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  • 1
    Publication Date: 2014-12-30
    Description: The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667810/" 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/PMC4667810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naik, Shruti -- Bouladoux, Nicolas -- Linehan, Jonathan L -- Han, Seong-Ji -- Harrison, Oliver J -- Wilhelm, Christoph -- Conlan, Sean -- Himmelfarb, Sarah -- Byrd, Allyson L -- Deming, Clayton -- Quinones, Mariam -- Brenchley, Jason M -- Kong, Heidi H -- Tussiwand, Roxanne -- Murphy, Kenneth M -- Merad, Miriam -- Segre, Julia A -- Belkaid, Yasmine -- R01 CA173861/CA/NCI NIH HHS/ -- R01 CA190400/CA/NCI NIH HHS/ -- U01 AI095611/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2015 Apr 2;520(7545):104-8. doi: 10.1038/nature14052. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA. ; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA [3] Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA. ; 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Immunopathogenesis Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA. ; Dermatology Branch, National Cancer Institute, NIH Bethesda, Maryland 20892, USA. ; Howard Hughes Medical Institute, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Bacterial/immunology ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Dendritic Cells/cytology/*immunology ; Humans ; Immunity, Innate/immunology ; Interleukin-17/immunology ; Langerhans Cells/cytology/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Primates ; Skin/cytology/*immunology/*microbiology ; Staphylococcus epidermidis/immunology ; Symbiosis/*immunology
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    Electronic ISSN: 1476-4687
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  • 2
    Publication Date: 2014-12-24
    Description: The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jihye -- Ishiguro, Kei-ichiro -- Nambu, Aya -- Akiyoshi, Bungo -- Yokobayashi, Shihori -- Kagami, Ayano -- Ishiguro, Tadashi -- Pendas, Alberto M -- Takeda, Naoki -- Sakakibara, Yogo -- Kitajima, Tomoya S -- Tanno, Yuji -- Sakuno, Takeshi -- Watanabe, Yoshinori -- England -- Nature. 2015 Jan 22;517(7535):466-71. doi: 10.1038/nature14097. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan. ; Instituto de Biologia Molecular y Celular del Cancer (CSIC-USAL), 37007 Salamanca, Spain. ; Center for Animal Resources and Development, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 Japan. ; Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/metabolism ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/deficiency/genetics/*metabolism ; *Conserved Sequence ; Female ; Humans ; Infertility/genetics/metabolism ; Kinetochores/*metabolism ; Male ; *Meiosis ; Mice ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Schizosaccharomyces pombe Proteins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-12-24
    Description: Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ- and injury-specific. Current models in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers. By contrast, here we define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEP) cells present within normal distal lung. Quiescent LNEPs activate a DeltaNp63 (a p63 splice variant) and cytokeratin 5 remodelling program after influenza or bleomycin injury in mice. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, at which point they differentiate towards mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single-cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signalling to activate the DeltaNp63 and cytokeratin 5 program, and subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signalling after injury led to parenchymal 'micro-honeycombing' (alveolar cysts), indicative of failed regeneration. Lungs from patients with fibrosis show analogous honeycomb cysts with evidence of hyperactive Notch signalling. Our findings indicate that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312207/" 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/PMC4312207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vaughan, Andrew E -- Brumwell, Alexis N -- Xi, Ying -- Gotts, Jeffrey E -- Brownfield, Doug G -- Treutlein, Barbara -- Tan, Kevin -- Tan, Victor -- Liu, Feng Chun -- Looney, Mark R -- Matthay, Michael A -- Rock, Jason R -- Chapman, Harold A -- F32 HL117600-01/HL/NHLBI NIH HHS/ -- R01 HL44712/HL/NHLBI NIH HHS/ -- U01 HL099995/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- U01 HL111054/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 29;517(7536):621-5. doi: 10.1038/nature14112. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA. ; Department of Biochemistry, Stanford University School of Medicine and Howard Hughes Medical Institute, Stanford, California 94305, USA. ; Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Anatomy, School of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533958" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bleomycin ; Cell Lineage ; Cell Proliferation ; Cell Separation ; Cysts/metabolism/pathology ; Epithelial Cells/*cytology/metabolism/*pathology ; Female ; Humans ; Keratin-5/metabolism ; Lung/*cytology/*pathology/physiology ; Lung Injury/chemically induced/*pathology/virology ; Male ; Mice ; Orthomyxoviridae Infections/pathology/virology ; Phosphoproteins/genetics/metabolism ; *Re-Epithelialization ; Receptors, Notch/metabolism ; Signal Transduction ; Stem Cell Transplantation ; Stem Cells/*cytology/metabolism ; Trans-Activators/genetics/metabolism
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  • 4
    Publication Date: 2014-12-24
    Description: Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deciphering Developmental Disorders Study -- 098395/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- CZD/16/6/Chief Scientist Office/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Department of Health/United Kingdom -- England -- Nature. 2015 Mar 12;519(7542):223-8. doi: 10.1038/nature14135. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533962" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Animals ; Carrier Proteins/genetics ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone/genetics ; Chromosome Aberrations ; DEAD-box RNA Helicases/genetics ; DNA-Binding Proteins/genetics ; Developmental Disabilities/*diagnosis/*genetics ; Dynamin I/genetics ; Exome/genetics ; Female ; Gene Expression Regulation, Developmental ; Genes, Dominant/genetics ; Genome, Human/genetics ; Great Britain ; Guanine Nucleotide Exchange Factors/genetics ; Homeodomain Proteins/genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation, Missense/genetics ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Parents ; Phosphoproteins/genetics ; Polycomb Repressive Complex 1/genetics ; Protein Phosphatase 2/genetics ; Protein-Serine-Threonine Kinases/genetics ; Rare Diseases/genetics ; Transcription Factors/genetics ; Transposases/genetics ; Zebrafish/genetics
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  • 5
    Publication Date: 2014-12-24
    Description: Models derived from human pluripotent stem cells that accurately recapitulate neural development in vitro and allow for the generation of specific neuronal subtypes are of major interest to the stem cell and biomedical community. Notch signalling, particularly through the Notch effector HES5, is a major pathway critical for the onset and maintenance of neural progenitor cells in the embryonic and adult nervous system. Here we report the transcriptional and epigenomic analysis of six consecutive neural progenitor cell stages derived from a HES5::eGFP reporter human embryonic stem cell line. Using this system, we aimed to model cell-fate decisions including specification, expansion and patterning during the ontogeny of cortical neural stem and progenitor cells. In order to dissect regulatory mechanisms that orchestrate the stage-specific differentiation process, we developed a computational framework to infer key regulators of each cell-state transition based on the progressive remodelling of the epigenetic landscape and then validated these through a pooled short hairpin RNA screen. We were also able to refine our previous observations on epigenetic priming at transcription factor binding sites and suggest here that they are mediated by combinations of core and stage-specific factors. Taken together, we demonstrate the utility of our system and outline a general framework, not limited to the context of the neural lineage, to dissect regulatory circuits of differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336237/" 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/PMC4336237/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ziller, Michael J -- Edri, Reuven -- Yaffe, Yakey -- Donaghey, Julie -- Pop, Ramona -- Mallard, William -- Issner, Robbyn -- Gifford, Casey A -- Goren, Alon -- Xing, Jeffrey -- Gu, Hongcang -- Cacchiarelli, Davide -- Tsankov, Alexander M -- Epstein, Charles -- Rinn, John L -- Mikkelsen, Tarjei S -- Kohlbacher, Oliver -- Gnirke, Andreas -- Bernstein, Bradley E -- Elkabetz, Yechiel -- Meissner, Alexander -- F32 DK095537/DK/NIDDK NIH HHS/ -- HG006911/HG/NHGRI NIH HHS/ -- P01 GM099117/GM/NIGMS NIH HHS/ -- P01GM099117/GM/NIGMS NIH HHS/ -- U01 ES017155/ES/NIEHS NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- England -- Nature. 2015 Feb 19;518(7539):355-9. doi: 10.1038/nature13990. Epub 2014 Dec 24.〈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. ; Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 6997801, Israel. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA [3] Center for Systems Biology and Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Applied Bioinformatics, Center for Bioinformatics and Quantitative Biology Center, University of Tubingen, Tubingen 72076, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533951" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Embryonic Stem Cells/*cytology/metabolism ; Epigenesis, Genetic/*genetics ; Epigenomics/*methods ; Humans ; Neural Stem Cells/*cytology/*metabolism ; RNA, Small Interfering/analysis/genetics ; Reproducibility of Results ; Transcription Factors/metabolism ; Transcription, Genetic/genetics
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  • 6
    Publication Date: 2014-12-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachibana-Konwalski, Kikue -- England -- Nature. 2015 Jan 22;517(7535):441-2. doi: 10.1038/nature14087. Epub 2014 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533954" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomal Proteins, Non-Histone/*metabolism ; *Conserved Sequence ; Female ; Humans ; Kinetochores/*metabolism ; Male ; *Meiosis
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    Electronic ISSN: 1476-4687
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  • 7
    Publication Date: 2014-12-24
    Description: Intrinsically disordered proteins play important roles in cell signalling, transcription, translation and cell cycle regulation. Although they lack stable tertiary structure, many intrinsically disordered proteins undergo disorder-to-order transitions upon binding to partners. Similarly, several folded proteins use regulated order-to-disorder transitions to mediate biological function. In principle, the function of intrinsically disordered proteins may be controlled by post-translational modifications that lead to structural changes such as folding, although this has not been observed. Here we show that multisite phosphorylation induces folding of the intrinsically disordered 4E-BP2, the major neural isoform of the family of three mammalian proteins that bind eIF4E and suppress cap-dependent translation initiation. In its non-phosphorylated state, 4E-BP2 interacts tightly with eIF4E using both a canonical YXXXXLPhi motif (starting at Y54) that undergoes a disorder-to-helix transition upon binding and a dynamic secondary binding site. We demonstrate that phosphorylation at T37 and T46 induces folding of residues P18-R62 of 4E-BP2 into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking its accessibility to eIF4E. The folded state of pT37pT46 4E-BP2 is weakly stable, decreasing affinity by 100-fold and leading to an order-to-disorder transition upon binding to eIF4E, whereas fully phosphorylated 4E-BP2 is more stable, decreasing affinity by a factor of approximately 4,000. These results highlight stabilization of a phosphorylation-induced fold as the essential mechanism for phospho-regulation of the 4E-BP:eIF4E interaction and exemplify a new mode of biological regulation mediated by intrinsically disordered proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bah, Alaji -- Vernon, Robert M -- Siddiqui, Zeba -- Krzeminski, Mickael -- Muhandiram, Ranjith -- Zhao, Charlie -- Sonenberg, Nahum -- Kay, Lewis E -- Forman-Kay, Julie D -- MOP-114985/Canadian Institutes of Health Research/Canada -- MOP-119579/Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Mar 5;519(7541):106-9. doi: 10.1038/nature13999. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada [2] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada. ; 1] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada. ; 1] Molecular Structure and Function Program, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada [2] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4] Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533957" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Eukaryotic Initiation Factor-4E/*chemistry/*metabolism ; Eukaryotic Initiation Factors/*chemistry/*metabolism ; Humans ; Intrinsically Disordered Proteins/*chemistry/*metabolism ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Phosphorylation ; Protein Binding ; *Protein Folding ; Protein Structure, Secondary ; Signal Transduction
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  • 8
    Publication Date: 2014-12-24
    Description: Obesity is an increasingly prevalent disease regulated by genetic and environmental factors. Emerging studies indicate that immune cells, including monocytes, granulocytes and lymphocytes, regulate metabolic homeostasis and are dysregulated in obesity. Group 2 innate lymphoid cells (ILC2s) can regulate adaptive immunity and eosinophil and alternatively activated macrophage responses, and were recently identified in murine white adipose tissue (WAT) where they may act to limit the development of obesity. However, ILC2s have not been identified in human adipose tissue, and the mechanisms by which ILC2s regulate metabolic homeostasis remain unknown. Here we identify ILC2s in human WAT and demonstrate that decreased ILC2 responses in WAT are a conserved characteristic of obesity in humans and mice. Interleukin (IL)-33 was found to be critical for the maintenance of ILC2s in WAT and in limiting adiposity in mice by increasing caloric expenditure. This was associated with recruitment of uncoupling protein 1 (UCP1)(+) beige adipocytes in WAT, a process known as beiging or browning that regulates caloric expenditure. IL-33-induced beiging was dependent on ILC2s, and IL-33 treatment or transfer of IL-33-elicited ILC2s was sufficient to drive beiging independently of the adaptive immune system, eosinophils or IL-4 receptor signalling. We found that ILC2s produce methionine-enkephalin peptides that can act directly on adipocytes to upregulate Ucp1 expression in vitro and that promote beiging in vivo. Collectively, these studies indicate that, in addition to responding to infection or tissue damage, ILC2s can regulate adipose function and metabolic homeostasis in part via production of enkephalin peptides that elicit beiging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447235/" 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/PMC4447235/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brestoff, Jonathan R -- Kim, Brian S -- Saenz, Steven A -- Stine, Rachel R -- Monticelli, Laurel A -- Sonnenberg, Gregory F -- Thome, Joseph J -- Farber, Donna L -- Lutfy, Kabirullah -- Seale, Patrick -- Artis, David -- 2-P30 CA016520/CA/NCI NIH HHS/ -- AI061570/AI/NIAID NIH HHS/ -- AI074878/AI/NIAID NIH HHS/ -- AI095466/AI/NIAID NIH HHS/ -- AI095608/AI/NIAID NIH HHS/ -- AI097333/AI/NIAID NIH HHS/ -- AI102942/AI/NIAID NIH HHS/ -- DP2 OD007288/OD/NIH HHS/ -- DP2OD007288/OD/NIH HHS/ -- DP5 OD012116/OD/NIH HHS/ -- DP5OD012116/OD/NIH HHS/ -- F30 AI112023/AI/NIAID NIH HHS/ -- F30-AI112023/AI/NIAID NIH HHS/ -- F31 AG047003/AG/NIA NIH HHS/ -- F31AG047003/AG/NIA NIH HHS/ -- K08 AR065577/AR/NIAMS NIH HHS/ -- KL2-RR024132/RR/NCRR NIH HHS/ -- P01 AI106697/AI/NIAID NIH HHS/ -- P01AI06697/AI/NIAID NIH HHS/ -- P30 AR057217/AR/NIAMS NIH HHS/ -- P30 DK019525/DK/NIDDK NIH HHS/ -- P30-DK050306/DK/NIDDK NIH HHS/ -- P30DK19525/DK/NIDDK NIH HHS/ -- R01 AI061570/AI/NIAID NIH HHS/ -- R01 AI074878/AI/NIAID NIH HHS/ -- R01 AI095466/AI/NIAID NIH HHS/ -- R01 AI097333/AI/NIAID NIH HHS/ -- R01 AI102942/AI/NIAID NIH HHS/ -- T32 AI060516/AI/NIAID NIH HHS/ -- T32-AI007532/AI/NIAID NIH HHS/ -- T32-AI060516/AI/NIAID NIH HHS/ -- U01 AI095608/AI/NIAID NIH HHS/ -- England -- Nature. 2015 Mar 12;519(7542):242-6. doi: 10.1038/nature14115. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Jill Roberts Institute for Research in IBD, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, New York 10021, USA [2] Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Institute for Diabetes, Obesity and Metabolism, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Jill Roberts Institute for Research in IBD, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, New York 10021, USA. ; 1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York 10032, USA [2] Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA. ; 1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York 10032, USA [2] Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA [3] Department of Surgery, Columbia University Medical Center, New York, New York 10032, USA. ; Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California 91766, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533952" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/drug effects ; Adipose Tissue, White/*cytology/*immunology ; Animals ; Energy Metabolism/immunology ; Enkephalin, Methionine/biosynthesis/metabolism ; Eosinophils/immunology/metabolism ; Female ; Homeostasis/drug effects ; Humans ; Immunity, Innate/*immunology ; Interleukins/immunology/pharmacology ; Ion Channels/metabolism ; Lymphocytes/cytology/immunology/*physiology ; Male ; Mice ; Mitochondrial Proteins/metabolism ; Obesity/*immunology/pathology ; Receptors, Interleukin-4/immunology/metabolism
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  • 9
    Publication Date: 2014-12-24
    Description: The orexin (also known as hypocretin) G protein-coupled receptors (GPCRs) respond to orexin neuropeptides in the central nervous system to regulate sleep and other behavioural functions in humans. Defects in orexin signalling are responsible for the human diseases of narcolepsy and cataplexy; inhibition of orexin receptors is an effective therapy for insomnia. The human OX2 receptor (OX2R) belongs to the beta branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant. Here, using lipid-mediated crystallization and protein engineering with a novel fusion chimaera, we solved the structure of the human OX2R bound to suvorexant at 2.5 A resolution. The structure reveals how suvorexant adopts a pi-stacked horseshoe-like conformation and binds to the receptor deep in the orthosteric pocket, stabilizing a network of extracellular salt bridges and blocking transmembrane helix motions necessary for activation. Computational docking suggests how other classes of synthetic antagonists may interact with the receptor at a similar position in an analogous pi-stacked fashion. Elucidation of the molecular architecture of the human OX2R expands our understanding of peptidergic GPCR ligand recognition and will aid further efforts to modulate orexin signalling for therapeutic ends.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yin, Jie -- Mobarec, Juan Carlos -- Kolb, Peter -- Rosenbaum, Daniel M -- England -- Nature. 2015 Mar 12;519(7542):247-50. doi: 10.1038/nature14035. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Pharmaceutical Chemistry, Philipps-University Marburg, 35032 Marburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533960" target="_blank"〉PubMed〈/a〉
    Keywords: Azepines/*chemistry/metabolism/*pharmacology ; Crystallography, X-Ray ; Humans ; Molecular Docking Simulation ; *Orexin Receptor Antagonists ; Orexin Receptors/*chemistry/metabolism ; Protein Conformation ; Receptors, G-Protein-Coupled/antagonists & inhibitors/chemistry/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Sleep Initiation and Maintenance Disorders/drug therapy ; Triazoles/*chemistry/metabolism/*pharmacology
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  • 10
    Publication Date: 2014-12-24
    Description: Resveratrol is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects by initiating a stress response that induces survival genes. Because human tyrosyl transfer-RNA (tRNA) synthetase (TyrRS) translocates to the nucleus under stress conditions, we considered the possibility that the tyrosine-like phenolic ring of resveratrol might fit into the active site pocket to effect a nuclear role. Here we present a 2.1 A co-crystal structure of resveratrol bound to the active site of TyrRS. Resveratrol nullifies the catalytic activity and redirects TyrRS to a nuclear function, stimulating NAD(+)-dependent auto-poly-ADP-ribosylation of poly(ADP-ribose) polymerase 1 (PARP1). Downstream activation of key stress signalling pathways are causally connected to TyrRS-PARP1-NAD(+) collaboration. This collaboration is also demonstrated in the mouse, and is specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analogue. In contrast to functionally diverse tRNA synthetase catalytic nulls created by alternative splicing events that ablate active sites, here a non-spliced TyrRS catalytic null reveals a new PARP1- and NAD(+)-dependent dimension to the physiological mechanism of resveratrol.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368482/" 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/PMC4368482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sajish, Mathew -- Schimmel, Paul -- CA92577/CA/NCI NIH HHS/ -- R01 CA092577/CA/NCI NIH HHS/ -- England -- Nature. 2015 Mar 19;519(7543):370-3. doi: 10.1038/nature14028. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research, Department of Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. ; 1] The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research, Department of Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] The Scripps Florida Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533949" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Animals ; Biocatalysis/drug effects ; Catalytic Domain ; Cell Nucleus/enzymology ; Crystallography, X-Ray ; Culture Media, Serum-Free ; Enzyme Activation/drug effects ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Poly Adenosine Diphosphate Ribose/metabolism ; Poly(ADP-ribose) Polymerases/chemistry/*metabolism ; Protein Conformation ; Signal Transduction/drug effects ; Sirtuin 1/metabolism ; Sirtuins/metabolism ; Stilbenes/antagonists & inhibitors/chemistry/*pharmacology ; Tyrosine-tRNA Ligase/*antagonists & inhibitors/chemistry/*metabolism
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  • 11
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- Kaiser, Jocelyn -- Service, Robert F -- Gibbons, Ann -- Vogel, Gretchen -- Underwood, Emily -- Hand, Eric -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1444-9. doi: 10.1126/science.346.6216.1444. Epub 2014 Dec 18.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525224" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*trends ; Humans ; Mice
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  • 12
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becher, Oren J -- Wechsler-Reya, Robert J -- R01 CA159859/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1458-9. doi: 10.1126/science.aaa3814.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pediatric Hematology-Oncology, Department of Pathology, and Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, 27710, USA. rwreya@sanfordburnham.org oren.becher@duke.edu. ; Tumor Initiation & Maintenance Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, 92037, USA. rwreya@sanfordburnham.org oren.becher@duke.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525232" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Stem Neoplasms/*genetics ; Cell Transformation, Neoplastic/*genetics ; Embryonic Stem Cells/*metabolism ; Glioma/*genetics ; Histones/*genetics ; Humans ; *Models, Genetic ; Neural Stem Cells/*metabolism
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1450-1. doi: 10.1126/science.346.6216.1450-b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525227" target="_blank"〉PubMed〈/a〉
    Keywords: *Global Health ; Hemorrhagic Fever, Ebola/*epidemiology ; Humans ; Liberia/epidemiology ; Missionaries ; World Health Organization
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2014 Dec 19;346(6216):1450. doi: 10.1126/science.346.6216.1450-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525226" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*trends ; Humans
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2014 Dec 19;346(6216):1449. doi: 10.1126/science.346.6216.1449.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525225" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*ethics/*trends ; Humans
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  • 16
    Publication Date: 2014-12-20
    Description: The conservation of large carnivores is a formidable challenge for biodiversity conservation. Using a data set on the past and current status of brown bears (Ursus arctos), Eurasian lynx (Lynx lynx), gray wolves (Canis lupus), and wolverines (Gulo gulo) in European countries, we show that roughly one-third of mainland Europe hosts at least one large carnivore species, with stable or increasing abundance in most cases in 21st-century records. The reasons for this overall conservation success include protective legislation, supportive public opinion, and a variety of practices making coexistence between large carnivores and people possible. The European situation reveals that large carnivores and people can share the same landscape.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapron, Guillaume -- Kaczensky, Petra -- Linnell, John D C -- von Arx, Manuela -- Huber, Djuro -- Andren, Henrik -- Lopez-Bao, Jose Vicente -- Adamec, Michal -- Alvares, Francisco -- Anders, Ole -- Balciauskas, Linas -- Balys, Vaidas -- Bedo, Peter -- Bego, Ferdinand -- Blanco, Juan Carlos -- Breitenmoser, Urs -- Broseth, Henrik -- Bufka, Ludek -- Bunikyte, Raimonda -- Ciucci, Paolo -- Dutsov, Alexander -- Engleder, Thomas -- Fuxjager, Christian -- Groff, Claudio -- Holmala, Katja -- Hoxha, Bledi -- Iliopoulos, Yorgos -- Ionescu, Ovidiu -- Jeremic, Jasna -- Jerina, Klemen -- Kluth, Gesa -- Knauer, Felix -- Kojola, Ilpo -- Kos, Ivan -- Krofel, Miha -- Kubala, Jakub -- Kunovac, Sasa -- Kusak, Josip -- Kutal, Miroslav -- Liberg, Olof -- Majic, Aleksandra -- Mannil, Peep -- Manz, Ralph -- Marboutin, Eric -- Marucco, Francesca -- Melovski, Dime -- Mersini, Kujtim -- Mertzanis, Yorgos -- Myslajek, Robert W -- Nowak, Sabina -- Odden, John -- Ozolins, Janis -- Palomero, Guillermo -- Paunovic, Milan -- Persson, Jens -- Potocnik, Hubert -- Quenette, Pierre-Yves -- Rauer, Georg -- Reinhardt, Ilka -- Rigg, Robin -- Ryser, Andreas -- Salvatori, Valeria -- Skrbinsek, Tomaz -- Stojanov, Aleksandar -- Swenson, Jon E -- Szemethy, Laszlo -- Trajce, Aleksander -- Tsingarska-Sedefcheva, Elena -- Vana, Martin -- Veeroja, Rauno -- Wabakken, Petter -- Wolfl, Manfred -- Wolfl, Sybille -- Zimmermann, Fridolin -- Zlatanova, Diana -- Boitani, Luigi -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1517-9. doi: 10.1126/science.1257553.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Grimso Wildlife Research Station, Department of Ecology, Swedish University of Agricultural Sciences, 73091 Riddarhyttan, Sweden. gchapron@carnivoreconservation.org guillaume.chapron@slu.se. ; Research Institute of Wildlife Ecology, University of Veterinary Medicine, Vienna, Savoyenstrasse 1, 1160 Vienna, Austria. ; Norwegian Institute for Nature Research, Post Office Box 5685 Sluppen, 7485 Trondheim, Norway. ; KORA, Thunstrasse 31, 3074 Muri bei Bern, Switzerland. ; Biology Department of the Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia. ; Grimso Wildlife Research Station, Department of Ecology, Swedish University of Agricultural Sciences, 73091 Riddarhyttan, Sweden. ; Grimso Wildlife Research Station, Department of Ecology, Swedish University of Agricultural Sciences, 73091 Riddarhyttan, Sweden. Research Unit of Biodiversity (UO/CSIC/PA), Oviedo University, 33600 Mieres, Spain. ; State Nature Conservancy of Slovak Republic, Tajovskeho 28B, 974 01 Banska Bystrica, Slovakia. ; CIBIO/InBio, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Universidade do Porto, 4485-661 Vairao, Portugal. ; Harz Nationalpark, Lindenallee 35, 38855 Wernigerode, Germany. ; Nature Research Centre, Akademijos 2, 08412 Vilnius, Lithuania. ; Association for Nature Conservation "Baltijos vilkas," Visoriu 6A-54, 08300 Vilnius, Lithuania. ; Slovak Wildlife Society, Post Office Box 72, 03301 Liptovsky Hradok, Slovakia. ; Biology Department of the Faculty of Natural Sciences, University of Tirana, Boulevard Zog I, Tirana, Albania. ; Wolf Project, Consultores en Biologia de la Conservacion, Calle Manuela Malasana 24, 28004 Madrid, Spain. ; KORA, Thunstrasse 31, 3074 Muri bei Bern, Switzerland. Centre for Fish and Wildlife Health, Vetsuisse Faculty, University of Bern, Langgassstrasse 122, 3012 Bern, Switzerland. ; Department of Game Management and Wildlife Biology, Czech University of Life Sciences in Prague, Kamycka 129, 165 21 Prague, Czech Republic. ; Ministry of Environment of the Republic of Lithuania, Jaksto 4/9, 01105 Vilnius, Lithuania. ; Department of Biology and Biotechnologies, University of Rome "La Sapienza," Viale dell'Universita 32, 00185 Roma, Italy. ; Balkani Wildlife Society, Boulevard Dragan Tzankov 8, 1164 Sofia, Bulgaria. ; Lynx Project Austria Northwest, Linzerstrasse 14, 4170 Haslach/Muhl, Austria. ; Nationalpark Kalkalpen, Nationalpark Zentrum Molln, Nationalpark Allee 1, 4591 Molln, Austria. ; Provincia Autonoma di Trento - Servizio Foreste e Fauna, Via Trener no. 3, 38100 Trento, Italy. ; Finnish Game and Fisheries Research Institute, Viikinkaari 4, 00790 Helsinki, Finland. ; Protection and Preservation of Natural Environment in Albania, Rruga Vangjush Furxhi 16/1/10, Tirana, Albania. ; Callisto Wildlife and Nature Conservation Society, Mitropoleos 123, 54621 Thessaloniki, Greece. ; Faculty of Silviculture and Forest Engineering, Department of Silviculture, Transilvania University, 1 Beethoven Lane, 500123 Brasov, Romania. Forest Research Institute (ICAS) Bulevardul Eroilor Number 128, Voluntari, Ilfov, 077190 Romania. ; State Institute for Nature Protection, Trg Mazuranica 5, 10000 Zagreb, Croatia. ; University of Ljubljana, Biotechnical Faculty, Jamnikarjeva 101, 1000 Ljubljana, Slovenia. ; LUPUS - German Institute for Wolf Mnitoring and Research, Dorfstrasse 20, 02979 Spreewitz, Germany. ; Finnish Game and Fisheries Research Institute, Oulu Game and Fisheries Research, Tutkijantie 2E, 90570 Oulu, Finland. ; Department of Forest Protection and Game Management, Faculty of Forestry, Technical University of Zvolen, T.G. Masaryka 20, 960 53 Zvolen, Slovakia. ; Faculty of Forestry, University of Sarajevo, Zagrebacka 20, 71000 Sarajevo, Bosnia and Herzegovina. ; Department of Forest Protection and Wildlife Management, Faculty of Forestry and Wood Technology, Mendel University in Brno, Zemedelska 3, 61300 Brno, Czech Republic. Friends of the Earth Czech Republic, Olomouc Branch, Dolni Namesti 38, 77900 Olomouc, Czech Republic. ; Estonian Environment Agency, Roomu tee 2, 51013 Tartu, Estonia. ; Office National de la Chasse et de la Faune Sauvage, ZI Mayencin, 5 Allee de Bethleem, 38610 Gieres, France. ; Centro Gestione e Conservazione Grandi Carnivori, Piazza Regina Elena 30, Valdieri 12010, Italy. ; Macedonian Ecological Society, Arhimedova 5, Skopje 1000, FYR Macedonia. Department of Wildlife Sciences, Georg-August University, Busgenweg 3, 37077 Gottingen, Germany. ; National Veterinary Epidemiology Unit, Food Safety and Veterinary Institute, Rruga Aleksander Moisiu 10 Tirana, Albania. ; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106 Warszawa, Poland. ; Association for Nature "Wolf," Twardorzeczka 229, 34-324 Lipowa, Poland. ; Latvian State Forest Research Institute "Silava," Rigas Iela 111, Salaspils, 2169 Latvia. ; Fundacion Oso Pardo, Calle San Luis 17, 4 degrees A, 39010 Santander, Spain. ; Natural History Museum, Njegoseva 51, 11000 Belgrade, Serbia. ; ONCFS-CNERA PAD, Equipe Ours, Chef de Projet, Impasse de la Chapelle, 31800 Villeneuve de Riviere, France. ; Istituto di Ecologia Applicata, Via B. Eustachio 10, 00161 Rome, Italy. ; Macedonian Ecological Society, Arhimedova 5, Skopje 1000, FYR Macedonia. ; Norwegian Institute for Nature Research, Post Office Box 5685 Sluppen, 7485 Trondheim, Norway. Department of Ecology and Natural Resource Management, Norwegian University of Life Sciences, Postbox 5003, 1432 As, Norway. ; St. Istvan Unversity Institute for Wildlife Conservation, Pater Karoly 1, 2103 Godollo, Hungary. ; Friends of the Earth Czech Republic, Olomouc Branch, Dolni Namesti 38, 77900 Olomouc, Czech Republic. ; Hedmark University College, Evenstad, 2480 Koppang, Norway. ; Bavarian Agency of Environment, Hans-Hogn-Strasse 12, 95030 Hof/Saale, Germany. ; Lynx Project Bavaria, Trailling 1a, 93462 Lam, Germany. ; Department of Zoology and Anthropology, Faculty of Biology/Sofia University "St. Kliment Ohridski," Boulevard Dragan Tzankov 8, 1164 Sofia, Bulgaria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525247" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; *Conservation of Natural Resources ; Europe ; Humans ; *Lynx ; *Mustelidae ; *Ursidae ; *Wolves
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  • 17
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorsch, Jon R -- Collins, Francis S -- Lippincott-Schwartz, Jennifer -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1452-3. doi: 10.1126/science.1259110.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Director, National Institute of General Medical Sciences, Bethesda, MD 20892, USA. jon.lorsch@nih.gov. ; Director, National Institutes of Health, Bethesda, MD 20892, USA. ; President, American Society for Cell Biology, Bethesda, MD 20814, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525228" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Specimen Banks/*standards ; Biomedical Research/*standards ; *Cell Line ; Drug Evaluation, Preclinical/*standards ; Humans ; National Institutes of Health (U.S.) ; Policy ; *Reproducibility of Results ; United States
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  • 18
    Publication Date: 2014-12-20
    Description: Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. The role of the H3.3K27M mutation in tumorigenesis is not fully understood. Here, we use a human embryonic stem cell system to model this tumor. We show that H3.3K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genome-wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin as an inhibitor of tumor cell growth in vitro and in mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Funato, Kosuke -- Major, Tamara -- Lewis, Peter W -- Allis, C David -- Tabar, Viviane -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1529-33. doi: 10.1126/science.1253799. Epub 2014 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery, Center for Stem Cell Biology and Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ; Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53715, USA. ; Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA. ; Department of Neurosurgery, Center for Stem Cell Biology and Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. tabarv@mskcc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525250" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology ; Brain Stem Neoplasms/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics/pathology ; Child ; Drug Screening Assays, Antitumor ; Embryonic Stem Cells/*metabolism/pathology ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Genome-Wide Association Study ; Glioma/*genetics/pathology ; Histones/*genetics ; Humans ; Mice ; *Models, Genetic ; Neural Stem Cells/*metabolism/pathology ; Proto-Oncogene Proteins/antagonists & inhibitors ; Tumor Suppressor Protein p53/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 19
    Publication Date: 2014-12-20
    Description: Immunological tolerance to self requires naturally occurring regulatory T (Treg) cells. Yet how they stably control autoimmune T cells remains obscure. Here, we show that Treg cells can render self-reactive human CD8(+) T cells anergic (i.e., hypoproliferative and cytokine hypoproducing upon antigen restimulation) in vitro, likely by controlling the costimulatory function of antigen-presenting cells. Anergic T cells were naive in phenotype, lower than activated T cells in T cell receptor affinity for cognate antigen, and expressed several coinhibitory molecules, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Using these criteria, we detected in healthy individuals anergic T cells reactive with a skin antigen targeted in the autoimmune disease vitiligo. Collectively, our results suggest that Treg cell-mediated induction of anergy in autoimmune T cells is important for maintaining self-tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maeda, Yuka -- Nishikawa, Hiroyoshi -- Sugiyama, Daisuke -- Ha, Danbee -- Hamaguchi, Masahide -- Saito, Takuro -- Nishioka, Megumi -- Wing, James B -- Adeegbe, Dennis -- Katayama, Ichiro -- Sakaguchi, Shimon -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1536-40. doi: 10.1126/science.aaa1292.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. ; Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. shimon@ifrec.osaka-u.ac.jp nisihiro@ifrec.osaka-u.ac.jp. ; Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan. ; Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525252" target="_blank"〉PubMed〈/a〉
    Keywords: Antigen-Presenting Cells/immunology ; Autoimmune Diseases/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; CTLA-4 Antigen ; *Clonal Anergy ; Humans ; Lymphocyte Activation ; Receptors, Antigen, T-Cell/immunology ; *Self Tolerance ; T-Lymphocytes, Regulatory/*immunology ; Vitiligo/immunology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1441. doi: 10.1126/science.346.6216.1441.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525222" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; Child ; *Child Development ; Child Welfare/*economics ; Federal Government ; Humans ; National Institutes of Health (U.S.) ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 21
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anastasiadou, Eleni -- Slack, Frank J -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1459-60. doi: 10.1126/science.aaa4024.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. ; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. fslack@bidmc.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525233" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Membrane Glycoproteins/*metabolism ; MicroRNAs/*blood ; Neoplasms/*blood ; RNA, Neoplasm/*blood ; Toll-Like Receptor 7/*metabolism ; Toll-Like Receptor 8/*metabolism
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  • 22
    Publication Date: 2014-12-20
    Description: To facilitate precision medicine and whole-genome annotation, we developed a machine-learning technique that scores how strongly genetic variants affect RNA splicing, whose alteration contributes to many diseases. Analysis of more than 650,000 intronic and exonic variants revealed widespread patterns of mutation-driven aberrant splicing. Intronic disease mutations that are more than 30 nucleotides from any splice site alter splicing nine times as often as common variants, and missense exonic disease mutations that have the least impact on protein function are five times as likely as others to alter splicing. We detected tens of thousands of disease-causing mutations, including those involved in cancers and spinal muscular atrophy. Examination of intronic and exonic variants found using whole-genome sequencing of individuals with autism revealed misspliced genes with neurodevelopmental phenotypes. Our approach provides evidence for causal variants and should enable new discoveries in precision medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362528/" 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/PMC4362528/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xiong, Hui Y -- Alipanahi, Babak -- Lee, Leo J -- Bretschneider, Hannes -- Merico, Daniele -- Yuen, Ryan K C -- Hua, Yimin -- Gueroussov, Serge -- Najafabadi, Hamed S -- Hughes, Timothy R -- Morris, Quaid -- Barash, Yoseph -- Krainer, Adrian R -- Jojic, Nebojsa -- Scherer, Stephen W -- Blencowe, Benjamin J -- Frey, Brendan J -- P30 CA045508/CA/NCI NIH HHS/ -- R37 GM042699/GM/NIGMS NIH HHS/ -- R37-GM42699A/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):1254806. doi: 10.1126/science.1254806. Epub 2014 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada. Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Program on Genetic Networks and Program on Neural Computation & Adaptive Perception, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada. ; Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada. Program on Genetic Networks and Program on Neural Computation & Adaptive Perception, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada. Department of Computer Science, University of Toronto, Toronto, Ontario M5S 3G4, Canada. ; McLaughlin Centre, University of Toronto, Toronto, Ontario M5G 0A4, Canada. Centre for Applied Genomics, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Program on Genetic Networks and Program on Neural Computation & Adaptive Perception, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada. Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Program on Genetic Networks and Program on Neural Computation & Adaptive Perception, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada. Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; eScience Group, Microsoft Research, Redmond, WA 98052, USA. ; Program on Genetic Networks and Program on Neural Computation & Adaptive Perception, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada. McLaughlin Centre, University of Toronto, Toronto, Ontario M5G 0A4, Canada. Centre for Applied Genomics, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. McLaughlin Centre, University of Toronto, Toronto, Ontario M5G 0A4, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada. Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Program on Genetic Networks and Program on Neural Computation & Adaptive Perception, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada. Department of Computer Science, University of Toronto, Toronto, Ontario M5S 3G4, Canada. McLaughlin Centre, University of Toronto, Toronto, Ontario M5G 0A4, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. eScience Group, Microsoft Research, Redmond, WA 98052, USA. frey@psi.toronto.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525159" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics ; *Artificial Intelligence ; Child Development Disorders, Pervasive/*genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics ; Computer Simulation ; DNA/genetics ; Exons/genetics ; Genetic Code ; Genetic Markers ; Genetic Variation ; Genome-Wide Association Study/*methods ; Humans ; Introns/genetics ; Models, Genetic ; Molecular Sequence Annotation/*methods ; Muscular Atrophy, Spinal/*genetics ; Mutation, Missense ; Nuclear Proteins/genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; RNA Splice Sites/genetics ; RNA Splicing/*genetics ; RNA-Binding Proteins/genetics
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 23
    Publication Date: 2014-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epstein, Joshua M -- Sauer, Lauren M -- Chelen, Julia -- Hatna, Erez -- Parker, Jon -- Rothman, Richard E -- Rubinson, Lewis -- England -- Nature. 2014 Dec 18;516(7531):323-5. doi: 10.1038/516323a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Advanced Modeling, and director for systems science of the Johns Hopkins Systems Institute, Johns Hopkins University, Baltimore, Maryland, USA. J.M.E. is also external professor at the Santa Fe Institute, Santa Fe, New Mexico, USA. ; Department of Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. ; Johns Hopkins Center for Advanced Modeling, Baltimore, Maryland, USA. ; Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ; R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519116" target="_blank"〉PubMed〈/a〉
    Keywords: Epidemics/*prevention & control ; Health Personnel/*standards ; Hemorrhagic Fever, Ebola/epidemiology/*prevention & control/*therapy ; Humans ; Immunity ; Risk ; Social Stigma ; *Survivors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 24
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayden, Erika Check -- England -- Nature. 2014 Dec 18;516(7531):295-6. doi: 10.1038/516295a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519108" target="_blank"〉PubMed〈/a〉
    Keywords: *Culture ; *Health Behavior ; Health Policy ; Hemorrhagic Fever, Ebola/*prevention & control/transmission ; Humans ; Quarantine ; Sierra Leone
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 25
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krug, Robert M -- England -- Nature. 2014 Dec 18;516(7531):338-9. doi: 10.1038/516338a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biosciences, Center for Infectious Disease, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519129" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Humans ; Influenza A virus/*enzymology ; Influenza B virus/*enzymology ; RNA/biosynthesis ; Virus Replication
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  • 26
    Publication Date: 2014-12-19
    Description: Naturally occurring variations of Polycomb repressive complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, autism susceptibility candidate 2 (AUTS2). Although AUTS2 is often disrupted in patients with neuronal disorders, the mechanism underlying the pathogenesis is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of P300 leads to gene activation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323097/" 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/PMC4323097/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Zhonghua -- Lee, Pedro -- Stafford, James M -- von Schimmelmann, Melanie -- Schaefer, Anne -- Reinberg, Danny -- 1DP2MH100012-01/DP/NCCDPHP CDC HHS/ -- 1F32GM105275/GM/NIGMS NIH HHS/ -- 5T32CA160002/CA/NCI NIH HHS/ -- DP2 MH100012/MH/NIMH NIH HHS/ -- F32AA022842/AA/NIAAA NIH HHS/ -- GM-64844/GM/NIGMS NIH HHS/ -- P30 CA016087/CA/NCI NIH HHS/ -- R01 GM064844/GM/NIGMS NIH HHS/ -- T32 CA160002/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 18;516(7531):349-54. doi: 10.1038/nature13921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, New York University Langone School of Medicine, Department of Biochemistry and Molecular Pharmacology, New York, New York 10016, USA. ; Friedman Brain Institute, Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519132" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/physiology ; Cell Cycle Proteins/genetics/*metabolism ; Central Nervous System/*metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation/*genetics ; Gene Knockout Techniques ; Genotype ; HEK293 Cells ; Histones/metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Proteins/genetics/*metabolism ; Ubiquitination
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  • 27
    Publication Date: 2014-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morello, Lauren -- Abbott, Alison -- Butler, Declan -- Callaway, Ewen -- Cyranoski, David -- Reardon, Sara -- Schiermeier, Quirin -- Witze, Alexandra -- England -- Nature. 2014 Dec 18;516(7531):300-3. doi: 10.1038/516300a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519112" target="_blank"〉PubMed〈/a〉
    Keywords: Genome, Human/genetics ; Hemorrhagic Fever, Ebola/mortality ; Humans ; Mars ; Meteoroids ; Science/*trends ; Spacecraft
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  • 28
    Publication Date: 2014-12-18
    Description: Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as alpha2a- and beta1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucrot, Emmanuel -- Ferreira, Antonio P A -- Almeida-Souza, Leonardo -- Debard, Sylvain -- Vallis, Yvonne -- Howard, Gillian -- Bertot, Laetitia -- Sauvonnet, Nathalie -- McMahon, Harvey T -- U105178805/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Jan 22;517(7535):460-5. doi: 10.1038/nature14067. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; 1] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK [2] Department of Biology, Ecole Normale Superieure de Cachan, 94235 Cachan, France. ; Institut Pasteur, Unite de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517094" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Cell Line ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Ligands ; Phosphatidylinositol Phosphates/metabolism ; Pseudopodia/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Interleukin-2/metabolism ; Signal Transduction ; Time Factors
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 29
    Publication Date: 2014-12-18
    Description: During endocytosis, energy is invested to narrow the necks of cargo-containing plasma membrane invaginations to radii at which the opposing segments spontaneously coalesce, thereby leading to the detachment by scission of endocytic uptake carriers. In the clathrin pathway, dynamin uses mechanical energy from GTP hydrolysis to this effect, assisted by the BIN/amphiphysin/Rvs (BAR) domain-containing protein endophilin. Clathrin-independent endocytic events are often less reliant on dynamin, and whether in these cases BAR domain proteins such as endophilin contribute to scission has remained unexplored. Here we show, in human and other mammalian cell lines, that endophilin-A2 (endoA2) specifically and functionally associates with very early uptake structures that are induced by the bacterial Shiga and cholera toxins, which are both clathrin-independent endocytic cargoes. In controlled in vitro systems, endoA2 reshapes membranes before scission. Furthermore, we demonstrate that endoA2, dynamin and actin contribute in parallel to the scission of Shiga-toxin-induced tubules. Our results establish a novel function of endoA2 in clathrin-independent endocytosis. They document that distinct scission factors operate in an additive manner, and predict that specificity within a given uptake process arises from defined combinations of universal modules. Our findings highlight a previously unnoticed link between membrane scaffolding by endoA2 and pulling-force-driven dynamic scission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342003/" 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/PMC4342003/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Renard, Henri-Francois -- Simunovic, Mijo -- Lemiere, Joel -- Boucrot, Emmanuel -- Garcia-Castillo, Maria Daniela -- Arumugam, Senthil -- Chambon, Valerie -- Lamaze, Christophe -- Wunder, Christian -- Kenworthy, Anne K -- Schmidt, Anne A -- McMahon, Harvey T -- Sykes, Cecile -- Bassereau, Patricia -- Johannes, Ludger -- R01 GM106720/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 22;517(7535):493-6. doi: 10.1038/nature14064. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut Curie - Centre de Recherche, Endocytic Trafficking and Therapeutic Delivery group, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] CNRS UMR3666, 75005 Paris, France [3] U1143 INSERM, 75005 Paris, France. ; 1] Institut Curie - Centre de Recherche, Membrane and Cell Functions group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] The University of Chicago, Department of Chemistry, 5735 S Ellis Ave, Chicago, Ilinois 60637, USA. ; 1] Institut Curie - Centre de Recherche, Biomimetism of Cell Movement group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] Universite Paris Diderot, Sorbonne Paris Cite, 75205 Paris, France. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; 1] CNRS UMR3666, 75005 Paris, France [2] U1143 INSERM, 75005 Paris, France [3] Institut Curie - Centre de Recherche, Membrane Dynamics and Mechanics of Intracellular Signaling group, 26 rue d'Ulm, 75248 Paris Cedex 05, France. ; Vanderbilt School of Medicine, Department of Molecular Physiology and Biophysics, 718 Light Hall, Nashville, Tennessee 37232, USA. ; CNRS, UMR7592, Institut Jacques Monod, Universite Paris Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris Cedex 13, France. ; Medical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Institut Curie - Centre de Recherche, Biomimetism of Cell Movement group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. ; Institut Curie - Centre de Recherche, Membrane and Cell Functions group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517096" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Animals ; Cell Line ; Cell Membrane/*metabolism ; Cholera Toxin/metabolism ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Rats ; Shiga Toxin/metabolism
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  • 30
    Publication Date: 2014-12-18
    Description: Mast cells are primary effectors in allergic reactions, and may have important roles in disease by secreting histamine and various inflammatory and immunomodulatory substances. Although they are classically activated by immunoglobulin (Ig)E antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions. The pathogenic roles of these substances have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, Mrgprb2, the orthologue of the human G-protein-coupled receptor MRGPRX2. Secretagogue-induced histamine release, inflammation and airway contraction are abolished in Mrgprb2-null mutant mice. Furthermore, we show that most classes of US Food and Drug Administration (FDA)-approved peptidergic drugs associated with allergic-type injection-site reactions also activate Mrgprb2 and MRGPRX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that Mrgprb2 and MRGPRX2 are targets of many small-molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice; and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MRGPRX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359082/" 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/PMC4359082/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNeil, Benjamin D -- Pundir, Priyanka -- Meeker, Sonya -- Han, Liang -- Undem, Bradley J -- Kulka, Marianna -- Dong, Xinzhong -- K99 NS087088/NS/NINDS NIH HHS/ -- R01 GM087369/GM/NIGMS NIH HHS/ -- R01 NS054791/NS/NINDS NIH HHS/ -- R01GM087369/GM/NIGMS NIH HHS/ -- R01NS054791/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Mar 12;519(7542):237-41. doi: 10.1038/nature14022. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Solomon H. Snyder Department of Neuroscience, Department of Neurosurgery, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada. ; Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada [2] National Institute for Nanotechnology, National Research Council Canada, Edmonton, Alberta T6G 2M9, Canada. ; 1] The Solomon H. Snyder Department of Neuroscience, Department of Neurosurgery, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA [2] Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517090" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; Drug Hypersensitivity/genetics/*immunology/prevention & control ; Female ; HEK293 Cells ; Histamine Release ; Humans ; Inflammation/immunology/metabolism ; Male ; Mast Cells/drug effects/*immunology/*metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/antagonists & inhibitors/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/deficiency/genetics/immunology/*metabolism ; Receptors, Neuropeptide/antagonists & inhibitors/metabolism
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  • 31
    Publication Date: 2014-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haucke, Volker -- England -- Nature. 2015 Jan 22;517(7535):446-7. doi: 10.1038/nature14081. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517097" target="_blank"〉PubMed〈/a〉
    Keywords: Acyltransferases/*metabolism ; Animals ; Cell Membrane/*metabolism ; *Endocytosis ; Humans
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Polka, Jessica K -- Krukenberg, Kristin A -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1422. doi: 10.1126/science.346.6215.1422.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Postdocs Jessica K. Polka and Kristin A. Krukenberg are organizers of the Future of Research Symposium held in Boston in early October and corresponding authors for the resulting report. For more on life and careers, visit www.sciencecareers.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504725" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; Career Mobility ; *Education, Graduate/economics ; Humans ; *Research Personnel/education ; *Science/education ; Training Support
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woolhouse, Mark -- Drury, Patrick -- Dye, Christopher -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1271. doi: 10.1126/science.aaa4117.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mark Woolhouse is a professor at the Centre for Immunity, Infection & Evolution at the University of Edinburgh, Edinburgh, UK.Patrick Drury is Manager of the Global Outbreak Alert and Response Network of the World Health Organization, Geneva, Switzerland.Christopher Dye is the Director of Strategy in the Office of the Director General at the World Health Organization, Geneva, Switzerland. ; Mark Woolhouse is a professor at the Centre for Immunity, Infection & Evolution at the University of Edinburgh, Edinburgh, UK.Patrick Drury is Manager of the Global Outbreak Alert and Response Network of the World Health Organization, Geneva, Switzerland.Christopher Dye is the Director of Strategy in the Office of the Director General at the World Health Organization, Geneva, Switzerland. dyec@who.int.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504691" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Communicable Disease Control ; Epidemics/*prevention & control ; Epidemiological Monitoring ; *Global Health ; Hemorrhagic Fever, Ebola/epidemiology/physiopathology/prevention & control ; Humans ; Interdisciplinary Communication ; *International Agencies ; *International Cooperation
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gutchess, Angela -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1307. doi: 10.1126/science.346.6215.1307-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA 02114, USA. gutchess@brandeis.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504708" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Brain/*growth & development ; *Cognition ; Humans ; *Neuronal Plasticity
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  • 35
    Publication Date: 2014-12-17
    Description: Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290850/" 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/PMC4290850/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGuire, Andrew T -- Dreyer, Anita M -- Carbonetti, Sara -- Lippy, Adriana -- Glenn, Jolene -- Scheid, Johannes F -- Mouquet, Hugo -- Stamatatos, Leonidas -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI094419-01/AI/NIAID NIH HHS/ -- U19 19AI109632-01/AI/NIAID NIH HHS/ -- U19 AI109632/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1380-3. doi: 10.1126/science.1259206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, WA 98109, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur and CNRS-URA 1961, 75015 Paris, France. ; Seattle Biomedical Research Institute, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98109, USA. lstamata@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504724" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; Antibodies, Neutralizing/*immunology ; Antibody Affinity ; B-Lymphocytes/immunology ; Binding, Competitive ; Epitopes/immunology ; HIV Antibodies/genetics/*immunology ; HIV-1/*immunology ; Humans ; Lymphocyte Activation ; Models, Molecular ; Receptors, Antigen, B-Cell/genetics/immunology ; Recombinant Proteins/immunology ; env Gene Products, Human Immunodeficiency Virus/chemistry/genetics/*immunology
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  • 36
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kordas, Katarzyna -- O'Hare, Dara -- Jacobs-Pearson, Makaela -- England -- Nature. 2014 Dec 11;516(7530):170. doi: 10.1038/516170d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Bristol, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503226" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*methods ; Humans ; *Patient Selection ; *Public Opinion ; *Research Design
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  • 37
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Dec 11;516(7530):157. doi: 10.1038/516157a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503215" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*economics/*organization & administration ; Cell Biology/*economics/*organization & administration ; Epithelial Cells/cytology ; Goals ; Humans ; Induced Pluripotent Stem Cells/cytology ; Models, Biological ; Myocytes, Cardiac/cytology ; Organ Specificity
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2014 Dec 11;516(7530):151-2. doi: 10.1038/516151a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503211" target="_blank"〉PubMed〈/a〉
    Keywords: *Communication ; Disaster Planning/economics/*methods ; Disasters/economics/*prevention & control ; Emergency Shelter ; Humans ; Indian Ocean ; Indonesia ; Maps as Topic ; Pilot Projects ; Time Factors ; *Tsunamis/economics
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  • 39
    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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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fratzl, Peter -- England -- Nature. 2014 Dec 11;516(7530):178-9. doi: 10.1038/516178a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503229" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomimetics/*methods ; Humans ; *Movement ; Nanotechnology/*methods ; Pattern Recognition, Automated/*methods ; *Sound ; Spiders/*physiology ; *Vibration
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2014 Dec 11;516(7530):154-5. doi: 10.1038/516154a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503213" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; *Early Diagnosis ; Ebolavirus/genetics/*isolation & purification ; Hemorrhagic Fever, Ebola/*diagnosis/epidemiology/*prevention & ; control/transmission ; Humans ; Quarantine ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; World Health Organization
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  • 42
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Casadevall, Arturo -- Pirofski, Liise-anne -- England -- Nature. 2014 Dec 11;516(7530):165-6. doi: 10.1038/516165a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Albert Einstein College of Medicine, Yeshiva University, New York, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503219" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Toxins/adverse effects/genetics/immunology ; Communicable Diseases/immunology/microbiology/pathology ; Host-Pathogen Interactions/genetics/immunology/*physiology ; Humans ; Inflammation/immunology/microbiology/pathology ; Microbiology/*trends ; Symbiosis ; Terminology as Topic ; Virulence/genetics
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  • 43
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2014 Dec 11;516(7530):156. doi: 10.1038/516156a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503214" target="_blank"〉PubMed〈/a〉
    Keywords: *Adoptive Transfer/adverse effects/economics ; Animals ; Antigens, CD19/immunology/metabolism ; Clinical Trials as Topic ; Drug Industry ; Genetic Engineering ; Humans ; Leukemia/genetics/immunology/*therapy ; Lymphoma/genetics/immunology/*therapy ; Mice ; Survival Rate ; T-Lymphocytes/*immunology/metabolism/*transplantation
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2014 Dec 11;516(7530):162-4. doi: 10.1038/516162a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nature from Shanghai.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503218" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Dedifferentiation/genetics ; Cellular Reprogramming/*physiology ; Chromosomes/chemistry/genetics/metabolism ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Histones/chemistry/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Mice ; Stem Cells/*cytology/*metabolism ; *Uncertainty
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  • 45
    Publication Date: 2014-12-17
    Description: Recently developed flexible mechanosensors based on inorganic silicon, organic semiconductors, carbon nanotubes, graphene platelets, pressure-sensitive rubber and self-powered devices are highly sensitive and can be applied to human skin. However, the development of a multifunctional sensor satisfying the requirements of ultrahigh mechanosensitivity, flexibility and durability remains a challenge. In nature, spiders sense extremely small variations in mechanical stress using crack-shaped slit organs near their leg joints. Here we demonstrate that sensors based on nanoscale crack junctions and inspired by the geometry of a spider's slit organ can attain ultrahigh sensitivity and serve multiple purposes. The sensors are sensitive to strain (with a gauge factor of over 2,000 in the 0-2 per cent strain range) and vibration (with the ability to detect amplitudes of approximately 10 nanometres). The device is reversible, reproducible, durable and mechanically flexible, and can thus be easily mounted on human skin as an electronic multipixel array. The ultrahigh mechanosensitivity is attributed to the disconnection-reconnection process undergone by the zip-like nanoscale crack junctions under strain or vibration. The proposed theoretical model is consistent with experimental data that we report here. We also demonstrate that sensors based on nanoscale crack junctions are applicable to highly selective speech pattern recognition and the detection of physiological signals. The nanoscale crack junction-based sensory system could be useful in diverse applications requiring ultrahigh displacement sensitivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Daeshik -- Pikhitsa, Peter V -- Choi, Yong Whan -- Lee, Chanseok -- Shin, Sung Soo -- Piao, Linfeng -- Park, Byeonghak -- Suh, Kahp-Yang -- Kim, Tae-il -- Choi, Mansoo -- England -- Nature. 2014 Dec 11;516(7530):222-6. doi: 10.1038/nature14002.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Global Frontier Center for Multiscale Energy Systems, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, South Korea [2] Division of WCU Multiscale Mechanical Design, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, South Korea. ; Global Frontier Center for Multiscale Energy Systems, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, South Korea. ; 1] Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 440-746, South Korea [2] School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 440-746, South Korea. ; 1] Global Frontier Center for Multiscale Energy Systems, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, South Korea [2] Division of WCU Multiscale Mechanical Design, Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, South Korea [3] Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 151-742, South Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503234" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomimetics/*methods ; Humans ; Mechanotransduction, Cellular/physiology ; *Movement ; Music ; Nanotechnology/instrumentation/*methods ; Pattern Recognition, Automated/*methods ; Platinum/chemistry ; Pliability ; Pressure ; Skin ; *Sound ; Speech ; Spiders/anatomy & histology/*physiology ; *Vibration ; Wings, Animal/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 46
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    Nature Publishing Group (NPG)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Dec 11;516(7530):143-4. doi: 10.1038/516143b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25503197" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic/*ethics ; Human Experimentation/*ethics ; Humans ; Informed Consent/ethics ; National Institutes of Health (U.S.)/ethics ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van den Noort, Maurits -- Lim, Sabina -- Bosch, Peggy -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1307. doi: 10.1126/science.346.6215.1307-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Group of Pain and Neuroscience, Kyung Hee University Seoul 130-701, Republic of Korea. info@mauritsvandennoort.com. ; Research Group of Pain and Neuroscience, Kyung Hee University Seoul 130-701, Republic of Korea. ; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525, HR Nijmegen, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504707" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Brain/*growth & development ; *Cognition ; Humans ; *Neuronal Plasticity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 48
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vaharautio, Anna -- Taipale, Jussi -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1291-2. doi: 10.1126/science.aaa3247.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome-Scale Biology Program, University of Helsinki, Finland. ; Genome-Scale Biology Program, University of Helsinki, Finland. Science for Life Laboratory, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. jussi.taipale@ki.se.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504702" target="_blank"〉PubMed〈/a〉
    Keywords: Basic Helix-Loop-Helix Transcription Factors/*genetics ; *DNA, Intergenic ; *Enhancer Elements, Genetic ; *Gene Expression Regulation, Neoplastic ; Humans ; *INDEL Mutation ; *Mutation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics ; Proto-Oncogene Proteins/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Armitage, Andrew E -- Drakesmith, Hal -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1299-300. doi: 10.1126/science.aaa2468.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. ; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. alexander.drakesmith@ndm.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504706" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Haemophilus influenzae/*metabolism ; Haplorhini/*genetics/*metabolism ; Humans ; Neisseria/*metabolism ; Transferrin/*genetics/*metabolism ; Transferrin-Binding Protein A/*genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 50
    Publication Date: 2014-12-17
    Description: Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385736/" 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/PMC4385736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pfenning, Andreas R -- Hara, Erina -- Whitney, Osceola -- Rivas, Miriam V -- Wang, Rui -- Roulhac, Petra L -- Howard, Jason T -- Wirthlin, Morgan -- Lovell, Peter V -- Ganapathy, Ganeshkumar -- Mouncastle, Jacquelyn -- Moseley, M Arthur -- Thompson, J Will -- Soderblom, Erik J -- Iriki, Atsushi -- Kato, Masaki -- Gilbert, M Thomas P -- Zhang, Guojie -- Bakken, Trygve -- Bongaarts, Angie -- Bernard, Amy -- Lein, Ed -- Mello, Claudio V -- Hartemink, Alexander J -- Jarvis, Erich D -- DP1 OD000448/OD/NIH HHS/ -- R01 DC007218/DC/NIDCD NIH HHS/ -- R01DC007218/DC/NIDCD NIH HHS/ -- R21 DC007478/DC/NIDCD NIH HHS/ -- R24 GM092842/GM/NIGMS NIH HHS/ -- R24GM092842/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1256846. doi: 10.1126/science.1256846.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. apfenning@csail.mit.edu amink@cs.duke.edu jarvis@neuro.duke.edu. ; Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. ; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA. ; Duke Proteomics and Metabolomics Core Facility, Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA. ; Laboratory for Symbolic Cognitive Development, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark. Trace and Environmental DNA Laboratory, Department of Environment and Agriculture, Curtin University, Perth, Western Australia 6102, Australia. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. Centre for Social Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark. ; Allen Institute for Brain Science, Seattle, WA 98103, USA. ; Department of Computer Science, Duke University, Durham, NC 27708, USA. apfenning@csail.mit.edu amink@cs.duke.edu jarvis@neuro.duke.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504733" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Birds/genetics/physiology ; Brain/anatomy & histology/*physiology ; Brain Mapping ; Corpus Striatum/anatomy & histology/physiology ; Evolution, Molecular ; Finches/*genetics/*physiology ; *Gene Expression Regulation ; Humans ; *Learning ; Male ; Motor Cortex/anatomy & histology/physiology ; Neural Pathways ; Species Specificity ; *Speech ; Transcription, Genetic ; *Transcriptome ; *Vocalization, Animal
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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