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  • Reproducibility of Results  (303)
  • Models, Biological  (251)
  • Nature Publishing Group (NPG)  (544)
  • Elsevier
  • MDPI Publishing
  • 2010-2014  (544)
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  • 1
    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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  • 2
    Publication Date: 2014-12-11
    Description: Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420636/" 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/PMC4420636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Konermann, Silvana -- Brigham, Mark D -- Trevino, Alexandro E -- Joung, Julia -- Abudayyeh, Omar O -- Barcena, Clea -- Hsu, Patrick D -- Habib, Naomi -- Gootenberg, Jonathan S -- Nishimasu, Hiroshi -- Nureki, Osamu -- Zhang, Feng -- DP1 MH100706/MH/NIMH NIH HHS/ -- DP1-MH100706/DP/NCCDPHP CDC HHS/ -- R01 NS062849/NS/NINDS NIH HHS/ -- R01 NS073124/NS/NINDS NIH HHS/ -- R01-NS07312401/NS/NINDS NIH HHS/ -- England -- Nature. 2015 Jan 29;517(7536):583-8. doi: 10.1038/nature14136. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA [2] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA [2] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, Massachusetts 02142, USA [2] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [5] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi Bunkyo, Tokyo 113-0032, Japan [2] JST, PRESTO 2-11-16 Yayoi Bunkyo, Tokyo 113-0032, Japan. ; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi Bunkyo, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25494202" target="_blank"〉PubMed〈/a〉
    Keywords: CRISPR-Associated Proteins/genetics/metabolism ; CRISPR-Cas Systems/*genetics ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; DNA, Complementary/biosynthesis/genetics ; Drug Resistance, Neoplasm/drug effects/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Gene Library ; Genetic Engineering/*methods ; Genetic Loci/genetics ; Genetic Testing ; Genome, Human/*genetics ; Humans ; Indoles/pharmacology ; Melanoma/drug therapy/*genetics ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; RNA, Untranslated/biosynthesis/genetics/metabolism ; Reproducibility of Results ; Sulfonamides/pharmacology ; Transcriptional Activation/*genetics ; Up-Regulation/genetics
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  • 3
    Publication Date: 2014-02-07
    Description: Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that, during development, AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 cells derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal. This stem-cell function is broadly activated by AT1 injury, and AT2 self-renewal is selectively induced by EGFR (epidermal growth factor receptor) ligands in vitro and oncogenic Kras(G12D) in vivo, efficiently generating multifocal, clonal adenomas. Thus, there is a switch after birth, when AT2 cells function as stem cells that contribute to alveolar renewal, repair and cancer. We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013278/" 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/PMC4013278/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Desai, Tushar J -- Brownfield, Douglas G -- Krasnow, Mark A -- P30 CA124435/CA/NCI NIH HHS/ -- U01 HL099995/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):190-4. doi: 10.1038/nature12930. Epub 2014 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA [2] Department of Internal Medicine, Division of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, California 94305-5307, USA. ; Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5307, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499815" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Transformation, Neoplastic/metabolism/pathology ; Cells, Cultured ; Cellular Reprogramming ; Clone Cells/cytology ; Female ; Lung/*cytology/embryology/*growth & development/pathology ; Lung Neoplasms/metabolism/*pathology ; Male ; Mice ; Models, Biological ; Multipotent Stem Cells/*cytology/metabolism/*pathology ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Pulmonary Alveoli/*cytology ; Receptor, Epidermal Growth Factor/metabolism ; *Regeneration ; Signal Transduction
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  • 4
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibney, Elizabeth -- England -- Nature. 2014 May 29;509(7502):544-5. doi: 10.1038/509544a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870523" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*organization & administration ; Biomedical Research/*manpower/methods/*organization & administration/trends ; Interdisciplinary Communication ; Interdisciplinary Studies/*trends ; London ; Models, Biological ; Physics/methods/*organization & administration ; *Research Personnel
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  • 5
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉See, Linda -- Fritz, Steffen -- McCallum, Ian -- England -- Nature. 2014 Oct 9;514(7521):168. doi: 10.1038/514168a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International Institute for Applied Systems Analysis, Laxenburg, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297427" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Biodiversity ; Calibration ; Environmental Monitoring ; *Information Dissemination ; Reproducibility of Results ; *Satellite Imagery ; Trees
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perrin, Steve -- England -- Nature. 2014 Mar 27;507(7493):423-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24678540" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/genetics/pathology/therapy ; Animals ; Cause of Death ; Clinical Trials as Topic/economics/standards ; *Disease Models, Animal ; Disease Progression ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical/economics/*methods/*standards ; False Positive Reactions ; Guidelines as Topic ; Half-Life ; Humans ; Mice ; Organ Specificity ; Reproducibility of Results ; *Research Design ; Superoxide Dismutase/deficiency/genetics/metabolism ; Survival Analysis ; Translational Medical Research/economics/*methods/*standards ; Treatment Failure
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  • 7
    Publication Date: 2014-04-18
    Description: The equilibrium theory of island biogeography is the basis for estimating extinction rates and a pillar of conservation science. The default strategy for conserving biodiversity is the designation of nature reserves, treated as islands in an inhospitable sea of human activity. Despite the profound influence of islands on conservation theory and practice, their mainland analogues, forest fragments in human-dominated landscapes, consistently defy expected biodiversity patterns based on island biogeography theory. Countryside biogeography is an alternative framework, which recognizes that the fate of the world's wildlife will be decided largely by the hospitality of agricultural or countryside ecosystems. Here we directly test these biogeographic theories by comparing a Neotropical countryside ecosystem with a nearby island ecosystem, and show that each supports similar bat biodiversity in fundamentally different ways. The island ecosystem conforms to island biogeographic predictions of bat species loss, in which the water matrix is not habitat. In contrast, the countryside ecosystem has high species richness and evenness across forest reserves and smaller forest fragments. Relative to forest reserves and fragments, deforested countryside habitat supports a less species-rich, yet equally even, bat assemblage. Moreover, the bat assemblage associated with deforested habitat is compositionally novel because of predictable changes in abundances by many species using human-made habitat. Finally, we perform a global meta-analysis of bat biogeographic studies, spanning more than 700 species. It generalizes our findings, showing that separate biogeographic theories for countryside and island ecosystems are necessary. A theory of countryside biogeography is essential to conservation strategy in the agricultural ecosystems that comprise roughly half of the global land surface and are likely to increase even further.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mendenhall, Chase D -- Karp, Daniel S -- Meyer, Christoph F J -- Hadly, Elizabeth A -- Daily, Gretchen C -- England -- Nature. 2014 May 8;509(7499):213-7. doi: 10.1038/nature13139. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Conservation Biology, Stanford University, Stanford, California 94305, USA [2] Department of Biology, Stanford University, Stanford, California 94305, USA. ; 1] Center for Conservation Biology, Stanford University, Stanford, California 94305, USA [2] Department of Biology, Stanford University, Stanford, California 94305, USA [3] Department of Environmental Science, Policy & Management, University of California, Berkeley, California 94720, USA [4] The Nature Conservancy, Berkeley, California 94705, USA. ; 1] Institute of Experimental Ecology, University of Ulm, 89069 Ulm, Germany [2] Centre for Environmental Biology, University of Lisbon, 1749-016 Lisbon, Portugal. ; Department of Biology, Stanford University, Stanford, California 94305, USA. ; 1] Center for Conservation Biology, Stanford University, Stanford, California 94305, USA [2] Department of Biology, Stanford University, Stanford, California 94305, USA [3] Woods Institute for the Environment, Stanford University, Stanford, California 94305, USA [4] Global Economic Dynamics and the Biosphere, Royal Swedish Academy of Sciences, Stockholm, SE-104 05, Sweden [5] Stockholm Resilience Centre, University of Stockholm, Stockholm, SE-106 91, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739971" target="_blank"〉PubMed〈/a〉
    Keywords: *Agriculture/methods ; Animals ; *Biodiversity ; Chiroptera/physiology ; *Conservation of Natural Resources ; Costa Rica ; Extinction, Biological ; *Geography ; Islands ; Lakes ; Models, Biological ; Population Dynamics ; Trees/*growth & development
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  • 8
    Publication Date: 2014-06-06
    Description: Advances in our understanding of the mechanisms that bring about the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators that include the lipoxin, resolvin, protectin and maresin families, collectively called specialized pro-resolving mediators. Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263681/" 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/PMC4263681/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Serhan, Charles N -- P01 GM095467/GM/NIGMS NIH HHS/ -- P01GM095467/GM/NIGMS NIH HHS/ -- R01 GM038765/GM/NIGMS NIH HHS/ -- R01GM038765/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 5;510(7503):92-101. doi: 10.1038/nature13479.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899309" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chronic Disease ; Docosahexaenoic Acids/metabolism ; Fatty Acids, Omega-3/*metabolism ; Fatty Acids, Unsaturated/metabolism ; Humans ; Immunity ; Infection/metabolism ; Inflammation/drug therapy/*metabolism/pathology ; Inflammation Mediators/*metabolism/therapeutic use ; Models, Biological ; Pain/metabolism ; Regeneration ; Translational Medical Research ; Wound Healing
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  • 9
    Publication Date: 2014-11-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitty, Christopher J M -- Farrar, Jeremy -- Ferguson, Neil -- Edmunds, W John -- Piot, Peter -- Leach, Melissa -- Davies, Sally C -- England -- Nature. 2014 Nov 13;515(7526):192-4. doi: 10.1038/515192a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25391946" target="_blank"〉PubMed〈/a〉
    Keywords: Bed Occupancy/statistics & numerical data ; Compassionate Use Trials/trends ; Contact Tracing/*methods ; Ebola Vaccines/supply & distribution ; Facility Design and Construction ; Great Britain ; Hemorrhagic Fever, Ebola/diagnosis/epidemiology/*prevention & ; control/*transmission ; Humans ; Models, Biological ; Patient Isolation/*methods ; Quarantine/*methods ; Self Report ; Sierra Leone/epidemiology ; Time Factors
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  • 10
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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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  • 11
    Publication Date: 2014-02-28
    Description: Nitrate is a primary nutrient for plant growth, but its levels in soil can fluctuate by several orders of magnitude. Previous studies have identified Arabidopsis NRT1.1 as a dual-affinity nitrate transporter that can take up nitrate over a wide range of concentrations. The mode of action of NRT1.1 is controlled by phosphorylation of a key residue, Thr 101; however, how this post-translational modification switches the transporter between two affinity states remains unclear. Here we report the crystal structure of unphosphorylated NRT1.1, which reveals an unexpected homodimer in the inward-facing conformation. In this low-affinity state, the Thr 101 phosphorylation site is embedded in a pocket immediately adjacent to the dimer interface, linking the phosphorylation status of the transporter to its oligomeric state. Using a cell-based fluorescence resonance energy transfer assay, we show that functional NRT1.1 dimerizes in the cell membrane and that the phosphomimetic mutation of Thr 101 converts the protein into a monophasic high-affinity transporter by structurally decoupling the dimer. Together with analyses of the substrate transport tunnel, our results establish a phosphorylation-controlled dimerization switch that allows NRT1.1 to uptake nitrate with two distinct affinity modes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968801/" 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/PMC3968801/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Ji -- Bankston, John R -- Payandeh, Jian -- Hinds, Thomas R -- Zagotta, William N -- Zheng, Ning -- NS074545/NS/NINDS NIH HHS/ -- R01EY10329/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 6;507(7490):73-7. doi: 10.1038/nature13074. Epub 2014 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA. ; Department of Physiology and Biophysics, Box 357290, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA [2] Department of Structural Biology, Genentech Inc., South San Francisco, California 94080, USA. ; 1] Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, Box 357280, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572362" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anion Transport Proteins/*chemistry/genetics/metabolism ; Arabidopsis/*chemistry/genetics ; Binding Sites ; Biological Transport ; Cell Membrane/chemistry/metabolism ; Crystallography, X-Ray ; Fluorescence Resonance Energy Transfer ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Mutation/genetics ; Nitrates/chemistry/metabolism ; Phosphorylation ; Phosphothreonine/chemistry/metabolism ; Plant Proteins/*chemistry/genetics/metabolism ; *Protein Multimerization ; Protein Structure, Quaternary ; Protons ; Structure-Activity Relationship
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  • 12
    Publication Date: 2014-09-26
    Description: For centuries, biogeographers have examined the factors that produce patterns of biodiversity across regions. The study of islands has proved particularly fruitful and has led to the theory that geographic area and isolation influence species colonization, extinction and speciation such that larger islands have more species and isolated islands have fewer species (that is, positive species-area and negative species-isolation relationships). However, experimental tests of this theory have been limited, owing to the difficulty in experimental manipulation of islands at the scales at which speciation and long-distance colonization are relevant. Here we have used the human-aided transport of exotic anole lizards among Caribbean islands as such a test at an appropriate scale. In accord with theory, as anole colonizations have increased, islands impoverished in native species have gained the most exotic species, the past influence of speciation on island biogeography has been obscured, and the species-area relationship has strengthened while the species-isolation relationship has weakened. Moreover, anole biogeography increasingly reflects anthropogenic rather than geographic processes. Unlike the island biogeography of the past that was determined by geographic area and isolation, in the Anthropocene--an epoch proposed for the present time interval--island biogeography is dominated by the economic isolation of human populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmus, Matthew R -- Mahler, D Luke -- Losos, Jonathan B -- England -- Nature. 2014 Sep 25;513(7519):543-6. doi: 10.1038/nature13739.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amsterdam Global Change Institute, Department of Animal Ecology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands. ; Center for Population Biology, University of California, Davis, California 95616, USA. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254475" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Commerce/history/statistics & numerical data ; Geography ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Human Activities/history/statistics & numerical data ; Introduced Species/history/*statistics & numerical data ; *Islands ; *Lizards/physiology ; Models, Biological ; Models, Economic ; Population Dynamics ; West Indies
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  • 13
    Publication Date: 2014-06-05
    Description: Transcriptional enhancers are crucial regulators of gene expression and animal development and the characterization of their genomic organization, spatiotemporal activities and sequence properties is a key goal in modern biology. Here we characterize the in vivo activity of 7,705 Drosophila melanogaster enhancer candidates covering 13.5% of the non-coding non-repetitive genome throughout embryogenesis. 3,557 (46%) candidates are active, suggesting a high density with 50,000 to 100,000 developmental enhancers genome-wide. The vast majority of enhancers display specific spatial patterns that are highly dynamic during development. Most appear to regulate their neighbouring genes, suggesting that the cis-regulatory genome is organized locally into domains, which are supported by chromosomal domains, insulator binding and genome evolution. However, 12 to 21 per cent of enhancers appear to skip non-expressed neighbours and regulate a more distal gene. Finally, we computationally identify cis-regulatory motifs that are predictive and required for enhancer activity, as we validate experimentally. This work provides global insights into the organization of an animal regulatory genome and the make-up of enhancer sequences and confirms and generalizes principles from previous studies. All enhancer patterns are annotated manually with a controlled vocabulary and all results are available through a web interface (http://enhancers.starklab.org), including the raw images of all microscopy slides for manual inspection at arbitrary zoom levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kvon, Evgeny Z -- Kazmar, Tomas -- Stampfel, Gerald -- Yanez-Cuna, J Omar -- Pagani, Michaela -- Schernhuber, Katharina -- Dickson, Barry J -- Stark, Alexander -- England -- Nature. 2014 Aug 7;512(7512):91-5. doi: 10.1038/nature13395. Epub 2014 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2] Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA (B.J.D.); Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA (E.Z.K.). ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria. ; 1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila melanogaster/*embryology/*genetics ; Embryonic Development/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Genome, Insect/*genetics ; Internet ; Nucleotide Motifs/genetics ; Organ Specificity/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; User-Computer Interface
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  • 14
    Publication Date: 2014-02-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, Simon L -- England -- Nature. 2014 Feb 27;506(7489):409. doi: 10.1038/506409a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572388" target="_blank"〉PubMed〈/a〉
    Keywords: *Climate Change ; *Dissent and Disputes ; Floods/statistics & numerical data ; Great Britain ; Journalism/standards ; Mass Media/standards ; *Public Opinion ; Rain ; Reproducibility of Results ; Uncertainty
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  • 15
    Publication Date: 2014-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanage, William P -- England -- Nature. 2014 Aug 21;512(7514):247-8. doi: 10.1038/512247a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard School of Public Health in Boston, Massachusetts, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143098" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; *Microbiota/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Science/*standards ; *Uncertainty
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  • 16
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2014 Jun 5;510(7503):26-8. doi: 10.1038/510026a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899289" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Alleles ; Alzheimer Disease/drug therapy/*genetics/metabolism/pathology ; Amyloid beta-Peptides/antagonists & inhibitors/metabolism ; Animals ; Apolipoprotein E2/genetics/metabolism ; Apolipoprotein E3/chemistry/genetics/metabolism ; Apolipoprotein E4/chemistry/*genetics/metabolism ; Case-Control Studies ; Chromosomes, Human, Pair 19/genetics ; Clinical Trials as Topic ; Genetic Predisposition to Disease/*genetics ; Humans ; Hypoglycemic Agents/pharmacology/therapeutic use ; Membrane Transport Proteins/genetics/metabolism ; Mice ; Mice, Transgenic ; Mitochondria/drug effects/pathology ; Models, Biological ; Thiazolidinediones/pharmacology/therapeutic use
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  • 17
    Publication Date: 2014-04-18
    Description: Ice volume (and hence sea level) and deep-sea temperature are key measures of global climate change. Sea level has been documented using several independent methods over the past 0.5 million years (Myr). Older periods, however, lack such independent validation; all existing records are related to deep-sea oxygen isotope (delta(18)O) data that are influenced by processes unrelated to sea level. For deep-sea temperature, only one continuous high-resolution (Mg/Ca-based) record exists, with related sea-level estimates, spanning the past 1.5 Myr. Here we present a novel sea-level reconstruction, with associated estimates of deep-sea temperature, which independently validates the previous 0-1.5 Myr reconstruction and extends it back to 5.3 Myr ago. We find that deep-sea temperature and sea level generally decreased through time, but distinctly out of synchrony, which is remarkable given the importance of ice-albedo feedbacks on the radiative forcing of climate. In particular, we observe a large temporal offset during the onset of Plio-Pleistocene ice ages, between a marked cooling step at 2.73 Myr ago and the first major glaciation at 2.15 Myr ago. Last, we tentatively infer that ice sheets may have grown largest during glacials with more modest reductions in deep-sea temperature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohling, E J -- Foster, G L -- Grant, K M -- Marino, G -- Roberts, A P -- Tamisiea, M E -- Williams, F -- England -- Nature. 2014 Apr 24;508(7497):477-82. doi: 10.1038/nature13230. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Research School of Earth Sciences, The Australian National University, Canberra 0200, Australia [2] Ocean and Earth Science, University of Southampton, National Oceanography Centre, Southampton SO14 3ZH, UK. ; Ocean and Earth Science, University of Southampton, National Oceanography Centre, Southampton SO14 3ZH, UK. ; Research School of Earth Sciences, The Australian National University, Canberra 0200, Australia. ; National Oceanography Centre, Joseph Proudman Building, Liverpool L3 5DA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739960" target="_blank"〉PubMed〈/a〉
    Keywords: Foraminifera ; History, Ancient ; Ice Cover ; Mediterranean Sea ; Oxygen Isotopes ; Reproducibility of Results ; Seawater/*analysis ; *Temperature ; Time Factors
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  • 18
    Publication Date: 2014-05-09
    Description: Electromagnetic noise is emitted everywhere humans use electronic devices. For decades, it has been hotly debated whether man-made electric and magnetic fields affect biological processes, including human health. So far, no putative effect of anthropogenic electromagnetic noise at intensities below the guidelines adopted by the World Health Organization has withstood the test of independent replication under truly blinded experimental conditions. No effect has therefore been widely accepted as scientifically proven. Here we show that migratory birds are unable to use their magnetic compass in the presence of urban electromagnetic noise. When European robins, Erithacus rubecula, were exposed to the background electromagnetic noise present in unscreened wooden huts at the University of Oldenburg campus, they could not orient using their magnetic compass. Their magnetic orientation capabilities reappeared in electrically grounded, aluminium-screened huts, which attenuated electromagnetic noise in the frequency range from 50 kHz to 5 MHz by approximately two orders of magnitude. When the grounding was removed or when broadband electromagnetic noise was deliberately generated inside the screened and grounded huts, the birds again lost their magnetic orientation capabilities. The disruptive effect of radiofrequency electromagnetic fields is not confined to a narrow frequency band and birds tested far from sources of electromagnetic noise required no screening to orient with their magnetic compass. These fully double-blinded tests document a reproducible effect of anthropogenic electromagnetic noise on the behaviour of an intact vertebrate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engels, Svenja -- Schneider, Nils-Lasse -- Lefeldt, Nele -- Hein, Christine Maira -- Zapka, Manuela -- Michalik, Andreas -- Elbers, Dana -- Kittel, Achim -- Hore, P J -- Mouritsen, Henrik -- England -- Nature. 2014 May 15;509(7500):353-6. doi: 10.1038/nature13290. Epub 2014 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut fur Biologie und Umweltwissenschaften, Universitat Oldenburg, D-26111 Oldenburg, Germany [2] Research Centre for Neurosensory Sciences, University of Oldenburg, D-26111 Oldenburg, Germany [3]. ; 1] Institut fur Biologie und Umweltwissenschaften, Universitat Oldenburg, D-26111 Oldenburg, Germany [2] Research Centre for Neurosensory Sciences, University of Oldenburg, D-26111 Oldenburg, Germany. ; Institute of Physics, University of Oldenburg, D-26111 Oldenburg, Germany. ; Department of Chemistry, University of Oxford, Physical and Theoretical Chemistry Laboratory, Oxford OX1 3QZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805233" target="_blank"〉PubMed〈/a〉
    Keywords: Aluminum ; Animal Migration/*physiology ; Animals ; Cities ; Conservation of Natural Resources ; Double-Blind Method ; Electricity/adverse effects ; Electromagnetic Fields/*adverse effects ; Electronics/instrumentation ; Germany ; Housing ; *Magnetic Fields ; Orientation/*physiology ; Radio Waves/adverse effects ; Reproducibility of Results ; Seasons ; Songbirds/*physiology ; Universities
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  • 19
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2014 Jan 9;505(7482):139-40. doi: 10.1038/505139a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402259" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Clinical Trials as Topic/adverse effects/*ethics/legislation & ; jurisprudence/standards ; Confidentiality/legislation & jurisprudence ; Foundations ; Humans ; Italy ; Mesenchymal Stromal Cells/cytology ; Neural Stem Cells/cytology/transplantation ; Reproducibility of Results ; Stem Cell Transplantation/*adverse effects/*ethics/legislation & ; jurisprudence/standards ; Uncertainty
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  • 20
    Publication Date: 2014-01-28
    Description: To resolve the mechanisms that switch competition to cooperation is key to understanding biological organization. This is particularly relevant for intrasexual competition, which often leads to males harming females. Recent theory proposes that kin selection may modulate female harm by relaxing competition among male relatives. Here we experimentally manipulate the relatedness of groups of male Drosophila melanogaster competing over females to demonstrate that, as expected, within-group relatedness inhibits male competition and female harm. Females exposed to groups of three brothers unrelated to the female had higher lifetime reproductive success and slower reproductive ageing compared to females exposed to groups of three males unrelated to each other. Triplets of brothers also fought less with each other, courted females less intensively and lived longer than triplets of unrelated males. However, associations among brothers may be vulnerable to invasion by minorities of unrelated males: when two brothers were matched with an unrelated male, the unrelated male sired on average twice as many offspring as either brother. These results demonstrate that relatedness can profoundly affect fitness through its modulation of intrasexual competition, as flies plastically adjust sexual behaviour in a manner consistent with kin-selection theory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carazo, Pau -- Tan, Cedric K W -- Allen, Felicity -- Wigby, Stuart -- Pizzari, Tommaso -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Jan 30;505(7485):672-5. doi: 10.1038/nature12949. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK [2]. ; Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Competitive Behavior/physiology ; *Cooperative Behavior ; Drosophila melanogaster/genetics/*physiology ; Female ; Heredity/physiology ; Longevity/genetics/physiology ; Male ; Models, Biological ; Reproduction/physiology ; Sexual Behavior, Animal/*physiology ; *Siblings
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  • 21
    Publication Date: 2014-01-17
    Description: Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephenson, N L -- Das, A J -- Condit, R -- Russo, S E -- Baker, P J -- Beckman, N G -- Coomes, D A -- Lines, E R -- Morris, W K -- Ruger, N -- Alvarez, E -- Blundo, C -- Bunyavejchewin, S -- Chuyong, G -- Davies, S J -- Duque, A -- Ewango, C N -- Flores, O -- Franklin, J F -- Grau, H R -- Hao, Z -- Harmon, M E -- Hubbell, S P -- Kenfack, D -- Lin, Y -- Makana, J-R -- Malizia, A -- Malizia, L R -- Pabst, R J -- Pongpattananurak, N -- Su, S-H -- Sun, I-F -- Tan, S -- Thomas, D -- van Mantgem, P J -- Wang, X -- Wiser, S K -- Zavala, M A -- England -- Nature. 2014 Mar 6;507(7490):90-3. doi: 10.1038/nature12914. Epub 2014 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Geological Survey, Western Ecological Research Center, Three Rivers, California 93271, USA. ; Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama. ; School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588, USA. ; Department of Forest and Ecosystem Science, University of Melbourne, Victoria 3121, Australia. ; 1] School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588, USA [2] Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio 43210, USA (N.G.B.); German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, 04103 Leipzig, Germany (N.R.). ; Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, UK. ; Department of Geography, University College London, London WC1E 6BT, UK. ; School of Botany, University of Melbourne, Victoria 3010, Australia. ; 1] Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama [2] Spezielle Botanik und Funktionelle Biodiversitat, Universitat Leipzig, 04103 Leipzig, Germany [3] Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio 43210, USA (N.G.B.); German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, 04103 Leipzig, Germany (N.R.). ; Jardin Botanico de Medellin, Calle 73, No. 51D-14, Medellin, Colombia. ; Instituto de Ecologia Regional, Universidad Nacional de Tucuman, 4107 Yerba Buena, Tucuman, Argentina. ; Research Office, Department of National Parks, Wildlife and Plant Conservation, Bangkok 10900, Thailand. ; Department of Botany and Plant Physiology, Buea, Southwest Province, Cameroon. ; Smithsonian Institution Global Earth Observatory-Center for Tropical Forest Science, Smithsonian Institution, PO Box 37012, Washington, DC 20013, USA. ; Universidad Nacional de Colombia, Departamento de Ciencias Forestales, Medellin, Colombia. ; Wildlife Conservation Society, Kinshasa/Gombe, Democratic Republic of the Congo. ; Unite Mixte de Recherche-Peuplements Vegetaux et Bioagresseurs en Milieu Tropical, Universite de la Reunion/CIRAD, 97410 Saint Pierre, France. ; School of Environmental and Forest Sciences, University of Washington, Seattle, Washington 98195, USA. ; State Key Laboratory of Forest and Soil Ecology, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110164, China. ; Department of Forest Ecosystems and Society, Oregon State University, Corvallis, Oregon 97331, USA. ; 1] Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama [2] Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA. ; Department of Life Science, Tunghai University, Taichung City 40704, Taiwan. ; Facultad de Ciencias Agrarias, Universidad Nacional de Jujuy, 4600 San Salvador de Jujuy, Argentina. ; Faculty of Forestry, Kasetsart University, ChatuChak Bangkok 10900, Thailand. ; Taiwan Forestry Research Institute, Taipei 10066, Taiwan. ; Department of Natural Resources and Environmental Studies, National Dong Hwa University, Hualien 97401, Taiwan. ; Sarawak Forestry Department, Kuching, Sarawak 93660, Malaysia. ; Department of Botany and Plant Pathology, Oregon State University, Corvallis, Oregon 97331, USA. ; US Geological Survey, Western Ecological Research Center, Arcata, California 95521, USA. ; Landcare Research, PO Box 40, Lincoln 7640, New Zealand. ; Forest Ecology and Restoration Group, Department of Life Sciences, University of Alcala, Alcala de Henares, 28805 Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24429523" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism ; Biomass ; *Body Size ; Carbon/*metabolism ; *Carbon Cycle ; Climate ; Geography ; Models, Biological ; Plant Leaves/growth & development/metabolism ; Sample Size ; Species Specificity ; Time Factors ; Trees/*anatomy & histology/classification/growth & development/*metabolism ; Tropical Climate
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  • 22
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    Nature Publishing Group (NPG)
    Publication Date: 2014-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, Virginia -- England -- Nature. 2014 Jul 17;511(7509):282-4. doi: 10.1038/511282a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030150" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bariatric Surgery ; Bile Acids and Salts/metabolism ; Biomarkers/analysis ; Biomedical Research ; Diabetes Mellitus/metabolism/prevention & control ; Gammaproteobacteria/isolation & purification/metabolism ; Ghrelin/metabolism ; Glucose/metabolism ; Gram-Positive Bacteria/isolation & purification/metabolism ; Humans ; Hunger/physiology ; Mice ; Models, Animal ; Models, Biological ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism ; Stomach/*surgery ; *Weight Loss
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  • 23
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nuzzo, Regina -- England -- Nature. 2014 Feb 13;506(7487):150-2. doi: 10.1038/506150a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gallaudet University in Washington DC.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522584" target="_blank"〉PubMed〈/a〉
    Keywords: *Data Interpretation, Statistical ; Data Mining ; Reproducibility of Results ; Research Design/*standards
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  • 24
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2014 Apr 17;508(7496):299. doi: 10.1038/508299a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740046" target="_blank"〉PubMed〈/a〉
    Keywords: Acids/pharmacology ; Cell Dedifferentiation/drug effects ; Induced Pluripotent Stem Cells/cytology/drug effects ; Japan ; Lymphocytes/cytology/drug effects ; Pressure ; Reproducibility of Results ; Research Personnel/*ethics/*psychology/standards ; *Scientific Misconduct ; Stem Cell Research/*ethics ; Uncertainty
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  • 25
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohle, Shannon -- England -- Nature. 2014 Feb 13;506(7487):159. doi: 10.1038/506159e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522589" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; *Internet/economics ; *Laboratories ; Patents as Topic ; *Records as Topic/economics ; Reproducibility of Results ; United States
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  • 26
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-01
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058759/" 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/PMC4058759/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis S -- Tabak, Lawrence A -- Z99 OD999999/Intramural NIH HHS/ -- England -- Nature. 2014 Jan 30;505(7485):612-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482835" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; Biomedical Research/*standards ; Disclosure/standards ; Female ; Humans ; Male ; *National Institutes of Health (U.S.) ; Pilot Projects ; Reproducibility of Results ; Research Design/*standards ; Scientific Misconduct/statistics & numerical data ; Sex Characteristics ; United States
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Vivien -- England -- Nature. 2014 May 29;509(7502):645-9. doi: 10.1038/509645a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nature and Nature Methods.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870547" target="_blank"〉PubMed〈/a〉
    Keywords: Anatomy, Artistic ; Antibodies/analysis/immunology ; Antibody Specificity ; Atlases as Topic ; Automation ; *Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Organ Specificity ; Protein Transport ; Proteome/analysis/genetics/*metabolism/secretion ; Reproducibility of Results ; Staining and Labeling ; Tissue Array Analysis
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  • 28
    Publication Date: 2014-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barbier, Edward B -- England -- Nature. 2014 Nov 6;515(7525):32-3. doi: 10.1038/515032a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Wyoming, Laramie, Wyoming, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25373661" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conservation of Natural Resources/*economics/*statistics & numerical data ; *Ecosystem ; *Models, Economic ; Pilot Projects ; Reproducibility of Results ; Rhizophoraceae ; Thailand ; Wood
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2014 Apr 3;508(7494):S8-9. doi: 10.1038/508S8a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695336" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antipsychotic Agents/therapeutic use ; Cognition/physiology ; Cognition Disorders/drug therapy/pathology/physiopathology ; *Disease Models, Animal ; Drug Discovery/*methods/standards ; Humans ; Mice ; Mice, Transgenic ; Multifactorial Inheritance/genetics ; Rats ; Reproducibility of Results ; *Schizophrenia/chemically induced/drug therapy/etiology/physiopathology
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  • 30
    Publication Date: 2014-04-04
    Description: Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gad, Helge -- Koolmeister, Tobias -- Jemth, Ann-Sofie -- Eshtad, Saeed -- Jacques, Sylvain A -- Strom, Cecilia E -- Svensson, Linda M -- Schultz, Niklas -- Lundback, Thomas -- Einarsdottir, Berglind Osk -- Saleh, Aljona -- Gokturk, Camilla -- Baranczewski, Pawel -- Svensson, Richard -- Berntsson, Ronnie P-A -- Gustafsson, Robert -- Stromberg, Kia -- Sanjiv, Kumar -- Jacques-Cordonnier, Marie-Caroline -- Desroses, Matthieu -- Gustavsson, Anna-Lena -- Olofsson, Roger -- Johansson, Fredrik -- Homan, Evert J -- Loseva, Olga -- Brautigam, Lars -- Johansson, Lars -- Hoglund, Andreas -- Hagenkort, Anna -- Pham, Therese -- Altun, Mikael -- Gaugaz, Fabienne Z -- Vikingsson, Svante -- Evers, Bastiaan -- Henriksson, Martin -- Vallin, Karl S A -- Wallner, Olov A -- Hammarstrom, Lars G J -- Wiita, Elisee -- Almlof, Ingrid -- Kalderen, Christina -- Axelsson, Hanna -- Djureinovic, Tatjana -- Puigvert, Jordi Carreras -- Haggblad, Maria -- Jeppsson, Fredrik -- Martens, Ulf -- Lundin, Cecilia -- Lundgren, Bo -- Granelli, Ingrid -- Jensen, Annika Jenmalm -- Artursson, Per -- Nilsson, Jonas A -- Stenmark, Pal -- Scobie, Martin -- Berglund, Ulrika Warpman -- Helleday, Thomas -- England -- Nature. 2014 Apr 10;508(7495):215-21. doi: 10.1038/nature13181. Epub 2014 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2]. ; Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden. ; Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Chemical Biology Consortium Sweden, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden. ; Sahlgrenska Translational Melanoma Group, Sahlgrenska Cancer Center, Department of Surgery, University of Gothenburg and Sahlgrenska University Hospital, S-405 30 Gothenburg, Sweden. ; Department of Analytical Chemistry, Stockholm University, S-106 91 Stockholm, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Department of Pharmacy, Uppsala University, S-751 23 Uppsala, Sweden. ; 1] Chemical Biology Consortium Sweden, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Department of Pharmacy, Uppsala University, S-751 23 Uppsala, Sweden. ; Department of Genetics, Microbiology and Toxicology, Stockholm University, S-106 91 Stockholm, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Clinical Pharmacology, Department of Medical and Health Sciences, Linkoping University, S-58185 Linkoping, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands (B.E.); Department of Immunology, Genetics, and Pathology, Uppsala University, S-751 23 Uppsala, Sweden (T.D.). ; 1] Department of Genetics, Microbiology and Toxicology, Stockholm University, S-106 91 Stockholm, Sweden [2] Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands (B.E.); Department of Immunology, Genetics, and Pathology, Uppsala University, S-751 23 Uppsala, Sweden (T.D.). ; Science for Life Laboratory, RNAi Cell Screening Facility, Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695224" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalytic Domain ; Cell Death/drug effects ; Cell Survival/drug effects ; Crystallization ; DNA Damage ; DNA Repair Enzymes/*antagonists & inhibitors/chemistry/metabolism ; Deoxyguanine Nucleotides/metabolism ; Enzyme Inhibitors/chemistry/pharmacokinetics/pharmacology/therapeutic use ; Female ; Humans ; Male ; Mice ; Models, Molecular ; Molecular Conformation ; Molecular Targeted Therapy ; Neoplasms/*drug therapy/*metabolism/pathology ; Nucleotides/*metabolism ; Oxidation-Reduction/drug effects ; Phosphoric Monoester Hydrolases/*antagonists & inhibitors/chemistry/metabolism ; Pyrimidines/chemistry/pharmacokinetics/pharmacology/therapeutic use ; Pyrophosphatases/antagonists & inhibitors ; Reproducibility of Results ; Xenograft Model Antitumor Assays
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  • 31
    Publication Date: 2014-04-25
    Description: The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180223/" 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/PMC4180223/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacArthur, D G -- Manolio, T A -- Dimmock, D P -- Rehm, H L -- Shendure, J -- Abecasis, G R -- Adams, D R -- Altman, R B -- Antonarakis, S E -- Ashley, E A -- Barrett, J C -- Biesecker, L G -- Conrad, D F -- Cooper, G M -- Cox, N J -- Daly, M J -- Gerstein, M B -- Goldstein, D B -- Hirschhorn, J N -- Leal, S M -- Pennacchio, L A -- Stamatoyannopoulos, J A -- Sunyaev, S R -- Valle, D -- Voight, B F -- Winckler, W -- Gunter, C -- P30 DK020595/DK/NIDDK NIH HHS/ -- P30 DK042086/DK/NIDDK NIH HHS/ -- R01 HG007022/HG/NHGRI NIH HHS/ -- R01 HL117626/HL/NHLBI NIH HHS/ -- R01 MH101810/MH/NIMH NIH HHS/ -- U54 HG006997/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Apr 24;508(7497):469-76. doi: 10.1038/nature13127.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [2] Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. ; Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. ; Division of Genetics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. ; 1] Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, Massachusetts 02139, USA [2] Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98115, USA. ; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. ; 1] NIH Undiagnosed Diseases Program, National Institutes of Health Office of Rare Diseases Research and National Human Genome Research Institute, Bethesda, Maryland 20892, USA [2] Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Departments of Bioengineering & Genetics, Stanford University, Stanford, California 94305, USA. ; 1] Department of Genetic Medicine, University of Geneva Medical School, 1211 Geneva, Switzerland [2] iGE3 Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland. ; Center for Inherited Cardiovascular Disease, Stanford University School of Medicine, Stanford, California 94305, USA. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK. ; Genetic Disease Research Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA. ; Departments of Genetics, Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, Alabama 35806, USA. ; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. ; 1] Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA [2] Departments of Computer Science, Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA. ; Center for Human Genome Variation, Duke University School of Medicine, Durham, North Carolina 27708, USA. ; 1] Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [2] Divisions of Genetics and Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA. ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA [2] US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA. ; Department of Genome Sciences, University of Washington, 1705 Northeast Pacific Street, Seattle, Washington 98195, USA. ; 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. ; Department of Pharmacology and Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA. ; 1] Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [2] Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA (W.W.); Marcus Autism Center, Children's Healthcare of Atlanta, Atlanta, Georgia 30329, USA (C.G.). ; 1] HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, Alabama 35806, USA [2] Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA (W.W.); Marcus Autism Center, Children's Healthcare of Atlanta, Atlanta, Georgia 30329, USA (C.G.).〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24759409" target="_blank"〉PubMed〈/a〉
    Keywords: *Disease ; False Positive Reactions ; Genes/genetics ; Genetic Predisposition to Disease/*genetics ; Genetic Variation/*genetics ; *Guidelines as Topic ; Humans ; Information Dissemination ; Publishing ; Reproducibility of Results ; Research Design ; Translational Medical Research/standards
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  • 32
    Publication Date: 2014-01-28
    Description: What mechanisms underlie the transitions responsible for the diverse shapes observed in the living world? Although bacteria exhibit a myriad of morphologies, the mechanisms responsible for the evolution of bacterial cell shape are not understood. We investigated morphological diversity in a group of bacteria that synthesize an appendage-like extension of the cell envelope called the stalk. The location and number of stalks varies among species, as exemplified by three distinct subcellular positions of stalks within a rod-shaped cell body: polar in the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis. Here we show that a developmental regulator of Caulobacter crescentus, SpmX, is co-opted in the genus Asticcacaulis to specify stalk synthesis either at the subpolar or bilateral positions. We also show that stepwise evolution of a specific region of SpmX led to the gain of a new function and localization of this protein, which drove the sequential transition in stalk positioning. Our results indicate that changes in protein function, co-option and modularity are key elements in the evolution of bacterial morphology. Therefore, similar evolutionary principles of morphological transitions apply to both single-celled prokaryotes and multicellular eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035126/" 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/PMC4035126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Chao -- Brown, Pamela J B -- Ducret, Adrien -- Brun, Yves V -- AI072992/AI/NIAID NIH HHS/ -- GM051986/GM/NIGMS NIH HHS/ -- R01 GM051986/GM/NIGMS NIH HHS/ -- S10RR028697-01/RR/NCRR NIH HHS/ -- England -- Nature. 2014 Feb 27;506(7489):489-93. doi: 10.1038/nature12900. Epub 2014 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Indiana University, Bloomington, Indiana 47405, USA. ; 1] Department of Biology, Indiana University, Bloomington, Indiana 47405, USA [2] Division of Biological Sciences, University of Missouri, Columbia, Missouri 65211, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463524" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*cytology/*metabolism ; Bacterial Proteins/*metabolism ; *Biological Evolution ; Caulobacter crescentus/cytology/metabolism ; Caulobacteraceae/cytology/metabolism ; Cell Membrane/metabolism ; *Cell Polarity ; Evolution, Molecular ; Models, Biological ; Molecular Sequence Data ; Phylogeny ; Protein Transport
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  • 33
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Nov 6;515(7525):7. doi: 10.1038/515007a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25373636" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*standards ; *Guidelines as Topic ; Periodicals as Topic/*standards ; Quality Control ; Reproducibility of Results ; Research Report/*standards
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  • 34
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Oct 30;514(7524):536. doi: 10.1038/514536a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355323" target="_blank"〉PubMed〈/a〉
    Keywords: Information Dissemination/*methods ; *Periodicals as Topic/standards ; Reproducibility of Results ; *Research ; *Software
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  • 35
    Publication Date: 2014-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pagan-Jimenez, Jaime R -- Rodriguez-Ramos, Reniel -- Oliver, Jose R -- England -- Nature. 2014 Jun 26;510(7506):473. doi: 10.1038/510473b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leiden University, the Netherlands. ; University of Puerto Rico, Utuado, Puerto Rico. ; University College London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24965639" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeology ; Bolivia/ethnology ; Crops, Agricultural/genetics/*history ; Culture ; DNA, Plant/analysis ; Feces/chemistry ; History, Ancient ; Humans ; Phylogeography ; Puerto Rico ; Reproducibility of Results ; *Zea mays/genetics
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  • 36
    Publication Date: 2014-09-05
    Description: Elucidating the role of molecular stochasticity in cellular growth is central to understanding phenotypic heterogeneity and the stability of cellular proliferation. The inherent stochasticity of metabolic reaction events should have negligible effect, because of averaging over the many reaction events contributing to growth. Indeed, metabolism and growth are often considered to be constant for fixed conditions. Stochastic fluctuations in the expression level of metabolic enzymes could produce variations in the reactions they catalyse. However, whether such molecular fluctuations can affect growth is unclear, given the various stabilizing regulatory mechanisms, the slow adjustment of key cellular components such as ribosomes, and the secretion and buffering of excess metabolites. Here we use time-lapse microscopy to measure fluctuations in the instantaneous growth rate of single cells of Escherichia coli, and quantify time-resolved cross-correlations with the expression of lac genes and enzymes in central metabolism. We show that expression fluctuations of catabolically active enzymes can propagate and cause growth fluctuations, with transmission depending on the limitation of the enzyme to growth. Conversely, growth fluctuations propagate back to perturb expression. Accordingly, enzymes were found to transmit noise to other unrelated genes via growth. Homeostasis is promoted by a noise-cancelling mechanism that exploits fluctuations in the dilution of proteins by cell-volume expansion. The results indicate that molecular noise is propagated not only by regulatory proteins but also by metabolic reactions. They also suggest that cellular metabolism is inherently stochastic, and a generic source of phenotypic heterogeneity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kiviet, Daniel J -- Nghe, Philippe -- Walker, Noreen -- Boulineau, Sarah -- Sunderlikova, Vanda -- Tans, Sander J -- England -- Nature. 2014 Oct 16;514(7522):376-9. doi: 10.1038/nature13582. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] FOM institute AMOLF, Science Park 104, 1098 XG Amsterdam, the Netherlands [2] Department of Environmental Systems Science, ETH Zurich, Universitaetsstrasse 16, 8092 Zurich, Switzerland [3] Department of Environmental Microbiology, Eawag, Ueberlandstrasse 133, 8600 Duebendorf, Switzerland [4]. ; 1] FOM institute AMOLF, Science Park 104, 1098 XG Amsterdam, the Netherlands [2] Laboratoire de Biochimie, UMR 8231 CNRS/ESPCI, Ecole Superieure de Physique et de Chimie industrielles, 10 rue Vauquelin, 75005 Paris, France. [3]. ; FOM institute AMOLF, Science Park 104, 1098 XG Amsterdam, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186725" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Enlargement ; Cell Proliferation ; Escherichia coli/enzymology/genetics/*growth & development/*metabolism ; Escherichia coli Proteins/genetics/metabolism ; Homeostasis ; Lac Operon/genetics ; Microscopy ; Models, Biological ; *Single-Cell Analysis ; Stochastic Processes ; Time-Lapse Imaging
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  • 37
    Publication Date: 2014-08-01
    Description: Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue. Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaukua, Nina -- Shahidi, Maryam Khatibi -- Konstantinidou, Chrysoula -- Dyachuk, Vyacheslav -- Kaucka, Marketa -- Furlan, Alessandro -- An, Zhengwen -- Wang, Longlong -- Hultman, Isabell -- Ahrlund-Richter, Lars -- Blom, Hans -- Brismar, Hjalmar -- Lopes, Natalia Assaife -- Pachnis, Vassilis -- Suter, Ueli -- Clevers, Hans -- Thesleff, Irma -- Sharpe, Paul -- Ernfors, Patrik -- Fried, Kaj -- Adameyko, Igor -- G0901599/Medical Research Council/United Kingdom -- MC_U117537087/Medical Research Council/United Kingdom -- England -- Nature. 2014 Sep 25;513(7519):551-4. doi: 10.1038/nature13536. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden [2]. ; 1] Department of Dental Medicine, Karolinska Institutet, Stockholm 17177, Sweden [2]. ; Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK. ; 1] Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden [2] A.V. Zhirmunsky Institute of Marine Biology of the Far Eastern Branch of the Russian Academy of Sciences, Vladivostok 690041, Russia. ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden. ; Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden. ; Department of Craniofacial Development and Stem Cell Biology, King's College London Dental Institute, Guy's Hospital, London SE1 3QD, UK. ; Department of Women's and Children's Health, Karolinska Institutet, Stockholm 17177, Sweden. ; Science for Life Laboratory, Royal Institute of Technology, Stockholm 17177, Sweden. ; Department of Biology, Institute of Molecular Health Sciences, ETH Zurich CH-8093, Switzerland. ; 1] Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen (KNAW), PO Box 85164, 3508 AD Utrecht, the Netherlands [2] Department of Molecular Genetics, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands. ; Institute of Biotechnology, Developmental Biology Program, University of Helsinki, Helsinki FI-00014, Finland. ; Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079316" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; *Cell Lineage ; Cell Tracking ; Clone Cells/cytology ; Dental Pulp/cytology ; Female ; Incisor/*cytology/embryology ; Male ; Mesenchymal Stromal Cells/*cytology ; Mice ; Models, Biological ; Neural Crest/cytology ; Neuroglia/*cytology ; Odontoblasts/cytology ; Regeneration ; Schwann Cells/cytology
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  • 38
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2014 Nov 6;515(7525):18. doi: 10.1038/515018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25373654" target="_blank"〉PubMed〈/a〉
    Keywords: Disaster Planning/methods ; Disease Outbreaks/*statistics & numerical data ; Hemorrhagic Fever, Ebola/*epidemiology/*transmission ; Humans ; Liberia/epidemiology ; *Models, Biological ; Reproducibility of Results ; Uncertainty
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  • 39
    Publication Date: 2014-07-22
    Description: A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486207/" 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/PMC4486207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whelan, Robert -- Watts, Richard -- Orr, Catherine A -- Althoff, Robert R -- Artiges, Eric -- Banaschewski, Tobias -- Barker, Gareth J -- Bokde, Arun L W -- Buchel, Christian -- Carvalho, Fabiana M -- Conrod, Patricia J -- Flor, Herta -- Fauth-Buhler, Mira -- Frouin, Vincent -- Gallinat, Juergen -- Gan, Gabriela -- Gowland, Penny -- Heinz, Andreas -- Ittermann, Bernd -- Lawrence, Claire -- Mann, Karl -- Martinot, Jean-Luc -- Nees, Frauke -- Ortiz, Nick -- Paillere-Martinot, Marie-Laure -- Paus, Tomas -- Pausova, Zdenka -- Rietschel, Marcella -- Robbins, Trevor W -- Smolka, Michael N -- Strohle, Andreas -- Schumann, Gunter -- Garavan, Hugh -- IMAGEN Consortium -- MH082116/MH/NIMH NIH HHS/ -- P20 GM103644/GM/NIGMS NIH HHS/ -- P20GM103644/GM/NIGMS NIH HHS/ -- P50 DA036114/DA/NIDA NIH HHS/ -- P50DA036114/DA/NIDA NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Aug 14;512(7513):185-9. doi: 10.1038/nature13402. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University College Dublin, Dublin 4, Ireland. ; Department of Radiology, University of Vermont, Burlington, Vermont 05401, USA. ; Vermont Center for Children, Youth, and Families, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Department of Pediatrics, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Institut National de la Sante et de la Recherche Medicale, INSERM CEA Unit 1000 "Imaging &Psychiatry", University Paris Sud, 91400 Orsay, France [2] Department of Psychiatry, Orsay Hospital, 4 place du General Leclerc, 91400 Orsay, France. ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. ; Institute of Psychiatry, King's College London, London SE5 8AF, UK. ; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland. ; 1] Department of Systems Neuroscience, Universitatsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany [2] Department of Psychology, Stanford University, Stanford, California 94305, USA. ; 1] Institute of Psychiatry, King's College London, London SE5 8AF, UK [2] Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal H3T 1C5, Canada. ; 1] Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany [2] Department of Addictive Behaviour and Addiction Medicine, Heidelberg University, 68159 Mannheim, Germany. ; 14 CEA, DSV, I2BM, Neurospin bat 145, 91191 Gif-Sur-Yvette, France. ; 1] Department of Systems Neuroscience, Universitatsklinikum Hamburg Eppendorf, 20246 Hamburg, Germany [2] Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany. ; Department of Psychiatry and Neuroimaging Center, Technische Universitat Dresden, 01062 Dresden, Germany. ; School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK. ; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany. ; Physikalisch-Technische Bundesanstalt (PTB), 10587 Berlin, Germany. ; School of Psychology, University of Nottingham, Nottingham NG7 2RD, UK. ; 1] Institut National de la Sante et de la Recherche Medicale, INSERM CEA Unit 1000 "Imaging &Psychiatry", University Paris Sud, 91400 Orsay, France [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75006 Paris, France. ; 1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Neuroscience Graduate Program, University of Vermont, Burlington, Vermont 05401, USA. ; 1] Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin 10117, Germany [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75006 Paris, France. ; 1] Rotman Research Institute, University of Toronto, Toronto, Ontario M5R 0A3, Canada [2] Montreal Neurological Institute, McGill University, H3A 2B4, Canada. ; The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada. ; Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge CB2 1TN, UK. ; 1] Institute of Psychiatry, King's College London, London SE5 8AF, UK [2] MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, London WC2R 2LS, UK. ; 1] Department of Psychiatry, University of Vermont, Burlington, Vermont 05401, USA [2] Department of Psychology, University of Vermont, Burlington, Vermont 05401, USA [3] Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043041" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Alcohol Drinking/*psychology ; Alcoholism/genetics/prevention & control/*psychology ; Artificial Intelligence ; Brain/physiology ; Cognition/physiology ; Environment ; Humans ; Life Change Events ; Longitudinal Studies ; *Models, Theoretical ; Personality/physiology ; Polymorphism, Single Nucleotide ; Psychology ; Reproducibility of Results ; Risk Factors
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  • 40
    Publication Date: 2014-02-07
    Description: The seasonality of sunlight and rainfall regulates net primary production in tropical forests. Previous studies have suggested that light is more limiting than water for tropical forest productivity, consistent with greening of Amazon forests during the dry season in satellite data. We evaluated four potential mechanisms for the seasonal green-up phenomenon, including increases in leaf area or leaf reflectance, using a sophisticated radiative transfer model and independent satellite observations from lidar and optical sensors. Here we show that the apparent green up of Amazon forests in optical remote sensing data resulted from seasonal changes in near-infrared reflectance, an artefact of variations in sun-sensor geometry. Correcting this bidirectional reflectance effect eliminated seasonal changes in surface reflectance, consistent with independent lidar observations and model simulations with unchanging canopy properties. The stability of Amazon forest structure and reflectance over seasonal timescales challenges the paradigm of light-limited net primary production in Amazon forests and enhanced forest growth during drought conditions. Correcting optical remote sensing data for artefacts of sun-sensor geometry is essential to isolate the response of global vegetation to seasonal and interannual climate variability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morton, Douglas C -- Nagol, Jyoteshwar -- Carabajal, Claudia C -- Rosette, Jacqueline -- Palace, Michael -- Cook, Bruce D -- Vermote, Eric F -- Harding, David J -- North, Peter R J -- England -- Nature. 2014 Feb 13;506(7487):221-4. doi: 10.1038/nature13006. Epub 2014 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA. ; 1] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [2] Global Land Cover Facility, College Park, Maryland 20740, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] Sigma Space Corporation, Lantham, Maryland 20706, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [3] Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK. ; Earth System Research Center, University of New Hampshire, Durham, New Hampshire 03824, USA. ; Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499816" target="_blank"〉PubMed〈/a〉
    Keywords: Artifacts ; Brazil ; Color ; *Droughts ; Ecosystem ; Fresh Water/analysis ; Models, Biological ; Photosynthesis ; Pigmentation/*physiology ; Plant Leaves/anatomy & histology/growth & development/*physiology ; Rain ; Satellite Imagery ; *Seasons ; *Sunlight ; Trees/anatomy & histology/growth & development/*physiology ; *Tropical Climate
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  • 41
    Publication Date: 2014-06-05
    Description: Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189846/" 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/PMC4189846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subramanian, Sathish -- Huq, Sayeeda -- Yatsunenko, Tanya -- Haque, Rashidul -- Mahfuz, Mustafa -- Alam, Mohammed A -- Benezra, Amber -- DeStefano, Joseph -- Meier, Martin F -- Muegge, Brian D -- Barratt, Michael J -- VanArendonk, Laura G -- Zhang, Qunyuan -- Province, Michael A -- Petri, William A Jr -- Ahmed, Tahmeed -- Gordon, Jeffrey I -- AI043596/AI/NIAID NIH HHS/ -- R01 AI043596/AI/NIAID NIH HHS/ -- T32 GM007067/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 19;510(7505):417-21. doi: 10.1038/nature13421. Epub 2014 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri 63108, USA. ; Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh. ; 1] Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri 63108, USA [2] Department of Anthropology, New School for Social Research, New York, New York 10003, USA. ; Division of Statistical Genomics, Washington University in St. Louis, St. Louis, Missouri 63108, USA. ; Departments of Medicine, Microbiology and Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896187" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/classification/genetics ; *Bacterial Physiological Phenomena ; Bangladesh ; *Biodiversity ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Infant ; Infant Nutrition Disorders/diet therapy/*microbiology ; Male ; *Microbiota ; Models, Biological ; Nutritional Status ; RNA, Ribosomal, 16S/genetics
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  • 42
    Publication Date: 2014-09-12
    Description: Since the recognition that allopatric speciation can be induced by large-scale reconfigurations of the landscape that isolate formerly continuous populations, such as the separation of continents by plate tectonics, the uplift of mountains or the formation of large rivers, landscape change has been viewed as a primary driver of biological diversification. This process is referred to in biogeography as vicariance. In the most species-rich region of the world, the Neotropics, the sundering of populations associated with the Andean uplift is ascribed this principal role in speciation. An alternative model posits that rather than being directly linked to landscape change, allopatric speciation is initiated to a greater extent by dispersal events, with the principal drivers of speciation being organism-specific abilities to persist and disperse in the landscape. Landscape change is not a necessity for speciation in this model. Here we show that spatial and temporal patterns of genetic differentiation in Neotropical birds are highly discordant across lineages and are not reconcilable with a model linking speciation solely to landscape change. Instead, the strongest predictors of speciation are the amount of time a lineage has persisted in the landscape and the ability of birds to move through the landscape matrix. These results, augmented by the observation that most species-level diversity originated after episodes of major Andean uplift in the Neogene period, suggest that dispersal and differentiation on a matrix previously shaped by large-scale landscape events was a major driver of avian speciation in lowland Neotropical rainforests.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Brian Tilston -- McCormack, John E -- Cuervo, Andres M -- Hickerson, Michael J -- Aleixo, Alexandre -- Cadena, Carlos Daniel -- Perez-Eman, Jorge -- Burney, Curtis W -- Xie, Xiaoou -- Harvey, Michael G -- Faircloth, Brant C -- Glenn, Travis C -- Derryberry, Elizabeth P -- Prejean, Jesse -- Fields, Samantha -- Brumfield, Robb T -- England -- Nature. 2014 Nov 20;515(7527):406-9. doi: 10.1038/nature13687. Epub 2014 Sep 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Ornithology, American Museum of Natural History, New York, New York 10024, USA [3]. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA [3] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; 1] Biology Department, City College of New York, New York, New York 10031, USA [2] Division of Invertebrate Zoology, American Museum of Natural History, New York, New York 10024, USA. ; Coordenacao de Zoologia, Museu Paraense Emilio Goeldi, Caixa Postal 399, CEP 66040-170, Belem, Brazil. ; Laboratorio de Biologia Evolutiva de Vertebrados, Departamento de Ciencias Biologicas, Universidad de los Andes, Bogota, Colombia. ; 1] Instituto de Zoologia y Ecologia Tropical, Universidad Central de Venezuela, Av. Los Ilustres, Los Chaguaramos, Apartado Postal 47058, Caracas 1041-A, Venezuela [2] Coleccion Ornitologica Phelps, Apartado 2009, Caracas 1010-A, Venezuela. ; Biology Department, City College of New York, New York, New York 10031, USA. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA. ; 1] Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA [2] Moore Laboratory of Zoology, Occidental College, 1600 Campus Road, Los Angeles, California 90041, USA (J.E.M.); Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, Louisiana 70118, USA (A.M.C. &E.P.D.); Department of Biology, 2355 Faculty Drive, Suite 2P483, United States Air Force Academy, Colorado 80840, USA (C.W.B.); Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA (B.C.F.). ; Department of Environmental Health Science, University of Georgia, Athens, Georgia 30602, USA. ; 1] Museum of Natural Science, Louisiana State University, Baton Rouge, Louisiana 70803, USA [2] Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209666" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Birds/*classification/*genetics ; *Genetic Speciation ; Models, Biological ; Molecular Sequence Data ; Panama ; *Phylogeny ; *Rainforest ; Rivers ; South America ; *Tropical Climate
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  • 43
    Publication Date: 2014-02-14
    Description: It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, En-Zhi -- Song, Chun-Qing -- Lin, Yuan -- Zhang, Wen-Hong -- Su, Pei-Fang -- Liu, Wen-Yuan -- Zhang, Pan -- Xu, Jiejia -- Lin, Na -- Zhan, Cheng -- Wang, Xianhua -- Shyr, Yu -- Cheng, Heping -- Dong, Meng-Qiu -- England -- Nature. 2014 Apr 3;508(7494):128-32. doi: 10.1038/nature13012. Epub 2014 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] College of Biological Sciences, China Agricultural University, Beijing 100094, China [2] National Institute of Biological Sciences, Beijing, Beijing 102206, China [3]. ; 1] State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China [2]. ; National Institute of Biological Sciences, Beijing, Beijing 102206, China. ; Department of Statistics, National Cheng Kung University, Tainan 70101, Taiwan. ; State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ; Vanderbilt Centre for Quantitative Sciences, Vanderbilt University, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522532" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/genetics/*metabolism/physiology ; Caenorhabditis elegans Proteins/genetics ; Death ; Energy Metabolism ; Environment ; Glyoxylates/metabolism ; Hermaphroditic Organisms ; *Longevity/genetics/physiology ; Male ; Mitochondria/*metabolism ; Models, Biological ; Muscles/cytology ; Mutation ; Oxidative Stress ; Receptor, Insulin/genetics ; Reproduction ; Stochastic Processes ; Superoxides/analysis/*metabolism ; Time Factors
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  • 44
    Publication Date: 2014-05-16
    Description: MicroRNA and protein sequestration by non-coding RNAs (ncRNAs) has recently generated much interest. In the bacterial Csr/Rsm system, which is considered to be the most general global post-transcriptional regulatory system responsible for bacterial virulence, ncRNAs such as CsrB or RsmZ activate translation initiation by sequestering homodimeric CsrA-type proteins from the ribosome-binding site of a subset of messenger RNAs. However, the mechanism of ncRNA-mediated protein sequestration is not understood at the molecular level. Here we show for Pseudomonas fluorescens that RsmE protein dimers assemble sequentially, specifically and cooperatively onto the ncRNA RsmZ within a narrow affinity range. This assembly yields two different native ribonucleoprotein structures. Using a powerful combination of nuclear magnetic resonance and electron paramagnetic resonance spectroscopy we elucidate these 70-kilodalton solution structures, thereby revealing the molecular mechanism of the sequestration process and how RsmE binding protects the ncRNA from RNase E degradation. Overall, our findings suggest that RsmZ is well-tuned to sequester, store and release RsmE and therefore can be viewed as an ideal protein 'sponge'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duss, Olivier -- Michel, Erich -- Yulikov, Maxim -- Schubert, Mario -- Jeschke, Gunnar -- Allain, Frederic H-T -- England -- Nature. 2014 May 29;509(7502):588-92. doi: 10.1038/nature13271. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, CH-8093 Zurich, Switzerland. ; Laboratory of Physical Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828038" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Electron Spin Resonance Spectroscopy ; Escherichia coli/chemistry/genetics/metabolism ; Escherichia coli Proteins/chemistry/*metabolism ; Methyltransferases/chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Molecular Weight ; Nuclear Magnetic Resonance, Biomolecular ; Nucleic Acid Conformation ; *Protein Binding ; Protein Multimerization ; RNA, Untranslated/chemistry/genetics/*metabolism ; Ribonucleases/metabolism ; Ribonucleoproteins/chemistry/genetics/metabolism
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  • 45
    Publication Date: 2014-05-30
    Description: The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403737/" 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/PMC4403737/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Min-Sik -- Pinto, Sneha M -- Getnet, Derese -- Nirujogi, Raja Sekhar -- Manda, Srikanth S -- Chaerkady, Raghothama -- Madugundu, Anil K -- Kelkar, Dhanashree S -- Isserlin, Ruth -- Jain, Shobhit -- Thomas, Joji K -- Muthusamy, Babylakshmi -- Leal-Rojas, Pamela -- Kumar, Praveen -- Sahasrabuddhe, Nandini A -- Balakrishnan, Lavanya -- Advani, Jayshree -- George, Bijesh -- Renuse, Santosh -- Selvan, Lakshmi Dhevi N -- Patil, Arun H -- Nanjappa, Vishalakshi -- Radhakrishnan, Aneesha -- Prasad, Samarjeet -- Subbannayya, Tejaswini -- Raju, Rajesh -- Kumar, Manish -- Sreenivasamurthy, Sreelakshmi K -- Marimuthu, Arivusudar -- Sathe, Gajanan J -- Chavan, Sandip -- Datta, Keshava K -- Subbannayya, Yashwanth -- Sahu, Apeksha -- Yelamanchi, Soujanya D -- Jayaram, Savita -- Rajagopalan, Pavithra -- Sharma, Jyoti -- Murthy, Krishna R -- Syed, Nazia -- Goel, Renu -- Khan, Aafaque A -- Ahmad, Sartaj -- Dey, Gourav -- Mudgal, Keshav -- Chatterjee, Aditi -- Huang, Tai-Chung -- Zhong, Jun -- Wu, Xinyan -- Shaw, Patrick G -- Freed, Donald -- Zahari, Muhammad S -- Mukherjee, Kanchan K -- Shankar, Subramanian -- Mahadevan, Anita -- Lam, Henry -- Mitchell, Christopher J -- Shankar, Susarla Krishna -- Satishchandra, Parthasarathy -- Schroeder, John T -- Sirdeshmukh, Ravi -- Maitra, Anirban -- Leach, Steven D -- Drake, Charles G -- Halushka, Marc K -- Prasad, T S Keshava -- Hruban, Ralph H -- Kerr, Candace L -- Bader, Gary D -- Iacobuzio-Donahue, Christine A -- Gowda, Harsha -- Pandey, Akhilesh -- HHSN268201000032C/HL/NHLBI NIH HHS/ -- HHSN268201000032C/PHS HHS/ -- P41 GM103504/GM/NIGMS NIH HHS/ -- P41GM103504/GM/NIGMS NIH HHS/ -- T32 GM007814/GM/NIGMS NIH HHS/ -- U24 CA160036/CA/NCI NIH HHS/ -- U24CA160036/CA/NCI NIH HHS/ -- U54 GM103520/GM/NIGMS NIH HHS/ -- U54GM103520/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 May 29;509(7502):575-81. doi: 10.1038/nature13302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Institute of Bioinformatics, International Tech Park, Bangalore 560066, India. ; 1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130, USA. ; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; 1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Pathology, Universidad de La Frontera, Center of Genetic and Immunological Studies-Scientific and Technological Bioresource Nucleus, Temuco 4811230, Chile. ; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; School of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. ; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Neurosurgery, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India. ; Department of Internal Medicine Armed Forces Medical College, Pune 411040, India. ; 1] Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India [2] Human Brain Tissue Repository, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore 560029, India. ; Department of Chemical and Biomolecular Engineering and Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong. ; Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India. ; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. ; 1] The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA [2] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; 1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; 1] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA [2] Departments of Immunology and Urology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; 1] Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine Baltimore, Maryland 21205, USA [2] Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; 1] The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA [2] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA [3] Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; 1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [3] Institute of Bioinformatics, International Tech Park, Bangalore 560066, India [4] Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130, USA [5] The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA [6] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA [7] Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870542" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Cells, Cultured ; Databases, Protein ; Fetus/metabolism ; Fourier Analysis ; Gene Expression Profiling ; Genome, Human/genetics ; Hematopoietic Stem Cells/cytology/metabolism ; Humans ; Internet ; Mass Spectrometry ; Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Protein Biosynthesis ; Protein Isoforms/analysis/genetics/metabolism ; Protein Sorting Signals ; Protein Transport ; Proteome/analysis/chemistry/genetics/*metabolism ; *Proteomics ; Pseudogenes/genetics ; RNA, Untranslated/genetics ; Reproducibility of Results ; Untranslated Regions/genetics
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  • 46
    Publication Date: 2014-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yarborough, Mark -- England -- Nature. 2014 Nov 20;515(7527):313. doi: 10.1038/515313a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409791" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Bias (Epidemiology) ; *Communication ; Conflict of Interest ; *Public Opinion ; Quality Control ; Reproducibility of Results ; Research Design ; *Research Personnel/ethics/standards ; Science/*standards ; *Trust
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  • 47
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Apr 3;508(7494):22. doi: 10.1038/508022a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695296" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aging/blood/genetics ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Body Mass Index ; Case-Control Studies ; DNA Methylation ; *Epigenomics/standards/trends ; Gene-Environment Interaction ; Genome-Wide Association Study/standards ; Humans ; Infant, Newborn ; Obesity/genetics ; Repressor Proteins/genetics ; Reproducibility of Results
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  • 48
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Mar 27;507(7493):414-6. doi: 10.1038/507414a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670743" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Animals ; Animals, Domestic/genetics ; Dogs ; *Evolution, Molecular ; Extinction, Biological ; Fossils ; Genomics/*methods/trends ; History, Ancient ; Hominidae/classification/genetics ; Horses/genetics ; Humans ; Models, Biological ; Neanderthals/*classification/*genetics ; Paleontology/methods/trends ; *Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA/methods ; Wolves/genetics
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  • 49
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anthes, Emily -- England -- Nature. 2014 Apr 3;508(7494):S16-7. doi: 10.1038/508S16a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695330" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aging, Premature/*complications/etiology/pathology/*physiopathology ; Antipsychotic Agents/adverse effects ; Brain/pathology/physiopathology ; Cardiovascular Diseases/complications ; Confounding Factors (Epidemiology) ; Diabetes Mellitus, Type 2/complications ; Glucose Intolerance/complications ; Health Surveys ; Humans ; Longevity/drug effects ; Middle Aged ; Models, Biological ; Schizophrenia/*complications/drug therapy/pathology/*physiopathology ; Telomere/metabolism ; Time Factors
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  • 50
    Publication Date: 2014-04-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hsu, Angel -- Malik, Omar -- Johnson, Laura -- Esty, Daniel C -- England -- Nature. 2014 Apr 3;508(7494):33-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24707525" target="_blank"〉PubMed〈/a〉
    Keywords: Bias (Epidemiology) ; Conservation of Natural Resources/*methods/*statistics & numerical data ; Crowdsourcing ; Ecology/*manpower/*methods ; Environmental Monitoring/standards ; Environmental Policy/legislation & jurisprudence ; Federal Government ; *Goals ; Politics ; *Program Evaluation/standards ; Reproducibility of Results ; United Nations/legislation & jurisprudence
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  • 51
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2014 May 1;509(7498):15-6. doi: 10.1038/509015a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784193" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/transplantation ; Clinical Trials, Phase III as Topic/economics/trends ; Heart Diseases/*therapy ; Heart Failure/therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Myocardial Infarction/therapy ; Randomized Controlled Trials as Topic/standards/*statistics & numerical data ; Reproducibility of Results ; *Stem Cell Transplantation
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  • 52
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    Nature Publishing Group (NPG)
    Publication Date: 2014-03-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marris, Emma -- England -- Nature. 2014 Mar 13;507(7491):158-60. doi: 10.1038/507158a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24622187" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Food Chain ; *Models, Biological ; Predatory Behavior/*physiology ; Reproducibility of Results ; Wolves/*physiology
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  • 53
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Barry -- Azad, Meghan -- England -- Nature. 2014 Oct 16;514(7522):S6-7. doi: 10.1038/514S6a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25317594" target="_blank"〉PubMed〈/a〉
    Keywords: Helicobacter pylori/genetics/isolation & purification/*pathogenicity ; History, 20th Century ; History, 21st Century ; Human Migration ; Humans ; Hygiene Hypothesis ; Job Satisfaction ; Male ; Nobel Prize ; Reproducibility of Results ; Stomach Ulcer/*etiology/history/*microbiology ; Stress, Psychological ; Vaccines, Edible
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  • 54
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    Nature Publishing Group (NPG)
    Publication Date: 2014-08-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Aug 28;512(7515):347. doi: 10.1038/512347b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164715" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Psychological ; *Attitude ; *Behavior ; Global Warming/prevention & control/*statistics & numerical data ; Human Activities ; Humans ; *Models, Psychological ; Reproducibility of Results
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  • 55
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    Nature Publishing Group (NPG)
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2014 Mar 20;507(7492):283. doi: 10.1038/507283a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24646974" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cellular Reprogramming ; Dissertations, Academic as Topic/standards ; Embryonic Stem Cells/cytology ; Induced Pluripotent Stem Cells/*cytology ; Japan ; Mice ; Reproducibility of Results ; Research Personnel/*ethics ; Retraction of Publication as Topic ; Scientific Misconduct/*legislation & jurisprudence ; Stem Cell Transplantation
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  • 56
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Victor, David G -- Kennel, Charles F -- England -- Nature. 2014 Oct 2;514(7520):30-1. doi: 10.1038/514030a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of International Relations and Pacific Studies, University of California, San Diego, La Jolla, California, USA. ; Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279903" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Carbon Dioxide/analysis ; Environmental Policy/*legislation & jurisprudence/trends ; Global Warming/*prevention & control/*statistics & numerical data ; *Goals ; Human Activities ; International Cooperation ; Models, Biological ; *Policy Making ; Risk Assessment ; Seawater/analysis ; *Temperature
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  • 57
    Publication Date: 2014-08-01
    Description: Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184961/" 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/PMC4184961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marusyk, Andriy -- Tabassum, Doris P -- Altrock, Philipp M -- Almendro, Vanessa -- Michor, Franziska -- Polyak, Kornelia -- U54 CA143798/CA/NCI NIH HHS/ -- U54CA143798/CA/NCI NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):54-8. doi: 10.1038/nature13556. Epub 2014 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] BBS Program, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA [3] Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [4] BBS Program, Harvard Medical School, Boston, Massachusetts 02115, USA [5] Harvard Stem Cell Institute and the Broad Institute, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079331" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Proliferation ; Clone Cells/*metabolism/*pathology ; Epigenesis, Genetic/genetics ; Female ; Interleukin-11/metabolism ; Mice ; Models, Biological ; Neoplasm Metastasis ; Neoplasms/*genetics/metabolism/*pathology ; Phenotype ; Tumor Microenvironment
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  • 58
    Publication Date: 2014-01-31
    Description: Recent clinical trials showed that targeting of inhibitory receptors on T cells induces durable responses in a subset of cancer patients, despite advanced disease. However, the regulatory switches controlling T-cell function in immunosuppressive tumours are not well understood. Here we show that such inhibitory mechanisms can be systematically discovered in the tumour microenvironment. We devised an in vivo pooled short hairpin RNA (shRNA) screen in which shRNAs targeting negative regulators became highly enriched in murine tumours by releasing a block on T-cell proliferation upon tumour antigen recognition. Such shRNAs were identified by deep sequencing of the shRNA cassette from T cells infiltrating tumour or control tissues. One of the target genes was Ppp2r2d, a regulatory subunit of the PP2A phosphatase family. In tumours, Ppp2r2d knockdown inhibited T-cell apoptosis and enhanced T-cell proliferation as well as cytokine production. Key regulators of immune function can therefore be discovered in relevant tissue microenvironments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052214/" 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/PMC4052214/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Penghui -- Shaffer, Donald R -- Alvarez Arias, Diana A -- Nakazaki, Yukoh -- Pos, Wouter -- Torres, Alexis J -- Cremasco, Viviana -- Dougan, Stephanie K -- Cowley, Glenn S -- Elpek, Kutlu -- Brogdon, Jennifer -- Lamb, John -- Turley, Shannon J -- Ploegh, Hidde L -- Root, David E -- Love, J Christopher -- Dranoff, Glenn -- Hacohen, Nir -- Cantor, Harvey -- Wucherpfennig, Kai W -- 1R01CA173750/CA/NCI NIH HHS/ -- DP3 DK097681/DK/NIDDK NIH HHS/ -- P01 AI045757/AI/NIAID NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- R01 CA173750/CA/NCI NIH HHS/ -- T32 AI007386/AI/NIAID NIH HHS/ -- T32 AI07386/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Feb 6;506(7486):52-7. doi: 10.1038/nature12988. Epub 2014 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2]. ; 1] Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] [3] Jounce Therapeutics, Cambridge, Massachusetts 02138, USA. ; Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. ; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; Whitehead Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] Jounce Therapeutics, Cambridge, Massachusetts 02138, USA. ; Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476824" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/immunology ; Apoptosis/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/cytology/immunology/secretion ; Cell Proliferation ; Cytokines/immunology/secretion ; Female ; Gene Knockdown Techniques ; High-Throughput Nucleotide Sequencing ; *Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating/cytology/immunology/metabolism/secretion ; Melanoma, Experimental/immunology ; Mice ; Mice, Inbred C57BL ; *Molecular Targeted Therapy ; Protein Phosphatase 2/deficiency/genetics/*metabolism ; RNA, Small Interfering/genetics ; Reproducibility of Results ; Tumor Microenvironment/*immunology
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  • 59
    Publication Date: 2014-04-11
    Description: Targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications. In contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed. Here we report the development of a focused CRISPR/Cas-based (clustered regularly interspaced short palindromic repeats/CRISPR-associated) lentiviral library in human cells and a method of gene identification based on functional screening and high-throughput sequencing analysis. Using knockout library screens, we successfully identified the host genes essential for the intoxication of cells by anthrax and diphtheria toxins, which were confirmed by functional validation. The broad application of this powerful genetic screening strategy will not only facilitate the rapid identification of genes important for bacterial toxicity but will also enable the discovery of genes that participate in other biological processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yuexin -- Zhu, Shiyou -- Cai, Changzu -- Yuan, Pengfei -- Li, Chunmei -- Huang, Yanyi -- Wei, Wensheng -- England -- Nature. 2014 May 22;509(7501):487-91. doi: 10.1038/nature13166. Epub 2014 Apr 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China [2]. ; State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China. ; Biodynamic Optical Imaging Centre (BIOPIC), College of Engineering, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717434" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Bacterial/pharmacology ; Bacterial Toxins/pharmacology ; CRISPR-Associated Proteins/*genetics ; Cell Line ; Cells/drug effects/*metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; Diphtheria Toxin/pharmacology ; *Gene Library ; Genomics/*methods ; High-Throughput Screening Assays/*methods ; Humans ; INDEL Mutation/genetics ; Lentivirus/genetics ; Organic Cation Transporter 1/genetics ; RNA, Guide/genetics ; Reproducibility of Results
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  • 60
    Publication Date: 2014-11-05
    Description: Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313871/" 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/PMC4313871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iossifov, Ivan -- O'Roak, Brian J -- Sanders, Stephan J -- Ronemus, Michael -- Krumm, Niklas -- Levy, Dan -- Stessman, Holly A -- Witherspoon, Kali T -- Vives, Laura -- Patterson, Karynne E -- Smith, Joshua D -- Paeper, Bryan -- Nickerson, Deborah A -- Dea, Jeanselle -- Dong, Shan -- Gonzalez, Luis E -- Mandell, Jeffrey D -- Mane, Shrikant M -- Murtha, Michael T -- Sullivan, Catherine A -- Walker, Michael F -- Waqar, Zainulabedin -- Wei, Liping -- Willsey, A Jeremy -- Yamrom, Boris -- Lee, Yoon-ha -- Grabowska, Ewa -- Dalkic, Ertugrul -- Wang, Zihua -- Marks, Steven -- Andrews, Peter -- Leotta, Anthony -- Kendall, Jude -- Hakker, Inessa -- Rosenbaum, Julie -- Ma, Beicong -- Rodgers, Linda -- Troge, Jennifer -- Narzisi, Giuseppe -- Yoon, Seungtai -- Schatz, Michael C -- Ye, Kenny -- McCombie, W Richard -- Shendure, Jay -- Eichler, Evan E -- State, Matthew W -- Wigler, Michael -- P30 CA016359/CA/NCI NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- U54 HD083091/HD/NICHD NIH HHS/ -- UL1 TR000142/TR/NCATS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Nov 13;515(7526):216-21. doi: 10.1038/nature13908. Epub 2014 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA [2] Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon 97208, USA. ; 1] Department of Psychiatry, University of California, San Francisco, San Francisco, California 94158, USA [2] Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA. ; Department of Psychiatry, University of California, San Francisco, San Francisco, California 94158, USA. ; 1] Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China. ; Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Yale Center for Genomic Analysis, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; 1] Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China [2] National Institute of Biological Sciences, Beijing 102206, China. ; 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] New York Genome Center, New York, New York 10013, USA. ; 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Department of Medical Biology, Bulent Ecevit University School of Medicine, 67600 Zonguldak, Turkey. ; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA. ; 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA [2] Howard Hughes Medical Institute, Seattle, Washington 98195, USA. ; 1] Department of Psychiatry, University of California, San Francisco, San Francisco, California 94158, USA [2] Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA [3] Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA [4] Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363768" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Child Development Disorders, Pervasive/*genetics ; Cluster Analysis ; Exome/genetics ; Female ; Genes ; Genetic Predisposition to Disease/*genetics ; Humans ; Intelligence Tests ; Male ; Mutation/*genetics ; Open Reading Frames/*genetics ; Reproducibility of Results
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  • 61
    Publication Date: 2014-01-17
    Description: Many species travel in highly organized groups. The most quoted function of these configurations is to reduce energy expenditure and enhance locomotor performance of individuals in the assemblage. The distinctive V formation of bird flocks has long intrigued researchers and continues to attract both scientific and popular attention. The well-held belief is that such aggregations give an energetic benefit for those birds that are flying behind and to one side of another bird through using the regions of upwash generated by the wings of the preceding bird, although a definitive account of the aerodynamic implications of these formations has remained elusive. Here we show that individuals of northern bald ibises (Geronticus eremita) flying in a V flock position themselves in aerodynamically optimum positions, in that they agree with theoretical aerodynamic predictions. Furthermore, we demonstrate that birds show wingtip path coherence when flying in V positions, flapping spatially in phase and thus enabling upwash capture to be maximized throughout the entire flap cycle. In contrast, when birds fly immediately behind another bird--in a streamwise position--there is no wingtip path coherence; the wing-beats are in spatial anti-phase. This could potentially reduce the adverse effects of downwash for the following bird. These aerodynamic accomplishments were previously not thought possible for birds because of the complex flight dynamics and sensory feedback that would be required to perform such a feat. We conclude that the intricate mechanisms involved in V formation flight indicate awareness of the spatial wake structures of nearby flock-mates, and remarkable ability either to sense or predict it. We suggest that birds in V formation have phasing strategies to cope with the dynamic wakes produced by flapping wings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Portugal, Steven J -- Hubel, Tatjana Y -- Fritz, Johannes -- Heese, Stefanie -- Trobe, Daniela -- Voelkl, Bernhard -- Hailes, Stephen -- Wilson, Alan M -- Usherwood, James R -- 095061/Wellcome Trust/United Kingdom -- 095061/Z/10/Z/Wellcome Trust/United Kingdom -- BB/J018007/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2014 Jan 16;505(7483):399-402. doi: 10.1038/nature12939.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structure & Motion Laboratory, the Royal Veterinary College, University of London, Hatfield, Hertfordshire AL9 7TA, UK. ; Waldrappteam, Schulgasse 28, 6162 Mutters, Austria. ; 1] Waldrappteam, Schulgasse 28, 6162 Mutters, Austria [2] Institute for Theoretical Biology, Humboldt University at Berlin, Invalidenstrasse 43, 10115 Berlin, Germany [3] Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. ; 1] Structure & Motion Laboratory, the Royal Veterinary College, University of London, Hatfield, Hertfordshire AL9 7TA, UK [2] Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24429637" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Birds/*physiology ; Flight, Animal/*physiology ; *Group Processes ; Models, Biological ; Movement/*physiology ; Wings, Animal/*physiology
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  • 62
    Publication Date: 2014-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCullough, Michael E -- Kelly, David L -- England -- Nature. 2014 Apr 17;508(7496):319. doi: 10.1038/508319c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Miami, Coral Gables, Florida, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740058" target="_blank"〉PubMed〈/a〉
    Keywords: Publishing/standards ; Reproducibility of Results ; Research/economics/*standards ; *Research Design ; Research Personnel/standards
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  • 63
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-05-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 May 22;509(7501):399.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24860878" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Specimen Banks ; Disease ; Disease Models, Animal ; Drug Discovery/methods ; Genome/*genetics ; Mice/*genetics ; Mice, Knockout/*genetics ; Mice, Mutant Strains ; *Phenotype ; Reproducibility of Results
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  • 64
    Publication Date: 2014-09-16
    Description: Curli are functional amyloid fibres that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria (predominantly of the alpha and gamma classes). They provide a fitness advantage in pathogenic strains and induce a strong pro-inflammatory response during bacteraemia. Curli formation requires a dedicated protein secretion machinery comprising the outer membrane lipoprotein CsgG and two soluble accessory proteins, CsgE and CsgF. Here we report the X-ray structure of Escherichia coli CsgG in a non-lipidated, soluble form as well as in its native membrane-extracted conformation. CsgG forms an oligomeric transport complex composed of nine anticodon-binding-domain-like units that give rise to a 36-stranded beta-barrel that traverses the bilayer and is connected to a cage-like vestibule in the periplasm. The transmembrane and periplasmic domains are separated by a 0.9-nm channel constriction composed of three stacked concentric phenylalanine, asparagine and tyrosine rings that may guide the extended polypeptide substrate through the secretion pore. The specificity factor CsgE forms a nonameric adaptor that binds and closes off the periplasmic face of the secretion channel, creating a 24,000 A(3) pre-constriction chamber. Our structural, functional and electrophysiological analyses imply that CsgG is an ungated, non-selective protein secretion channel that is expected to employ a diffusion-based, entropy-driven transport mechanism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268158/" 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/PMC4268158/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goyal, Parveen -- Krasteva, Petya V -- Van Gerven, Nani -- Gubellini, Francesca -- Van den Broeck, Imke -- Troupiotis-Tsailaki, Anastassia -- Jonckheere, Wim -- Pehau-Arnaudet, Gerard -- Pinkner, Jerome S -- Chapman, Matthew R -- Hultgren, Scott J -- Howorka, Stefan -- Fronzes, Remi -- Remaut, Han -- R01 A1073847/PHS HHS/ -- R01 AI048689/AI/NIAID NIH HHS/ -- R01 AI073847/AI/NIAID NIH HHS/ -- R01 AI099099/AI/NIAID NIH HHS/ -- R56 AI073847/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Dec 11;516(7530):250-3. doi: 10.1038/nature13768. Epub 2014 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium [2] Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; 1] Unite G5 Biologie structurale de la secretion bacterienne, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France [2] UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France. ; Structure et Fonction des Membranes Biologiques (SFMB), Universite Libre de Bruxelles, 1050 Brussels, Belgium. ; UMR 3528, CNRS, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France. ; Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St Louis, Missouri 63110-1010, USA. ; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA. ; Department of Chemistry, Institute for Structural and Molecular Biology, University College London, London WC1H 0AJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25219853" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*secretion ; Biofilms ; Cell Membrane ; Crystallography, X-Ray ; Diffusion ; Entropy ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Lipoproteins/*chemistry/*metabolism ; Membrane Transport Proteins/metabolism ; Models, Biological ; Models, Molecular ; Periplasm/metabolism ; Protein Conformation ; Protein Transport
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  • 65
    Publication Date: 2014-08-01
    Description: Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate 〈 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qin, Nan -- Yang, Fengling -- Li, Ang -- Prifti, Edi -- Chen, Yanfei -- Shao, Li -- Guo, Jing -- Le Chatelier, Emmanuelle -- Yao, Jian -- Wu, Lingjiao -- Zhou, Jiawei -- Ni, Shujun -- Liu, Lin -- Pons, Nicolas -- Batto, Jean Michel -- Kennedy, Sean P -- Leonard, Pierre -- Yuan, Chunhui -- Ding, Wenchao -- Chen, Yuanting -- Hu, Xinjun -- Zheng, Beiwen -- Qian, Guirong -- Xu, Wei -- Ehrlich, S Dusko -- Zheng, Shusen -- Li, Lanjuan -- England -- Nature. 2014 Sep 4;513(7516):59-64. doi: 10.1038/nature13568. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China [3]. ; 1] State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China [2]. ; 1] Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France [2]. ; State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China. ; Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France. ; 1] State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China. ; 1] Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France [2] King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London Bridge, London SE1 9RT, UK. ; 1] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China [2] Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University, 310003 Hangzhou, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079328" target="_blank"〉PubMed〈/a〉
    Keywords: Case-Control Studies ; Chronic Disease ; Diabetes Mellitus, Type 2/microbiology ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Genetic Markers/genetics ; Health ; Humans ; Inflammatory Bowel Diseases/microbiology ; Liver Cirrhosis/*diagnosis/*microbiology ; *Metagenomics ; Microbiota/*genetics/*physiology ; Mouth/microbiology ; Phylogeny ; Reproducibility of Results
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  • 66
    Publication Date: 2014-05-09
    Description: The motor cortex is capable of reliably driving complex movements yet exhibits considerable plasticity during motor learning. These observations suggest that the fundamental relationship between motor cortex activity and movement may not be fixed but is instead shaped by learning; however, to what extent and how motor learning shapes this relationship are not fully understood. Here we addressed this issue by using in vivo two-photon calcium imaging to monitor the activity of the same population of hundreds of layer 2/3 neurons while mice learned a forelimb lever-press task over two weeks. Excitatory and inhibitory neurons were identified by transgenic labelling. Inhibitory neuron activity was relatively stable and balanced local excitatory neuron activity on a movement-by-movement basis, whereas excitatory neuron activity showed higher dynamism during the initial phase of learning. The dynamics of excitatory neurons during the initial phase involved the expansion of the movement-related population which explored various activity patterns even during similar movements. This was followed by a refinement into a smaller population exhibiting reproducible spatiotemporal sequences of activity. This pattern of activity associated with the learned movement was unique to expert animals and not observed during similar movements made during the naive phase, and the relationship between neuronal activity and individual movements became more consistent with learning. These changes in population activity coincided with a transient increase in dendritic spine turnover in these neurons. Our results indicate that a novel and reproducible activity-movement relationship develops as a result of motor learning, and we speculate that synaptic plasticity within the motor cortex underlies the emergence of reproducible spatiotemporal activity patterns for learned movements. These results underscore the profound influence of learning on the way that the cortex produces movements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peters, Andrew J -- Chen, Simon X -- Komiyama, Takaki -- AG000216/AG/NIA NIH HHS/ -- England -- Nature. 2014 Jun 12;510(7504):263-7. doi: 10.1038/nature13235. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurobiology Section, Center for Neural Circuits and Behavior, and Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA. ; 1] Neurobiology Section, Center for Neural Circuits and Behavior, and Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA [2] JST, PRESTO, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805237" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Dendritic Spines/physiology ; Female ; Forelimb/physiology ; Learning/*physiology ; Male ; Mice ; Models, Neurological ; Motor Cortex/*physiology ; Motor Skills/*physiology ; Neural Inhibition ; Neuronal Plasticity/physiology ; Reproducibility of Results ; *Spatio-Temporal Analysis
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  • 67
    Publication Date: 2014-06-05
    Description: Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532372/" 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/PMC4532372/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Linghua -- Yamaguchi, Shigeru -- Burstein, Matthew D -- Terashima, Keita -- Chang, Kyle -- Ng, Ho-Keung -- Nakamura, Hideo -- He, Zongxiao -- Doddapaneni, Harshavardhan -- Lewis, Lora -- Wang, Mark -- Suzuki, Tomonari -- Nishikawa, Ryo -- Natsume, Atsushi -- Terasaka, Shunsuke -- Dauser, Robert -- Whitehead, William -- Adekunle, Adesina -- Sun, Jiayi -- Qiao, Yi -- Marth, Gabor -- Muzny, Donna M -- Gibbs, Richard A -- Leal, Suzanne M -- Wheeler, David A -- Lau, Ching C -- 5T15 LM07093-18/LM/NLM NIH HHS/ -- 5T15 LM07093-19/LM/NLM NIH HHS/ -- 5U54HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Jul 10;511(7508):241-5. doi: 10.1038/nature13296. Epub 2014 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Structural and Computational Biology and Molecular Biophysics Program, Baylor College of Medicine, Houston, Texas 77030, USA [2] Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA. ; 1] Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas 77030, USA [2] National Center for Child Health and Development, Tokyo, 157-8535, Japan. ; Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. ; Department of Neurosurgery, Kumamoto University, Kumamoto, 860-0862, Japan. ; Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Neurosurgery, Saitama Medical University, Saitama, 350-0495, Japan. ; Department of Neurosurgery, Nagoya University, Nagoya, 466-8550, Japan. ; Department of Neurosurgery, Hokkaido University, Hokkaido Prefecture, 060-0808, Japan. ; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Biology, Boston College, Chestnut Hill, Maryland 02467, USA. ; 1] Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas 77030, USA [2] Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA [3] Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896186" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Brain Neoplasms/*genetics/pathology ; Child ; Female ; Germ-Line Mutation/*genetics ; Humans ; Japan ; Male ; Mutation/*genetics ; Neoplasms, Germ Cell and Embryonal/*genetics/pathology ; Oncogene Protein v-akt/genetics ; Proto-Oncogene Proteins c-kit/genetics ; Reproducibility of Results ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics ; Young Adult ; ras Proteins/genetics
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  • 68
    Publication Date: 2014-05-23
    Description: The glucose transporter GLUT1 catalyses facilitative diffusion of glucose into erythrocytes and is responsible for glucose supply to the brain and other organs. Dysfunctional mutations may lead to GLUT1 deficiency syndrome, whereas overexpression of GLUT1 is a prognostic indicator for cancer. Despite decades of investigation, the structure of GLUT1 remains unknown. Here we report the crystal structure of human GLUT1 at 3.2 A resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides an insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homologue XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Dong -- Xu, Chao -- Sun, Pengcheng -- Wu, Jianping -- Yan, Chuangye -- Hu, Mingxu -- Yan, Nieng -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 5;510(7503):121-5. doi: 10.1038/nature13306. Epub 2014 May 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3] Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China [4]. ; 1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3]. ; 1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. ; 1] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3] Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24847886" target="_blank"〉PubMed〈/a〉
    Keywords: Carbohydrate Metabolism, Inborn Errors/genetics ; Crystallography, X-Ray ; Escherichia coli Proteins ; Glucose Transporter Type 1/*chemistry/deficiency/genetics/metabolism ; Humans ; Ligands ; Models, Biological ; Models, Molecular ; Monosaccharide Transport Proteins/deficiency/genetics ; Mutation/genetics ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Symporters
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  • 69
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-06-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Jun 5;510(7503):8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24910867" target="_blank"〉PubMed〈/a〉
    Keywords: *Awards and Prizes ; China ; Diffusion of Innovation ; Ireland ; *Mentors ; *Periodicals as Topic ; Reproducibility of Results ; Research/*standards ; Research Personnel/*ethics/*standards ; Truth Disclosure/ethics
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  • 70
    Publication Date: 2014-02-28
    Description: Epistasis is the phenomenon whereby one polymorphism's effect on a trait depends on other polymorphisms present in the genome. The extent to which epistasis influences complex traits and contributes to their variation is a fundamental question in evolution and human genetics. Although often demonstrated in artificial gene manipulation studies in model organisms, and some examples have been reported in other species, few examples exist for epistasis among natural polymorphisms in human traits. Its absence from empirical findings may simply be due to low incidence in the genetic control of complex traits, but an alternative view is that it has previously been too technically challenging to detect owing to statistical and computational issues. Here we show, using advanced computation and a gene expression study design, that many instances of epistasis are found between common single nucleotide polymorphisms (SNPs). In a cohort of 846 individuals with 7,339 gene expression levels measured in peripheral blood, we found 501 significant pairwise interactions between common SNPs influencing the expression of 238 genes (P 〈 2.91 x 10(-16)). Replication of these interactions in two independent data sets showed both concordance of direction of epistatic effects (P = 5.56 x 10(-31)) and enrichment of interaction P values, with 30 being significant at a conservative threshold of P 〈 9.98 x 10(-5). Forty-four of the genetic interactions are located within 5 megabases of regions of known physical chromosome interactions (P = 1.8 x 10(-10)). Epistatic networks of three SNPs or more influence the expression levels of 129 genes, whereby one cis-acting SNP is modulated by several trans-acting SNPs. For example, MBNL1 is influenced by an additive effect at rs13069559, which itself is masked by trans-SNPs on 14 different chromosomes, with nearly identical genotype-phenotype maps for each cis-trans interaction. This study presents the first evidence, to our knowledge, for many instances of segregating common polymorphisms interacting to influence human traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984375/" 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/PMC3984375/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hemani, Gibran -- Shakhbazov, Konstantin -- Westra, Harm-Jan -- Esko, Tonu -- Henders, Anjali K -- McRae, Allan F -- Yang, Jian -- Gibson, Greg -- Martin, Nicholas G -- Metspalu, Andres -- Franke, Lude -- Montgomery, Grant W -- Visscher, Peter M -- Powell, Joseph E -- AA014041/AA/NIAAA NIH HHS/ -- AA07535/AA/NIAAA NIH HHS/ -- AA10248/AA/NIAAA NIH HHS/ -- AA13320/AA/NIAAA NIH HHS/ -- AA13321/AA/NIAAA NIH HHS/ -- AA13326/AA/NIAAA NIH HHS/ -- DA12854/DA/NIDA NIH HHS/ -- GM057091/GM/NIGMS NIH HHS/ -- GM099568/GM/NIGMS NIH HHS/ -- P01 GM099568/GM/NIGMS NIH HHS/ -- R01 GM075091/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Apr 10;508(7495):249-53. doi: 10.1038/nature13005. Epub 2014 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia [2] University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4072, Australia. ; Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. ; 1] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia [2] Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA [3] Divisions of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA. ; Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia. ; Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia. ; School of Biology and Centre for Integrative Genomics, Georgia Institute of Technology, Atlanta, Georgia 30332, USA. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; 1] Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia [2]. ; 1] Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia [2] University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4072, Australia [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572353" target="_blank"〉PubMed〈/a〉
    Keywords: Cohort Studies ; Epistasis, Genetic/*genetics ; Europe/ethnology ; Female ; Gene Expression Profiling ; Gene Expression Regulation/*genetics ; Genetic Association Studies ; Humans ; Linkage Disequilibrium ; Male ; Pedigree ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci ; Reproducibility of Results ; Transcription, Genetic/*genetics
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  • 71
    Publication Date: 2014-10-14
    Description: Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-beta plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-beta peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-beta-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-beta species and phosphorylated tau but did not demonstrate amyloid-beta plaques or neurofibrillary tangles. Here we report that FAD mutations in beta-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-beta, including amyloid-beta plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-beta generation with beta- or gamma-secretase inhibitors not only decreased amyloid-beta pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-beta-mediated tau phosphorylation. We have successfully recapitulated amyloid-beta and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366007/" 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/PMC4366007/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Se Hoon -- Kim, Young Hye -- Hebisch, Matthias -- Sliwinski, Christopher -- Lee, Seungkyu -- D'Avanzo, Carla -- Chen, Hechao -- Hooli, Basavaraj -- Asselin, Caroline -- Muffat, Julien -- Klee, Justin B -- Zhang, Can -- Wainger, Brian J -- Peitz, Michael -- Kovacs, Dora M -- Woolf, Clifford J -- Wagner, Steven L -- Tanzi, Rudolph E -- Kim, Doo Yeon -- 5P01AG15379/AG/NIA NIH HHS/ -- 5R37MH060009/MH/NIMH NIH HHS/ -- P01 AG004953/AG/NIA NIH HHS/ -- P01 AG015379/AG/NIA NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P30 NS045776/NS/NINDS NIH HHS/ -- P50 AG005134/AG/NIA NIH HHS/ -- R01 AG014713/AG/NIA NIH HHS/ -- R01 NS045860/NS/NINDS NIH HHS/ -- R21 AG031483/AG/NIA NIH HHS/ -- RF1 AG048080/AG/NIA NIH HHS/ -- England -- Nature. 2014 Nov 13;515(7526):274-8. doi: 10.1038/nature13800. Epub 2014 Oct 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2]. ; 1] Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2] Division of Mass Spectrometry Research, Korea Basic Science Institute, Cheongju-si, Chungbuk 363-883, South Korea [3]. ; 1] Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2] Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, 53127 Bonn, Germany. ; Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. ; FM Kirby Neurobiology Center, Boston Children's Hospital and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA. ; The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ; Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, 53127 Bonn, Germany. ; Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25307057" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/genetics/*metabolism/*pathology ; Amyloid beta-Peptides/chemistry/genetics/metabolism ; Cell Culture Techniques/*methods ; Cell Differentiation ; Drug Evaluation, Preclinical/methods ; Extracellular Space/metabolism ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Microtubule-Associated Proteins/metabolism ; *Models, Biological ; Neural Stem Cells/*metabolism/pathology ; Neurites/metabolism ; Phosphorylation ; Presenilin-1/metabolism ; Protein Aggregation, Pathological ; Reproducibility of Results ; tau Proteins/chemistry/metabolism
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  • 72
    Publication Date: 2014-02-18
    Description: The rapid turnover of the mammalian intestinal epithelium is supported by stem cells located around the base of the crypt. In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the crypt base region. Previous quantitative clonal fate analyses have led to the proposal that homeostasis occurs as the consequence of neutral competition between dividing stem cells. However, the short-term behaviour of individual Lgr5(+) cells positioned at different locations within the crypt base compartment has not been resolved. Here we establish the short-term dynamics of intestinal stem cells using the novel approach of continuous intravital imaging of Lgr5- Confetti mice. We find that Lgr5(+) cells in the upper part of the niche (termed 'border cells') can be passively displaced into the transit-amplifying domain, after the division of proximate cells, implying that the determination of stem-cell fate can be uncoupled from division. Through quantitative analysis of individual clonal lineages, we show that stem cells at the crypt base, termed 'central cells', experience a survival advantage over border stem cells. However, through the transfer of stem cells between the border and central regions, all Lgr5(+) cells are endowed with long-term self-renewal potential. These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964820/" 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/PMC3964820/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ritsma, Laila -- Ellenbroek, Saskia I J -- Zomer, Anoek -- Snippert, Hugo J -- de Sauvage, Frederic J -- Simons, Benjamin D -- Clevers, Hans -- van Rheenen, Jacco -- 092096/Wellcome Trust/United Kingdom -- 098357/Wellcome Trust/United Kingdom -- 098357/Z/12/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Mar 20;507(7492):362-5. doi: 10.1038/nature12972. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Cancer Genomics Netherlands, Hubrecht Institute-KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands [2]. ; Cancer Genomics Netherlands, Hubrecht Institute-KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. ; University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. ; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; 1] Cavendish Laboratory, Department of Physics, J. J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK [2] The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [3] The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531760" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Lineage ; Cell Survival ; Clone Cells/cytology ; Female ; *Homeostasis ; Intestinal Mucosa/*cytology ; Male ; Mice ; Models, Biological ; Molecular Imaging ; Receptors, G-Protein-Coupled/genetics/metabolism ; *Single-Cell Analysis ; Stem Cells/*cytology
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  • 73
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Franz-Josef -- Loring, Jeanne F -- England -- Nature. 2014 Sep 25;513(7519):498-9. doi: 10.1038/513498a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zentrum fur Integrative Psychiatrie Kiel, Universitatsklinikum Schleswig-Holstein, 24105 Kiel, Germany. ; Department of Chemical Physiology, Center for Regenerative Medicine, The Scripps Research Institute, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254472" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Cell Differentiation/*genetics ; *Cell Engineering/methods ; Cellular Reprogramming/genetics ; Epigenesis, Genetic ; Gene Expression Profiling/methods ; Gene Regulatory Networks/*genetics ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Models, Biological ; Regenerative Medicine ; Social Networking ; *Software ; Stem Cells/*cytology/*metabolism
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  • 74
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laland, Kevin -- Uller, Tobias -- Feldman, Marc -- Sterelny, Kim -- Muller, Gerd B -- Moczek, Armin -- Jablonka, Eva -- Odling-Smee, John -- Wray, Gregory A -- Hoekstra, Hopi E -- Futuyma, Douglas J -- Lenski, Richard E -- Mackay, Trudy F C -- Schluter, Dolph -- Strassmann, Joan E -- England -- Nature. 2014 Oct 9;514(7521):161-4. doi: 10.1038/514161a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297418" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/genetics ; Animals ; *Biological Evolution ; *Developmental Biology/trends ; Ecosystem ; Epigenesis, Genetic ; *Gene-Environment Interaction ; Genetic Speciation ; *Models, Biological ; Models, Genetic ; Phenotype ; Reproducibility of Results ; Selection, Genetic
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  • 75
    Publication Date: 2014-01-28
    Description: Tropical forests are important reservoirs of biodiversity, but the processes that maintain this diversity remain poorly understood. The Janzen-Connell hypothesis suggests that specialized natural enemies such as insect herbivores and fungal pathogens maintain high diversity by elevating mortality when plant species occur at high density (negative density dependence; NDD). NDD has been detected widely in tropical forests, but the prediction that NDD caused by insects and pathogens has a community-wide role in maintaining tropical plant diversity remains untested. We show experimentally that changes in plant diversity and species composition are caused by fungal pathogens and insect herbivores. Effective plant species richness increased across the seed-to-seedling transition, corresponding to large changes in species composition. Treating seeds and young seedlings with fungicides significantly reduced the diversity of the seedling assemblage, consistent with the Janzen-Connell hypothesis. Although suppressing insect herbivores using insecticides did not alter species diversity, it greatly increased seedling recruitment and caused a marked shift in seedling species composition. Overall, seedling recruitment was significantly reduced at high conspecific seed densities and this NDD was greatest for the species that were most abundant as seeds. Suppressing fungi reduced the negative effects of density on recruitment, confirming that the diversity-enhancing effect of fungi is mediated by NDD. Our study provides an overall test of the Janzen-Connell hypothesis and demonstrates the crucial role that insects and pathogens have both in structuring tropical plant communities and in maintaining their remarkable diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bagchi, Robert -- Gallery, Rachel E -- Gripenberg, Sofia -- Gurr, Sarah J -- Narayan, Lakshmi -- Addis, Claire E -- Freckleton, Robert P -- Lewis, Owen T -- England -- Nature. 2014 Feb 6;506(7486):85-8. doi: 10.1038/nature12911. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK [2] Ecosystem Management Group, Institute of Terrestrial Ecosystems, ETH Zurich, Universitatstrasse 16, 8092 Zurich, Switzerland. ; 1] Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK [2] School of Natural Resources and the Environment, University of Arizona, Tucson, Arizona 85721, USA. ; 1] Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK [2] Section of Biodiversity and Environmental Research, Department of Biology, University of Turku, 20014 Turku, Finland. ; 1] Department of BioSciences, Geoffrey Pope Building, University of Exeter, Exeter EX4 4QD, UK [2] Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Department of Animal and Plant Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463522" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Belize ; *Biodiversity ; Fungi/drug effects/*physiology ; Fungicides, Industrial/pharmacology ; *Herbivory ; Insecticides/pharmacology ; Insects/drug effects/*physiology ; Methacrylates/pharmacology ; Models, Biological ; Pyrimidines/pharmacology ; Seedlings/drug effects/microbiology/parasitology/physiology ; Seeds/drug effects/physiology ; Trees/drug effects/*microbiology/parasitology/*physiology ; Tropical Climate
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  • 76
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baell, Jonathan -- Walters, Michael A -- England -- Nature. 2014 Sep 25;513(7519):481-3. doi: 10.1038/513481a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254460" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Artifacts ; Binding Sites ; Drug Discovery/methods/*standards ; Humans ; Pharmacology/methods/*standards ; Protein Binding ; Reproducibility of Results ; Research Personnel/standards
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  • 77
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Nov 20;515(7527):312. doi: 10.1038/515312a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409790" target="_blank"〉PubMed〈/a〉
    Keywords: Datasets as Topic/*utilization ; *Editorial Policies ; Information Dissemination/*methods ; *Periodicals as Topic ; Reproducibility of Results
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  • 78
    Publication Date: 2014-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrett, Paul M -- Munt, Martin C -- England -- Nature. 2014 Aug 7;512(7512):28. doi: 10.1038/512028a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Natural History Museum, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25100472" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; Animals ; *Birds ; Germany ; *Paleontology ; *Private Sector ; Reproducibility of Results
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  • 79
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2014 May 15;509(7500):270-1. doi: 10.1038/509270a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828170" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Climate Change/statistics & numerical data ; Ecosystem ; Environmental Monitoring ; Human Activities ; Reproducibility of Results ; *Seawater/analysis ; *Temperature ; *Water Movements
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  • 80
    Publication Date: 2014-05-09
    Description: If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127035/" 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/PMC4127035/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Berlo, Jop H -- Kanisicak, Onur -- Maillet, Marjorie -- Vagnozzi, Ronald J -- Karch, Jason -- Lin, Suh-Chin J -- Middleton, Ryan C -- Marban, Eduardo -- Molkentin, Jeffery D -- P01 HL108806/HL/NHLBI NIH HHS/ -- P50 HL052318/HL/NHLBI NIH HHS/ -- P50 HL077101/HL/NHLBI NIH HHS/ -- R00 HL112852/HL/NHLBI NIH HHS/ -- R01 HL105924/HL/NHLBI NIH HHS/ -- R37 HL060562/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 15;509(7500):337-41. doi: 10.1038/nature13309. Epub 2014 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA [3]. ; 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2]. ; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. ; Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA. ; 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805242" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Cell Differentiation ; Cell Fusion ; *Cell Lineage ; Endothelial Cells/cytology/metabolism ; Female ; Heart/growth & development ; Heart Injuries/*pathology ; Integrases/genetics/metabolism ; Male ; Mice ; Models, Biological ; Myoblasts, Cardiac/*cytology/*metabolism ; Myocardium/*cytology ; Myocytes, Cardiac/*cytology/metabolism ; Proto-Oncogene Proteins c-kit/*metabolism ; Regeneration/physiology ; Tamoxifen/pharmacology
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  • 81
    Publication Date: 2014-05-23
    Description: Cellular senescence has historically been viewed as an irreversible cell-cycle arrest mechanism that acts to protect against cancer, but recent discoveries have extended its known role to complex biological processes such as development, tissue repair, ageing and age-related disorders. New insights indicate that, unlike a static endpoint, senescence represents a series of progressive and phenotypically diverse cellular states acquired after the initial growth arrest. A deeper understanding of the molecular mechanisms underlying the multi-step progression of senescence and the development and function of acute versus chronic senescent cells may lead to new therapeutic strategies for age-related pathologies and extend healthy lifespan.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/" 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/PMC4214092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Deursen, Jan M -- AG41122-01P2/AG/NIA NIH HHS/ -- R01 CA096985/CA/NCI NIH HHS/ -- R01 CA166347/CA/NCI NIH HHS/ -- R01CA166347/CA/NCI NIH HHS/ -- R01CA96985/CA/NCI NIH HHS/ -- England -- Nature. 2014 May 22;509(7501):439-46. doi: 10.1038/nature13193.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric and Adolescent Medicine and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24848057" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*pathology ; Animals ; Cell Aging/*physiology ; Disease ; Humans ; Longevity ; Mitosis ; Models, Biological
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  • 82
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, Rachel -- England -- Nature. 2014 Apr 3;508(7494):139-40.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24712027" target="_blank"〉PubMed〈/a〉
    Keywords: Allergy and Immunology/education/manpower ; Humans ; Immunotherapy/economics/*trends ; Leukemia, B-Cell/immunology/therapy ; Lymphoma, B-Cell/immunology/therapy ; Neoplasms/drug therapy/genetics/*immunology/*therapy ; Precision Medicine/methods/trends ; Reproducibility of Results ; T-Lymphocytes/immunology ; *Translational Medical Research/manpower/trends
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  • 83
    Publication Date: 2014-04-11
    Description: Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns. Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea's basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells and make 'synapse-like' contacts with slowly adapting type I (SAI) afferents. These complexes, which encode spatial features such as edges and texture, localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell-neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell-neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097312/" 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/PMC4097312/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maksimovic, Srdjan -- Nakatani, Masashi -- Baba, Yoshichika -- Nelson, Aislyn M -- Marshall, Kara L -- Wellnitz, Scott A -- Firozi, Pervez -- Woo, Seung-Hyun -- Ranade, Sanjeev -- Patapoutian, Ardem -- Lumpkin, Ellen A -- 5T32HL087745-05/HL/NHLBI NIH HHS/ -- F32 NS080544/NS/NINDS NIH HHS/ -- F32NS080544/NS/NINDS NIH HHS/ -- P30 AR044535/AR/NIAMS NIH HHS/ -- P30 CA125123/CA/NCI NIH HHS/ -- P30AR044535/AR/NIAMS NIH HHS/ -- P30CA013696/CA/NCI NIH HHS/ -- P30CA125123/CA/NCI NIH HHS/ -- R01 AR051219/AR/NIAMS NIH HHS/ -- R01 DE022358/DE/NIDCR NIH HHS/ -- R01AR051219/AR/NIAMS NIH HHS/ -- R01DE022358/DE/NIDCR NIH HHS/ -- R21 AR062307/AR/NIAMS NIH HHS/ -- R21AR062307/AR/NIAMS NIH HHS/ -- T32 HL087745/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 29;509(7502):617-21. doi: 10.1038/nature13250. Epub 2014 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2]. ; 1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2] Graduate School of System Design and Management, Keio University, Yokohama 223-8526, Japan [3]. ; 1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2] Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77006, USA. ; Department of Dermatology, Columbia University, New York, New York 10032, USA. ; Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77006, USA. ; Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla California 92037, USA. ; 1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2] Department of Physiology & Cellular Biophysics, Columbia University, New York, New York 10032, USA [3] Program in Neurobiology & Behavior, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717432" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; *Afferent Pathways ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Electric Conductivity ; Epidermis/*cytology/*innervation ; Female ; Ion Channels/metabolism ; Male ; *Mechanotransduction, Cellular ; Merkel Cells/*metabolism ; Mice ; Models, Biological ; Neurites/metabolism ; Neurons, Afferent/metabolism ; Optogenetics ; Pressure ; Touch/*physiology
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  • 84
    Publication Date: 2014-12-10
    Description: The concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years (refs 1 - 3). Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359913/" 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/PMC4359913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hashimshony, Tamar -- Feder, Martin -- Levin, Michal -- Hall, Brian K -- Yanai, Itai -- 310927/European Research Council/International -- England -- Nature. 2015 Mar 12;519(7542):219-22. doi: 10.1038/nature13996. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel. ; Department of Biology, Dalhousie University, Halifax, Nova Scotia B3H 4JI, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487147" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/cytology/*embryology/*genetics ; Cell Lineage ; Eating ; Ectoderm/cytology/embryology/metabolism ; Endoderm/cytology/embryology/*metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/*genetics ; Mesoderm/cytology/embryology/metabolism ; Models, Biological ; Porifera/cytology/embryology/genetics ; Sea Anemones/cytology/embryology/genetics ; *Spatio-Temporal Analysis ; Time Factors ; Transcriptome/*genetics ; Xenopus/embryology/genetics
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  • 85
    Publication Date: 2014-12-30
    Description: Hox genes regulate regionalization of the axial skeleton in vertebrates, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox gene expression domains, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phylogenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior-posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number, not by changes in the function of primaxial Hox genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Head, Jason J -- Polly, P David -- England -- Nature. 2015 Apr 2;520(7545):86-9. doi: 10.1038/nature14042. Epub 2015 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth and Atmospheric Sciences and Nebraska State Museum of Natural History, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0340, USA. ; Departments of Geological Sciences, Biology and Anthropology, Indiana University, Bloomington, Indiana 47405-1405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25539083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cloaca ; Developmental Biology ; Extremities/anatomy & histology ; *Fossils ; Genes, Homeobox/*genetics ; Lizards/anatomy & histology ; Models, Biological ; *Phylogeny ; Sacrum ; Snakes/*anatomy & histology/*genetics ; Spine/*anatomy & histology
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  • 86
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Oct 9;514(7521):139-40. doi: 10.1038/514139b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297397" target="_blank"〉PubMed〈/a〉
    Keywords: Aluminum Oxide/standards ; Biological Science Disciplines ; *Information Dissemination ; *Knowledge ; Reproducibility of Results
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  • 87
    Publication Date: 2014-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schooler, Jonathan W -- England -- Nature. 2014 Nov 6;515(7525):9. doi: 10.1038/515009a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25373639" target="_blank"〉PubMed〈/a〉
    Keywords: Psychology/standards ; Publishing/standards ; Reproducibility of Results ; Research/*standards ; *Research Design ; Research Report/*standards
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 88
    Publication Date: 2014-12-10
    Description: A defining feature of vertebrates (craniates) is a pronounced head that is supported and protected by a robust cellular endoskeleton. In the first vertebrates, this skeleton probably consisted of collagenous cellular cartilage, which forms the embryonic skeleton of all vertebrates and the adult skeleton of modern jawless and cartilaginous fish. In the head, most cellular cartilage is derived from a migratory cell population called the neural crest, which arises from the edges of the central nervous system. Because collagenous cellular cartilage and neural crest cells have not been described in invertebrates, the appearance of cellular cartilage derived from neural crest cells is considered a turning point in vertebrate evolution. Here we show that a tissue with many of the defining features of vertebrate cellular cartilage transiently forms in the larvae of the invertebrate chordate Branchiostoma floridae (Florida amphioxus). We also present evidence that during evolution, a key regulator of vertebrate cartilage development, SoxE, gained new cis-regulatory sequences that subsequently directed its novel expression in neural crest cells. Together, these results suggest that the origin of the vertebrate head skeleton did not depend on the evolution of a new skeletal tissue, as is commonly thought, but on the spread of this tissue throughout the head. We further propose that the evolution of cis-regulatory elements near an ancient regulator of cartilage differentiation was a major factor in the evolution of the vertebrate head skeleton.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jandzik, David -- Garnett, Aaron T -- Square, Tyler A -- Cattell, Maria V -- Yu, Jr-Kai -- Medeiros, Daniel M -- England -- Nature. 2015 Feb 26;518(7540):534-7. doi: 10.1038/nature14000. Epub 2014 Dec 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, Colorado 80309, USA [2] Department of Zoology, Comenius University, Bratislava 84215, Slovakia. ; Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, Colorado 80309, USA. ; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487155" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Cartilage/cytology/metabolism ; Fibroblast Growth Factors/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/genetics ; Genes, Reporter/genetics ; *Head ; Lancelets/*anatomy & histology/cytology/*growth & development ; Larva/anatomy & histology/cytology ; Models, Biological ; Mouth/anatomy & histology ; Neural Crest/cytology ; SOXE Transcription Factors/genetics/metabolism ; Signal Transduction ; *Skull/cytology/metabolism ; Vertebrates/*anatomy & histology ; Zebrafish/embryology/genetics
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  • 89
    Publication Date: 2014-10-21
    Description: Reproduction in jawed vertebrates (gnathostomes) involves either external or internal fertilization. It is commonly argued that internal fertilization can evolve from external, but not the reverse. Male copulatory claspers are present in certain placoderms, fossil jawed vertebrates retrieved as a paraphyletic segment of the gnathostome stem group in recent studies. This suggests that internal fertilization could be primitive for gnathostomes, but such a conclusion depends on demonstrating that copulation was not just a specialized feature of certain placoderm subgroups. The reproductive biology of antiarchs, consistently identified as the least crownward placoderms and thus of great interest in this context, has until now remained unknown. Here we show that certain antiarchs possessed dermal claspers in the males, while females bore paired dermal plates inferred to have facilitated copulation. These structures are not associated with pelvic fins. The clasper morphology resembles that of ptyctodonts, a more crownward placoderm group, suggesting that all placoderm claspers are homologous and that internal fertilization characterized all placoderms. This implies that external fertilization and spawning, which characterize most extant aquatic gnathostomes, must be derived from internal fertilization, even though this transformation has been thought implausible. Alternatively, the substantial morphological evidence for placoderm paraphyly must be rejected.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, John A -- Mark-Kurik, Elga -- Johanson, Zerina -- Lee, Michael S Y -- Young, Gavin C -- Min, Zhu -- Ahlberg, Per E -- Newman, Michael -- Jones, Roger -- den Blaauwen, Jan -- Choo, Brian -- Trinajstic, Kate -- England -- Nature. 2015 Jan 8;517(7533):196-9. doi: 10.1038/nature13825. Epub 2014 Oct 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] School of Biological Sciences, Flinders University, 2100, Adelaide, South Australia 5001, Australia [2] Natural History Museum of Los Angeles County, 900 Exposition Boulevard, Los Angeles, California 9007, USA [3] Museum Victoria, PO Box 666, Melbourne, Victoria 3001, Australia. ; Institute of Geology at Tallinn University of Technology, Ehitajate tee 5, 19086 Tallinn, Estonia. ; Department of Earth Sciences, Natural History Museum, London SW7 5BD, UK. ; 1] South Australian Museum, North Terrace, Adelaide, South Australia 5000, Australia [2] School of Earth and Environmental Sciences, The University of Adelaide, South Australia 5005, Australia. ; Research School of Earth Sciences, The Australian National University, Canberra, Australian Capital Territory 0200, Australia. ; Key Laboratory of Evolutionary Systematics of Vertebrates, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, PO Box 643, Beijing 100044, China. ; Department of Organismal Biology, Evolutionary Biology Centre, Uppsala University, Norbyvagen 18A, 752 36 Uppsala, Sweden. ; Vine Lodge, Vine Road, Johnston, Haverfordwest, Pembrokeshire SA62 3NZ, UK. ; 6 Burghley Road, Wimbledon, London SW19 5BH, UK. ; University of Amsterdam, Science Park 904, 1098XH, Amsterdam, The Netherlands. ; School of Biological Sciences, Flinders University, 2100, Adelaide, South Australia 5001, Australia. ; 1] Western Australian Organic and Isotope Geochemistry Centre, Department of Chemistry, Curtin University, Perth, Western Australia 6102, Australia [2] Earth and Planetary Sciences, Western Australian Museum, Perth, Western Australia 6000, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25327249" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Copulation/*physiology ; Female ; Fertilization/*physiology ; Fishes/*anatomy & histology/*physiology ; Fossils ; *Jaw ; Male ; Models, Biological ; Phylogeny ; Sex Characteristics ; Vertebrates/anatomy & histology/*physiology
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  • 90
    Publication Date: 2014-12-24
    Description: The plant cell wall is an important factor for determining cell shape, function and response to the environment. Secondary cell walls, such as those found in xylem, are composed of cellulose, hemicelluloses and lignin and account for the bulk of plant biomass. The coordination between transcriptional regulation of synthesis for each polymer is complex and vital to cell function. A regulatory hierarchy of developmental switches has been proposed, although the full complement of regulators remains unknown. Here we present a protein-DNA network between Arabidopsis thaliana transcription factors and secondary cell wall metabolic genes with gene expression regulated by a series of feed-forward loops. This model allowed us to develop and validate new hypotheses about secondary wall gene regulation under abiotic stress. Distinct stresses are able to perturb targeted genes to potentially promote functional adaptation. These interactions will serve as a foundation for understanding the regulation of a complex, integral plant component.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333722/" 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/PMC4333722/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor-Teeples, M -- Lin, L -- de Lucas, M -- Turco, G -- Toal, T W -- Gaudinier, A -- Young, N F -- Trabucco, G M -- Veling, M T -- Lamothe, R -- Handakumbura, P P -- Xiong, G -- Wang, C -- Corwin, J -- Tsoukalas, A -- Zhang, L -- Ware, D -- Pauly, M -- Kliebenstein, D J -- Dehesh, K -- Tagkopoulos, I -- Breton, G -- Pruneda-Paz, J L -- Ahnert, S E -- Kay, S A -- Hazen, S P -- Brady, S M -- R01 GM056006/GM/NIGMS NIH HHS/ -- R01 GM107311/GM/NIGMS NIH HHS/ -- R01GM056006/GM/NIGMS NIH HHS/ -- R01GM107311/GM/NIGMS NIH HHS/ -- R25 GM056765/GM/NIGMS NIH HHS/ -- RC2 GM092412/GM/NIGMS NIH HHS/ -- RC2GM092412/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 29;517(7536):571-5. doi: 10.1038/nature14099. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Plant Biology, University of California Davis, One Shields Avenue, Davis, California 95616, USA [2] Genome Center, University of California Davis, One Shields Avenue, Davis, California 95616, USA. ; Biology Department, University of Massachusetts, Amherst, Massachusetts 01003, USA. ; Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, California 94720, USA. ; Department of Plant Biology, University of California Davis, One Shields Avenue, Davis, California 95616, USA. ; Department of Plant Sciences, University of California Davis, One Shields Avenue, Davis, California 95616, USA. ; 1] Genome Center, University of California Davis, One Shields Avenue, Davis, California 95616, USA [2] Department of Computer Science, University of California Davis, One Shields Avenue, Davis, California 95616, USA. ; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] US Department of Agriculture, Agricultural Research Service, Ithaca, New York 14853, USA. ; Section of Cell and Developmental Biology, Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA. ; Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533953" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/metabolism ; Cell Wall/*metabolism ; DNA, Plant/genetics/metabolism ; E2F Transcription Factors/metabolism ; Feedback ; Gene Expression Regulation, Developmental/genetics ; Gene Expression Regulation, Plant/*genetics ; Gene Regulatory Networks/*genetics ; Iron/deficiency ; Organ Specificity ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Salinity ; Time Factors ; Transcription Factors/*metabolism ; Xylem/genetics/growth & development/metabolism
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  • 91
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2013-01-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Dec 20;492(7429):311.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23281497" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Pyridinylmethylsulfinylbenzimidazoles ; Clinical Trials as Topic/statistics & numerical data ; Drug Approval/legislation & jurisprudence ; Drug Industry/economics/ethics/*legislation & jurisprudence ; Drug Prescriptions/standards ; *Freedom ; Humans ; Marketing/*ethics/*legislation & jurisprudence ; Off-Label Use/*ethics/*legislation & jurisprudence ; Patient Advocacy/legislation & jurisprudence ; Reproducibility of Results ; Sodium Oxybate ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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  • 92
    Publication Date: 2013-06-07
    Description: G-protein-gated inward rectifier K(+) (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5 A resolution crystal structure of the mammalian GIRK2 channel in complex with betagamma G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K(+) channel activity. Short-range atomic and long-range electrostatic interactions stabilize four betagamma G-protein subunits at the interfaces between four K(+) channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation that is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with 'membrane delimited' activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) and intracellular Na(+) ions participate in multi-ligand regulation of GIRK channels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654628/" 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/PMC4654628/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whorton, Matthew R -- MacKinnon, Roderick -- 1S10RR022321-01/RR/NCRR NIH HHS/ -- 1S10RR027037-01/RR/NCRR NIH HHS/ -- S10 RR027037/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 13;498(7453):190-7. doi: 10.1038/nature12241. Epub 2013 Jun 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23739333" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; G Protein-Coupled Inwardly-Rectifying Potassium ; Channels/*chemistry/genetics/metabolism ; Heterotrimeric GTP-Binding Proteins/*chemistry/genetics/metabolism ; Humans ; Ion Channel Gating ; Models, Biological ; Models, Molecular ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Subunits/chemistry/metabolism ; Sodium/metabolism ; Static Electricity
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  • 93
    Publication Date: 2013-01-22
    Description: Interferon-induced proteins with tetratricopeptide repeats (IFITs) are innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation-initiation machinery. However, it was recently discovered that IFITs can directly recognize viral RNA bearing a 5'-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an amino-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single-stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double-stranded viral PPP-RNA, retinoic acid-inducible gene I (RIG-I, also known as DDX58). Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence-specific manner and requires a 5'-overhang of approximately three nucleotides. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 was found to cause a defect in the antiviral response by human embryonic kidney cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA, and lend insight into their downstream effector function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbas, Yazan M -- Pichlmair, Andreas -- Gorna, Maria W -- Superti-Furga, Giulio -- Nagar, Bhushan -- MOP-82929/Canadian Institutes of Health Research/Canada -- England -- Nature. 2013 Feb 7;494(7435):60-4. doi: 10.1038/nature11783. Epub 2013 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Groupe de Recherche Axe sur la Structure des Proteines, McGill University, Montreal, Quebec H3G 0B1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23334420" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Binding Sites ; Carrier Proteins/*chemistry/*metabolism ; Humans ; Immunity, Innate/immunology ; Models, Molecular ; Neoplasm Proteins/*chemistry/*metabolism ; Phosphorylation ; Protein Conformation ; RNA, Viral/*chemistry/genetics/*metabolism ; Reproducibility of Results ; Substrate Specificity
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  • 94
    Publication Date: 2013-06-19
    Description: Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919509/" 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/PMC3919509/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawrence, Michael S -- Stojanov, Petar -- Polak, Paz -- Kryukov, Gregory V -- Cibulskis, Kristian -- Sivachenko, Andrey -- Carter, Scott L -- Stewart, Chip -- Mermel, Craig H -- Roberts, Steven A -- Kiezun, Adam -- Hammerman, Peter S -- McKenna, Aaron -- Drier, Yotam -- Zou, Lihua -- Ramos, Alex H -- Pugh, Trevor J -- Stransky, Nicolas -- Helman, Elena -- Kim, Jaegil -- Sougnez, Carrie -- Ambrogio, Lauren -- Nickerson, Elizabeth -- Shefler, Erica -- Cortes, Maria L -- Auclair, Daniel -- Saksena, Gordon -- Voet, Douglas -- Noble, Michael -- DiCara, Daniel -- Lin, Pei -- Lichtenstein, Lee -- Heiman, David I -- Fennell, Timothy -- Imielinski, Marcin -- Hernandez, Bryan -- Hodis, Eran -- Baca, Sylvan -- Dulak, Austin M -- Lohr, Jens -- Landau, Dan-Avi -- Wu, Catherine J -- Melendez-Zajgla, Jorge -- Hidalgo-Miranda, Alfredo -- Koren, Amnon -- McCarroll, Steven A -- Mora, Jaume -- Lee, Ryan S -- Crompton, Brian -- Onofrio, Robert -- Parkin, Melissa -- Winckler, Wendy -- Ardlie, Kristin -- Gabriel, Stacey B -- Roberts, Charles W M -- Biegel, Jaclyn A -- Stegmaier, Kimberly -- Bass, Adam J -- Garraway, Levi A -- Meyerson, Matthew -- Golub, Todd R -- Gordenin, Dmitry A -- Sunyaev, Shamil -- Lander, Eric S -- Getz, Gad -- ES065073/ES/NIEHS NIH HHS/ -- T32 CA009172/CA/NCI NIH HHS/ -- T32 CA009216/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U24 CA143845/CA/NCI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):214-8. doi: 10.1038/nature12213. Epub 2013 Jun 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23770567" target="_blank"〉PubMed〈/a〉
    Keywords: Artifacts ; DNA Replication Timing ; Exome/genetics ; False Positive Reactions ; Gene Expression ; *Genetic Heterogeneity ; Genome, Human/genetics ; Humans ; Lung Neoplasms/genetics ; Mutation/*genetics ; Mutation Rate ; Neoplasms/classification/*genetics/pathology ; Neoplasms, Squamous Cell/genetics ; Oncogenes/*genetics ; Reproducibility of Results ; Sample Size
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  • 95
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2013-07-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2013 Jul 25;499(7459):390. doi: 10.1038/499390a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23887410" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Separation ; *Cell Size ; Embryo, Mammalian/cytology ; Humans ; Mice ; Reproducibility of Results ; Stem Cell Transplantation ; Stem Cells/*cytology ; *Uncertainty
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  • 96
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2013-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2013 Nov 7;503(7474):18-9. doi: 10.1038/503018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24201261" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archaeology/methods ; Collagen/analysis/genetics ; Elephants/*classification/metabolism ; Evolution, Molecular ; Fossils ; Humans ; Mass Spectrometry ; Phylogeny ; Proteomics/*methods ; Reproducibility of Results ; Sequence Analysis, DNA
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  • 97
    Publication Date: 2013-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2013 May 2;497(7447):16. doi: 10.1038/497016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23636371" target="_blank"〉PubMed〈/a〉
    Keywords: *Cues ; Humans ; *Intelligence Tests ; Psychology/standards ; Reproducibility of Results ; Scientific Misconduct ; Sociology/standards ; *Unconscious (Psychology)
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  • 98
    Publication Date: 2013-10-15
    Description: The mechanisms by which genetic variation affects transcription regulation and phenotypes at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding, epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994126/" 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/PMC3994126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinz, S -- Romanoski, C E -- Benner, C -- Allison, K A -- Kaikkonen, M U -- Orozco, L D -- Glass, C K -- 5T32DK007494/DK/NIDDK NIH HHS/ -- CA17390/CA/NCI NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK091183/DK/NIDDK NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- R01 CA173903/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- T32 AR059033/AR/NIAMS NIH HHS/ -- England -- Nature. 2013 Nov 28;503(7477):487-92. doi: 10.1038/nature12615. Epub 2013 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Mail Code 0651, La Jolla, California 92093, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24121437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics ; Animals ; Base Sequence ; Cell Lineage/genetics ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Genetic Variation/*genetics ; Histones/chemistry/metabolism ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Biological ; Mutation/genetics ; NF-kappa B/metabolism ; Protein Binding ; Reproducibility of Results ; Selection, Genetic/*genetics ; Transcription Factor RelA/metabolism ; Transcription Factors/*metabolism
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  • 99
    Publication Date: 2013-10-15
    Description: The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proved challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determine binding sites, bound conformations and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic-level simulations in which the modulators spontaneously associate with the receptor. Despite substantial structural diversity, all modulators form cation-pi interactions with clusters of aromatic residues in the receptor extracellular vestibule, approximately 15 A from the classical, 'orthosteric' ligand-binding site. We validate the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, either to increase or to decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that substantially alter a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dror, Ron O -- Green, Hillary F -- Valant, Celine -- Borhani, David W -- Valcourt, James R -- Pan, Albert C -- Arlow, Daniel H -- Canals, Meritxell -- Lane, J Robert -- Rahmani, Raphael -- Baell, Jonathan B -- Sexton, Patrick M -- Christopoulos, Arthur -- Shaw, David E -- England -- Nature. 2013 Nov 14;503(7475):295-9. doi: 10.1038/nature12595. Epub 2013 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] D. E. Shaw Research, 120 West 45th Street, 39th Floor, New York, New York 10036, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24121438" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/physiology ; Animals ; Binding Sites ; CHO Cells ; Cricetulus ; *Drug Design ; Humans ; Models, Chemical ; Molecular Conformation ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Receptors, G-Protein-Coupled/*antagonists & inhibitors/*chemistry/genetics ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
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    Nature Publishing Group (NPG)
    Publication Date: 2013-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2013 Feb 14;494(7436):155-6. doi: 10.1038/494155a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23407515" target="_blank"〉PubMed〈/a〉
    Keywords: Crowdsourcing ; Data Mining/*methods ; *Epidemiological Monitoring ; Humans ; Influenza A Virus, H3N2 Subtype/isolation & purification/pathogenicity ; Influenza, Human/*epidemiology/mortality/virology ; *Internet ; Reproducibility of Results ; Social Media ; United States/epidemiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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