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  • Animals  (6,308)
  • Crystallography, X-Ray  (537)
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  • Nature Publishing Group (NPG)  (6,712)
  • RAND Corporation  (22)
  • 1
    Publication Date: 2023-10-05
    Description: This report documents key technological innovations in the energy sector; identifies best practices of educational and training programs that have successfully responded to evolving labor markets in other sectors; analyzes four case-study energy-sector education and training programs in southwestern Pennsylvania; and provides recommendations for the energy-sector education and training system in the region.
    Keywords: Physics ; History ; Education ; Business ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management ; bic Book Industry Communication::J Society & social sciences::JN Education::JNM Higher & further education, tertiary education ; bic Book Industry Communication::H Humanities::HB History::HBJ Regional & national history::HBJK History of the Americas ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHD Classical mechanics::PHDY Energy
    Language: English
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  • 2
    Publication Date: 2024-04-04
    Description: Most environmental analyses focus on changing existing processes to use less energy and produce fewer emissions. This report uses energy service analysis (ESA) to examine possibilities for instead changing how a service is delivered. The ESA framework is used to analyze how changes in the provision of two services—news delivery and personal mobility—might reduce greenhouse-gas emissions and suggests other areas in which ESA could be applied.
    Keywords: Political Science ; Physics ; Technology ; Transportation Studies ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHD Classical mechanics::PHDY Energy ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RB Earth sciences::RBP Meteorology & climatology ; bic Book Industry Communication::W Lifestyle, sport & leisure::WG Transport: general interest::WGC Road & motor vehicles: general interest::WGCF Buses, trams & commercial vehicles: general interest ; thema EDItEUR::P Mathematics and Science::PH Physics::PHD Classical mechanics::PHDY Energy ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology ; thema EDItEUR::W Lifestyle, Hobbies and Leisure::WG Transport: general interest::WGC Road and motor vehicles: general interest::WGCF Buses, trams and commercial vehicles: general interest
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  • 3
    Publication Date: 2024-03-29
    Description: This report describes an approach for planning under deep uncertainty, Robust Decision Making (RDM), and demonstrates its use by the El Dorado Irrigation District (EID). Using RDM, the authors and EID tested the robustness of current long-term water management plans and more robust alternatives across more than 50 futures reflecting different assumptions about future climate, urban growth, and the availability of important new supplies.
    Keywords: Political Science ; Physics ; thema EDItEUR::J Society and Social Sciences::JP Politics and government::JPV Political control and freedoms ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RN The environment::RND Environmental policy and protocols ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology
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  • 4
    Publication Date: 2024-03-30
    Description: Communities, companies, and governments at all levels in the United States are making decisions that will influence where, what and how infrastructure will be built. This report describes insights about exposures from natural hazards now and in the future, as well as gaps in data that, if filled, could improve the nation’s ability to assess infrastructure risk and improve infrastructure resilience.
    Keywords: Business ; Physics ; Population Studies ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCS Economic systems and structures ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology ; thema EDItEUR::J Society and Social Sciences::JH Sociology and anthropology::JHB Sociology::JHBD Population and demography
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  • 5
    Publication Date: 2023-10-05
    Description: Nigeria is an important oil producer, but security shortfalls impede oil production and new investment. Important new finds of oil and natural gas have been reported in the territorial waters of Nigeria and nearby nations. Making the offshore petroleum infrastructure more secure would promote additional oil field investment, leading to greater production. The U.S. Air Force has expertise that could help build local security capabilities.
    Keywords: Political Science ; Business ; Physics ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KNB Energy industries & utilities ; bic Book Industry Communication::L Law::LB International law::LBB Public international law::LBBC Treaties & other sources of international law ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RN The environment::RND Environmental policy & protocols ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHD Classical mechanics::PHDY Energy
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  • 6
    Publication Date: 2023-10-05
    Description: RAND researchers and collaborators present a comprehensive approach for water utilities to assess climate risks to their systems and evaluate adaptation strategies. The approach, based on Robust Decision Making, is demonstrated through pilot studies with two water utilities: Colorado Springs Utilities and New York City Department of Environmental Protection.
    Keywords: Political Science ; Physics ; Technology ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RN The environment::RND Environmental policy & protocols ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RB Earth sciences::RBP Meteorology & climatology ; bic Book Industry Communication::T Technology, engineering, agriculture::TQ Environmental science, engineering & technology::TQS Sanitary & municipal engineering::TQSW Water supply & treatment
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  • 7
    Publication Date: 2023-10-05
    Description: Space is now a congested, contested, and competitive environment. Space systems must become more resilient to potential adversary actions and system failures, but changes to space systems are costly. To reduce costs, the Air Force asked RAND to identify non-materiel means—doctrine, organization, training, leadership and education, personnel, facilities, and policy—to enhance space resilience over the near and far terms.
    Keywords: Physics ; Business ; History ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management ; bic Book Industry Communication::H Humanities::HB History::HBW Military history ; bic Book Industry Communication::J Society & social sciences::JW Warfare & defence::JWG Air forces & warfare ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHV Applied physics::PHVB Astrophysics
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  • 8
    Publication Date: 2024-04-02
    Description: The U.S. Environmental Protection Agency and its partners develop implementation plans to meet water quality standards. Climate change and other key drivers may significantly affect these plans, but are often neglected due to uncertainty. This study uses two case studies to demonstrate how Robust Decision Making (RDM) can help to address future uncertainty by identifying vulnerabilities in water quality plans and suggesting appropriate responses.
    Keywords: Political Science ; History ; Mathematics ; Physics ; thema EDItEUR::N History and Archaeology::NH History::NHK History of the Americas ; thema EDItEUR::P Mathematics and Science::PB Mathematics::PBK Calculus and mathematical analysis::PBKD Complex analysis, complex variables ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RN The environment::RND Environmental policy and protocols ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology
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  • 9
    Publication Date: 2024-04-04
    Description: The E-Vision 2002 Conference, held in May 2002, was sponsored by the U.S. Department of Energy as a step toward implementing a key recommendation of the Bush administration's National Energy Policy. It gathered 150 of the nation's leading energy experts to discuss ways of reducing the country's energy intensity. This volume and the additional volume enclosed on CD-ROM contain the presentations and discussions that took place at the conference, including the identification of goals and the means to achieve them. It is a key work for those involved in implementing the National Energy Policy.
    Keywords: Physics ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHD Classical mechanics::PHDY Energy ; thema EDItEUR::P Mathematics and Science::PH Physics::PHD Classical mechanics::PHDY Energy
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  • 10
    Publication Date: 2024-04-05
    Description: The Global Methane Initiative (GMI) is a voluntary international partnership that promotes methane recovery and reuse activities in developing and transition economies. The U.S. Department of State requested an evaluation of the activities and outcomes supported in whole or in part by its contributions to GMI to gauge its value added to the program.
    Keywords: Physics ; Environmental Science ; Chemistry ; thema EDItEUR::P Mathematics and Science::PN Chemistry ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TQ Environmental science, engineering and technology ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology
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  • 11
    Publication Date: 2023-10-05
    Description: The 2012 Colorado River Basin Study evaluated the resiliency of the Colorado River system over the next 50 years to climate change and other factors, and then compared different options and strategies for ensuring successful management of the river’s resources. This report describes RAND’s contribution to this study. It focuses on the Robust Decision Making methodologies used to identify vulnerabilities and compare portfolios of options.
    Keywords: Physics ; Political Science ; Technology ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RN The environment::RND Environmental policy & protocols ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RB Earth sciences::RBP Meteorology & climatology ; bic Book Industry Communication::T Technology, engineering, agriculture::TQ Environmental science, engineering & technology::TQS Sanitary & municipal engineering::TQSW Water supply & treatment
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  • 12
    Publication Date: 2024-03-30
    Description: Air pollution has been one of the most pernicious consequences of China’s last three decades of economic transformation and growth. This report estimates the costs of three measures to reduce air pollution in China: replacing coal with natural gas for residential and commercial heating, replacing half of China's coal-fired electric power generation with renewables or nuclear power, and scrapping highly polluting vehicles.
    Keywords: History ; Political Science ; Business ; Physics ; thema EDItEUR::K Economics, Finance, Business and Management::KN Industry and industrial studies::KNB Energy industries and utilities ; thema EDItEUR::N History and Archaeology::NH History::NHF Asian history ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RN The environment::RND Environmental policy and protocols ; thema EDItEUR::P Mathematics and Science::PH Physics::PHD Classical mechanics::PHDY Energy
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  • 13
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    RAND Corporation
    Publication Date: 2024-03-29
    Description: The National Intelligence Council's 2008 report "Global Trends 2025: A Transformed World" projects what the world will look like in 2025 based on recent trends. This paper asks: How should U.S. policy adapt now to account for these trends and the future that will result from them? The author explores such issues as climate change, defense, international relations, and the structure of the federal government.
    Keywords: Political Science ; Physics ; thema EDItEUR::J Society and Social Sciences::JP Politics and government::JPS International relations ; thema EDItEUR::J Society and Social Sciences::JW Warfare and defence ; thema EDItEUR::P Mathematics and Science::PH Physics::PHD Classical mechanics::PHDY Energy
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  • 14
    Publication Date: 2023-10-05
    Description: If policies aimed at large reductions of carbon dioxide (CO2) emissions are enacted, more carbon capture and storage will be needed. RAND researchers explored the ability of the industrial base supporting the transportation and sequestration of CO2 to expand, assessing the industrial base for transportation and injection of CO2 for both geologic storage and enhanced oil recovery.
    Keywords: Political Science ; Environmental Science ; Business ; Physics ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KNB Energy industries & utilities ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RN The environment::RND Environmental policy & protocols ; bic Book Industry Communication::T Technology, engineering, agriculture::TQ Environmental science, engineering & technology
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  • 15
    Publication Date: 2024-03-30
    Description: This report serves as the technical documentation and reference document for the data, methods, and analytic approach used in the analysis of national exposures to infrastructure from natural disasters. The analysis includes 11 natural hazards and five infrastructure sectors. Analytic findings about current and future exposures of infrastructure in the United States drawn from this data analysis are documented in a separate report.
    Keywords: Business ; Physics ; Population Studies ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCS Economic systems and structures ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology ; thema EDItEUR::J Society and Social Sciences::JH Sociology and anthropology::JHB Sociology::JHBD Population and demography
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  • 16
    Publication Date: 2023-10-05
    Description: This book discusses the opportunities and risks the government of Israel faces in shifting to a greater reliance on domestic and imported natural gas. By applying newly developed methods for strategic planning and decisionmaking under deep uncertainty, the analysis seeks to help the Israeli government engage in managed change by choosing robust strategies that minimize potential consequences of relying more heavily on natural gas.
    Keywords: Physics ; Business ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KNB Energy industries & utilities ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHD Classical mechanics::PHDY Energy
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  • 17
    Publication Date: 2024-04-14
    Description: Limiting climate change will require transformation of energy and other systems. This report presents an agent-based, game theoretic model designed to compare the long-term sustainability of alternative carbon emission reduction policies. The model tracks the co-evolution of an industry sector, its technology base, and political coalitions that influence government policy. It uses robust decision making methods to compare alternative policies.
    Keywords: Physics ; Mathematics ; Technology ; thema EDItEUR::U Computing and Information Technology::UN Databases::UNA Database design and theory ; thema EDItEUR::P Mathematics and Science::PB Mathematics::PBU Optimization::PBUD Game theory ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology
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  • 18
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    RAND Corporation
    Publication Date: 2024-04-05
    Description: Orbital space debris represents a growing threat to the operation of man-made systems in space. With the goal of guiding future mitigation or remediation efforts, this monograph examines nine comparable problems that share similarities with orbital debris: acid rain, U.S. commercial airline security, asbestos, chlorofluorocarbons, hazardous waste, oil spills, radon, email spam, and U.S. border control.
    Keywords: Technology ; Physics ; Environmental Science ; thema EDItEUR::P Mathematics and Science::PH Physics::PHV Applied physics::PHVB Astrophysics ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TQ Environmental science, engineering and technology ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TR Transport technology and trades::TRP Aerospace and aviation technology
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  • 19
    Publication Date: 2024-04-02
    Description: This report describes a proof-of-concept analysis using Robust Decision Making to evaluate water resource management response packages for California’s Central Valley under future uncertainty. This analytic approach will be used to develop a more comprehensive analysis for the California Water Plan Update 2013.
    Keywords: History ; Political Science ; Physics ; thema EDItEUR::N History and Archaeology::NH History::NHK History of the Americas ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RN The environment::RND Environmental policy and protocols ; thema EDItEUR::R Earth Sciences, Geography, Environment, Planning::RB Earth sciences::RBP Meteorology and climatology
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  • 20
    Publication Date: 2023-10-05
    Description: To determine whether the industrial base for the U.S. domestic coal-based electricity generation industry can maintain the capability to design, construct, operate, and maintain coal-fired electricity generating units within reasonable cost, schedule, performance, environmental, and quality expectations, this book reviews interviews with stakeholders and data describing key elements of industry capability and validation or verification of concerns.
    Keywords: Physics ; Law ; Management & Organizational Behavior ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KNB Energy industries & utilities ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHD Classical mechanics::PHDY Energy
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  • 21
    Publication Date: 2024-03-30
    Description: RAND Corporation researchers review the current technical, regulatory, and economic context of the electricity market and theoretical benefits of developing a smart grid; discuss some entrepreneurial opportunities associated with smart-grid data; examine empirical evidence related to smart-grid adoption and implementation; and offer policy suggestions for overcoming identified barriers.
    Keywords: Law ; Physics ; Business ; thema EDItEUR::K Economics, Finance, Business and Management::KN Industry and industrial studies::KNB Energy industries and utilities ; thema EDItEUR::P Mathematics and Science::PH Physics::PHD Classical mechanics::PHDY Energy
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  • 22
    Publication Date: 2023-10-05
    Description: Nuclear power is receiving renewed interest because of its low greenhouse gas emissions. However, if nuclear power is to be sustainable option for the United States, methods for managing spent fuel that meet stringent safety and environmental standards must be implemented. This report examines technical and institutional approaches to spent fuel management and highlights policy implications of pursuing alternative strategies.
    Keywords: Physics ; Environmental Science ; Business ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KNB Energy industries & utilities ; bic Book Industry Communication::T Technology, engineering, agriculture::TQ Environmental science, engineering & technology ; bic Book Industry Communication::P Mathematics & science::PH Physics::PHN Nuclear physics
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  • 23
    Publication Date: 2016-02-06
    Description: The position of Xenacoelomorpha in the tree of life remains a major unresolved question in the study of deep animal relationships. Xenacoelomorpha, comprising Acoela, Nemertodermatida, and Xenoturbella, are bilaterally symmetrical marine worms that lack several features common to most other bilaterians, for example an anus, nephridia, and a circulatory system. Two conflicting hypotheses are under debate: Xenacoelomorpha is the sister group to all remaining Bilateria (= Nephrozoa, namely protostomes and deuterostomes) or is a clade inside Deuterostomia. Thus, determining the phylogenetic position of this clade is pivotal for understanding the early evolution of bilaterian features, or as a case of drastic secondary loss of complexity. Here we show robust phylogenomic support for Xenacoelomorpha as the sister taxon of Nephrozoa. Our phylogenetic analyses, based on 11 novel xenacoelomorph transcriptomes and using different models of evolution under maximum likelihood and Bayesian inference analyses, strongly corroborate this result. Rigorous testing of 25 experimental data sets designed to exclude data partitions and taxa potentially prone to reconstruction biases indicates that long-branch attraction, saturation, and missing data do not influence these results. The sister group relationship between Nephrozoa and Xenacoelomorpha supported by our phylogenomic analyses implies that the last common ancestor of bilaterians was probably a benthic, ciliated acoelomate worm with a single opening into an epithelial gut, and that excretory organs, coelomic cavities, and nerve cords evolved after xenacoelomorphs separated from the stem lineage of Nephrozoa.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cannon, Johanna Taylor -- Vellutini, Bruno Cossermelli -- Smith, Julian 3rd -- Ronquist, Fredrik -- Jondelius, Ulf -- Hejnol, Andreas -- England -- Nature. 2016 Feb 4;530(7588):89-93. doi: 10.1038/nature16520.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Naturhistoriska Riksmuseet, PO Box 50007, SE-104 05 Stockholm, Sweden. ; Sars International Centre for Marine Molecular Biology, University of Bergen, Thormohlensgate 55, 5008 Bergen, Norway. ; Department of Biology, Winthrop University, 701 Oakland Avenue, Rock Hill, South Carolina 29733, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842059" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Structures/anatomy & histology ; Animals ; Aquatic Organisms/*classification/genetics ; Bayes Theorem ; Genes ; Likelihood Functions ; Male ; Models, Biological ; *Phylogeny ; Transcriptome
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 24
    Publication Date: 2016-01-21
    Description: Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westermann, Alexander J -- Forstner, Konrad U -- Amman, Fabian -- Barquist, Lars -- Chao, Yanjie -- Schulte, Leon N -- Muller, Lydia -- Reinhardt, Richard -- Stadler, Peter F -- Vogel, Jorg -- England -- Nature. 2016 Jan 28;529(7587):496-501. doi: 10.1038/nature16547. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Wurzburg, RNA Biology Group, Institute for Molecular Infection Biology, Josef-Schneider-Strasse 2/D15, D-97080 Wurzburg, Germany. ; University of Wurzburg, Core Unit Systems Medicine, Josef-Schneider-Strasse 2/D15, D-97080 Wurzburg, Germany. ; University of Leipzig, Department of Computer Science and Interdisciplinary Center for Bioinformatics, Hartelstrasse 16-18, D-04107 Leipzig, Germany. ; University of Vienna, Theoretical Biochemistry Group, Institute for Theoretical Chemistry, Wahringer Strasse 17, A-1090 Vienna, Austria. ; Max Planck Genome Centre Cologne, Max Planck Institute for Plant Breeding Research, Carl-von-Linne-Weg 10, D-50829 Cologne, Germany. ; Max Planck Institute for Mathematics in the Sciences, Inselstrasse 22, D-04103 Leipzig, Germany. ; Santa Fe Institute, 1399 Hyde Park Rd, Santa Fe, New Mexico 87501, USA. ; Research Centre for Infectious Diseases (ZINF), University of Wurzburg, D-97070 Wurzburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26789254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/metabolism ; Female ; Gene Expression Regulation/*genetics ; Genes, Bacterial/genetics ; HeLa Cells ; Host-Pathogen Interactions/*genetics ; Humans ; Janus Kinases/metabolism ; Mice ; Microbial Viability/genetics ; RNA, Bacterial/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Untranslated/*genetics/metabolism ; STAT Transcription Factors/metabolism ; Salmonella typhimurium/cytology/*genetics/pathogenicity ; Signal Transduction/genetics ; Transcriptome/genetics ; Virulence/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 25
    Publication Date: 2016-02-19
    Description: Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realization that cell-intrinsic mechanisms play important and persistent roles. Here we use the Drosophila melanogaster intestine to investigate the nature and importance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncovers the key role this identity has in controlling organ size, reproductive plasticity and response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms that control cell cycle duration and involve a new doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognized.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hudry, Bruno -- Khadayate, Sanjay -- Miguel-Aliaga, Irene -- Medical Research Council/United Kingdom -- England -- Nature. 2016 Feb 18;530(7590):344-8. doi: 10.1038/nature16953.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887495" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; Cell Cycle ; Cell Proliferation ; Cell Transformation, Neoplastic ; Dosage Compensation, Genetic ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*anatomy & histology/*cytology/genetics/growth & ; development ; Female ; Intestines/*cytology ; Male ; Nuclear Proteins/metabolism ; *Organ Size ; RNA-Binding Proteins/metabolism ; Reproduction ; Ribonucleoproteins/metabolism ; *Sex Characteristics ; Sex Differentiation/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 26
    Publication Date: 2016-03-24
    Description: Developmental disabilities, including attention-deficit hyperactivity disorder (ADHD), intellectual disability (ID), and autism spectrum disorders (ASD), affect one in six children in the USA. Recently, gene mutations in patched domain containing 1 (PTCHD1) have been found in ~1% of patients with ID and ASD. Individuals with PTCHD1 deletion show symptoms of ADHD, sleep disruption, hypotonia, aggression, ASD, and ID. Although PTCHD1 is probably critical for normal development, the connection between its deletion and the ensuing behavioural defects is poorly understood. Here we report that during early post-natal development, mouse Ptchd1 is selectively expressed in the thalamic reticular nucleus (TRN), a group of GABAergic neurons that regulate thalamocortical transmission, sleep rhythms, and attention. Ptchd1 deletion attenuates TRN activity through mechanisms involving small conductance calcium-dependent potassium currents (SK). TRN-restricted deletion of Ptchd1 leads to attention deficits and hyperactivity, both of which are rescued by pharmacological augmentation of SK channel activity. Global Ptchd1 deletion recapitulates learning impairment, hyper-aggression, and motor defects, all of which are insensitive to SK pharmacological targeting and not found in the TRN-restricted deletion mouse. This study maps clinically relevant behavioural phenotypes onto TRN dysfunction in a human disease model, while also identifying molecular and circuit targets for intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875756/" 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/PMC4875756/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wells, Michael F -- Wimmer, Ralf D -- Schmitt, L Ian -- Feng, Guoping -- Halassa, Michael M -- F31 MH098641/MH/NIMH NIH HHS/ -- R00 NS078115/NS/NINDS NIH HHS/ -- R01 MH097104/MH/NIMH NIH HHS/ -- R01 MH107680/MH/NIMH NIH HHS/ -- R01MH097104/MH/NIMH NIH HHS/ -- R01MH10768/MH/NIMH NIH HHS/ -- England -- Nature. 2016 Apr 7;532(7597):58-63. doi: 10.1038/nature17427. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Neuroscience Institute, New York University Langone Medical Center, New York, New York 10016, USA. ; Department of Neuroscience and Physiology, New York University Langone Medical Center, New York, New York 10016, USA. ; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; Department of Psychiatry, New York University Langone Medical Center, New York, New York 10016, USA. ; Center for Neural Science, New York University, New York, New York 1003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007844" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression ; Animals ; Animals, Newborn ; Attention ; Attention Deficit Disorder with ; Hyperactivity/genetics/*physiopathology/*psychology ; Behavior, Animal ; Disease Models, Animal ; Electric Conductivity ; Female ; GABAergic Neurons/metabolism/pathology ; *Gene Deletion ; Humans ; Learning Disorders/genetics/physiopathology ; Male ; Membrane Proteins/*deficiency/*genetics/metabolism ; Mice ; Mice, Knockout ; Motor Disorders/genetics/physiopathology ; Neural Inhibition ; Potassium Channels, Calcium-Activated/metabolism ; Sleep ; Sleep Deprivation/genetics/physiopathology ; Thalamic Nuclei/pathology/*physiopathology
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Owens, Brian -- England -- Nature. 2016 May 11;533(7602):S71-2. doi: 10.1038/533S71a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27167398" target="_blank"〉PubMed〈/a〉
    Keywords: *Academies and Institutes/economics ; *Access to Information ; Animals ; *Diffusion of Innovation ; Drug Industry/economics/methods ; Humans ; *Information Dissemination ; Mice ; Neurosciences/economics/manpower/*methods/organization & administration ; Patents as Topic ; Public Sector/economics ; Public-Private Sector Partnerships ; Quebec
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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caron, David A -- England -- Nature. 2016 Apr 28;532(7600):444-5. doi: 10.1038/nature17892. Epub 2016 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-0371, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27096370" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquatic Organisms/*metabolism ; *Biomass ; *Biota ; Carbon/*metabolism ; *Ecosystem ; *Oceans and Seas ; Plankton/*metabolism ; Rhizaria/*isolation & purification ; Seawater/*chemistry ; Zooplankton/*isolation & purification
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  • 29
    Publication Date: 2016-01-07
    Description: Endothelial cells (ECs) are plastic cells that can switch between growth states with different bioenergetic and biosynthetic requirements. Although quiescent in most healthy tissues, ECs divide and migrate rapidly upon proangiogenic stimulation. Adjusting endothelial metabolism to the growth state is central to normal vessel growth and function, yet it is poorly understood at the molecular level. Here we report that the forkhead box O (FOXO) transcription factor FOXO1 is an essential regulator of vascular growth that couples metabolic and proliferative activities in ECs. Endothelial-restricted deletion of FOXO1 in mice induces a profound increase in EC proliferation that interferes with coordinated sprouting, thereby causing hyperplasia and vessel enlargement. Conversely, forced expression of FOXO1 restricts vascular expansion and leads to vessel thinning and hypobranching. We find that FOXO1 acts as a gatekeeper of endothelial quiescence, which decelerates metabolic activity by reducing glycolysis and mitochondrial respiration. Mechanistically, FOXO1 suppresses signalling by MYC (also known as c-MYC), a powerful driver of anabolic metabolism and growth. MYC ablation impairs glycolysis, mitochondrial function and proliferation of ECs while its EC-specific overexpression fuels these processes. Moreover, restoration of MYC signalling in FOXO1-overexpressing endothelium normalizes metabolic activity and branching behaviour. Our findings identify FOXO1 as a critical rheostat of vascular expansion and define the FOXO1-MYC transcriptional network as a novel metabolic checkpoint during endothelial growth and proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilhelm, Kerstin -- Happel, Katharina -- Eelen, Guy -- Schoors, Sandra -- Oellerich, Mark F -- Lim, Radiance -- Zimmermann, Barbara -- Aspalter, Irene M -- Franco, Claudio A -- Boettger, Thomas -- Braun, Thomas -- Fruttiger, Marcus -- Rajewsky, Klaus -- Keller, Charles -- Bruning, Jens C -- Gerhardt, Holger -- Carmeliet, Peter -- Potente, Michael -- K08CA090438/CA/NCI NIH HHS/ -- Cancer Research UK/United Kingdom -- England -- Nature. 2016 Jan 14;529(7585):216-20. doi: 10.1038/nature16498. Epub 2016 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Angiogenesis &Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, D-61231 Bad Nauheim, Germany. ; Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, Department of Oncology, University of Leuven, Leuven 3000, Belgium. ; Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, VIB, Leuven 3000, Belgium. ; Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK. ; Vascular Morphogenesis Laboratory, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon 1649-028, Portugal. ; Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, D-61231 Bad Nauheim, Germany. ; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK. ; Max Delbruck Center for Molecular Medicine (MDC), D-13125 Berlin, Germany. ; Children's Cancer Therapy Development Institute, Beaverton, Oregon 97005, USA. ; Max Planck Institute for Metabolism Research, Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University of Cologne, D-50931 Cologne, Germany. ; Vascular Patterning Laboratory, Vesalius Research Center, VIB and University of Leuven, Leuven 3000, Belgium. ; DZHK (German Center for Cardiovascular Research), partner site Berlin, D-13347 Berlin, Germany. ; Berlin Institute of Health (BIH), D-10117 Berlin, Germany. ; International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. ; DZHK (German Center for Cardiovascular Research), partner site Frankfurt Rhine-Main, D-13347 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26735015" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Cell Respiration ; Endothelium, Vascular/cytology/*growth & development/*metabolism ; Female ; Forkhead Transcription Factors/deficiency/genetics/*metabolism ; Glycolysis ; Human Umbilical Vein Endothelial Cells/cytology/metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-myc/deficiency/genetics/metabolism ; Signal Transduction
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willyard, Cassandra -- England -- Nature. 2016 Apr 14;532(7598):166-8. doi: 10.1038/532166a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075079" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/economics/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/economics/*therapeutic use ; Clinical Trials as Topic ; DNA Mutational Analysis ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm/*drug effects/genetics ; *Evolution, Molecular ; Female ; Humans ; Immunotherapy, Adoptive/economics/trends ; Mice ; Molecular Targeted Therapy/economics/*methods/trends ; Mutation/*genetics ; Neoplasm Metastasis/drug therapy/genetics/pathology ; Neoplasm Recurrence, Local/chemically induced/genetics/prevention & control ; Neoplasms/*drug therapy/*genetics/pathology ; Selection, Genetic/*drug effects/genetics ; Tumor Microenvironment/drug effects
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  • 31
    Publication Date: 2016-04-14
    Description: Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Itkin, Tomer -- Gur-Cohen, Shiri -- Spencer, Joel A -- Schajnovitz, Amir -- Ramasamy, Saravana K -- Kusumbe, Anjali P -- Ledergor, Guy -- Jung, Yookyung -- Milo, Idan -- Poulos, Michael G -- Kalinkovich, Alexander -- Ludin, Aya -- Kollet, Orit -- Shakhar, Guy -- Butler, Jason M -- Rafii, Shahin -- Adams, Ralf H -- Scadden, David T -- Lin, Charles P -- Lapidot, Tsvee -- EB017274/EB/NIBIB NIH HHS/ -- HL100402/HL/NHLBI NIH HHS/ -- R01 EB017274/EB/NIBIB NIH HHS/ -- U01 HL100402/HL/NHLBI NIH HHS/ -- England -- Nature. 2016 Apr 21;532(7599):323-8. doi: 10.1038/nature17624. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. ; Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Harvard Stem Cell Institute, Cambridge, Massachusetts 02114, USA. ; Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis and Faculty of Medicine, University of Munster, D-48149 Munster, Germany. ; Internal Medicine Department, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239, Israel. ; Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074509" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Ly/metabolism ; Arteries/cytology/physiology ; Blood Vessels/*cytology/*physiology ; Bone Marrow/*blood supply ; Bone Marrow Cells/cytology ; Cell Differentiation ; Cell Movement ; Cell Self Renewal ; Cell Survival ; Chemokine CXCL12/metabolism ; Endothelial Cells/physiology ; Female ; *Hematopoiesis ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology ; Leukocytes/cytology ; Male ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Nestin/metabolism ; Pericytes/physiology ; Permeability ; Plasma/metabolism ; Reactive Oxygen Species/metabolism ; Receptors, CXCR4/metabolism
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  • 32
    Publication Date: 2016-01-19
    Description: Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Seung-Kyun -- Murphy, Rory K J -- Hwang, Suk-Won -- Lee, Seung Min -- Harburg, Daniel V -- Krueger, Neil A -- Shin, Jiho -- Gamble, Paul -- Cheng, Huanyu -- Yu, Sooyoun -- Liu, Zhuangjian -- McCall, Jordan G -- Stephen, Manu -- Ying, Hanze -- Kim, Jeonghyun -- Park, Gayoung -- Webb, R Chad -- Lee, Chi Hwan -- Chung, Sangjin -- Wie, Dae Seung -- Gujar, Amit D -- Vemulapalli, Bharat -- Kim, Albert H -- Lee, Kyung-Mi -- Cheng, Jianjun -- Huang, Younggang -- Lee, Sang Hoon -- Braun, Paul V -- Ray, Wilson Z -- Rogers, John A -- F31MH101956/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Feb 4;530(7588):71-6. doi: 10.1038/nature16492. Epub 2016 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-701, Republic of Korea. ; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Department of Engineering Science and Mechanics, Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; Institute of High Performance Computing, Singapore 138632, Singapore. ; Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Biomicrosystem Technology, Korea University, Seoul 136-701, South Korea. ; Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-713, South Korea. ; Weldon School of Biomedical Engineering, School of Mechanical Engineering, The Center for Implantable Devices, Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, USA. ; School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907, USA. ; Department of Mechanical Engineering, Civil and Environmental Engineering, Materials Science and Engineering, and Skin Disease Research Center, Northwestern University, Evanston, Illinois 60208, USA. ; Department of Biomedical Engineering, College of Health Science, Korea University, Seoul 136-703, South Korea. ; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26779949" target="_blank"〉PubMed〈/a〉
    Keywords: *Absorbable Implants/adverse effects ; Administration, Cutaneous ; Animals ; Body Temperature ; Brain/*metabolism/surgery ; Electronics/*instrumentation ; Equipment Design ; Hydrolysis ; Male ; Monitoring, Physiologic/adverse effects/*instrumentation ; Organ Specificity ; Pressure ; *Prostheses and Implants/adverse effects ; Rats ; Rats, Inbred Lew ; *Silicon ; Telemetry/instrumentation ; Wireless Technology/instrumentation
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  • 33
    Publication Date: 2016-02-24
    Description: Eukaryotic cells restrict protein synthesis under various stress conditions, by inhibiting the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, a heterotrimeric G protein consisting of alpha-, beta- and gamma-subunits. eIF2B exchanges GDP for GTP on the gamma-subunit of eIF2 (eIF2gamma), and is inhibited by stress-induced phosphorylation of eIF2alpha. eIF2B is a heterodecameric complex of two copies each of the alpha-, beta-, gamma-, delta- and epsilon-subunits; its alpha-, beta- and delta-subunits constitute the regulatory subcomplex, while the gamma- and epsilon-subunits form the catalytic subcomplex. The three-dimensional structure of the entire eIF2B complex has not been determined. Here we present the crystal structure of Schizosaccharomyces pombe eIF2B with an unprecedented subunit arrangement, in which the alpha2beta2delta2 hexameric regulatory subcomplex binds two gammaepsilon dimeric catalytic subcomplexes on its opposite sides. A structure-based in vitro analysis by a surface-scanning site-directed photo-cross-linking method identified the eIF2alpha-binding and eIF2gamma-binding interfaces, located far apart on the regulatory and catalytic subcomplexes, respectively. The eIF2gamma-binding interface is located close to the conserved 'NF motif', which is important for nucleotide exchange. A structural model was constructed for the complex of eIF2B with phosphorylated eIF2alpha, which binds to eIF2B more strongly than the unphosphorylated form. These results indicate that the eIF2alpha phosphorylation generates the 'nonproductive' eIF2-eIF2B complex, which prevents nucleotide exchange on eIF2gamma, and thus provide a structural framework for the eIF2B-mediated mechanism of stress-induced translational control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kashiwagi, Kazuhiro -- Takahashi, Mari -- Nishimoto, Madoka -- Hiyama, Takuya B -- Higo, Toshiaki -- Umehara, Takashi -- Sakamoto, Kensaku -- Ito, Takuhiro -- Yokoyama, Shigeyuki -- England -- Nature. 2016 Mar 3;531(7592):122-5. doi: 10.1038/nature16991. Epub 2016 Feb 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. ; RIKEN Systems and Structural Biology Center, Tsurumi-ku, Yokohama 230-0045, Japan. ; RIKEN Center for Life Science Technologies, Tsurumi-ku, Yokohama 230-0045, Japan. ; RIKEN Structural Biology Laboratory, Tsurumi-ku, Yokohama 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26901872" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Binding Sites ; Biocatalysis ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; Eukaryotic Initiation Factor-2B/*chemistry/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Models, Molecular ; Phosphorylation ; Protein Binding ; Protein Biosynthesis ; Protein Structure, Quaternary ; Protein Subunits/chemistry/metabolism ; Schizosaccharomyces/*chemistry
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  • 34
    Publication Date: 2016-04-15
    Description: Numerous natural systems contain surfaces or threads that enable directional water transport. This behaviour is usually ascribed to hierarchical structural features at the microscale and nanoscale, with gradients in surface energy and gradients in Laplace pressure thought to be the main driving forces. Here we study the prey-trapping pitcher organs of the carnivorous plant Nepenthes alata. We find that continuous, directional water transport occurs on the surface of the 'peristome'--the rim of the pitcher--because of its multiscale structure, which optimizes and enhances capillary rise in the transport direction, and prevents backflow by pinning in place any water front that is moving in the reverse direction. This results not only in unidirectional flow despite the absence of any surface-energy gradient, but also in a transport speed that is much higher than previously thought. We anticipate that the basic 'design' principles underlying this behaviour could be used to develop artificial fluid-transport systems with practical applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Huawei -- Zhang, Pengfei -- Zhang, Liwen -- Liu, Hongliang -- Jiang, Ying -- Zhang, Deyuan -- Han, Zhiwu -- Jiang, Lei -- England -- Nature. 2016 Apr 7;532(7597):85-9. doi: 10.1038/nature17189.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Mechanical Engineering and Automation, Beihang University, Beijing 100191, China. ; Laboratory of Bio-inspired Smart Interface Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China. ; School of Chemistry and Environment, Beihang University, Beijing 100191, China. ; Key Laboratory for Bionic Engineering, Ministry of Education, Jilin University, Changchun 130022, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078568" target="_blank"〉PubMed〈/a〉
    Keywords: Angiosperms/*anatomy & histology/*metabolism ; Animals ; Biological Transport ; Biomimetics ; Insects ; Plant Epidermis/anatomy & histology/metabolism ; Surface Properties ; Water/*metabolism ; Water Movements
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  • 35
    Publication Date: 2016-05-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Jihong -- Liu, Xiang -- England -- Nature. 2016 May 18;533(7603):321. doi: 10.1038/533321d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Shanghai Maritime University, China. ; Rutgers University, Piscataway, New Jersey, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27193671" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Dissent and Disputes ; *Ecosystem ; *Environmental Monitoring ; *Models, Economic ; *Transportation
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  • 36
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pincus, Zachary -- England -- Nature. 2016 Feb 4;530(7588):37-8. doi: 10.1038/nature16873. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Developmental Biology and Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814974" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*physiology ; Animals ; Caenorhabditis elegans/*physiology ; Longevity/*physiology
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  • 37
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Jun -- Wang, Bo -- Jarzembowski, Edmund A -- England -- Nature. 2016 Apr 28;532(7600):441. doi: 10.1038/532441a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Linyi University, China. ; Nanjing Institute of Geology and Palaeontology, China. ; Natural History Museum, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121830" target="_blank"〉PubMed〈/a〉
    Keywords: Amber/*economics ; Animals ; China ; Coal ; *Fossils ; Insects/anatomy & histology/physiology ; Kaolin/isolation & purification ; Mining ; *Paleontology
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  • 38
    Publication Date: 2016-01-28
    Description: Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pillay, S -- Meyer, N L -- Puschnik, A S -- Davulcu, O -- Diep, J -- Ishikawa, Y -- Jae, L T -- Wosen, J E -- Nagamine, C M -- Chapman, M S -- Carette, J E -- DP2 AI104557/AI/NIAID NIH HHS/ -- R01 GM066875/GM/NIGMS NIH HHS/ -- U19 AI109662/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Feb 4;530(7588):108-12. doi: 10.1038/nature16465. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, California 94305, USA. ; Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health &Science University, 3181 Sam Jackson Park Road, Portland, Oregon 97239-3098, USA. ; Shriners Hospital for Children, 3101 Sam Jackson Park Road, Portland, Oregon 97239, USA. ; Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. ; Department of Comparative Medicine, Stanford University School of Medicine, 287 Campus Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814968" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology/pharmacology ; Cell Line ; Dependovirus/classification/drug effects/*physiology ; Endocytosis/drug effects ; Female ; Gene Deletion ; Genetic Therapy/methods ; Host Specificity ; Humans ; Male ; Mice ; Parvoviridae Infections/*metabolism/*virology ; Receptors, Cell Surface/antagonists & inhibitors/deficiency/genetics/*metabolism ; Receptors, Virus/antagonists & inhibitors/deficiency/genetics/*metabolism ; *Viral Tropism/drug effects ; Virus Internalization/drug effects ; trans-Golgi Network/drug effects
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  • 39
    Publication Date: 2016-02-13
    Description: The palaeobiological record of 12 million to 7 million years ago (Ma) is crucial to the elucidation of African ape and human origins, but few fossil assemblages of this period have been reported from sub-Saharan Africa. Since the 1970s, the Chorora Formation, Ethiopia, has been widely considered to contain ~10.5 million year (Myr) old mammalian fossils. More recently, Chororapithecus abyssinicus, a probable primitive member of the gorilla clade, was discovered from the formation. Here we report new field observations and geochemical, magnetostratigraphic and radioisotopic results that securely place the Chorora Formation sediments to between ~9 and ~7 Ma. The C. abyssinicus fossils are ~8.0 Myr old, forming a revised age constraint of the human-gorilla split. Other Chorora fossils range in age from ~8.5 to 7 Ma and comprise the first sub-Saharan mammalian assemblage that spans this period. These fossils suggest indigenous African evolution of multiple mammalian lineages/groups between 10 and 7 Ma, including a possible ancestral-descendent relationship between the ~9.8 Myr old Nakalipithecus nakayamai and C. abyssinicus. The new chronology and fossils suggest that faunal provinciality between eastern Africa and Eurasia had intensified by ~9 Ma, with decreased faunal interchange thereafter. The Chorora evidence supports the hypothesis of in situ African evolution of the Gorilla-Pan-human clade, and is concordant with the deeper divergence estimates of humans and great apes based on lower mutation rates of ~0.5 x 10(-9) per site per year (refs 13 - 15).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katoh, Shigehiro -- Beyene, Yonas -- Itaya, Tetsumaru -- Hyodo, Hironobu -- Hyodo, Masayuki -- Yagi, Koshi -- Gouzu, Chitaro -- WoldeGabriel, Giday -- Hart, William K -- Ambrose, Stanley H -- Nakaya, Hideo -- Bernor, Raymond L -- Boisserie, Jean-Renaud -- Bibi, Faysal -- Saegusa, Haruo -- Sasaki, Tomohiko -- Sano, Katsuhiro -- Asfaw, Berhane -- Suwa, Gen -- England -- Nature. 2016 Feb 11;530(7589):215-8. doi: 10.1038/nature16510.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Natural History, Hyogo Museum of Nature and Human Activities, Sanda 669-1546, Japan. ; Association for Conservation of Culture Awassa, PO Box 6686, Addis Ababa, Ethiopia. ; Centre francais des etudes ethiopiennes (CFEE), USR CNRS 3137, French Ministry for Foreign Affairs, PO Box 5554, Addis Ababa, Ethiopia. ; Research Institute of Natural Sciences, Okayama University of Science, Okayama 700-0005, Japan. ; Research Center for Inland Seas, Kobe University, Kobe 657-8501, Japan. ; Hiruzen Institute for Geology and Chronology, Okayama 703-8252, Japan. ; EES-14/MS D462, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. ; Department of Geology and Environmental Earth Science, Miami University, 133 Culler Hall, Oxford, Ohio 45056, USA. ; Department of Anthropology, University of Illinois, Urbana, Illinois 61801, USA. ; Department of Earth and Environmental Sciences, Kagoshima University, Kagoshima 890-0065, Japan. ; Department of Anatomy, Howard University, Washington DC 20059, USA. ; Institut de Paleoprimatologie, Paleontologie Humaine : Evolution et Paleoenvironnements (IPHEP), UMR CNRS 7262, Universite de Poitiers, 86022 Poitiers, France. ; Museum fur Naturkunde - Leibniz Institute for Evolution and Biodiversity Science, Invalidenstrasse 43, 10115 Berlin, Germany. ; Institute of Natural and Environmental Sciences, University of Hyogo, Sanda 669-1546, Japan. ; The University Museum, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; Rift Valley Research Service, PO Box 5717, Addis Ababa, Ethiopia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863981" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ethiopia ; *Fossils ; Geologic Sediments/chemistry ; *Gorilla gorilla/genetics ; Humans ; Mutation Rate ; *Phylogeny ; *Radiometric Dating ; Time Factors
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  • 40
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pollock, Kevin -- England -- Nature. 2016 Mar 17;531(7594):S64-6. doi: 10.1038/531S64a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26981733" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cities ; *City Planning ; Feedback ; Humans ; *Physics ; Plague/epidemiology ; Rats ; *Urbanization ; Vietnam/epidemiology
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  • 41
    Publication Date: 2016-01-07
    Description: Catalysis in biology is restricted to RNA (ribozymes) and protein enzymes, but synthetic biomolecular catalysts can also be made of DNA (deoxyribozymes) or synthetic genetic polymers. In vitro selection from synthetic random DNA libraries identified DNA catalysts for various chemical reactions beyond RNA backbone cleavage. DNA-catalysed reactions include RNA and DNA ligation in various topologies, hydrolytic cleavage and photorepair of DNA, as well as reactions of peptides and small molecules. In spite of comprehensive biochemical studies of DNA catalysts for two decades, fundamental mechanistic understanding of their function is lacking in the absence of three-dimensional models at atomic resolution. Early attempts to solve the crystal structure of an RNA-cleaving deoxyribozyme resulted in a catalytically irrelevant nucleic acid fold. Here we report the crystal structure of the RNA-ligating deoxyribozyme 9DB1 (ref. 14) at 2.8 A resolution. The structure captures the ligation reaction in the post-catalytic state, revealing a compact folding unit stabilized by numerous tertiary interactions, and an unanticipated organization of the catalytic centre. Structure-guided mutagenesis provided insights into the basis for regioselectivity of the ligation reaction and allowed remarkable manipulation of substrate recognition and reaction rate. Moreover, the structure highlights how the specific properties of deoxyribose are reflected in the backbone conformation of the DNA catalyst, in support of its intricate three-dimensional organization. The structural principles underlying the catalytic ability of DNA elucidate differences and similarities in DNA versus RNA catalysts, which is relevant for comprehending the privileged position of folded RNA in the prebiotic world and in current organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ponce-Salvatierra, Almudena -- Wawrzyniak-Turek, Katarzyna -- Steuerwald, Ulrich -- Hobartner, Claudia -- Pena, Vladimir -- England -- Nature. 2016 Jan 14;529(7585):231-4. doi: 10.1038/nature16471. Epub 2016 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Research Group Nucleic Acid Chemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany. ; Research Group Macromolecular Crystallography, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany. ; Institute for Organic and Biomolecular Chemistry, Georg-August-University Gottingen, Tammannstr. 2, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26735012" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; DNA, Catalytic/chemical synthesis/*chemistry/metabolism ; Deoxyribose/chemistry/metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Nucleotides/chemistry/metabolism ; Polynucleotide Ligases/chemistry/metabolism ; RNA/chemistry/metabolism ; RNA Folding ; Substrate Specificity
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  • 42
    Publication Date: 2016-03-05
    Description: How does an animal know where it is when it stops moving? Hippocampal place cells fire at discrete locations as subjects traverse space, thereby providing an explicit neural code for current location during locomotion. In contrast, during awake immobility, the hippocampus is thought to be dominated by neural firing representing past and possible future experience. The question of whether and how the hippocampus constructs a representation of current location in the absence of locomotion has been unresolved. Here we report that a distinct population of hippocampal neurons, located in the CA2 subregion, signals current location during immobility, and does so in association with a previously unidentified hippocampus-wide network pattern. In addition, signalling of location persists into brief periods of desynchronization prevalent in slow-wave sleep. The hippocampus thus generates a distinct representation of current location during immobility, pointing to mnemonic processing specific to experience occurring in the absence of locomotion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kay, Kenneth -- Sosa, Marielena -- Chung, Jason E -- Karlsson, Mattias P -- Larkin, Margaret C -- Frank, Loren M -- R01 MH090188/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 10;531(7593):185-90. doi: 10.1038/nature17144. Epub 2016 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UCSF Center for Integrative Neuroscience and Department of Physiology, University of California San Francisco, California 94158, USA. ; Howard Hughes Medical Institute, University of California San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934224" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Hippocampus/anatomy & histology/*cytology/*physiology ; Male ; Models, Neurological ; Movement ; Neurons/*physiology ; Orientation/*physiology ; Rats ; Rats, Long-Evans ; Sleep/*physiology ; Space Perception/*physiology ; Spatial Memory/physiology
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  • 43
    Publication Date: 2016-01-21
    Description: RNA polymerase (Pol) II produces messenger RNA during transcription of protein-coding genes in all eukaryotic cells. The Pol II structure is known at high resolution from X-ray crystallography for two yeast species. Structural studies of mammalian Pol II, however, remain limited to low-resolution electron microscopy analysis of human Pol II and its complexes with various proteins. Here we report the 3.4 A resolution cryo-electron microscopy structure of mammalian Pol II in the form of a transcribing complex comprising DNA template and RNA transcript. We use bovine Pol II, which is identical to the human enzyme except for seven amino-acid residues. The obtained atomic model closely resembles its yeast counterpart, but also reveals unknown features. Binding of nucleic acids to the polymerase involves 'induced fit' of the mobile Pol II clamp and active centre region. DNA downstream of the transcription bubble contacts a conserved 'TPSA motif' in the jaw domain of the Pol II subunit RPB5, an interaction that is apparently already established during transcription initiation. Upstream DNA emanates from the active centre cleft at an angle of approximately 105 degrees with respect to downstream DNA. This position of upstream DNA allows for binding of the general transcription elongation factor DSIF (SPT4-SPT5) that we localize over the active centre cleft in a conserved position on the clamp domain of Pol II. Our results define the structure of mammalian Pol II in its functional state, indicate that previous crystallographic analysis of yeast Pol II is relevant for understanding gene transcription in all eukaryotes, and provide a starting point for a mechanistic analysis of human transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernecky, Carrie -- Herzog, Franz -- Baumeister, Wolfgang -- Plitzko, Jurgen M -- Cramer, Patrick -- England -- Nature. 2016 Jan 28;529(7587):551-4. doi: 10.1038/nature16482. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Gottingen, Germany. ; Gene Center Munich, Ludwig-Maximilians-Universitat Munchen, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. ; Max Planck Institute for Biochemistry, Department of Molecular Structural Biology, Am Klopferspitz 18, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26789250" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Motifs ; Animals ; Catalytic Domain ; Cattle ; *Cryoelectron Microscopy ; DNA/genetics/metabolism/ultrastructure ; Humans ; Models, Molecular ; Nucleic Acids/chemistry/metabolism ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; RNA Polymerase II/chemistry/*metabolism/*ultrastructure ; RNA, Messenger/biosynthesis/genetics/ultrastructure ; Saccharomyces cerevisiae/enzymology ; Templates, Genetic ; *Transcription Elongation, Genetic
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  • 44
    Publication Date: 2016-01-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Betsholtz, Christer -- England -- Nature. 2016 Jan 14;529(7585):160-1. doi: 10.1038/nature16866. Epub 2016 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Genetics and Pathology at Uppsala University, and the Department of Medical Biochemistry and Biophysics at the Karolinska Institutet, Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26735011" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Endothelium, Vascular/*growth & development/*metabolism ; Female ; Forkhead Transcription Factors/*metabolism ; Humans ; Male
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  • 45
    Publication Date: 2016-03-17
    Description: Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica', particularly the 'weird wonders' of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCoy, Victoria E -- Saupe, Erin E -- Lamsdell, James C -- Tarhan, Lidya G -- McMahon, Sean -- Lidgard, Scott -- Mayer, Paul -- Whalen, Christopher D -- Soriano, Carmen -- Finney, Lydia -- Vogt, Stefan -- Clark, Elizabeth G -- Anderson, Ross P -- Petermann, Holger -- Locatelli, Emma R -- Briggs, Derek E G -- England -- Nature. 2016 Apr 28;532(7600):496-9. doi: 10.1038/nature16992. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, Yale University, 210 Whitney Avenue, New Haven, Connecticut 06511, USA. ; American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA. ; Field Museum of Natural History, 1400 S. Lake Shore Drive, Chicago, Illinois 60605, USA. ; X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois 60439, USA. ; Yale Peabody Museum of Natural History, 170 Whitney Avenue, New Haven, Connecticut 06511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982721" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Fins/anatomy & histology ; Animals ; Extinction, Biological ; Eye/anatomy & histology ; *Fossils ; Gastrointestinal Tract/anatomy & histology ; Illinois ; Lampreys/classification ; Notochord/anatomy & histology ; *Phylogeny ; Tooth/anatomy & histology ; Vertebrates/anatomy & histology/*classification
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  • 46
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGilvray, Annabel -- England -- Nature. 2016 May 11;533(7602):S65-7. doi: 10.1038/533S65a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27167395" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; Anti-Bacterial Agents/*analysis/*chemistry/pharmacology ; *Crowdsourcing/economics ; Diffusion of Innovation ; Drug Evaluation, Preclinical/economics/*methods ; Drug Industry/economics/methods ; *High-Throughput Screening Assays/economics ; *Information Dissemination ; Intellectual Property ; Microbial Sensitivity Tests
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  • 47
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGilvray, Annabel -- England -- Nature. 2016 Mar 3;531(7592):S4-5. doi: 10.1038/531S4a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934524" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates/pharmacology/therapeutic use ; Aging/blood/drug effects/pathology/*psychology ; Alzheimer Disease/blood/therapy ; Animals ; Anti-Asthmatic Agents/pharmacology/therapeutic use ; Cognition Disorders/pathology/physiopathology/*prevention & control/*therapy ; Estrogens/pharmacology ; Female ; Hippocampus/drug effects/pathology/physiology/physiopathology ; Humans ; Inflammation Mediators/immunology ; Leukotrienes/immunology ; Macaca mulatta ; Male ; Mice ; Neuronal Plasticity/drug effects ; Parkinson Disease/therapy ; Plasma/chemistry/physiology ; Prefrontal Cortex/drug effects/pathology/physiology/physiopathology ; Quinolines/pharmacology/therapeutic use ; Rats ; Rejuvenation/*physiology/*psychology ; Synapses/drug effects/metabolism/pathology
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  • 48
    Publication Date: 2016-04-21
    Description: Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871315/" 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/PMC4871315/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beura, Lalit K -- Hamilton, Sara E -- Bi, Kevin -- Schenkel, Jason M -- Odumade, Oludare A -- Casey, Kerry A -- Thompson, Emily A -- Fraser, Kathryn A -- Rosato, Pamela C -- Filali-Mouhim, Ali -- Sekaly, Rafick P -- Jenkins, Marc K -- Vezys, Vaiva -- Haining, W Nicholas -- Jameson, Stephen C -- Masopust, David -- 1R01AI111671/AI/NIAID NIH HHS/ -- R01 AI075168/AI/NIAID NIH HHS/ -- R01 AI084913/AI/NIAID NIH HHS/ -- R01 AI111671/AI/NIAID NIH HHS/ -- R01 AI116678/AI/NIAID NIH HHS/ -- R01AI075168/AI/NIAID NIH HHS/ -- R01AI084913/AI/NIAID NIH HHS/ -- R01AI116678/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Apr 28;532(7600):512-6. doi: 10.1038/nature17655. Epub 2016 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota 55414, USA. ; Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55414, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Pediatric Hematology and Oncology, Children's Hospital, Boston, Massachusetts 02115, USA. ; Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27096360" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animal Husbandry/*methods ; Animals ; Animals, Laboratory/*immunology ; Animals, Wild/*immunology ; Cell Differentiation ; *Environment ; Environmental Exposure ; Female ; Humans ; Immune System/*immunology ; Immunity/*immunology ; Immunity, Innate/immunology ; Immunologic Memory ; Infant, Newborn ; Male ; Mice ; *Models, Animal ; Phenotype ; Specific Pathogen-Free Organisms ; T-Lymphocytes/cytology/immunology ; Virus Diseases/immunology/virology
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  • 49
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharya, Shaoni -- England -- Nature. 2016 Jan 28;529(7587):452-5. doi: 10.1038/529452a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819027" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration ; Animals ; Conservation of Natural Resources/*methods ; *Cooking ; Crime/legislation & jurisprudence/*prevention & control/*statistics & numerical ; data ; Cyprus ; Extinction, Biological ; Population Density ; *Songbirds/physiology
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  • 50
    Publication Date: 2016-03-05
    Description: Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5(+) intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-delta) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-delta recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-delta-dependent manner. Notably, HFD- and agonist-activated PPAR-delta signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-delta signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-delta activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846772/" 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/PMC4846772/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beyaz, Semir -- Mana, Miyeko D -- Roper, Jatin -- Kedrin, Dmitriy -- Saadatpour, Assieh -- Hong, Sue-Jean -- Bauer-Rowe, Khristian E -- Xifaras, Michael E -- Akkad, Adam -- Arias, Erika -- Pinello, Luca -- Katz, Yarden -- Shinagare, Shweta -- Abu-Remaileh, Monther -- Mihaylova, Maria M -- Lamming, Dudley W -- Dogum, Rizkullah -- Guo, Guoji -- Bell, George W -- Selig, Martin -- Nielsen, G Petur -- Gupta, Nitin -- Ferrone, Cristina R -- Deshpande, Vikram -- Yuan, Guo-Cheng -- Orkin, Stuart H -- Sabatini, David M -- Yilmaz, Omer H -- AI47389/AI/NIAID NIH HHS/ -- DK043351/DK/NIDDK NIH HHS/ -- K08 CA198002/CA/NCI NIH HHS/ -- K99 AG041765/AG/NIA NIH HHS/ -- K99 AG045144/AG/NIA NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- R00 AG041765/AG/NIA NIH HHS/ -- R00 AG045144/AG/NIA NIH HHS/ -- R01 AI047389/AI/NIAID NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R01 CA129105/CA/NCI NIH HHS/ -- R37 AI047389/AI/NIAID NIH HHS/ -- T32DK007191/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 3;531(7592):53-8. doi: 10.1038/nature17173.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, Massachusetts 02139, USA. ; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Division of Gastroenterology and Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA. ; Departments of Pathology, Gastroenterology, and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA. ; Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Department of Biology, MIT, Cambridge, Massachusetts 02142, USA. ; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. ; Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. ; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, Missisippi 39216, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26935695" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Count ; Cell Self Renewal/drug effects ; Cell Transformation, Neoplastic/*drug effects ; Colonic Neoplasms/*pathology ; Diet, High-Fat/*adverse effects ; Female ; Genes, APC ; Humans ; Intestines/*pathology ; Male ; Mice ; Obesity/chemically induced/pathology ; Organoids/drug effects/metabolism/pathology ; PPAR delta/metabolism ; Signal Transduction/drug effects ; Stem Cell Niche/drug effects ; Stem Cells/*drug effects/metabolism/*pathology ; beta Catenin/metabolism
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  • 51
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKinlay, Roger -- England -- Nature. 2016 Mar 31;531(7596):573-5. doi: 10.1038/531573a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Royal Institute of Navigation, and a former head of engineering at Thales UK. He sits on the EPSRC Quantum Technology Strategic Advisory Board.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Facility Design and Construction ; Geographic Information Systems/instrumentation/*utilization ; Hippocampus/anatomy & histology/physiology ; Humans ; Maps as Topic ; Orientation/physiology ; Satellite Communications/utilization ; Smartphone/utilization ; Spatial Learning/*physiology ; Spatial Memory/physiology ; Spatial Navigation/*physiology
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  • 52
    Publication Date: 2016-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2016 May 10;533(7602):156-7. doi: 10.1038/533156a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27172025" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biology/instrumentation/*methods ; Cesium Radioisotopes/*supply & distribution ; Immune System/immunology/radiation effects ; Immunologic Techniques/instrumentation/methods ; Internationality ; *Laboratories ; Mice ; *Research Design ; *Research Personnel ; *Security Measures/trends ; X-Rays
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 53
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biewener, Andrew A -- Wilson, Alan -- England -- Nature. 2016 Apr 28;532(7600):442. doi: 10.1038/532442a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University in Cambridge, Massachusetts, USA, and director of the Concord Field Station, where he collaborated with Neill Alexander. ; Royal Veterinary College in London. Alexander examined Wilson's PhD thesis.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121834" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Dinosaurs/physiology ; Gait/*physiology ; Great Britain ; History, 20th Century ; History, 21st Century ; Movement/physiology ; Zoology/*history
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  • 54
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meharg, Andrew A -- England -- Nature. 2016 Mar 17;531(7594):S60. doi: 10.1038/531S60a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Queen's University Belfast, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26981731" target="_blank"〉PubMed〈/a〉
    Keywords: *Agriculture ; Animals ; Carbon Footprint ; *Cities ; *Environmental Monitoring ; Environmental Pollution ; Insect Vectors ; Water Supply
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  • 55
    Publication Date: 2016-04-21
    Description: Planktonic organisms play crucial roles in oceanic food webs and global biogeochemical cycles. Most of our knowledge about the ecological impact of large zooplankton stems from research on abundant and robust crustaceans, and in particular copepods. A number of the other organisms that comprise planktonic communities are fragile, and therefore hard to sample and quantify, meaning that their abundances and effects on oceanic ecosystems are poorly understood. Here, using data from a worldwide in situ imaging survey of plankton larger than 600 mum, we show that a substantial part of the biomass of this size fraction consists of giant protists belonging to the Rhizaria, a super-group of mostly fragile unicellular marine organisms that includes the taxa Phaeodaria and Radiolaria (for example, orders Collodaria and Acantharia). Globally, we estimate that rhizarians in the top 200 m of world oceans represent a standing stock of 0.089 Pg carbon, equivalent to 5.2% of the total oceanic biota carbon reservoir. In the vast oligotrophic intertropical open oceans, rhizarian biomass is estimated to be equivalent to that of all other mesozooplankton (plankton in the size range 0.2-20 mm). The photosymbiotic association of many rhizarians with microalgae may be an important factor in explaining their distribution. The previously overlooked importance of these giant protists across the widest ecosystem on the planet changes our understanding of marine planktonic ecosystems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biard, Tristan -- Stemmann, Lars -- Picheral, Marc -- Mayot, Nicolas -- Vandromme, Pieter -- Hauss, Helena -- Gorsky, Gabriel -- Guidi, Lionel -- Kiko, Rainer -- Not, Fabrice -- England -- Nature. 2016 Apr 28;532(7600):504-7. doi: 10.1038/nature17652. Epub 2016 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sorbonne Universites, UPMC Universite Paris 06, CNRS, Laboratoire Adaptation et Diversite en Milieu Marin UMR7144, Station Biologique de Roscoff, 29688 Roscoff, France. ; Sorbonne Universites, UPMC Universite Paris 06, CNRS, Laboratoire d'Oceanographie de Villefranche (LOV) UMR7093, Observatoire Oceanologique, 06230 Villefranche-sur-Mer, France. ; GEOMAR Helmholtz Centre for Ocean Research Kiel, Wischhofstrasse 1-3, 24148 Kiel, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27096373" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biomass ; *Biota ; Carbon/metabolism ; Carbon Sequestration ; Earth (Planet) ; Microalgae/metabolism ; *Oceans and Seas ; Photosynthesis ; Rhizaria/classification/*isolation & purification/metabolism ; Seawater/chemistry ; Symbiosis ; Zooplankton/classification/*isolation & purification/metabolism
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  • 56
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Melott, Adrian L -- England -- Nature. 2016 Apr 7;532(7597):40-1. doi: 10.1038/532040a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Astronomy, University of Kansas, Lawrence, Kansas 66045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078562" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Climate Change/history ; *Earth (Planet) ; Extinction, Biological ; Geologic Sediments/chemistry ; History, Ancient ; Humans ; Iron Radioisotopes/*analysis/chemistry ; Stars, Celestial/*chemistry ; Time Factors
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  • 57
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2016 Mar 3;531(7592):20-1. doi: 10.1038/531020a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26935677" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthozoa ; Coral Reefs ; *Data Collection ; Droughts ; *El Nino-Southern Oscillation/adverse effects ; Floods ; Oceans and Seas ; Rain ; *Research/economics ; Seawater/analysis ; Temperature ; *Weather
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  • 58
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2016-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qiu, Jane -- England -- Nature. 2016 Jan 14;529(7585):142-5. doi: 10.1038/529142a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26762440" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry/*economics/legislation & jurisprudence/statistics & numerical ; data/*trends ; Animals ; China ; Climate Change ; Conservation of Natural Resources/methods ; Government Regulation ; *Grassland ; Livestock/physiology ; Policy Making ; Socioeconomic Factors ; Tibet ; Transients and Migrants/*statistics & numerical data ; Water Supply/statistics & numerical data
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  • 59
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Jan 28;529(7587):437-8. doi: 10.1038/529437b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819007" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; China ; Cities ; Congo ; Conservation of Natural Resources/*legislation & jurisprudence ; Ecosystem ; Great Britain ; *Parks, Recreational/legislation & jurisprudence ; Pleasure ; Uganda ; United States ; *Wilderness
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  • 60
    Publication Date: 2016-03-16
    Description: A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals. However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, Matthias -- Arsuaga, Juan-Luis -- de Filippo, Cesare -- Nagel, Sarah -- Aximu-Petri, Ayinuer -- Nickel, Birgit -- Martinez, Ignacio -- Gracia, Ana -- Bermudez de Castro, Jose Maria -- Carbonell, Eudald -- Viola, Bence -- Kelso, Janet -- Prufer, Kay -- Paabo, Svante -- England -- Nature. 2016 Mar 24;531(7595):504-7. doi: 10.1038/nature17405. Epub 2016 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Centro de Investigacion Sobre la Evolucion y Comportamiento Humanos, Universidad Complutense de Madrid-Instituto de Salud Carlos III, 28029 Madrid, Spain. ; Departamento de Paleontologia, Facultad de Ciencias Geologicas, Universidad Complutense de Madrid, 28040 Madrid, Spain. ; Area de Paleontologia, Departamento de Geografia y Geologia, Universidad de Alcala, Alcala de Henares, 28871 Madrid, Spain. ; Centro Nacional de Investigacion sobre la Evolucion Humana, Paseo Sierra de Atapuerca, 09002 Burgos, Spain. ; Institut Catala de Paleoecologia Humana i Evolucio Social, C/Marcel.li Domingo s/n (Edifici W3), Campus Sescelades, 43007 Tarragona, Spain. ; Area de Prehistoria, Departament d'Historia i Historia de l'Art, Universitat Rovira i Virgili, Facultat de Lletres, Avinguda de Catalunya, 35, 43002 Tarragona, Spain. ; Department of Anthropology, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26976447" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; DNA, Mitochondrial/genetics ; Fossils ; Genome, Mitochondrial/genetics ; Hominidae/classification/*genetics ; Male ; Neanderthals/classification/genetics ; *Phylogeny ; Sequence Alignment ; Spain
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  • 61
    Publication Date: 2016-03-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bolkan, Scott -- Gordon, Joshua A -- England -- Nature. 2016 Apr 7;532(7597):45-6. doi: 10.1038/nature17311. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Columbia University, New York, New York 10032, USA. ; Department of Psychiatry, Columbia University.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007842" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Attention Deficit Disorder with Hyperactivity/*physiopathology/*psychology ; Female ; *Gene Deletion ; Humans ; Male ; Membrane Proteins/*deficiency/*genetics ; Thalamic Nuclei/*physiopathology
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  • 62
    Publication Date: 2016-03-17
    Description: The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischaemia. Acute kidney injury (AKI) affects 3% of all hospitalized patients. Here we show that the mitochondrial biogenesis regulator, PGC1alpha, is a pivotal determinant of renal recovery from injury by regulating nicotinamide adenine dinucleotide (NAD) biosynthesis. Following renal ischaemia, Pgc1alpha(-/-) (also known as Ppargc1a(-/-)) mice develop local deficiency of the NAD precursor niacinamide (NAM, also known as nicotinamide), marked fat accumulation, and failure to re-establish normal function. Notably, exogenous NAM improves local NAD levels, fat accumulation, and renal function in post-ischaemic Pgc1alpha(-/-) mice. Inducible tubular transgenic mice (iNephPGC1alpha) recapitulate the effects of NAM supplementation, including more local NAD and less fat accumulation with better renal function after ischaemia. PGC1alpha coordinately upregulates the enzymes that synthesize NAD de novo from amino acids whereas PGC1alpha deficiency or AKI attenuates the de novo pathway. NAM enhances NAD via the enzyme NAMPT and augments production of the fat breakdown product beta-hydroxybutyrate, leading to increased production of prostaglandin PGE2 (ref. 5), a secreted autacoid that maintains renal function. NAM treatment reverses established ischaemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of beta-hydroxybutyrate signalling or prostaglandin production similarly abolishes PGC1alpha-dependent renoprotection. Given the importance of mitochondrial health in ageing and the function of metabolically active organs, the results implicate NAM and NAD as key effectors for achieving PGC1alpha-dependent stress resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tran, Mei T -- Zsengeller, Zsuzsanna K -- Berg, Anders H -- Khankin, Eliyahu V -- Bhasin, Manoj K -- Kim, Wondong -- Clish, Clary B -- Stillman, Isaac E -- Karumanchi, S Ananth -- Rhee, Eugene P -- Parikh, Samir M -- K08-DK090142/DK/NIDDK NIH HHS/ -- K08-DK101560/DK/NIDDK NIH HHS/ -- P30-DK079337/DK/NIDDK NIH HHS/ -- R01 DK095072/DK/NIDDK NIH HHS/ -- R01-DK095072/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 24;531(7595):528-32. doi: 10.1038/nature17184. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Nephrology and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Division of Clinical Chemistry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Bioinformatics and Systems Biology Core, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Nephrology and Endocrine Divisions, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA. ; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982719" target="_blank"〉PubMed〈/a〉
    Keywords: 3-Hydroxybutyric Acid/metabolism ; Acute Kidney Injury/drug therapy/*metabolism ; Adipose Tissue/drug effects/metabolism ; Amino Acids/metabolism ; Animals ; Cytokines/metabolism ; Dinoprostone/biosynthesis/metabolism ; Humans ; Ischemia/drug therapy/metabolism ; Kidney/drug effects/*metabolism/physiology/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; NAD/*biosynthesis ; Niacinamide/deficiency/pharmacology/therapeutic use ; Nicotinamide Phosphoribosyltransferase/metabolism ; Oxidation-Reduction ; Signal Transduction/drug effects ; Stress, Physiological ; Transcription Factors/deficiency/*metabolism
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  • 63
    Publication Date: 2016-02-24
    Description: All Gram-negative bacteria, mitochondria and chloroplasts have outer membrane proteins (OMPs) that perform many fundamental biological processes. The OMPs in Gram-negative bacteria are inserted and folded into the outer membrane by the beta-barrel assembly machinery (BAM). The mechanism involved is poorly understood, owing to the absence of a structure of the entire BAM complex. Here we report two crystal structures of the Escherichia coli BAM complex in two distinct states: an inward-open state and a lateral-open state. Our structures reveal that the five polypeptide transport-associated domains of BamA form a ring architecture with four associated lipoproteins, BamB-BamE, in the periplasm. Our structural, functional studies and molecular dynamics simulations indicate that these subunits rotate with respect to the integral membrane beta-barrel of BamA to induce movement of the beta-strands of the barrel and promote insertion of the nascent OMP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gu, Yinghong -- Li, Huanyu -- Dong, Haohao -- Zeng, Yi -- Zhang, Zhengyu -- Paterson, Neil G -- Stansfeld, Phillip J -- Wang, Zhongshan -- Zhang, Yizheng -- Wang, Wenjian -- Dong, Changjiang -- G1100110/1/Medical Research Council/United Kingdom -- WT106121MA/Wellcome Trust/United Kingdom -- England -- Nature. 2016 Mar 3;531(7592):64-9. doi: 10.1038/nature17199. Epub 2016 Feb 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK. ; Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE, UK. ; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. ; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China. ; Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, Sichuan Key Laboratory of Molecular Biology and Biotechnology, College of Life Sciences, Sichuan University, Chengdu 610064, China. ; Laboratory of Department of Surgery, the First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26901871" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/*metabolism ; Lipoproteins/chemistry/metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Movement ; Multiprotein Complexes/*chemistry/*metabolism ; Periplasm/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Rotation
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  • 64
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉King, Anthony -- England -- Nature. 2016 Mar 3;531(7592):S18-9. doi: 10.1038/531S18a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934522" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/metabolism ; Animals ; Brain/*physiology ; Bullying ; DNA Methylation ; Depression/complications/prevention & control/therapy ; Emotional Adjustment ; Epigenesis, Genetic/genetics ; Female ; Hippocampus/metabolism ; Humans ; Hydrocortisone/metabolism ; Maternal Behavior ; Memory/physiology ; Mice ; Models, Animal ; Oxytocin/metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects/genetics ; Psychological Trauma/complications/genetics/metabolism ; Rats ; *Resilience, Psychological ; Social Isolation/psychology ; Stress, Psychological/complications/genetics/metabolism/therapy
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  • 65
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gupta, Sujata -- England -- Nature. 2016 Mar 3;531(7592):S12-3. doi: 10.1038/531S12a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934519" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Biological Availability ; Brain/*physiology ; Child ; Cognition/*physiology ; Dendrites/physiology ; Dietary Proteins ; Docosahexaenoic Acids/metabolism ; Eicosapentaenoic Acid/metabolism ; Female ; Humans ; Iron/administration & dosage/pharmacology ; *Meat ; Pregnancy ; Primates/physiology ; Vitamin B Complex ; Zinc
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  • 66
    Publication Date: 2016-01-15
    Description: Sulawesi is the largest and oldest island within Wallacea, a vast zone of oceanic islands separating continental Asia from the Pleistocene landmass of Australia and Papua (Sahul). By one million years ago an unknown hominin lineage had colonized Flores immediately to the south, and by about 50 thousand years ago, modern humans (Homo sapiens) had crossed to Sahul. On the basis of position, oceanic currents and biogeographical context, Sulawesi probably played a pivotal part in these dispersals. Uranium-series dating of speleothem deposits associated with rock art in the limestone karst region of Maros in southwest Sulawesi has revealed that humans were living on the island at least 40 thousand years ago (ref. 5). Here we report new excavations at Talepu in the Walanae Basin northeast of Maros, where in situ stone artefacts associated with fossil remains of megafauna (Bubalus sp., Stegodon and Celebochoerus) have been recovered from stratified deposits that accumulated from before 200 thousand years ago until about 100 thousand years ago. Our findings suggest that Sulawesi, like Flores, was host to a long-established population of archaic hominins, the ancestral origins and taxonomic status of which remain elusive.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van den Bergh, Gerrit D -- Li, Bo -- Brumm, Adam -- Grun, Rainer -- Yurnaldi, Dida -- Moore, Mark W -- Kurniawan, Iwan -- Setiawan, Ruly -- Aziz, Fachroel -- Roberts, Richard G -- Suyono -- Storey, Michael -- Setiabudi, Erick -- Morwood, Michael J -- England -- Nature. 2016 Jan 14;529(7585):208-11. doi: 10.1038/nature16448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Archaeological Science, School of Earth &Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; Naturalis Biodiversity Center, 2333 CR Leiden, The Netherlands. ; Research Centre for Human Evolution, Environmental Futures Research Institute, Griffith University, Nathan, Queensland 4111, Australia. ; School of Earth and Environmental Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia. ; Geology Museum Bandung, Geological Agency, Jalan Diponegoro 57, Bandung 40122, Indonesia. ; Archaeology, School of Humanities, University of New England, Armidale, New South Wales 2350, Australia. ; Quadlab, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 13 DK-1350 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26762458" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Fossils ; History, Ancient ; *Hominidae ; Human Migration/history ; Humans ; Indonesia ; Tool Use Behavior
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  • 67
    Publication Date: 2016-03-10
    Description: Many biopolymers, including polysaccharides, must be translocated across at least one membrane to reach their site of biological function. Cellulose is a linear glucose polymer synthesized and secreted by a membrane-integrated cellulose synthase. Here, in crystallo enzymology with the catalytically active bacterial cellulose synthase BcsA-BcsB complex reveals structural snapshots of a complete cellulose biosynthesis cycle, from substrate binding to polymer translocation. Substrate- and product-bound structures of BcsA provide the basis for substrate recognition and demonstrate the stepwise elongation of cellulose. Furthermore, the structural snapshots show that BcsA translocates cellulose via a ratcheting mechanism involving a 'finger helix' that contacts the polymer's terminal glucose. Cooperating with BcsA's gating loop, the finger helix moves 'up' and 'down' in response to substrate binding and polymer elongation, respectively, thereby pushing the elongated polymer into BcsA's transmembrane channel. This mechanism is validated experimentally by tethering BcsA's finger helix, which inhibits polymer translocation but not elongation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843519/" 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/PMC4843519/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morgan, Jacob L W -- McNamara, Joshua T -- Fischer, Michael -- Rich, Jamie -- Chen, Hong-Ming -- Withers, Stephen G -- Zimmer, Jochen -- 1R01GM101001/GM/NIGMS NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 GM101001/GM/NIGMS NIH HHS/ -- S10 RR029205/RR/NCRR NIH HHS/ -- England -- Nature. 2016 Mar 17;531(7594):329-34. doi: 10.1038/nature16966. Epub 2016 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Virginia School of Medicine, Center for Membrane Biology, Molecular Physiology and Biological Physics, 480 Ray C. Hunt Drive, Charlottesville, Virginia 22908, USA. ; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26958837" target="_blank"〉PubMed〈/a〉
    Keywords: Cellulose/*biosynthesis/chemistry/*metabolism ; Crystallography, X-Ray ; Glucose/metabolism ; Glucosyltransferases/*chemistry/*metabolism ; Intracellular Membranes/chemistry/*metabolism ; Models, Molecular ; Movement ; Protein Structure, Secondary ; Proteolipids/chemistry/metabolism ; Rhodobacter sphaeroides/enzymology ; Substrate Specificity
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  • 68
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morishita, Joji -- England -- Nature. 2016 Mar 3;531(7592):35. doi: 10.1038/531035a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Research Institute of Far Seas Fisheries, Shizuoka, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26935687" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Minke Whale ; Research/*legislation & jurisprudence/*standards
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  • 69
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamilton, Garry -- England -- Nature. 2016 Mar 24;531(7595):432-4. doi: 10.1038/531432a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008951" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Food Chain ; Marine Biology/trends ; Population Density ; Predatory Behavior ; Scyphozoa/*physiology
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  • 70
    Publication Date: 2016-04-12
    Description: Asymmetric cell division, the partitioning of cellular components in response to polarizing cues during mitosis, has roles in differentiation and development. It is important for the self-renewal of fertilized zygotes in Caenorhabditis elegans and neuroblasts in Drosophila, and in the development of mammalian nervous and digestive systems. T lymphocytes, upon activation by antigen-presenting cells (APCs), can undergo asymmetric cell division, wherein the daughter cell proximal to the APC is more likely to differentiate into an effector-like T cell and the distal daughter is more likely to differentiate into a memory-like T cell. Upon activation and before cell division, expression of the transcription factor c-Myc drives metabolic reprogramming, necessary for the subsequent proliferative burst. Here we find that during the first division of an activated T cell in mice, c-Myc can sort asymmetrically. Asymmetric distribution of amino acid transporters, amino acid content, and activity of mammalian target of rapamycin complex 1 (mTORC1) is correlated with c-Myc expression, and both amino acids and mTORC1 activity sustain the differences in c-Myc expression in one daughter cell compared to the other. Asymmetric c-Myc levels in daughter T cells affect proliferation, metabolism, and differentiation, and these effects are altered by experimental manipulation of mTORC1 activity or c-Myc expression. Therefore, metabolic signalling pathways cooperate with transcription programs to maintain differential cell fates following asymmetric T-cell division.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851250/" 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/PMC4851250/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Verbist, Katherine C -- Guy, Cliff S -- Milasta, Sandra -- Liedmann, Swantje -- Kaminski, Marcin M -- Wang, Ruoning -- Green, Douglas R -- R01 GM096208/GM/NIGMS NIH HHS/ -- R37 GM052735/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Apr 21;532(7599):389-93. doi: 10.1038/nature17442. Epub 2016 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA. ; Center for Childhood Cancer and Blood Disease, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27064903" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Transport Systems/metabolism ; Amino Acids/metabolism ; Animals ; CD8-Positive T-Lymphocytes/*cytology/*metabolism ; Cell Differentiation/genetics ; *Cell Division ; *Cell Polarity/genetics ; Female ; *Lymphocyte Activation ; Male ; Mice ; Multiprotein Complexes/metabolism ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/metabolism ; Transcription, Genetic
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  • 71
    Publication Date: 2016-01-14
    Description: The myelin sheaths wrapped around axons by oligodendrocytes are crucial for brain function. In ischaemia myelin is damaged in a Ca(2+)-dependent manner, abolishing action potential propagation. This has been attributed to glutamate release activating Ca(2+)-permeable N-methyl-D-aspartate (NMDA) receptors. Surprisingly, we now show that NMDA does not raise the intracellular Ca(2+) concentration ([Ca(2+)]i) in mature oligodendrocytes and that, although ischaemia evokes a glutamate-triggered membrane current, this is generated by a rise of extracellular [K(+)] and decrease of membrane K(+) conductance. Nevertheless, ischaemia raises oligodendrocyte [Ca(2+)]i, [Mg(2+)]i and [H(+)]i, and buffering intracellular pH reduces the [Ca(2+)]i and [Mg(2+)]i increases, showing that these are evoked by the rise of [H(+)]i. The H(+)-gated [Ca(2+)]i elevation is mediated by channels with characteristics of TRPA1, being inhibited by ruthenium red, isopentenyl pyrophosphate, HC-030031, A967079 or TRPA1 knockout. TRPA1 block reduces myelin damage in ischaemia. These data suggest that TRPA1-containing ion channels could be a therapeutic target in white matter ischaemia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733665/" 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/PMC4733665/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamilton, Nicola B -- Kolodziejczyk, Karolina -- Kougioumtzidou, Eleni -- Attwell, David -- Wellcome Trust/United Kingdom -- England -- Nature. 2016 Jan 28;529(7587):523-7. doi: 10.1038/nature16519. Epub 2016 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Physiology &Pharmacology, University College London, Gower St., London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26760212" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Ischemia/*metabolism/*pathology ; Calcium/*metabolism ; Calcium Signaling/drug effects ; Electric Conductivity ; Female ; Hydrogen-Ion Concentration ; Magnesium/metabolism ; Male ; Mice ; Mice, Transgenic ; Multiple Sclerosis/metabolism/pathology ; Myelin Sheath/drug effects/*metabolism/*pathology ; N-Methylaspartate/metabolism/pharmacology ; Oligodendroglia/drug effects/metabolism/pathology ; Potassium/metabolism ; *Protons ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Stroke/metabolism/pathology ; Transient Receptor Potential Channels/antagonists & ; inhibitors/deficiency/genetics/*metabolism ; White Matter/metabolism/pathology
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  • 72
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2016 Jan 28;529(7587):449. doi: 10.1038/529449a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819024" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation ; Animals ; Animals, Laboratory ; Autistic Disorder/*genetics/physiopathology/psychology ; CRISPR-Cas Systems ; China ; DNA Copy Number Variations/genetics ; Deep Brain Stimulation ; *Disease Models, Animal ; Female ; *Genetic Engineering ; Humans ; Japan ; Macaca fascicularis/*genetics/psychology ; Male ; Methyl-CpG-Binding Protein 2/genetics ; Monkey Diseases/*genetics/physiopathology/psychology ; Neuroimaging
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  • 73
    Publication Date: 2016-03-24
    Description: Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin-releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising 〈5% of the olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kondoh, Kunio -- Lu, Zhonghua -- Ye, Xiaolan -- Olson, David P -- Lowell, Bradford B -- Buck, Linda B -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Apr 7;532(7597):103-6. doi: 10.1038/nature17156. Epub 2016 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA. ; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center 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/27001694" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenocorticotropic Hormone/blood ; Animals ; Corticosterone/blood ; Corticotropin-Releasing Hormone/blood/metabolism ; Escape Reaction ; Fear ; Female ; Hippocampus/cytology/physiology ; Hormones/blood/*metabolism ; Instinct ; Male ; Mice ; Neurons/metabolism ; Odors/*analysis ; Olfactory Cortex/*anatomy & histology/cytology/*physiology ; *Olfactory Pathways ; Olfactory Perception/physiology ; *Predatory Behavior ; Smell/*physiology ; *Stress, Psychological ; Telencephalon/anatomy & histology/cytology/physiology
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  • 74
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    Publication Date: 2016-03-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2016 Mar 10;531(7593):160-3. doi: 10.1038/531160a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26961640" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/genetics/physiology ; African Swine Fever/immunology/virology ; Animal Culling/methods ; Animals ; Animals, Wild/genetics ; Bees/genetics/parasitology/physiology ; Breeding ; CRISPR-Cas Systems/*genetics ; Carps/anatomy & histology/genetics ; Cattle/genetics/immunology/physiology ; Chick Embryo/immunology ; Chickens/genetics ; Conservation of Natural Resources/methods ; Culicidae/genetics/parasitology ; Disease Models, Animal ; Disease Vectors ; Egg Hypersensitivity/prevention & control ; Elephants/genetics/physiology ; Extinction, Biological ; Female ; Food, Genetically Modified ; Genetic Engineering/*methods/trends ; Humans ; Infertility, Female/genetics ; Lyme Disease/prevention & control/transmission ; Macaca/genetics ; Malaria/prevention & control/transmission ; Mammoths/genetics/physiology ; Pets/anatomy & histology/genetics ; Rett Syndrome/genetics/physiopathology/psychology ; Salmon/genetics/growth & development ; Schistosomiasis/prevention & control/transmission ; Swine ; Swine, Miniature/anatomy & histology/genetics/immunology/virology
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  • 75
    Publication Date: 2016-01-15
    Description: Nonribosomal peptide synthetases (NRPSs) are very large proteins that produce small peptide molecules with wide-ranging biological activities, including environmentally friendly chemicals and many widely used therapeutics. NRPSs are macromolecular machines, with modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites. In addition to the core domains required to link the substrates, they often include specialized tailoring domains, which introduce chemical modifications and allow the product to access a large expanse of chemical space. It is still unknown how the NRPS tailoring domains are structurally accommodated into megaenzymes or how they have adapted to function in nonribosomal peptide synthesis. Here we present a series of crystal structures of the initiation module of an antibiotic-producing NRPS, linear gramicidin synthetase. This module includes the specialized tailoring formylation domain, and states are captured that represent every major step of the assembly-line synthesis in the initiation module. The transitions between conformations are large in scale, with both the peptidyl carrier protein domain and the adenylation subdomain undergoing huge movements to transport substrate between distal active sites. The structures highlight the great versatility of NRPSs, as small domains repurpose and recycle their limited interfaces to interact with their various binding partners. Understanding tailoring domains is important if NRPSs are to be utilized in the production of novel therapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reimer, Janice M -- Aloise, Martin N -- Harrison, Paul M -- Schmeing, T Martin -- 106615/Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Jan 14;529(7585):239-42. doi: 10.1038/nature16503.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, McGill University, 3649 Promenade Sir-William-Osler, Montreal, Quebec H3G 0B1, Canada. ; Department of Biology, McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec H3A 1B1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26762462" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Isomerases/chemistry/metabolism ; Anti-Bacterial Agents/biosynthesis ; Binding Sites ; *Biocatalysis ; Brevibacillus/*enzymology ; Carbohydrate Metabolism ; Carrier Proteins/chemistry/metabolism ; Catalytic Domain ; Coenzymes/metabolism ; Crystallography, X-Ray ; Gramicidin/*biosynthesis ; Hydroxymethyl and Formyl Transferases/chemistry/metabolism ; Models, Molecular ; Multienzyme Complexes/chemistry/metabolism ; Pantetheine/analogs & derivatives/metabolism ; Peptide Synthases/*chemistry/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; RNA, Transfer/chemistry/metabolism
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  • 76
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Feb 11;530(7589):129-30. doi: 10.1038/530130a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Eradication/economics/*statistics & numerical data/*trends ; Dog Diseases/epidemiology/parasitology ; Dogs ; Dracunculiasis/*epidemiology/*parasitology/prevention & control/transmission ; *Dracunculus Nematode/isolation & purification ; Drinking Water/parasitology/standards ; Female ; Ghana/epidemiology ; Goals ; Malaria/epidemiology/parasitology/prevention & control/transmission ; Male ; Mosquito Control/methods ; Poliomyelitis/epidemiology ; Time Factors
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  • 77
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2016 Apr 21;532(7599):300-2. doi: 10.1038/532300a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nature from Shanghai, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27111614" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry ; Animal Welfare/economics/legislation & jurisprudence/standards ; Animals ; *Animals, Laboratory/genetics ; Biological Evolution ; Biomedical Research/economics/legislation & jurisprudence/*methods/*trends ; CRISPR-Cas Systems/genetics ; Callithrix ; China ; Cooperative Behavior ; Disease Models, Animal ; Genetic Engineering ; *Haplorhini/genetics ; Humans ; International Cooperation ; Japan ; Neurosciences/methods/trends ; Research Personnel/organization & administration
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  • 78
    Publication Date: 2016-04-29
    Description: Umbilical cord blood-derived haematopoietic stem cells (HSCs) are essential for many life-saving regenerative therapies. However, despite their advantages for transplantation, their clinical use is restricted because HSCs in cord blood are found only in small numbers. Small molecules that enhance haematopoietic stem and progenitor cell (HSPC) expansion in culture have been identified, but in many cases their mechanisms of action or the nature of the pathways they impinge on are poorly understood. A greater understanding of the molecular circuitry that underpins the self-renewal of human HSCs will facilitate the development of targeted strategies that expand HSCs for regenerative therapies. Whereas transcription factor networks have been shown to influence the self-renewal and lineage decisions of human HSCs, the post-transcriptional mechanisms that guide HSC fate have not been closely investigated. Here we show that overexpression of the RNA-binding protein Musashi-2 (MSI2) induces multiple pro-self-renewal phenotypes, including a 17-fold increase in short-term repopulating cells and a net 23-fold ex vivo expansion of long-term repopulating HSCs. By performing a global analysis of MSI2-RNA interactions, we show that MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signalling through post-transcriptional downregulation of canonical AHR pathway components in cord blood HSPCs. Our study gives mechanistic insight into RNA networks controlled by RNA-binding proteins that underlie self-renewal and provides evidence that manipulating such networks ex vivo can enhance the regenerative potential of human HSCs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880456/" 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/PMC4880456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rentas, Stefan -- Holzapfel, Nicholas T -- Belew, Muluken S -- Pratt, Gabriel A -- Voisin, Veronique -- Wilhelm, Brian T -- Bader, Gary D -- Yeo, Gene W -- Hope, Kristin J -- HG004659/HG/NHGRI NIH HHS/ -- MOP-126030/Canadian Institutes of Health Research/Canada -- NS075449/NS/NINDS NIH HHS/ -- England -- Nature. 2016 Apr 28;532(7600):508-11. doi: 10.1038/nature17665.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biomedical Sciences, Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario L8S 4K1, Canada. ; Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92037, USA. ; Bioinformatics Graduate Program, University of California, San Diego, La Jolla, California 92037, USA. ; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3C 3J7, Canada. ; Department of Physiology, National University of Singapore and Molecular Engineering Laboratory, A*STAR, Singapore 138632, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121842" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Cell Count ; *Cell Self Renewal/genetics ; Down-Regulation/genetics ; Female ; Fetal Blood/cytology ; Gene Knockdown Techniques ; Hematopoietic Stem Cells/*cytology/*metabolism ; Humans ; Male ; Mice ; Protein Binding ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; *Signal Transduction/genetics
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  • 79
    Publication Date: 2016-03-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2016 Mar 24;531(7595):424-5. doi: 10.1038/nature.2016.19590.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Mapping/trends ; China ; Conservation of Natural Resources/trends ; Environmental Pollution/prevention & control ; Humans ; Neurosciences/trends ; Oceanography/trends ; Science/*trends ; Stem Cell Research
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  • 80
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wald, Chelsea -- England -- Nature. 2016 May 5;533(7601):S47. doi: 10.1038/533S47a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27144610" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Austria ; Entrepreneurship/economics/organization & administration ; Humans ; Inventions/economics ; Inventors/economics/education/psychology ; Research/*economics/*organization & administration ; Research Personnel/economics/education/psychology ; *Technology Transfer ; Uncertainty
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  • 81
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Feb 4;530(7588):5. doi: 10.1038/530005a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842018" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/*virology ; Animals ; Brazil/epidemiology ; Female ; Humans ; Infectious Disease Transmission, Vertical/prevention & control/statistics & ; numerical data ; Microcephaly/epidemiology/etiology/virology ; Mosquito Control/*methods ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology/prevention & control/virology ; Rubella/epidemiology ; Tropical Climate ; Virology/*trends ; Zika Virus/isolation & purification/*pathogenicity ; Zika Virus Infection/*epidemiology/prevention & control/virology
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  • 82
    Publication Date: 2016-04-28
    Description: The primary visual cortex contains a detailed map of the visual scene, which is represented according to multiple stimulus dimensions including spatial location, ocular dominance and stimulus orientation. The maps for spatial location and ocular dominance arise from the spatial arrangement of thalamic afferent axons in the cortex. However, the origins of the other maps remain unclear. Here we show that the cortical maps for orientation, direction and retinal disparity in the cat (Felis catus) are all strongly related to the organization of the map for spatial location of light (ON) and dark (OFF) stimuli, an organization that we show is OFF-dominated, OFF-centric and runs orthogonal to ocular dominance columns. Because this ON-OFF organization originates from the clustering of ON and OFF thalamic afferents in the visual cortex, we conclude that all main features of visual cortical topography, including orientation, direction and retinal disparity, follow a common organizing principle that arranges thalamic axons with similar retinotopy and ON-OFF polarity in neighbouring cortical regions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860131/" 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/PMC4860131/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kremkow, Jens -- Jin, Jianzhong -- Wang, Yushi -- Alonso, Jose M -- EY005253/EY/NEI NIH HHS/ -- R01 EY005253/EY/NEI NIH HHS/ -- R01 EY020679/EY/NEI NIH HHS/ -- England -- Nature. 2016 May 5;533(7601):52-7. doi: 10.1038/nature17936. Epub 2016 Apr 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Center for Vision Research, State University of New York, College of Optometry, 33 West 42nd Street, New York, New York 10036, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120164" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways/radiation effects ; Animals ; Axons/physiology ; *Brain Mapping ; Cats ; Darkness ; Dominance, Ocular/physiology ; Light ; Macaca mulatta ; Male ; Models, Neurological ; Orientation/physiology/radiation effects ; Photic Stimulation ; Retina/physiology/radiation effects ; Space Perception/*physiology/radiation effects ; Thalamus/physiology/radiation effects ; Visual Cortex/*physiology/radiation effects ; Visual Fields/*physiology
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  • 83
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dance, Amber -- England -- Nature. 2016 Mar 3;531(7592):S2-3. doi: 10.1038/531S2a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934523" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Amphetamines/adverse effects/pharmacology ; Animals ; Benzhydryl Compounds/pharmacology ; Biomedical Enhancement/ethics/*methods ; Caffeine/pharmacology ; Child ; Cognition/drug effects ; Dopamine/metabolism ; Healthy Volunteers ; Humans ; Intelligence/*drug effects ; Intelligence Tests ; Methylphenidate/adverse effects/pharmacology ; Neurotransmitter Agents/metabolism ; Nicotine/adverse effects/pharmacology ; Norepinephrine/metabolism ; Off-Label Use ; Performance-Enhancing Substances/adverse effects/*pharmacology ; Prefrontal Cortex/drug effects/physiology ; Rats ; Substance-Related Disorders/etiology ; Video Games/psychology
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  • 84
    Publication Date: 2016-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuratani, Shigeru -- Hirasawa, Tatsuya -- England -- Nature. 2016 Apr 28;532(7600):447-8. doi: 10.1038/nature17885. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Evolutionary Morphology Laboratory, RIKEN, Kobe, Hyogo 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074506" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Eye ; *Fossils ; *Phylogeny ; Vertebrates/*classification
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  • 85
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagata, Shigekazu -- England -- Nature. 2016 May 18;533(7604):474-6. doi: 10.1038/nature18439.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27225115" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspases/*metabolism ; *Cell Differentiation ; Cytochrome c Group/*metabolism ; Drosophila melanogaster/*cytology ; Male ; Spermatozoa/*cytology/*metabolism
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  • 86
    Publication Date: 2016-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nardone, Roland M -- MacLeod, Roderick A F -- Capes-Davis, Amanda -- England -- Nature. 2016 Apr 21;532(7599):313.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27127813" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; DNA Contamination ; Databases, Factual ; *Disease Models, Animal ; Guidelines as Topic ; Heterografts/*standards ; Humans ; National Cancer Institute (U.S.) ; Neoplasms/*pathology ; Quality Control ; Reproducibility of Results ; United States ; Xenograft Model Antitumor Assays/*standards
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  • 87
    Publication Date: 2016-02-09
    Description: The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 A resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins, implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walls, Alexandra C -- Tortorici, M Alejandra -- Bosch, Berend-Jan -- Frenz, Brandon -- Rottier, Peter J M -- DiMaio, Frank -- Rey, Felix A -- Veesler, David -- GM103310/GM/NIGMS NIH HHS/ -- T32GM008268/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Mar 3;531(7592):114-7. doi: 10.1038/nature16988. Epub 2016 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA. ; Institut Pasteur, Unite de Virologie Structurale, 75015 Paris, France. ; CNRS UMR 3569 Virologie, 75015 Paris, France. ; Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26855426" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Cell Line ; Coronavirus Infections/immunology/virology ; *Cryoelectron Microscopy ; Drosophila melanogaster ; Mice ; Models, Molecular ; Molecular Sequence Data ; Murine hepatitis virus/*chemistry/immunology/*ultrastructure ; Protein Multimerization ; Protein Structure, Tertiary ; Spike Glycoprotein, Coronavirus/*chemistry/immunology/*ultrastructure ; Viral Vaccines/chemistry/immunology ; Virus Internalization
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  • 88
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2016 Apr 14;532(7598):155-6. doi: 10.1038/532155a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075072" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/virology ; Angola/epidemiology ; Animals ; Asia/epidemiology ; Child ; Cities/epidemiology ; Disease Outbreaks/statistics & numerical data ; *Fear ; Haplorhini/virology ; Humans ; South America/epidemiology ; Strategic Stockpile/statistics & numerical data ; Vaccination/statistics & numerical data ; World Health Organization ; Yellow Fever/*epidemiology/*transmission/virology ; Yellow Fever Vaccine/administration & dosage/supply & distribution
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  • 89
    Publication Date: 2016-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wan, Zheng -- Zhu, Mo -- Chen, Shun -- Sperling, Daniel -- England -- Nature. 2016 Feb 18;530(7590):275-7. doi: 10.1038/530275a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Transportation Studies, at the University of California, Davis, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conservation of Natural Resources/*legislation & jurisprudence/methods/trends ; Environmental Pollution/*legislation & jurisprudence/*prevention & ; control/statistics & numerical data ; *International Cooperation ; Ships/instrumentation/*legislation & jurisprudence/methods ; Vehicle Emissions/analysis/*legislation & jurisprudence/*prevention & control
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  • 90
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Helen -- England -- Nature. 2016 Feb 18;530(7590):281. doi: 10.1038/530281d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NERC Centre for Ecology and Hydrology, Wallingford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887485" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Diseases/epidemiology/*microbiology ; Animals ; Animals, Wild/*microbiology ; Biodiversity ; Biological Evolution ; Endangered Species/statistics & numerical data ; Host Specificity ; Humans ; Introduced Species/*statistics & numerical data
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  • 91
    Publication Date: 2016-01-28
    Description: ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Dieuleveult, Maud -- Yen, Kuangyu -- Hmitou, Isabelle -- Depaux, Arnaud -- Boussouar, Faycal -- Dargham, Daria Bou -- Jounier, Sylvie -- Humbertclaude, Helene -- Ribierre, Florence -- Baulard, Celine -- Farrell, Nina P -- Park, Bongsoo -- Keime, Celine -- Carriere, Lucie -- Berlivet, Soizick -- Gut, Marta -- Gut, Ivo -- Werner, Michel -- Deleuze, Jean-Francois -- Olaso, Robert -- Aude, Jean-Christophe -- Chantalat, Sophie -- Pugh, B Franklin -- Gerard, Matthieu -- HG004160/HG/NHGRI NIH HHS/ -- R01 HG004160/HG/NHGRI NIH HHS/ -- England -- Nature. 2016 Feb 4;530(7588):113-6. doi: 10.1038/nature16505. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Universite Paris-Sud, Universite Paris-Saclay, 91198 Gif-sur-Yvette, France. ; Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. ; Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; INSERM, U823; Universite Grenoble Alpes; Institut Albert Bonniot Grenoble, 38700 Grenoble, France. ; Centre National de Genotypage, Institut de Genomique, CEA, 91057 Evry, France. ; IGBMC (Institut de Genetique et de Biologie Moleculaire et Cellulaire), INSERM, U964, CNRS, UMR7104, Universite de Strasbourg, 67404 Illkirch, France. ; Centre Nacional D'Analisi Genomica, 08028 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814966" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chromatin Assembly and Disassembly ; DNA Helicases/metabolism ; DNA-Binding Proteins/*metabolism ; *Gene Expression Regulation ; Genome/*genetics ; Histones/metabolism ; Mice ; Micrococcal Nuclease/metabolism ; Mouse Embryonic Stem Cells/cytology/*metabolism ; Nuclear Proteins/metabolism ; Nucleosomes/*genetics/*metabolism ; Promoter Regions, Genetic/genetics ; RNA Polymerase II/metabolism ; Substrate Specificity ; Trans-Activators/metabolism ; Transcription Factors/metabolism ; Transcription Initiation Site
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  • 92
    Publication Date: 2016-03-17
    Description: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847731/" 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/PMC4847731/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Dheeraj S -- Arons, Autumn -- Mitchell, Teryn I -- Pignatelli, Michele -- Ryan, Tomas J -- Tonegawa, Susumu -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 24;531(7595):508-12. doi: 10.1038/nature17172. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982728" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Alzheimer Disease/*pathology/*physiopathology ; Amnesia/pathology/physiopathology ; Amyloid beta-Protein Precursor/genetics ; Animals ; Dendritic Spines/pathology/physiology ; Dentate Gyrus/*cytology/pathology/*physiology/physiopathology ; *Disease Models, Animal ; Early Medical Intervention ; Humans ; Long-Term Potentiation ; Male ; Memory, Episodic ; Memory, Long-Term/*physiology ; Mice ; Mice, Transgenic ; Optogenetics ; Plaque, Amyloid ; Presenilin-1/genetics ; Synapses/metabolism ; Transgenes/genetics ; tau Proteins/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 93
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 May 11;533(7602):145. doi: 10.1038/533145a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27172008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety ; Biomedical Research/*trends ; Breast Feeding/*adverse effects ; Clinical Trials as Topic/ethics/methods ; Female ; Humans ; Infant ; Infant, Newborn ; Milk, Human/*chemistry/*metabolism ; Mothers/psychology ; Pharmaceutical Preparations/*administration & dosage/*metabolism ; Risk Assessment ; Safety ; *Uncertainty ; United States ; United States Food and Drug Administration
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 94
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2016-05-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 May 5;533(7601):8. doi: 10.1038/533008a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27146997" target="_blank"〉PubMed〈/a〉
    Keywords: Adiposity/physiology ; Animals ; Athletes ; Bicycling/physiology ; Brain/anatomy & histology/metabolism ; Dietary Fats/administration & dosage/metabolism ; Energy Metabolism/*physiology ; Heart Rate ; Hominidae/anatomy & histology/metabolism ; Humans ; Male
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  • 95
    Publication Date: 2016-01-21
    Description: Ubiquitination is a central process affecting all facets of cellular signalling and function. A critical step in ubiquitination is the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate or a growing ubiquitin chain, which is mediated by E3 ubiquitin ligases. RING-type E3 ligases typically facilitate the transfer of ubiquitin from the E2 directly to the substrate. The RING-between-RING (RBR) family of RING-type E3 ligases, however, breaks this paradigm by forming a covalent intermediate with ubiquitin similarly to HECT-type E3 ligases. The RBR family includes Parkin and HOIP, the central catalytic factor of the LUBAC (linear ubiquitin chain assembly complex). While structural insights into the RBR E3 ligases Parkin and HHARI in their overall auto-inhibited forms are available, no structures exist of intact fully active RBR E3 ligases or any of their complexes. Thus, the RBR mechanism of action has remained largely unknown. Here we present the first structure, to our knowledge, of the fully active human HOIP RBR in its transfer complex with an E2~ubiquitin conjugate, which elucidates the intricate nature of RBR E3 ligases. The active HOIP RBR adopts a conformation markedly different from that of auto-inhibited RBRs. HOIP RBR binds the E2~ubiquitin conjugate in an elongated fashion, with the E2 and E3 catalytic centres ideally aligned for ubiquitin transfer, which structurally both requires and enables a HECT-like mechanism. In addition, three distinct helix-IBR-fold motifs inherent to RBRs form ubiquitin-binding regions that engage the activated ubiquitin of the E2~ubiquitin conjugate and, surprisingly, an additional regulatory ubiquitin molecule. The features uncovered reveal critical states of the HOIP RBR E3 ligase cycle, and comparison with Parkin and HHARI suggests a general mechanism for RBR E3 ligases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lechtenberg, Bernhard C -- Rajput, Akhil -- Sanishvili, Ruslan -- Dobaczewska, Malgorzata K -- Ware, Carl F -- Mace, Peter D -- Riedl, Stefan J -- P30 CA030199/CA/NCI NIH HHS/ -- P30CA030199/CA/NCI NIH HHS/ -- R01AA017238/AA/NIAAA NIH HHS/ -- England -- Nature. 2016 Jan 28;529(7587):546-50. doi: 10.1038/nature16511. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. ; Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. ; X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA. ; Biochemistry Department, University of Otago, 710 Cumberland Street, Dunedin 9054, New Zealand.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26789245" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Motifs ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Multiprotein Complexes/*chemistry/*metabolism ; *RING Finger Domains ; Ubiquitin/*chemistry/metabolism ; Ubiquitin-Conjugating Enzymes/*chemistry/metabolism ; Ubiquitin-Protein Ligases/*chemistry/*metabolism
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  • 96
    Publication Date: 2016-03-18
    Description: Chronic hepatitis B virus infection is a leading cause of cirrhosis and liver cancer. Hepatitis B virus encodes the regulatory HBx protein whose primary role is to promote transcription of the viral genome, which persists as an extrachromosomal DNA circle in infected cells. HBx accomplishes this task by an unusual mechanism, enhancing transcription only from extrachromosomal DNA templates. Here we show that HBx achieves this by hijacking the cellular DDB1-containing E3 ubiquitin ligase to target the 'structural maintenance of chromosomes' (Smc) complex Smc5/6 for degradation. Blocking this event inhibits the stimulatory effect of HBx both on extrachromosomal reporter genes and on hepatitis B virus transcription. Conversely, silencing the Smc5/6 complex enhances extrachromosomal reporter gene transcription in the absence of HBx, restores replication of an HBx-deficient hepatitis B virus, and rescues wild-type hepatitis B virus in a DDB1-knockdown background. The Smc5/6 complex associates with extrachromosomal reporters and the hepatitis B virus genome, suggesting a direct mechanism of transcriptional inhibition. These results uncover a novel role for the Smc5/6 complex as a restriction factor selectively blocking extrachromosomal DNA transcription. By destroying this complex, HBx relieves the inhibition to allow productive hepatitis B virus gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Decorsiere, Adrien -- Mueller, Henrik -- van Breugel, Pieter C -- Abdul, Fabien -- Gerossier, Laetitia -- Beran, Rudolf K -- Livingston, Christine M -- Niu, Congrong -- Fletcher, Simon P -- Hantz, Olivier -- Strubin, Michel -- England -- Nature. 2016 Mar 17;531(7594):386-9. doi: 10.1038/nature17170.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Medicine, University Medical Centre (C.M.U.), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. ; CRCL, INSERM U1052, CNRS 5286, Universite de Lyon, 151, Cours A Thomas, 69424 Lyon Cedex, France. ; Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, California 94404, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26983541" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/*metabolism ; Cell Line, Tumor ; DNA, Viral/genetics/metabolism ; Genes, Reporter ; Genome, Viral/genetics ; Hepatitis B/virology ; Hepatitis B virus/genetics/*physiology ; Hepatocytes/virology ; *Host Specificity ; Humans ; Liver/metabolism/virology ; Male ; Mice ; Plasmids/genetics/metabolism ; Protein Binding ; Proteolysis ; Trans-Activators/*metabolism ; Transcription, Genetic ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Virus Replication
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  • 97
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Jan 28;529(7587):446-7. doi: 10.1038/529446a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819022" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; *Disease Models, Animal ; Dog Diseases/*genetics ; Dogs/*genetics/*psychology ; Female ; Humans ; Male ; Obsessive-Compulsive Disorder/genetics ; Surveys and Questionnaires
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  • 98
    Publication Date: 2016-03-24
    Description: (beta-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs). They bind to active, phosphorylated GPCRs and thereby shut off 'classical' signalling to G proteins, trigger internalization of GPCRs via interaction with the clathrin machinery and mediate signalling via 'non-classical' pathways. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) beta-arrestin proteins (beta-arrestin1 and beta-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (beta-)arrestins that have recently been solved by X-ray crystallography. Here we investigate both the interaction of beta-arrestin with GPCRs, and the beta-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based beta-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in beta-arrestin2 that occur rapidly after the receptor-beta-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and beta-arrestins. They further indicate that beta-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of beta-arrestins, which permits their active signalling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nuber, Susanne -- Zabel, Ulrike -- Lorenz, Kristina -- Nuber, Andreas -- Milligan, Graeme -- Tobin, Andrew B -- Lohse, Martin J -- Hoffmann, Carsten -- 1 R01 DA038882/DA/NIDA NIH HHS/ -- BB/K019864/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2016 Mar 31;531(7596):661-4. doi: 10.1038/nature17198. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Rudolf Virchow Center, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Comprehensive Heart Failure Center, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. ; MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/chemistry/*metabolism ; Biosensing Techniques ; Cattle ; Cell Line ; Cell Membrane/metabolism ; Cell Survival ; Crystallography, X-Ray ; Fluorescence Resonance Energy Transfer ; Humans ; Kinetics ; Models, Molecular ; Protein Binding ; Protein Conformation ; Receptors, G-Protein-Coupled/chemistry/*metabolism ; Signal Transduction ; Substrate Specificity ; Time Factors
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  • 99
    Publication Date: 2016-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watson, Traci -- England -- Nature. 2016 May 5;533(7602):155. doi: 10.1038/nature.2016.19864.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27172024" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Egypt ; Female ; *Flowers ; History, Ancient ; Humans ; Infrared Rays ; *Mummies/history ; Religion/history ; *Symbolism ; Tattooing/*history
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  • 100
    Publication Date: 2016-03-05
    Description: The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Travis K -- Jordan, Robert -- Lo, Michael K -- Ray, Adrian S -- Mackman, Richard L -- Soloveva, Veronica -- Siegel, Dustin -- Perron, Michel -- Bannister, Roy -- Hui, Hon C -- Larson, Nate -- Strickley, Robert -- Wells, Jay -- Stuthman, Kelly S -- Van Tongeren, Sean A -- Garza, Nicole L -- Donnelly, Ginger -- Shurtleff, Amy C -- Retterer, Cary J -- Gharaibeh, Dima -- Zamani, Rouzbeh -- Kenny, Tara -- Eaton, Brett P -- Grimes, Elizabeth -- Welch, Lisa S -- Gomba, Laura -- Wilhelmsen, Catherine L -- Nichols, Donald K -- Nuss, Jonathan E -- Nagle, Elyse R -- Kugelman, Jeffrey R -- Palacios, Gustavo -- Doerffler, Edward -- Neville, Sean -- Carra, Ernest -- Clarke, Michael O -- Zhang, Lijun -- Lew, Willard -- Ross, Bruce -- Wang, Queenie -- Chun, Kwon -- Wolfe, Lydia -- Babusis, Darius -- Park, Yeojin -- Stray, Kirsten M -- Trancheva, Iva -- Feng, Joy Y -- Barauskas, Ona -- Xu, Yili -- Wong, Pamela -- Braun, Molly R -- Flint, Mike -- McMullan, Laura K -- Chen, Shan-Shan -- Fearns, Rachel -- Swaminathan, Swami -- Mayers, Douglas L -- Spiropoulou, Christina F -- Lee, William A -- Nichol, Stuart T -- Cihlar, Tomas -- Bavari, Sina -- R01 AI113321/AI/NIAID NIH HHS/ -- R01AI113321/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Mar 17;531(7594):381-5. doi: 10.1038/nature17180. Epub 2016 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA. ; United States Army Medical Research Institute of Infectious Diseases, Therapeutic Development Center, Frederick, Maryland 21702, USA. ; Gilead Sciences, Foster City, California 94404, USA. ; Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. ; Boston University School of Medicine, Boston, Massachusetts 02118, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934220" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine/*analogs & derivatives/pharmacokinetics/pharmacology/therapeutic use ; Amino Acid Sequence ; Animals ; Antiviral Agents/pharmacokinetics/pharmacology/*therapeutic use ; Cell Line, Tumor ; Ebolavirus/drug effects ; Female ; HeLa Cells ; Hemorrhagic Fever, Ebola/*drug therapy/prevention & control ; Humans ; Macaca mulatta/*virology ; Male ; Molecular Sequence Data ; Organ Specificity ; Prodrugs/pharmacokinetics/pharmacology/therapeutic use ; Ribonucleotides/pharmacokinetics/pharmacology/*therapeutic use
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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