Mekhoubad, Shila -- Regev, Aviv -- Eggan, Kevin -- Meissner, Alexander -- 1P50HG006193-01/HG/NHGRI NIH HHS/ -- 5DP1OD003958/OD/NIH HHS/ -- P01 GM099117/GM/NIGMS NIH HHS/ -- P01GM099117/GM/NIGMS NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- U01 ES017155/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 31;511(7511):611-5. doi: 10.1038/nature13581. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5]. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3]. ; 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Division of Reproductive Endocrinology &Infertility, Department of Obstetrics &Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA [3] Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02215, USA [4] Boston IVF, Waltham, Massachusetts 02451, USA [5] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [6]. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079558" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*metabolism ; Cell Line ; CpG Islands/physiology ; DNA/metabolism ; *DNA Methylation ; Embryonic Stem Cells ; Female ; Gene Expression Regulation, Developmental ; Humans ; Male ; Mice ; Mice, Inbred C57BL
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  • 137
    Publication Date: 2014-01-31
    Description: Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such 'talented' producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus 'Entotheonella' with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. 'Entotheonella' spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum 'Tectomicrobia'. The pronounced bioactivities and chemical uniqueness of 'Entotheonella' compounds provide significant opportunities for ecological studies and drug discovery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Micheal C -- Mori, Tetsushi -- Ruckert, Christian -- Uria, Agustinus R -- Helf, Maximilian J -- Takada, Kentaro -- Gernert, Christine -- Steffens, Ursula A E -- Heycke, Nina -- Schmitt, Susanne -- Rinke, Christian -- Helfrich, Eric J N -- Brachmann, Alexander O -- Gurgui, Cristian -- Wakimoto, Toshiyuki -- Kracht, Matthias -- Crusemann, Max -- Hentschel, Ute -- Abe, Ikuro -- Matsunaga, Shigeki -- Kalinowski, Jorn -- Takeyama, Haruko -- Piel, Jorn -- England -- Nature. 2014 Feb 6;506(7486):58-62. doi: 10.1038/nature12959. Epub 2014 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Microbiology, Eidgenossische Technische Hochschule Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland [2] Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany [3]. ; 1] Faculty of Science and Engineering, Waseda University Center for Advanced Biomedical Sciences, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan [2]. ; Institute for Genome Research and Systems Biology, Center for Biotechnology, Universitat Bielefeld, Universitatstrasse 25, 33594 Bielefeld, Germany. ; 1] Institute of Microbiology, Eidgenossische Technische Hochschule Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland [2] Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany. ; Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. ; Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Wurzburg, Julius-von-Sachs-Platz 3, 97082 Wurzburg, Germany. ; Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany. ; Department of Earth and Environmental Sciences, Palaeontology and Geobiology, Ludwig Maximilians University Munich, Richard-Wagner-Strasse 10, 80333 Munich, Germany. ; Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, California 94598, USA. ; Institute of Microbiology, Eidgenossische Technische Hochschule Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. ; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; Faculty of Science and Engineering, Waseda University Center for Advanced Biomedical Sciences, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476823" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biosynthetic Pathways/genetics ; Deltaproteobacteria/*classification/genetics/*metabolism/physiology ; *Drug Discovery ; Environmental Microbiology ; Genes, Bacterial/genetics ; Genome, Bacterial/genetics ; Metagenomics ; Molecular Sequence Data ; Multigene Family/genetics ; Peptides/metabolism ; Polyketides/metabolism ; Porifera/metabolism/microbiology ; Single-Cell Analysis ; Symbiosis
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  • 138
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Minteer, Ben -- England -- Nature. 2014 May 15;509(7500):261. doi: 10.1038/509261a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Arizona State University in Tempe.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828156" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Cloning, Organism/*contraindications/*ethics ; Conservation of Natural Resources/*methods/trends ; *Extinction, Biological ; Human Characteristics ; *Introduced Species ; Morals
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  • 139
    Publication Date: 2014-11-11
    Description: Autophagy is an evolutionarily conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis. Its acute regulation by nutrient-sensing signalling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors peroxisome proliferator-activated receptor-alpha (PPARalpha) and farnesoid X receptor (FXR) are activated in the fasted and fed liver, respectively. Here we show that both PPARalpha and FXR regulate hepatic autophagy in mice. Pharmacological activation of PPARalpha reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPARalpha knockout (Ppara(-/-), also known as Nr1c1(-/-)) mice, which are partially defective in the induction of autophagy by fasting. Pharmacological activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (Fxr(-/-), also known as Nr1h4(-/-)) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPARalpha and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267857/" 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/PMC4267857/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jae Man -- Wagner, Martin -- Xiao, Rui -- Kim, Kang Ho -- Feng, Dan -- Lazar, Mitchell A -- Moore, David D -- DK43806/DK/NIDDK NIH HHS/ -- P30 DK019525/DK/NIDDK NIH HHS/ -- P30DX56338-05A2/PHS HHS/ -- P39CA125123-04/CA/NCI NIH HHS/ -- R01 DK049780/DK/NIDDK NIH HHS/ -- R01 DK49780/DK/NIDDK NIH HHS/ -- R37 DK043806/DK/NIDDK NIH HHS/ -- S10RR027783-01A1/RR/NCRR NIH HHS/ -- U54HD-07495-39/HD/NICHD NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):112-5. doi: 10.1038/nature13961. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Division of Endocrinology, Diabetes, and Metabolism and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/genetics/*physiology ; Cell Line ; Cells, Cultured ; Fasting/physiology ; Gene Expression Regulation ; Hepatocytes/metabolism ; Liver/cytology/*metabolism/ultrastructure ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins/genetics/metabolism ; PPAR alpha ; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
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  • 140
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Seung-Hee -- Kwan, Alex C -- Dan, Yang -- England -- Nature. 2014 Apr 3;508(7494):E1-2. doi: 10.1038/nature13128.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA [2] Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea (S.-H.L.); Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA (A.C.K.). ; Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695313" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/*physiology ; Animals ; Interneurons/*metabolism/*physiology ; Neural Inhibition/*physiology ; Neural Pathways/*physiology ; Neurons/*physiology ; Parvalbumins/*metabolism ; Visual Cortex/*cytology/*physiology ; Visual Perception/*physiology
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  • 141
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinemann, Bo -- Nielsen, Jesper Morten -- Hudlebusch, Heidi Rye -- Lees, Michael J -- Larsen, Dorthe Vang -- Boesen, Thomas -- Labelle, Marc -- Gerlach, Lars-Ole -- Birk, Peter -- Helin, Kristian -- England -- Nature. 2014 Oct 2;514(7520):E1-2. doi: 10.1038/nature13688.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉EpiTherapeutics Aps, Ole Maaloes Vej 3, 2200 Copenhagen, Denmark. ; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. ; 1] Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark [2] Centre for Epigenetics, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark [3] The Danish Stem Cell Center (DanStem), University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279926" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Inhibitors/*pharmacology ; Humans ; Jumonji Domain-Containing Histone Demethylases/*antagonists & inhibitors ; Macrophages/*drug effects/*immunology
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  • 142
    Publication Date: 2014-08-22
    Description: Cys-loop receptors are neurotransmitter-gated ion channels that are essential mediators of fast chemical neurotransmission and are associated with a large number of neurological diseases and disorders, as well as parasitic infections. Members of this ion channel superfamily mediate excitatory or inhibitory neurotransmission depending on their ligand and ion selectivity. Structural information for Cys-loop receptors comes from several sources including electron microscopic studies of the nicotinic acetylcholine receptor, high-resolution X-ray structures of extracellular domains and X-ray structures of bacterial orthologues. In 2011 our group published structures of the Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in complex with the allosteric partial agonist ivermectin, which provided insights into the structure of a possibly open state of a eukaryotic Cys-loop receptor, the basis for anion selectivity and channel block, and the mechanism by which ivermectin and related molecules stabilize the open state and potentiate neurotransmitter binding. However, there remain unanswered questions about the mechanism of channel opening and closing, the location and nature of the shut ion channel gate, the transitions between the closed/resting, open/activated and closed/desensitized states, and the mechanism by which conformational changes are coupled between the extracellular, orthosteric agonist binding domain and the transmembrane, ion channel domain. Here we present two conformationally distinct structures of C. elegans GluCl in the absence of ivermectin. Structural comparisons reveal a quaternary activation mechanism arising from rigid-body movements between the extracellular and transmembrane domains and a mechanism for modulation of the receptor by phospholipids.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255919/" 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/PMC4255919/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Althoff, Thorsten -- Hibbs, Ryan E -- Banerjee, Surajit -- Gouaux, Eric -- F32 NS061404/NS/NINDS NIH HHS/ -- F32NS061404/NS/NINDS NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 GM100400/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Aug 21;512(7514):333-7. doi: 10.1038/nature13669.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Vollum Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2] Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1751, USA (T.A.); Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9111, USA (R.E.H.). [3]. ; NE-CAT/Cornell University, 9700 South Cass Avenue, Building 436 E001, Argonne, Illinois 60439, USA. ; 1] Vollum Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2] Howard Hughes Medical Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143115" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/drug effects ; Animals ; Apoproteins/*chemistry/metabolism ; Binding Sites ; Binding, Competitive/drug effects ; Caenorhabditis elegans/*chemistry ; Cell Membrane/metabolism ; Chloride Channels/*chemistry/*metabolism ; Crystallography, X-Ray ; Cysteine Loop Ligand-Gated Ion Channel Receptors/*chemistry/*metabolism ; Drug Partial Agonism ; Glutamic Acid/metabolism ; Ion Channel Gating ; Ivermectin/chemistry/metabolism/pharmacology ; Ligands ; Models, Molecular ; Movement/drug effects ; Phosphatidylcholines/chemistry/metabolism/pharmacology ; Protein Binding ; Protein Multimerization/drug effects ; Protein Structure, Tertiary/drug effects ; Structure-Activity Relationship
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  • 143
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alvarez-Buylla, Arturo -- England -- Nature. 2014 Sep 4;513(7516):34. doi: 10.1038/513034a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, San Francisco, USA. He collaborated with Yoshiki Sasai between 2008 and 2014.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186892" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Embryonic Development ; History, 20th Century ; History, 21st Century ; Humans ; Neural Stem Cells/cytology ; Organoids/cytology ; Regenerative Medicine/*history ; Stem Cell Research/*history
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  • 144
    Publication Date: 2014-10-03
    Description: Bone-marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independently of haematological progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor-beta-deficient (Csf2rb(-/-)) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well-tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236859/" 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/PMC4236859/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Takuji -- Arumugam, Paritha -- Sakagami, Takuro -- Lachmann, Nico -- Chalk, Claudia -- Sallese, Anthony -- Abe, Shuichi -- Trapnell, Cole -- Carey, Brenna -- Moritz, Thomas -- Malik, Punam -- Lutzko, Carolyn -- Wood, Robert E -- Trapnell, Bruce C -- 8UL1TR000077-05/TR/NCATS NIH HHS/ -- AR-47363/AR/NIAMS NIH HHS/ -- DK78392/DK/NIDDK NIH HHS/ -- DK90971/DK/NIDDK NIH HHS/ -- P30 AR047363/AR/NIAMS NIH HHS/ -- R01 HL069549/HL/NHLBI NIH HHS/ -- R01 HL085453/HL/NHLBI NIH HHS/ -- R01 HL118342/HL/NHLBI NIH HHS/ -- R01HL085453/HL/NHLBI NIH HHS/ -- R01HL118342/HL/NHLBI NIH HHS/ -- R21 HL106134/HL/NHLBI NIH HHS/ -- U54 HL127672/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):450-4. doi: 10.1038/nature13807. Epub 2014 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. ; Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. ; RG Reprograming and Gene Therapy, Institute of Experimental Hematology, Hannover Medical School, Carl Neuberg-Str. 1, 30625 Hannover, Germany. ; 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02138, USA. ; Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. ; 1] Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA [2] Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA [3] Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25274301" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Separation ; *Cell Transplantation ; Cytokine Receptor Common beta Subunit/deficiency/*genetics ; Female ; *Genetic Therapy ; Lung/*cytology/metabolism/pathology ; Macrophages, Alveolar/*metabolism/*transplantation ; Male ; Mice ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Pulmonary Alveolar Proteinosis/genetics/pathology/*therapy ; Time Factors
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  • 145
    Publication Date: 2014-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hejnol, Andreas -- England -- Nature. 2014 Jun 5;510(7503):38-9. doi: 10.1038/nature13340. Epub 2014 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sars International Centre for Marine Molecular Biology, University of Bergen, 5008 Bergen, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24847878" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ctenophora/*genetics ; *Evolution, Molecular ; Genome/*genetics ; *Nervous System
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  • 146
    Publication Date: 2014-04-25
    Description: Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated androgen receptor (AR) signalling. Despite the success of recently approved therapies targeting AR signalling, such as abiraterone and second-generation anti-androgens including MDV3100 (also known as enzalutamide), durable responses are limited, presumably owing to acquired resistance. Recently, JQ1 and I-BET762 two selective small-molecule inhibitors that target the amino-terminal bromodomains of BRD4, have been shown to exhibit anti-proliferative effects in a range of malignancies. Here we show that AR-signalling-competent human CRPC cell lines are preferentially sensitive to bromodomain and extraterminal (BET) inhibition. BRD4 physically interacts with the N-terminal domain of AR and can be disrupted by JQ1 (refs 11, 13). Like the direct AR antagonist MDV3100, JQ1 disrupted AR recruitment to target gene loci. By contrast with MDV3100, JQ1 functions downstream of AR, and more potently abrogated BRD4 localization to AR target loci and AR-mediated gene transcription, including induction of the TMPRSS2-ERG gene fusion and its oncogenic activity. In vivo, BET bromodomain inhibition was more efficacious than direct AR antagonism in CRPC xenograft mouse models. Taken together, these studies provide a novel epigenetic approach for the concerted blockade of oncogenic drivers in advanced prostate cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075966/" 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/PMC4075966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asangani, Irfan A -- Dommeti, Vijaya L -- Wang, Xiaoju -- Malik, Rohit -- Cieslik, Marcin -- Yang, Rendong -- Escara-Wilke, June -- Wilder-Romans, Kari -- Dhanireddy, Sudheer -- Engelke, Carl -- Iyer, Mathew K -- Jing, Xiaojun -- Wu, Yi-Mi -- Cao, Xuhong -- Qin, Zhaohui S -- Wang, Shaomeng -- Feng, Felix Y -- Chinnaiyan, Arul M -- P50 CA069568/CA/NCI NIH HHS/ -- P50CA69568/CA/NCI NIH HHS/ -- T32 GM007863/GM/NIGMS NIH HHS/ -- U01 CA111275/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 12;510(7504):278-82. doi: 10.1038/nature13229. Epub 2014 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia 30329, USA. ; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; 1] Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; 1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [4] Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [5] Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24759320" target="_blank"〉PubMed〈/a〉
    Keywords: Androgen Antagonists/pharmacology ; Androgens/metabolism ; Animals ; Azepines/*pharmacology/therapeutic use ; Cell Line, Tumor ; Disease Models, Animal ; Epigenesis, Genetic ; Humans ; Male ; Mice ; Nuclear Proteins/*chemistry ; Oncogene Proteins, Fusion/genetics/metabolism ; Prostatic Neoplasms, Castration-Resistant/*drug therapy/genetics ; Protein Structure, Tertiary/drug effects ; Receptors, Androgen/chemistry/metabolism ; Signal Transduction/drug effects ; Transcription Factors/*chemistry ; Triazoles/*pharmacology/therapeutic use
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  • 147
    Publication Date: 2014-01-10
    Description: Throughout the animal kingdom, adaptive colouration serves critical functions ranging from inconspicuous camouflage to ostentatious sexual display, and can provide important information about the environment and biology of a particular organism. The most ubiquitous and abundant pigment, melanin, also has a diverse range of non-visual roles, including thermoregulation in ectotherms. However, little is known about the functional evolution of this important biochrome through deep time, owing to our limited ability to unambiguously identify traces of it in the fossil record. Here we present direct chemical evidence of pigmentation in fossilized skin, from three distantly related marine reptiles: a leatherback turtle, a mosasaur and an ichthyosaur. We demonstrate that dark traces of soft tissue in these fossils are dominated by molecularly preserved eumelanin, in intimate association with fossilized melanosomes. In addition, we suggest that contrary to the countershading of many pelagic animals, at least some ichthyosaurs were uniformly dark-coloured in life. Our analyses expand current knowledge of pigmentation in fossil integument beyond that of feathers, allowing for the reconstruction of colour over much greater ranges of extinct taxa and anatomy. In turn, our results provide evidence of convergent melanism in three disparate lineages of secondarily aquatic tetrapods. Based on extant marine analogues, we propose that the benefits of thermoregulation and/or crypsis are likely to have contributed to this melanisation, with the former having implications for the ability of each group to exploit cold environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindgren, Johan -- Sjovall, Peter -- Carney, Ryan M -- Uvdal, Per -- Gren, Johan A -- Dyke, Gareth -- Schultz, Bo Pagh -- Shawkey, Matthew D -- Barnes, Kenneth R -- Polcyn, Michael J -- England -- Nature. 2014 Feb 27;506(7489):484-8. doi: 10.1038/nature12899. Epub 2014 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology, Lund University, SE-223 62 Lund, Sweden. ; SP Technical Research Institute of Sweden, Chemistry, Materials and Surfaces, SE-501 15 Boras, Sweden. ; Department of Ecology and Evolutionary Biology, Brown University, Providence, Rhode Island 02906, USA. ; 1] MAX-IV laboratory, Lund University, SE-221 00 Lund, Sweden [2] Chemical Physics, Department of Chemistry, Lund University, SE-221 00 Lund, Sweden. ; 1] Ocean and Earth Sciences, University of Southampton, Southampton SO14 3ZH, UK [2] Institute for Life Sciences, University of Southampton, Southampton SO14 3ZH, UK. ; MUSERUM, Natural History Division, Havnevej 14, 7800 Skive, Denmark. ; Integrated Bioscience Program, University of Akron, Akron, Ohio 44325, USA. ; Mosasaur Ranch Museum, Lajitas, Texas 79852, USA. ; Roy M. Huffington Department of Earth Sciences, Southern Methodist University, Dallas, Texas 75275, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402224" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms/*physiology ; *Biological Evolution ; Body Temperature Regulation ; Color ; *Extinction, Biological ; *Fossils ; Melanins/analysis ; Melanosis/*metabolism ; Melanosomes/chemistry ; Phylogeny ; Reptiles/*physiology ; Skin/chemistry ; *Skin Pigmentation ; Turtles/physiology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 148
    Publication Date: 2014-11-21
    Description: To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human-mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and with genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343047/" 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/PMC4343047/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Yong -- Ma, Zhihai -- Kim, Bong-Hyun -- Wu, Weisheng -- Cayting, Philip -- Boyle, Alan P -- Sundaram, Vasavi -- Xing, Xiaoyun -- Dogan, Nergiz -- Li, Jingjing -- Euskirchen, Ghia -- Lin, Shin -- Lin, Yiing -- Visel, Axel -- Kawli, Trupti -- Yang, Xinqiong -- Patacsil, Dorrelyn -- Keller, Cheryl A -- Giardine, Belinda -- Mouse ENCODE Consortium -- Kundaje, Anshul -- Wang, Ting -- Pennacchio, Len A -- Weng, Zhiping -- Hardison, Ross C -- Snyder, Michael P -- 1U54HG00699/HG/NHGRI NIH HHS/ -- 3RC2HG005602/HG/NHGRI NIH HHS/ -- 5U54HG006996/HG/NHGRI NIH HHS/ -- R01 DK065806/DK/NIDDK NIH HHS/ -- R01 DK096266/DK/NIDDK NIH HHS/ -- R01 ES024992/ES/NIEHS NIH HHS/ -- R01 EY021482/EY/NEI NIH HHS/ -- R01 GM083337/GM/NIGMS NIH HHS/ -- R01 HG003988/HG/NHGRI NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG007175/HG/NHGRI NIH HHS/ -- R01 HG007348/HG/NHGRI NIH HHS/ -- R01 HG007354/HG/NHGRI NIH HHS/ -- R01DK065806/DK/NIDDK NIH HHS/ -- R01HG003988/HG/NHGRI NIH HHS/ -- R37 DK044746/DK/NIDDK NIH HHS/ -- RC2 HG005573/HG/NHGRI NIH HHS/ -- RC2 HG005602/HG/NHGRI NIH HHS/ -- RC2HG005573/HG/NHGRI NIH HHS/ -- U01 DE024427/DE/NIDCR NIH HHS/ -- U41 HG007234/HG/NHGRI NIH HHS/ -- U54 HG006996/HG/NHGRI NIH HHS/ -- U54 HG006997/HG/NHGRI NIH HHS/ -- U54 HG006998/HG/NHGRI NIH HHS/ -- U54 HG007004/HG/NHGRI NIH HHS/ -- U54HG006997/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Nov 20;515(7527):371-5. doi: 10.1038/nature13985.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University, Stanford, California 94305, USA. ; Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; 1] Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] BRCF Bioinformatics Core, University of Michigan, Ann Arbor, Michigan 48105, USA. ; Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA. ; Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Department of Genetics, Stanford University, Stanford, California 94305, USA [2] Division of Cardiovascular Medicine, Stanford University, Stanford, California 94304, USA. ; 1] Department of Genetics, Stanford University, Stanford, California 94305, USA [2] Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California 94701, USA [2] Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA [3] School of Natural Sciences, University of California, Merced, California 95343, USA. ; 1] Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California 94701, USA [2] Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409826" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chromatin/genetics/metabolism ; Conserved Sequence/*genetics ; Enhancer Elements, Genetic/genetics ; Genome/*genetics ; *Genomics ; Humans ; Mice ; Polymorphism, Single Nucleotide/genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; Transcription Factors/*metabolism
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  • 149
    Publication Date: 2014-08-15
    Description: The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production. The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moura-Alves, Pedro -- Fae, Kellen -- Houthuys, Erica -- Dorhoi, Anca -- Kreuchwig, Annika -- Furkert, Jens -- Barison, Nicola -- Diehl, Anne -- Munder, Antje -- Constant, Patricia -- Skrahina, Tatsiana -- Guhlich-Bornhof, Ute -- Klemm, Marion -- Koehler, Anne-Britta -- Bandermann, Silke -- Goosmann, Christian -- Mollenkopf, Hans-Joachim -- Hurwitz, Robert -- Brinkmann, Volker -- Fillatreau, Simon -- Daffe, Mamadou -- Tummler, Burkhard -- Kolbe, Michael -- Oschkinat, Hartmut -- Krause, Gerd -- Kaufmann, Stefan H E -- England -- Nature. 2014 Aug 28;512(7515):387-92. doi: 10.1038/nature13684. Epub 2014 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany [2]. ; Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Max Planck Institute for Infection Biology, Structural Systems Biology, Chariteplatz 1, 10117 Berlin, Germany. ; Clinical Research Group, Clinic for Pediatric Pneumology, Allergology and Neonatology, OE 6710, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. ; Institute of Pharmacology and Structural Biology (IPBS), CNRS and University of Toulouse (Toulouse III), 205 Route de Narbonne, 31077, Toulouse cedex 04, Toulouse, France. ; Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany. ; Microscopy Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany. ; Microarray Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany. ; Protein Purification Core Facility, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany. ; German Rheumatism Research Centre Berlin (DRFZ), a Leibniz Institute, Chariteplatz 1, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119038" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/metabolism ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Bone Marrow Cells/cytology ; Cytokines/immunology/metabolism ; Feedback, Physiological ; Humans ; Ligands ; Macrophage Activation ; Mice ; Mycobacterium tuberculosis/growth & development/*immunology/metabolism ; Phenazines/metabolism ; Pigments, Biological/chemistry/*metabolism ; Pseudomonas Infections/metabolism ; Pseudomonas aeruginosa/*immunology/metabolism ; Pyocyanine/metabolism ; Receptors, Aryl Hydrocarbon/*metabolism ; Receptors, Pattern Recognition/*metabolism ; Virulence Factors/chemistry/metabolism
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  • 150
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moyer, Melinda Wenner -- England -- Nature. 2014 Jun 26;510(7506):462-4. doi: 10.1038/510462a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24965635" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Beriberi/diet therapy/etiology/history/prevention & control ; *Dietary Supplements/utilization ; History, 20th Century ; Humans ; Nutritional Status/*drug effects ; Scurvy/diet therapy/etiology/history/prevention & control ; *Uncertainty ; Vitamins/history/*pharmacology
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  • 151
    Publication Date: 2014-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leeman, Dena S -- Brunet, Anne -- P01 AG036695/AG/NIA NIH HHS/ -- England -- Nature. 2014 Jan 23;505(7484):488-90. doi: 10.1038/505488a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, the Cancer Biology Program, and the Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24451537" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Estrogens/*metabolism ; Female ; Hematopoietic Stem Cells/*cytology/*metabolism ; Male ; Pregnancy
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  • 152
    Publication Date: 2014-09-26
    Description: For centuries, biogeographers have examined the factors that produce patterns of biodiversity across regions. The study of islands has proved particularly fruitful and has led to the theory that geographic area and isolation influence species colonization, extinction and speciation such that larger islands have more species and isolated islands have fewer species (that is, positive species-area and negative species-isolation relationships). However, experimental tests of this theory have been limited, owing to the difficulty in experimental manipulation of islands at the scales at which speciation and long-distance colonization are relevant. Here we have used the human-aided transport of exotic anole lizards among Caribbean islands as such a test at an appropriate scale. In accord with theory, as anole colonizations have increased, islands impoverished in native species have gained the most exotic species, the past influence of speciation on island biogeography has been obscured, and the species-area relationship has strengthened while the species-isolation relationship has weakened. Moreover, anole biogeography increasingly reflects anthropogenic rather than geographic processes. Unlike the island biogeography of the past that was determined by geographic area and isolation, in the Anthropocene--an epoch proposed for the present time interval--island biogeography is dominated by the economic isolation of human populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmus, Matthew R -- Mahler, D Luke -- Losos, Jonathan B -- England -- Nature. 2014 Sep 25;513(7519):543-6. doi: 10.1038/nature13739.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amsterdam Global Change Institute, Department of Animal Ecology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands. ; Center for Population Biology, University of California, Davis, California 95616, USA. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254475" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Commerce/history/statistics & numerical data ; Geography ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Human Activities/history/statistics & numerical data ; Introduced Species/history/*statistics & numerical data ; *Islands ; *Lizards/physiology ; Models, Biological ; Models, Economic ; Population Dynamics ; West Indies
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  • 153
    Publication Date: 2014-12-04
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757426/" 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/PMC4757426/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fernandez, Ariel -- Lynch, Michael -- England -- Nature. 2014 Dec 18;516(7531):440. doi: 10.1038/nature13141. Epub 2014 Nov 26.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470052" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Evolution, Molecular ; *Genetic Drift ; Humans ; Metabolic Networks and Pathways/*physiology ; Proteins/*metabolism
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  • 154
    Publication Date: 2014-03-22
    Description: The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, and pharmacological reversal of this decline allowed the restoration of bone mass.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kusumbe, Anjali P -- Ramasamy, Saravana K -- Adams, Ralf H -- England -- Nature. 2014 Mar 20;507(7492):323-8. doi: 10.1038/nature13145. Epub 2014 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, D-48149 Munster, Germany [2]. ; 1] Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, D-48149 Munster, Germany [2] University of Munster, Faculty of Medicine, D-48149 Munster, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24646994" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism/pathology ; Animals ; Blood Vessels/anatomy & histology/cytology/growth & development/*physiology ; Bone and Bones/*blood supply/cytology ; Endothelial Cells/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic/*physiology ; Osteoblasts/cytology/metabolism ; Osteogenesis/*physiology ; Oxygen/metabolism ; Stem Cells/cytology/metabolism
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  • 155
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    Nature Publishing Group (NPG)
    Publication Date: 2014-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Aug 21;512(7514):242. doi: 10.1038/512242a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143094" target="_blank"〉PubMed〈/a〉
    Keywords: Acculturation/history ; Animals ; Bone and Bones/*chemistry ; Europe ; *Fossils ; History, Ancient ; Humans ; Hybridization, Genetic ; *Neanderthals/genetics ; Radiometric Dating ; Time Factors ; Uncertainty
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  • 156
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sohn, Emily -- England -- Nature. 2014 Nov 27;515(7528):S172-3. doi: 10.1038/515S172a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25427211" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; *Dogs ; Drug Evaluation, Preclinical/history ; Genetic Therapy ; Hemophilia A/*therapy ; Hemophilia B/*therapy ; History, 20th Century ; Research/trends
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  • 157
    Publication Date: 2014-01-31
    Description: The assessment of changes in tropical cyclone activity within the context of anthropogenically influenced climate change has been limited by the short temporal resolution of the instrumental tropical cyclone record (less than 50 years). Furthermore, controversy exists regarding the robustness of the observational record, especially before 1990. Here we show, on the basis of a new tropical cyclone activity index (CAI), that the present low levels of storm activity on the mid west and northeast coasts of Australia are unprecedented over the past 550 to 1,500 years. The CAI allows for a direct comparison between the modern instrumental record and long-term palaeotempest (prehistoric tropical cyclone) records derived from the (18)O/(16)O ratio of seasonally accreting carbonate layers of actively growing stalagmites. Our results reveal a repeated multicentennial cycle of tropical cyclone activity, the most recent of which commenced around AD 1700. The present cycle includes a sharp decrease in activity after 1960 in Western Australia. This is in contrast to the increasing frequency and destructiveness of Northern Hemisphere tropical cyclones since 1970 in the Atlantic Ocean and the western North Pacific Ocean. Other studies project a decrease in the frequency of tropical cyclones towards the end of the twenty-first century in the southwest Pacific, southern Indian and Australian regions. Our results, although based on a limited record, suggest that this may be occurring much earlier than expected.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haig, Jordahna -- Nott, Jonathan -- Reichart, Gert-Jan -- England -- Nature. 2014 Jan 30;505(7485):667-71. doi: 10.1038/nature12882.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Earth and Environmental Sciences, James Cook University, Cairns, Queensland 4870, Australia. ; 1] Department of Geochemistry, Utrecht University, Utrecht 3508 TA, The Netherlands [2] Geology Department, Royal Netherlands Institute for Sea Research, Den Hoorn (Texel) 1797 SZ, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476890" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Australia ; Carbon Isotopes ; Carbonates/analysis/chemistry ; Cyclonic Storms/*statistics & numerical data ; Global Warming/statistics & numerical data ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Human Activities ; Oxygen Isotopes ; Pacific Ocean ; Rain ; Seasons ; *Tropical Climate
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  • 158
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    Publication Date: 2014-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Feb 6;506(7486):5. doi: 10.1038/506005a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499880" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation/*legislation & jurisprudence ; Animal Rights/*legislation & jurisprudence ; Animals ; Humans ; *Primates
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  • 159
    Publication Date: 2014-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rowe, Nicholas -- England -- Nature. 2014 May 8;509(7499):164. doi: 10.1038/509164e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Lapland, Rovaniemi, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805335" target="_blank"〉PubMed〈/a〉
    Keywords: *Congresses as Topic/history/trends ; History, 20th Century ; History, 21st Century ; *Posters as Topic ; *Research Personnel
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  • 160
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    Publication Date: 2014-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hakim, Antoine M -- England -- Nature. 2014 Jun 26;510(7506):S12. doi: 10.1038/510S12a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Canadian Stroke Network and director of the Neuroscience Research Program at the Ottawa Hospital Research Institute and the University of Ottawa in Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24964022" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Pressure ; Dementia/epidemiology/*etiology/physiopathology/*prevention & control ; Humans ; Hypertension/complications/drug therapy/physiopathology/*therapy ; Ischemic Attack, Transient/diagnosis/epidemiology/physiopathology/*psychology ; Rats ; Stroke/complications/epidemiology/physiopathology/*psychology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 161
    Publication Date: 2014-06-05
    Description: Transcriptional enhancers are crucial regulators of gene expression and animal development and the characterization of their genomic organization, spatiotemporal activities and sequence properties is a key goal in modern biology. Here we characterize the in vivo activity of 7,705 Drosophila melanogaster enhancer candidates covering 13.5% of the non-coding non-repetitive genome throughout embryogenesis. 3,557 (46%) candidates are active, suggesting a high density with 50,000 to 100,000 developmental enhancers genome-wide. The vast majority of enhancers display specific spatial patterns that are highly dynamic during development. Most appear to regulate their neighbouring genes, suggesting that the cis-regulatory genome is organized locally into domains, which are supported by chromosomal domains, insulator binding and genome evolution. However, 12 to 21 per cent of enhancers appear to skip non-expressed neighbours and regulate a more distal gene. Finally, we computationally identify cis-regulatory motifs that are predictive and required for enhancer activity, as we validate experimentally. This work provides global insights into the organization of an animal regulatory genome and the make-up of enhancer sequences and confirms and generalizes principles from previous studies. All enhancer patterns are annotated manually with a controlled vocabulary and all results are available through a web interface (http://enhancers.starklab.org), including the raw images of all microscopy slides for manual inspection at arbitrary zoom levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kvon, Evgeny Z -- Kazmar, Tomas -- Stampfel, Gerald -- Yanez-Cuna, J Omar -- Pagani, Michaela -- Schernhuber, Katharina -- Dickson, Barry J -- Stark, Alexander -- England -- Nature. 2014 Aug 7;512(7512):91-5. doi: 10.1038/nature13395. Epub 2014 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2] Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA (B.J.D.); Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA (E.Z.K.). ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria. ; 1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila melanogaster/*embryology/*genetics ; Embryonic Development/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Genome, Insect/*genetics ; Internet ; Nucleotide Motifs/genetics ; Organ Specificity/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; User-Computer Interface
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  • 162
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    Nature Publishing Group (NPG)
    Publication Date: 2014-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sohn, Emily -- England -- Nature. 2014 Jul 10;511(7508):144-6. doi: 10.1038/511144a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008507" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Culicidae/*physiology ; Dogs ; Humans ; Insect Vectors/*physiology ; Malaria/*prevention & control ; Mali ; *Mosquito Control ; Seasons
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  • 163
    Publication Date: 2014-03-29
    Description: Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976267/" 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/PMC3976267/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, Catherine N -- Reynell, Clare -- Gesslein, Bodil -- Hamilton, Nicola B -- Mishra, Anusha -- Sutherland, Brad A -- O'Farrell, Fergus M -- Buchan, Alastair M -- Lauritzen, Martin -- Attwell, David -- 075232/Wellcome Trust/United Kingdom -- G0500495/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Apr 3;508(7494):55-60. doi: 10.1038/nature13165. Epub 2014 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK [2]. ; 1] Department of Neuroscience and Pharmacology and Center for Healthy Aging, University of Copenhagen, DK-2200 Copenhagen N, Denmark [2]. ; Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK. ; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK. ; 1] Department of Neuroscience and Pharmacology and Center for Healthy Aging, University of Copenhagen, DK-2200 Copenhagen N, Denmark [2] Department of Clinical Neurophysiology, Glostrup University Hospital, DK-2600 Glostrup, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670647" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arterioles/physiology ; Blood-Brain Barrier/pathology/physiopathology ; Brain Ischemia/pathology ; Capillaries/*cytology/drug effects ; Cell Death ; Cerebellum/blood supply ; Cerebral Cortex/blood supply/cytology ; Cerebrovascular Circulation/drug effects/*physiology ; Dinoprostone/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; Functional Neuroimaging ; Glutamic Acid/pharmacology ; Hydroxyeicosatetraenoic Acids/biosynthesis ; In Vitro Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Pericytes/cytology/drug effects/pathology/*physiology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, Glutamate/metabolism ; Signal Transduction/drug effects ; Stroke/pathology ; Vasoconstriction ; Vasodilation/drug effects
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  • 164
    Publication Date: 2014-05-03
    Description: The response of the tropical climate in the Indian Ocean realm to abrupt climate change events in the North Atlantic Ocean is contentious. Repositioning of the intertropical convergence zone is thought to have been responsible for changes in tropical hydroclimate during North Atlantic cold spells, but the dearth of high-resolution records outside the monsoon realm in the Indian Ocean precludes a full understanding of this remote relationship and its underlying mechanisms. Here we show that slowdowns of the Atlantic meridional overturning circulation during Heinrich stadials and the Younger Dryas stadial affected the tropical Indian Ocean hydroclimate through changes to the Hadley circulation including a southward shift in the rising branch (the intertropical convergence zone) and an overall weakening over the southern Indian Ocean. Our results are based on new, high-resolution sea surface temperature and seawater oxygen isotope records of well-dated sedimentary archives from the tropical eastern Indian Ocean for the past 45,000 years, combined with climate model simulations of Atlantic circulation slowdown under Marine Isotope Stages 2 and 3 boundary conditions. Similar conditions in the east and west of the basin rule out a zonal dipole structure as the dominant forcing of the tropical Indian Ocean hydroclimate of millennial-scale events. Results from our simulations and proxy data suggest dry conditions in the northern Indian Ocean realm and wet and warm conditions in the southern realm during North Atlantic cold spells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohtadi, Mahyar -- Prange, Matthias -- Oppo, Delia W -- De Pol-Holz, Ricardo -- Merkel, Ute -- Zhang, Xiao -- Steinke, Stephan -- Luckge, Andreas -- England -- Nature. 2014 May 1;509(7498):76-80. doi: 10.1038/nature13196.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MARUM-Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany. ; Geology and Geophysics, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543, USA. ; Department of Oceanography, University of Concepcion, Concepcion, Chile. ; Federal Institute for Geosciences and Natural Resources, 30655 Hannover, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784218" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Air ; Atlantic Ocean ; Borneo ; Geologic Sediments/chemistry ; Greenland ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humidity ; Hydrology ; Ice Cover ; Indian Ocean ; Indonesia ; Lakes ; *Models, Theoretical ; Oxygen Isotopes ; Rain ; Salinity ; Seasons ; Seawater/analysis/chemistry ; Temperature ; Time Factors ; *Tropical Climate ; Water Movements
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  • 165
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 May 29;509(7502):546. doi: 10.1038/509546a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870524" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry/*history ; Animals ; Biological Evolution ; Breeding/*history ; *Chickens/classification/genetics ; Diet/veterinary ; Eggs ; Food Supply/history ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Meat ; Oviposition/genetics ; *Research
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  • 166
    Publication Date: 2014-04-30
    Description: Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help to refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded semaphorin 3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a leads to dysregulated alpha-motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of alpha- but not of adjacent gamma-motor neurons. In addition, a subset of TrkA(+) sensory afferents projects to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057936/" 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/PMC4057936/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Molofsky, Anna V -- Kelley, Kevin W -- Tsai, Hui-Hsin -- Redmond, Stephanie A -- Chang, Sandra M -- Madireddy, Lohith -- Chan, Jonah R -- Baranzini, Sergio E -- Ullian, Erik M -- Rowitch, David H -- 1DP2OD006507-01/OD/NIH HHS/ -- 5T32MH089920-04/MH/NIMH NIH HHS/ -- F31 NS081905/NS/NINDS NIH HHS/ -- R01 MH099595/MH/NIMH NIH HHS/ -- R01 NS059893/NS/NINDS NIH HHS/ -- R01 NS062796/NS/NINDS NIH HHS/ -- R01MH099595-01/MH/NIMH NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- T32 MH089920/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 8;509(7499):189-94. doi: 10.1038/nature13161. Epub 2014 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Psychiatry, University of California San Francisco, San Francisco, California 94143, USA. ; 1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA [4] Medical Scientist Training Program, University of California San Francisco, San Francisco, California 94143, USA [5] Neuroscience Graduate Program, University of California San Francisco, San Francisco, California 94143, USA [6]. ; 1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA [4]. ; 1] Neuroscience Graduate Program, University of California San Francisco, San Francisco, California 94143, USA [2] Department of Neurology, University of California San Francisco, San Francisco, California 94143, USA. ; 1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA. ; Department of Neurology, University of California San Francisco, San Francisco, California 94143, USA. ; Department of Ophthalmology, University of California San Francisco, San Francisco, California 94143, USA. ; 1] Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA [3] Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA [4] Department of Neurosurgery, University of California San Francisco, San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24776795" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/cytology/*physiology ; Axons/physiology ; Cell Polarity ; Cell Survival/drug effects ; Humans ; Mice ; Motor Neurons/cytology/drug effects/*physiology ; Neural Pathways/*physiology ; Semaphorin-3A/deficiency/genetics/metabolism/pharmacology ; Sensory Receptor Cells/cytology/*physiology ; Spinal Cord/cytology ; Synapses/metabolism
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  • 167
    Publication Date: 2014-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 Nov 27;515(7528):476. doi: 10.1038/515476a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25428477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Artificial Limbs/ethics/*standards/trends ; Brain Waves/physiology ; *Device Approval ; Electrodes, Implanted ; Humans ; United States
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  • 168
    Publication Date: 2014-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, Stephen S -- England -- Nature. 2014 Jan 2;505(7481):14-7. doi: 10.1038/505014a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New York University.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24380939" target="_blank"〉PubMed〈/a〉
    Keywords: *Aggression ; Animals ; Canada ; *Epigenomics ; Female ; Humans ; Infant ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects/*genetics
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  • 169
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 May 22;509(7501):414-7. doi: 10.1038/509414a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24848045" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Child, Preschool ; Clinical Trials as Topic ; Cytoplasm/metabolism ; Female ; Great Britain ; Humans ; Infant ; Leigh Disease/genetics/*pathology/*prevention & control ; Macaca mulatta ; Male ; *Mitochondria/genetics/pathology ; *Nuclear Transfer Techniques ; Ovum/cytology/metabolism/pathology ; Reproductive Medicine/*methods ; United States ; United States Food and Drug Administration
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  • 170
    Publication Date: 2014-05-16
    Description: Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood-brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily--Mfsd2a (previously an orphan transporter)--as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood-brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nguyen, Long N -- Ma, Dongliang -- Shui, Guanghou -- Wong, Peiyan -- Cazenave-Gassiot, Amaury -- Zhang, Xiaodong -- Wenk, Markus R -- Goh, Eyleen L K -- Silver, David L -- England -- Nature. 2014 May 22;509(7501):503-6. doi: 10.1038/nature13241. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore. ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore. ; Department of Biochemistry, National University of Singapore, 8 Medical Drive, Block MD7, 117597 Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/physiopathology ; Biological Transport ; Blood-Brain Barrier/metabolism ; Brain/*metabolism/pathology/physiopathology ; Cognition Disorders/pathology/physiopathology ; Docosahexaenoic Acids/deficiency/*metabolism ; Endothelium, Vascular/metabolism ; Female ; Lysophosphatidylcholines/chemistry/metabolism ; Male ; Membrane Transport Proteins/deficiency/genetics/*metabolism ; Mice ; Mice, Knockout ; Microcephaly/metabolism/pathology ; Microvessels/metabolism ; Neurons/metabolism/pathology ; Organ Size ; Sodium/metabolism
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  • 171
    Publication Date: 2014-01-07
    Description: Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials. The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome. Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human-murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo. As predicted from preclinical and clinical studies, rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly-approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939040/" 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/PMC3939040/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lisowski, Leszek -- Dane, Allison P -- Chu, Kirk -- Zhang, Yue -- Cunningham, Sharon C -- Wilson, Elizabeth M -- Nygaard, Sean -- Grompe, Markus -- Alexander, Ian E -- Kay, Mark A -- DK048252/DK/NIDDK NIH HHS/ -- HL064274/HL/NHLBI NIH HHS/ -- HL092096/HL/NHLBI NIH HHS/ -- R01 DK048252/DK/NIDDK NIH HHS/ -- R01 HL064274/HL/NHLBI NIH HHS/ -- R01 HL092096/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Feb 20;506(7488):382-6. doi: 10.1038/nature12875. Epub 2013 Dec 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Stanford University, School of Medicine, Departments of Pediatrics and Genetics, 269 Campus Drive, Stanford, California 94305, USA [2] Gene Transfer, Targeting and Therapeutics Core, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd, San Diego, California 92037, USA (L.L.); Department of Haematology, University College London Cancer Institute, London WC1E 6BT, UK (A.P.D.). ; 1] Gene Therapy Research Unit, The Children's Hospital at Westmead and Children's Medical Research Institute, Locked Bag 4001, Westmead, 2145 New South Wales, Australia [2] Gene Transfer, Targeting and Therapeutics Core, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd, San Diego, California 92037, USA (L.L.); Department of Haematology, University College London Cancer Institute, London WC1E 6BT, UK (A.P.D.). ; Stanford University, School of Medicine, Departments of Pediatrics and Genetics, 269 Campus Drive, Stanford, California 94305, USA. ; Gene Therapy Research Unit, The Children's Hospital at Westmead and Children's Medical Research Institute, Locked Bag 4001, Westmead, 2145 New South Wales, Australia. ; Yecuris Corporation, Portland, Oregon 97062, USA. ; Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97239, USA. ; 1] Gene Therapy Research Unit, The Children's Hospital at Westmead and Children's Medical Research Institute, Locked Bag 4001, Westmead, 2145 New South Wales, Australia [2] Discipline of Paediatrics and Child Health, The University of Sydney, 2145 New South Wales, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390344" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capsid/metabolism ; Capsid Proteins/genetics/metabolism ; Carcinoma, Hepatocellular/genetics/pathology ; Cell Line, Tumor ; Cells, Cultured ; Chimera/genetics/metabolism ; Clinical Trials as Topic ; Dependovirus/*genetics/isolation & purification ; Disease Models, Animal ; Female ; Genetic Therapy/*methods ; Genetic Vectors/*genetics ; Hepatocytes/cytology/metabolism/pathology/transplantation ; Heterografts/*metabolism ; Humans ; Liver/cytology/*metabolism/pathology ; Male ; Mice ; Species Specificity ; Transduction, Genetic/*methods ; Transgenes/*genetics
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  • 172
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    Publication Date: 2014-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thew, Michelle -- England -- Nature. 2014 Nov 20;515(7527):343. doi: 10.1038/515343d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BUAV, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409818" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Rights ; Animals ; *Animals, Laboratory ; Biomedical Research/*methods ; *Communication ; Haplorhini/*physiology ; *Research Personnel
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  • 173
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fields, R Douglas -- England -- Nature. 2014 Jun 19;510(7505):340. doi: 10.1038/510340a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24943947" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Experimentation ; Animals ; Biomedical Research/*methods ; Female ; Humans ; Male ; *National Institutes of Health (U.S.) ; *Research Design ; *Sex Characteristics ; *Sex Ratio
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  • 174
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    Publication Date: 2014-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2014 Oct 30;514(7524):546. doi: 10.1038/514546a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355339" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*drug effects ; Animals ; Clinical Trials as Topic/*veterinary ; Dogs/*physiology ; Female ; Humans ; Longevity/*drug effects ; Male ; Mice ; Models, Animal ; Pets/*physiology ; Pilot Projects ; Sirolimus/administration & dosage/adverse effects/*pharmacology
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  • 175
    Publication Date: 2014-09-26
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476531/" 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/PMC4476531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fieni, Francesca -- Johnson, Derrick E -- Hudmon, Andy -- Kirichok, Yuriy -- R01 NS078171/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Sep 25;513(7519):E1-2. doi: 10.1038/nature13626.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California San Francisco, San Francisco, California 94158, USA. ; Department of Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254480" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism ; Female ; Mitochondria, Heart/*metabolism/*pathology ; Myocardium/*enzymology/*pathology ; *Stress, Physiological
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  • 176
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heymann, David L -- England -- Nature. 2014 Oct 16;514(7522):299-300. doi: 10.1038/514299a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25318509" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Cities/epidemiology ; *Clinical Trials as Topic/ethics ; Congo/epidemiology ; *Contact Tracing ; Cross Infection/epidemiology ; Disease Outbreaks/prevention & control/statistics & numerical data ; Fever/diagnosis ; Funeral Rites ; *Hemorrhagic Fever, Ebola/diagnosis/epidemiology/prevention & ; control/therapy/transmission ; History, 20th Century ; History, 21st Century ; Humans ; Plasmapheresis/utilization ; Protective Clothing ; *Quarantine ; Rural Population/statistics & numerical data ; Survivors ; Time Factors ; Urban Population/statistics & numerical data ; World Health Organization
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  • 177
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-20
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429762/" 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/PMC4429762/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muoio, Deborah M -- Newgard, Christopher B -- P01 DK058398/DK/NIDDK NIH HHS/ -- R01 DK089312/DK/NIDDK NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):49-50. doi: 10.1038/nature14070. Epub 2014 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, and the Departments of Pharmacology and Cancer Biology and Medicine, Duke University Medical Center, Durham, North Carolina 27701, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409152" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/*metabolism ; Animals ; Diabetes Mellitus, Type 2/*metabolism ; Esters/*metabolism ; Fatty Acids/*metabolism ; Female ; Humans ; Male
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  • 178
    Publication Date: 2014-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller-Landau, Helene C -- England -- Nature. 2014 Feb 6;506(7486):44-5. doi: 10.1038/nature12851. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Smithsonian Tropical Research Institute, Apartado Postal 0843-03092, Panama City, Panama.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463509" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Fungi/*physiology ; *Herbivory ; Insects/*physiology ; Trees/*microbiology/*physiology
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  • 179
    Publication Date: 2014-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andreone, Franco -- England -- Nature. 2014 Aug 21;512(7514):253. doi: 10.1038/512253c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Museo Regionale di Scienze Naturali, Turin, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143105" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Bufonidae/*physiology ; *Conservation of Natural Resources ; Humans ; *Introduced Species
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  • 180
    Publication Date: 2014-08-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeuchi, Tomonori -- Morris, Richard G M -- England -- Nature. 2014 Sep 18;513(7518):323-4. doi: 10.1038/nature13745. Epub 2014 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh EH8 9JZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25162529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Hippocampus/*physiology ; Male ; Memory/*physiology
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  • 181
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    Publication Date: 2014-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2014 Oct 30;514(7524):554-7. doi: 10.1038/514554a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355344" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Animals ; Chiroptera/virology ; Disease Outbreaks/*statistics & numerical data ; Disease Reservoirs/*virology ; Ebolavirus/*isolation & purification/*pathogenicity/physiology ; Global Health ; Hemorrhagic Fever, Ebola/*epidemiology/immunology/therapy/*virology ; Humans ; Immunity, Innate ; Primates/virology ; Survival Rate ; Swine/virology ; Virology
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  • 182
    Publication Date: 2014-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fierer, Noah -- Cary, Craig -- England -- Nature. 2014 Aug 21;512(7514):253. doi: 10.1038/512253b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Colorado, Boulder, USA. ; University of Waikato, Hamilton, New Zealand.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143104" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Specimen Banks ; DNA/analysis/genetics ; *Microbiological Techniques ; Specimen Handling
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    Publication Date: 2014-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 Oct 23;514(7523):411-2. doi: 10.1038/514411a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25341765" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biohazard Release/*prevention & control ; Biological Warfare/prevention & control ; Directed Molecular Evolution/*legislation & jurisprudence ; Ferrets/virology ; Humans ; Influenza A Virus, H5N1 Subtype/genetics/pathogenicity ; Risk Assessment ; *Security Measures ; United States ; Virology/*legislation & jurisprudence
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  • 184
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Angela -- Robbins, Trevor -- England -- Nature. 2014 Dec 11;516(7530):170. doi: 10.1038/516170e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503225" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*physiology ; *Brain Mapping ; Callithrix/*physiology ; Humans ; *Models, Animal ; *Research
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  • 185
    Publication Date: 2014-08-15
    Description: The role of long noncoding RNA (lncRNA) in adult hearts is unknown; also unclear is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes undergo antisense transcription, including myosin heavy chain 7 (Myh7), which encodes molecular motor proteins for heart contraction. Here we identify a cluster of lncRNA transcripts from Myh7 loci and demonstrate a new lncRNA-chromatin mechanism for heart failure. In mice, these transcripts, which we named myosin heavy-chain-associated RNA transcripts (Myheart, or Mhrt), are cardiac-specific and abundant in adult hearts. Pathological stress activates the Brg1-Hdac-Parp chromatin repressor complex to inhibit Mhrt transcription in the heart. Such stress-induced Mhrt repression is essential for cardiomyopathy to develop: restoring Mhrt to the pre-stress level protects the heart from hypertrophy and failure. Mhrt antagonizes the function of Brg1, a chromatin-remodelling factor that is activated by stress to trigger aberrant gene expression and cardiac myopathy. Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus inhibiting chromatin targeting and gene regulation by Brg1. It does so by binding to the helicase domain of Brg1, a domain that is crucial for tethering Brg1 to chromatinized DNA targets. Brg1 helicase has dual nucleic-acid-binding specificities: it is capable of binding lncRNA (Mhrt) and chromatinized--but not naked--DNA. This dual-binding feature of helicase enables a competitive inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets to prevent chromatin remodelling. A Mhrt-Brg1 feedback circuit is thus crucial for heart function. Human MHRT also originates from MYH7 loci and is repressed in various types of myopathic hearts, suggesting a conserved lncRNA mechanism in human cardiomyopathy. Our studies identify a cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodelling factors, and establish a new paradigm for lncRNA-chromatin interaction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184960/" 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/PMC4184960/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Pei -- Li, Wei -- Lin, Chiou-Hong -- Yang, Jin -- Shang, Ching -- Nurnberg, Sylvia T -- Jin, Kevin Kai -- Xu, Weihong -- Lin, Chieh-Yu -- Lin, Chien-Jung -- Xiong, Yiqin -- Chien, Huan-Chieh -- Zhou, Bin -- Ashley, Euan -- Bernstein, Daniel -- Chen, Peng-Sheng -- Chen, Huei-Sheng Vincent -- Quertermous, Thomas -- Chang, Ching-Pin -- HL105194/HL/NHLBI NIH HHS/ -- HL109512/HL/NHLBI NIH HHS/ -- HL111770/HL/NHLBI NIH HHS/ -- HL116997/HL/NHLBI NIH HHS/ -- HL118087/HL/NHLBI NIH HHS/ -- HL121197/HL/NHLBI NIH HHS/ -- HL71140/HL/NHLBI NIH HHS/ -- HL78931/HL/NHLBI NIH HHS/ -- R01 HL111770/HL/NHLBI NIH HHS/ -- R01 HL116997/HL/NHLBI NIH HHS/ -- R01 HL121197/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):102-6. doi: 10.1038/nature13596. Epub 2014 Aug 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA [2] Division of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Division of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA [2]. ; Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Division of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA. ; Stanford Genome Technology Center, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Genetics, Pediatrics, and Medicine (Cardiology), Albert Einstein College of Medicine of Yeshiva University, 1301 Morris Park Avenue, Price Center 420, Bronx, New York 10461, USA. ; Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA. ; Del E. Webb Neuroscience, Aging &Stem Cell Research Center, Sanford/Burnham Medical Research Institute, La Jolla, California 92037, USA. ; 1] Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA [2] Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA [3] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119045" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiac Myosins/genetics ; Cardiomegaly/*genetics/*pathology/prevention & control ; Cardiomyopathies/genetics/pathology/prevention & control ; Chromatin/genetics/metabolism ; Chromatin Assembly and Disassembly ; DNA Helicases/antagonists & inhibitors/chemistry/genetics/metabolism ; Feedback, Physiological ; Heart Failure/genetics/pathology/prevention & control ; Histone Deacetylases/metabolism ; Humans ; Mice ; Myocardium/metabolism/pathology ; Myosin Heavy Chains/*genetics ; Nuclear Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Organ Specificity ; Poly(ADP-ribose) Polymerases/metabolism ; Protein Binding ; Protein Structure, Tertiary ; RNA, Long Noncoding/antagonists & inhibitors/*genetics/metabolism ; Transcription Factors/antagonists & inhibitors/chemistry/genetics/metabolism
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  • 186
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    Publication Date: 2014-08-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 Aug 14;512(7513):121-2. doi: 10.1038/512121a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119217" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms ; California ; *Droughts ; *Ecosystem ; Introduced Species
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  • 187
    Publication Date: 2014-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- Sutikna, Thomas -- Roberts, Richard -- Saptomo, Wahyu -- Brown, Peter -- Gee, Henry -- Dayton, Leigh -- Jungers, Bill -- Henneberg, Maciej -- Falk, Dean -- Martin, Robert -- Aiello, Leslie -- England -- Nature. 2014 Oct 23;514(7523):422-6. doi: 10.1038/514422a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25341771" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Caves ; Expeditions ; Female ; *Fossils ; Hominidae/*anatomy & histology/*classification ; Humans ; Indonesia ; Islands ; Microcephaly ; Skeleton ; Skull/anatomy & histology/pathology ; Species Specificity
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  • 188
    Publication Date: 2014-02-14
    Description: Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and that this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16(INK4a) (also called Cdkn2a). On injury, these cells fail to activate and expand, undergoing accelerated entry into a full senescence state (geroconversion), even in a youthful environment. p16(INK4a) silencing in geriatric satellite cells restores quiescence and muscle regenerative functions. Our results demonstrate that maintenance of quiescence in adult life depends on the active repression of senescence pathways. As p16(INK4a) is dysregulated in human geriatric satellite cells, these findings provide the basis for stem-cell rejuvenation in sarcopenic muscles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sousa-Victor, Pedro -- Gutarra, Susana -- Garcia-Prat, Laura -- Rodriguez-Ubreva, Javier -- Ortet, Laura -- Ruiz-Bonilla, Vanessa -- Jardi, Merce -- Ballestar, Esteban -- Gonzalez, Susana -- Serrano, Antonio L -- Perdiguero, Eusebio -- Munoz-Canoves, Pura -- England -- Nature. 2014 Feb 20;506(7488):316-21. doi: 10.1038/nature13013. Epub 2014 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University, CIBER on Neurodegenerative diseases, E-08003 Barcelona, Spain [2] Buck Institute for Research on Aging, Novato, California 94945, USA. ; 1] Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University, CIBER on Neurodegenerative diseases, E-08003 Barcelona, Spain [2]. ; Chromatin and Disease Group, Cancer Epigenetics and Biology Programme, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, E-08907 Barcelona, Spain. ; Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University, CIBER on Neurodegenerative diseases, E-08003 Barcelona, Spain. ; Stem Cell Aging Group, Centro Nacional de Investigaciones Cardiovasculares, E-28029 Madrid, Spain. ; 1] Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University, CIBER on Neurodegenerative diseases, E-08003 Barcelona, Spain [2] Institucio Catalana de Recerca i Estudis Avancats, E-08010 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522534" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aging/*metabolism ; Animals ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/deficiency/genetics/*metabolism ; E2F1 Transcription Factor/metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Progeria/metabolism/pathology ; Regeneration ; Rejuvenation ; Retinoblastoma Protein/metabolism ; Satellite Cells, Skeletal Muscle/*cytology/*metabolism ; Young Adult
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  • 189
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mooers, Arne O -- England -- Nature. 2014 May 8;509(7499):171-2. doi: 10.1038/nature13332. Epub 2014 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department and the Human Evolutionary Studies Program, Simon Fraser University, Burnaby, British Columbia V5A1S6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24776802" target="_blank"〉PubMed〈/a〉
    Keywords: *Altitude ; Animals ; *Ecosystem ; *Genetic Speciation ; Songbirds/*classification/*physiology
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  • 190
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉El-Boustani, Sami -- Wilson, Nathan R -- Runyan, Caroline A -- Sur, Mriganka -- England -- Nature. 2014 Apr 3;508(7494):E3-4. doi: 10.1038/nature13130.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695315" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Neural Inhibition/*physiology ; Neural Pathways/*physiology ; Neurons/*physiology ; Visual Cortex/*cytology/*physiology
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  • 191
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    Nature Publishing Group (NPG)
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 Sep 25;513(7519):471. doi: 10.1038/513471a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254455" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Diseases/drug therapy/microbiology/*prevention & control ; Animals ; Animals, Domestic/growth & development/microbiology ; *Anti-Bacterial Agents/administration & dosage/pharmacology/therapeutic use ; Bacterial Infections/*drug therapy/prevention & control/transmission/veterinary ; Clinical Trials as Topic ; *Drug Discovery ; *Drug Resistance, Microbial/drug effects ; Government Regulation ; Humans ; Time Factors ; United States ; United States Food and Drug Administration/legislation & jurisprudence ; Zoonoses/microbiology/prevention & control
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  • 192
    Publication Date: 2014-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanage, William P -- England -- Nature. 2014 Aug 21;512(7514):247-8. doi: 10.1038/512247a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard School of Public Health in Boston, Massachusetts, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143098" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; *Microbiota/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Science/*standards ; *Uncertainty
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  • 193
    Publication Date: 2014-10-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomassen, Mary Jane -- Kavuru, Mani S -- England -- Nature. 2014 Oct 23;514(7523):438-40. doi: 10.1038/nature13758. Epub 2014 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, North Carolina 27834, USA. ; Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania 19107, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25274303" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Transplantation ; Cytokine Receptor Common beta Subunit/*genetics ; Female ; *Genetic Therapy ; Lung/*cytology ; Macrophages, Alveolar/*metabolism/*transplantation ; Male ; Pulmonary Alveolar Proteinosis/*therapy
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  • 194
    Publication Date: 2014-02-21
    Description: Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murthy, Aditya -- Li, Yun -- Peng, Ivan -- Reichelt, Mike -- Katakam, Anand Kumar -- Noubade, Rajkumar -- Roose-Girma, Merone -- DeVoss, Jason -- Diehl, Lauri -- Graham, Robert R -- van Lookeren Campagne, Menno -- England -- Nature. 2014 Feb 27;506(7489):456-62. doi: 10.1038/nature13044. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; ITGR Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553140" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Autophagy/genetics ; Carrier Proteins/chemistry/*genetics/*metabolism ; Caspase 3/deficiency/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Crohn Disease/*genetics/pathology ; Cytokines/immunology ; Enzyme Activation ; Female ; Food Deprivation ; Humans ; Macrophages/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mutagenesis, Site-Directed ; Polymorphism, Single Nucleotide/*genetics ; *Proteolysis ; Stress, Physiological ; Yersinia enterocolitica/immunology
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  • 195
    Publication Date: 2014-06-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hirsch, Emilio -- Novelli, Francesco -- England -- Nature. 2014 Jun 19;510(7505):342-3. doi: 10.1038/nature13503. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy. ; Center for Experimental Research and Medical Studies, Department of Molecular Biotechnology and Health Sciences, University of Turin.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919150" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Inhibitors/*pharmacology ; Immune Tolerance/*drug effects ; Neoplasms/*enzymology/*immunology ; Phosphatidylinositol 3-Kinases/*metabolism ; T-Lymphocytes, Regulatory/*drug effects
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  • 196
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 May 29;509(7502):542-3. doi: 10.1038/509542a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870521" target="_blank"〉PubMed〈/a〉
    Keywords: Alaska ; Animals ; Aquatic Organisms ; Arctic Regions ; Ecology/*instrumentation ; *Ecosystem ; *Expeditions ; Ice Cover ; Oceanography/*instrumentation ; *Ships
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  • 197
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 Jun 12;510(7504):196-7. doi: 10.1038/510196a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919901" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Environmental Monitoring/instrumentation/methods ; Humans ; Hypogravity ; Laboratories/*utilization ; Mice ; *Research/trends ; Russia ; *Spacecraft ; Time Factors ; United States ; United States National Aeronautics and Space Administration
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  • 198
    Publication Date: 2014-02-28
    Description: The hippocampus is critical for encoding declarative memory, our repository of knowledge of who, what, where and when. Mnemonic information is processed in the hippocampus through several parallel routes involving distinct subregions. In the classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to dentate gyrus to CA3 and then to CA1, the main hippocampal output. Genetic lesions of EC (ref. 3) and hippocampal dentate gyrus (ref. 4), CA3 (ref. 5) and CA1 (ref. 6) regions have revealed their distinct functions in learning and memory. In contrast, little is known about the role of CA2, a relatively small area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic circuit linking EC input with CA1 output. Here we report a novel transgenic mouse line that enabled us to selectively examine the synaptic connections and behavioural role of the CA2 region in adult mice. Genetically targeted inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory--the ability of an animal to remember a conspecific--with no change in sociability or several other hippocampus-dependent behaviours, including spatial and contextual memory. These behavioural and anatomical results thus reveal CA2 as a critical hub of sociocognitive memory processing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000264/" 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/PMC4000264/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hitti, Frederick L -- Siegelbaum, Steven A -- F30 MH098633/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 3;508(7494):88-92. doi: 10.1038/nature13028. Epub 2014 Feb 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Drive, New York, New York 10032, USA. ; 1] Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Drive, New York, New York 10032, USA [2] Department of Pharmacology, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Drive, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572357" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/physiopathology ; CA2 Region, Hippocampal/cytology/*physiology ; Electrophysiology ; Female ; Integrases/genetics/metabolism ; Male ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pyramidal Cells/physiology ; Schizophrenia/physiopathology ; *Social Behavior ; Space Perception/physiology ; Synapses/metabolism
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  • 199
    Publication Date: 2014-07-22
    Description: Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized by elevated glycogen levels and fat deposition. These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs) secondary to von Hippel-Lindau (VHL) mutations that occur in over 90% of ccRCC tumours. However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation, suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1-associated protein-1, among others), indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients. Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin, thereby inhibiting a potential Warburg effect. Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162811/" 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/PMC4162811/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Bo -- Qiu, Bo -- Lee, David S M -- Walton, Zandra E -- Ochocki, Joshua D -- Mathew, Lijoy K -- Mancuso, Anthony -- Gade, Terence P F -- Keith, Brian -- Nissim, Itzhak -- Simon, M Celeste -- CA104838/CA/NCI NIH HHS/ -- DK053761/DK/NIDDK NIH HHS/ -- F30 CA177106/CA/NCI NIH HHS/ -- F32 CA192758/CA/NCI NIH HHS/ -- P01 CA104838/CA/NCI NIH HHS/ -- P30 CA016520/CA/NCI NIH HHS/ -- R01 DK053761/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Sep 11;513(7517):251-5. doi: 10.1038/nature13557. Epub 2014 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [3] Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Department of Pediatrics, Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Division of Child Development and Metabolic Disease, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19104, USA [3] Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043030" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Carcinoma, Renal Cell/*enzymology/genetics/physiopathology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Epithelial Cells/metabolism ; Fructose-Bisphosphatase/chemistry/genetics/*metabolism ; Glycolysis ; Humans ; Kidney Neoplasms/*enzymology/genetics/physiopathology ; Models, Molecular ; NADP/metabolism ; Protein Structure, Tertiary ; Swine
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  • 200
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2014 Oct 9;514(7521):154-7. doi: 10.1038/514154a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297416" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Entorhinal Cortex/*cytology/*physiology ; History, 21st Century ; Humans ; Memory/physiology ; Neurosciences/*history ; *Nobel Prize ; Norway ; Orientation/*physiology ; Rats ; Space Perception/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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