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  • Humans  (5)
  • *Forests  (1)
  • Nature Publishing Group (NPG)  (6)
  • 1
    Publication Date: 2008-10-25
    Description: Countries must learn how to capitalize on their citizens' cognitive resources if they are to prosper, both economically and socially. Early interventions will be key.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beddington, John -- Cooper, Cary L -- Field, John -- Goswami, Usha -- Huppert, Felicia A -- Jenkins, Rachel -- Jones, Hannah S -- Kirkwood, Tom B L -- Sahakian, Barbara J -- Thomas, Sandy M -- BB/C008200/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400574/Medical Research Council/United Kingdom -- England -- Nature. 2008 Oct 23;455(7216):1057-60. doi: 10.1038/4551057a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Government Office for Science, London.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948946" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged, 80 and over ; Aging/psychology ; Child ; Child Development ; Cost of Illness ; Depression/economics ; Great Britain ; Humans ; Learning Disorders/economics ; Mental Disorders/*economics/prevention & control/psychology ; *Mental Health ; Risk Factors ; Work/psychology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-11-01
    Description: A full description of the human proteome relies on the challenging task of detecting mature and changing forms of protein molecules in the body. Large-scale proteome analysis has routinely involved digesting intact proteins followed by inferred protein identification using mass spectrometry. This 'bottom-up' process affords a high number of identifications (not always unique to a single gene). However, complications arise from incomplete or ambiguous characterization of alternative splice forms, diverse modifications (for example, acetylation and methylation) and endogenous protein cleavages, especially when combinations of these create complex patterns of intact protein isoforms and species. 'Top-down' interrogation of whole proteins can overcome these problems for individual proteins, but has not been achieved on a proteome scale owing to the lack of intact protein fractionation methods that are well integrated with tandem mass spectrometry. Here we show, using a new four-dimensional separation system, identification of 1,043 gene products from human cells that are dispersed into more than 3,000 protein species created by post-translational modification (PTM), RNA splicing and proteolysis. The overall system produced greater than 20-fold increases in both separation power and proteome coverage, enabling the identification of proteins up to 105 kDa and those with up to 11 transmembrane helices. Many previously undetected isoforms of endogenous human proteins were mapped, including changes in multiply modified species in response to accelerated cellular ageing (senescence) induced by DNA damage. Integrated with the latest version of the Swiss-Prot database, the data provide precise correlations to individual genes and proof-of-concept for large-scale interrogation of whole protein molecules. The technology promises to improve the link between proteomics data and complex phenotypes in basic biology and disease research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237778/" 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/PMC3237778/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tran, John C -- Zamdborg, Leonid -- Ahlf, Dorothy R -- Lee, Ji Eun -- Catherman, Adam D -- Durbin, Kenneth R -- Tipton, Jeremiah D -- Vellaichamy, Adaikkalam -- Kellie, John F -- Li, Mingxi -- Wu, Cong -- Sweet, Steve M M -- Early, Bryan P -- Siuti, Nertila -- LeDuc, Richard D -- Compton, Philip D -- Thomas, Paul M -- Kelleher, Neil L -- F30 DA026672/DA/NIDA NIH HHS/ -- F30 DA026672-03/DA/NIDA NIH HHS/ -- GM 067193-08/GM/NIGMS NIH HHS/ -- P30 DA018310/DA/NIDA NIH HHS/ -- P30 DA018310-06/DA/NIDA NIH HHS/ -- P30DA 018310/DA/NIDA NIH HHS/ -- R01 GM067193/GM/NIGMS NIH HHS/ -- R01 GM067193-08/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Oct 30;480(7376):254-8. doi: 10.1038/nature10575.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, and the Institute for Genomic Biology, 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/22037311" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Cell Aging/genetics ; Cell Line ; DNA Damage ; Databases, Protein ; HMGA1a Protein/analysis ; HMGA1b Protein/analysis ; HeLa Cells ; Humans ; Phenotype ; Protein Isoforms/*analysis/*chemistry ; Protein Processing, Post-Translational ; Proteolysis ; Proteome/*analysis/*chemistry ; Proteomics/instrumentation/*methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2011-10-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Black, Richard -- Bennett, Stephen R G -- Thomas, Sandy M -- Beddington, John R -- England -- Nature. 2011 Oct 20;478(7370):447-9. doi: 10.1038/478477a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Global Studies, University of Sussex, Falmer, Brighton BN1 9SJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22012304" target="_blank"〉PubMed〈/a〉
    Keywords: *Acclimatization ; *Climate Change ; Disasters ; Emigration and Immigration/*statistics & numerical data/*trends ; *Environment ; Floods ; Humans ; Policy Making ; Politics ; Poverty ; Risk ; Socioeconomic Factors ; Urban Population
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 4
    Publication Date: 2011-06-17
    Description: Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572410/" 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/PMC3572410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Skarnes, William C -- Rosen, Barry -- West, Anthony P -- Koutsourakis, Manousos -- Bushell, Wendy -- Iyer, Vivek -- Mujica, Alejandro O -- Thomas, Mark -- Harrow, Jennifer -- Cox, Tony -- Jackson, David -- Severin, Jessica -- Biggs, Patrick -- Fu, Jun -- Nefedov, Michael -- de Jong, Pieter J -- Stewart, A Francis -- Bradley, Allan -- 077188/Wellcome Trust/United Kingdom -- U01-HG004080/HG/NHGRI NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2011 Jun 15;474(7351):337-42. doi: 10.1038/nature10163.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. skarnes@sanger.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21677750" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Computational Biology ; Embryonic Stem Cells/cytology/metabolism ; *Gene Deletion ; Gene Knockout Techniques/*methods ; Genes/*genetics ; Genes, Lethal/genetics ; Genetic Association Studies/*methods ; Genetic Vectors/genetics ; Genome/*genetics ; Genomics ; Genotype ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout/*genetics ; Mutagenesis, Insertional/methods ; Phenotype ; Polymerase Chain Reaction ; Rats
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-08-01
    Description: In BRAF(V600)-mutant tumours, most mechanisms of resistance to drugs that target the BRAF and/or MEK kinases rely on reactivation of the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway, on activation of the alternative, PI(3)K-AKT-mTOR, pathway (which is ERK independent) or on modulation of the caspase-dependent apoptotic cascade. All three pathways converge to regulate the formation of the eIF4F eukaryotic translation initiation complex, which binds to the 7-methylguanylate cap (m(7)G) at the 5' end of messenger RNA, thereby modulating the translation of specific mRNAs. Here we show that the persistent formation of the eIF4F complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, is associated with resistance to anti-BRAF, anti-MEK and anti-BRAF plus anti-MEK drug combinations in BRAF(V600)-mutant melanoma, colon and thyroid cancer cell lines. Resistance to treatment and maintenance of eIF4F complex formation is associated with one of three mechanisms: reactivation of MAPK signalling, persistent ERK-independent phosphorylation of the inhibitory eIF4E-binding protein 4EBP1 or increased pro-apoptotic BCL-2-modifying factor (BMF)-dependent degradation of eIF4G. The development of an in situ method to detect the eIF4E-eIF4G interactions shows that eIF4F complex formation is decreased in tumours that respond to anti-BRAF therapy and increased in resistant metastases compared to tumours before treatment. Strikingly, inhibiting the eIF4F complex, either by blocking the eIF4E-eIF4G interaction or by targeting eIF4A, synergizes with inhibiting BRAF(V600) to kill the cancer cells. eIF4F not only appears to be an indicator of both innate and acquired resistance but also is a promising therapeutic target. Combinations of drugs targeting BRAF (and/or MEK) and eIF4F may overcome most of the resistance mechanisms arising in BRAF(V600)-mutant cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boussemart, Lise -- Malka-Mahieu, Helene -- Girault, Isabelle -- Allard, Delphine -- Hemmingsson, Oskar -- Tomasic, Gorana -- Thomas, Marina -- Basmadjian, Christine -- Ribeiro, Nigel -- Thuaud, Frederic -- Mateus, Christina -- Routier, Emilie -- Kamsu-Kom, Nyam -- Agoussi, Sandrine -- Eggermont, Alexander M -- Desaubry, Laurent -- Robert, Caroline -- Vagner, Stephan -- England -- Nature. 2014 Sep 4;513(7516):105-9. doi: 10.1038/nature13572. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Inserm UMR981, Villejuif F-94805, France [2] Universite Paris-Sud XI, Kremlin-Bicetre F-94276, France [3] Gustave Roussy, Dermato-Oncology, Villejuif F-94805, France [4]. ; 1] Inserm UMR981, Villejuif F-94805, France [2] Universite Paris-Sud XI, Kremlin-Bicetre F-94276, France [3]. ; 1] Inserm UMR981, Villejuif F-94805, France [2]. ; Inserm UMR981, Villejuif F-94805, France. ; 1] Inserm UMR981, Villejuif F-94805, France [2] Department of Surgical and Perioperative Sciences, Umea University, Umea SE-90187, Sweden (O.H.); CNRS UMR3348, Institut Curie, Orsay F-91405, France (S.V.). ; Gustave Roussy, Pathology Department, Villejuif F-94805, France. ; Gustave Roussy, Dermato-Oncology, Villejuif F-94805, France. ; CNRS-Strasbourg University, UMR7200, Illkirch F-67400, France. ; 1] Universite Paris-Sud XI, Kremlin-Bicetre F-94276, France [2] Gustave Roussy, Dermato-Oncology, Villejuif F-94805, France. ; 1] Inserm UMR981, Villejuif F-94805, France [2] Universite Paris-Sud XI, Kremlin-Bicetre F-94276, France [3] Gustave Roussy, Dermato-Oncology, Villejuif F-94805, France. ; 1] Inserm UMR981, Villejuif F-94805, France [2] Universite Paris-Sud XI, Kremlin-Bicetre F-94276, France [3] Gustave Roussy, Dermato-Oncology, Villejuif F-94805, France [4] Department of Surgical and Perioperative Sciences, Umea University, Umea SE-90187, Sweden (O.H.); CNRS UMR3348, Institut Curie, Orsay F-91405, France (S.V.).〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology ; Cell Death/drug effects ; Cell Line, Tumor ; Colonic Neoplasms/pathology ; *Drug Resistance, Neoplasm/drug effects ; Drug Synergism ; Eukaryotic Initiation Factor-4A/antagonists & inhibitors/metabolism ; Eukaryotic Initiation Factor-4E/metabolism ; Eukaryotic Initiation Factor-4F/*antagonists & inhibitors/chemistry/*metabolism ; Eukaryotic Initiation Factor-4G/metabolism ; Female ; Humans ; Indoles/pharmacology ; MAP Kinase Signaling System/drug effects ; Melanoma/*drug therapy/genetics/pathology ; Mice ; Mitogen-Activated Protein Kinase Kinases/*antagonists & inhibitors ; Phosphorylation/drug effects ; Protein Binding/drug effects ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/genetics ; Signal Transduction/drug effects ; Sulfonamides/pharmacology ; Thyroid Neoplasms/pathology ; Triterpenes/pharmacology ; Xenograft Model Antitumor Assays
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  • 6
    Publication Date: 2015-09-04
    Description: The global extent and distribution of forest trees is central to our understanding of the terrestrial biosphere. We provide the first spatially continuous map of forest tree density at a global scale. This map reveals that the global number of trees is approximately 3.04 trillion, an order of magnitude higher than the previous estimate. Of these trees, approximately 1.39 trillion exist in tropical and subtropical forests, with 0.74 trillion in boreal regions and 0.61 trillion in temperate regions. Biome-level trends in tree density demonstrate the importance of climate and topography in controlling local tree densities at finer scales, as well as the overwhelming effect of humans across most of the world. Based on our projected tree densities, we estimate that over 15 billion trees are cut down each year, and the global number of trees has fallen by approximately 46% since the start of human civilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crowther, T W -- Glick, H B -- Covey, K R -- Bettigole, C -- Maynard, D S -- Thomas, S M -- Smith, J R -- Hintler, G -- Duguid, M C -- Amatulli, G -- Tuanmu, M-N -- Jetz, W -- Salas, C -- Stam, C -- Piotto, D -- Tavani, R -- Green, S -- Bruce, G -- Williams, S J -- Wiser, S K -- Huber, M O -- Hengeveld, G M -- Nabuurs, G-J -- Tikhonova, E -- Borchardt, P -- Li, C-F -- Powrie, L W -- Fischer, M -- Hemp, A -- Homeier, J -- Cho, P -- Vibrans, A C -- Umunay, P M -- Piao, S L -- Rowe, C W -- Ashton, M S -- Crane, P R -- Bradford, M A -- England -- Nature. 2015 Sep 10;525(7568):201-5. doi: 10.1038/nature14967. Epub 2015 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yale School of Forestry and Environmental Studies, Yale University, New Haven, Connecticut 06511, USA. ; Department of Environmental Sciences, University of Helsinki, Helsinki 00014, Finland. ; Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA. ; Department of Life Sciences, Silwood Park, Imperial College, London SL5 7PY, UK. ; Departamento de Ciencias Forestales, Universidad de La Frontera, Temuco 4811230, Chile. ; RedCastle Resources, Salt Lake City, Utah 84103, USA. ; Universidade Federal do Sul da Bahia, Ferradas, Itabuna 45613-204, Brazil. ; Forestry Department, Food and Agriculture Organization of the United Nations, Rome 00153, Italy. ; Operation Wallacea, Spilbsy, Lincolnshire PE23 4EX, UK. ; Durrell Institute of Conservation and Ecology (DICE), School of Anthropology and Conservation (SAC), University of Kent, Canterbury ME4 4AG, UK. ; Molecular Imaging Research Center MIRCen/CEA, CNRS URA 2210, 91401 Orsay Cedex, France. ; Landcare Research, Lincoln 7640, New Zealand. ; WSL, Swiss Federal Institute for Forest, Snow and Landscape Research, 8903 Birmensdorf, Switzerland. ; Environmental Science Group, Wageningen University &Research Centre, 6708 PB, The Netherlands. ; Center for Forest Ecology and Productivity RAS, Moscow 117997, Russia. ; CEN Center for Earth System Research and Sustainability, Institute of Geography, University of Hamburg, Hamburg 20146, Germany. ; Department of Botany and Zoology, Masaryk University, Brno 61137, Czech Republic. ; South African National Biodiversity Institute, Kirstenbosch Research Centre, Claremont 7735, South Africa. ; Institute of Plant Sciences, Botanical Garden, and Oeschger Centre for Climate Change Research, University of Bern, 3013 Bern, Switzerland. ; Senckenberg Gesellschaft fur Naturforschung, Biodiversity and Climate Research Centre (BIK-F), 60325 Frankfurt, Germany. ; Department of Plant Systematics, University of Bayreuth, 95447 Bayreuth, Germany. ; Albrecht von Haller Institute of Plant Sciences, Georg August University of Gottingen, 37073 Gottingen, Germany. ; Tropical Ecology Research Group, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK. ; Universidade Regional de Blumenau, Departamento de Engenharia Florestal, Blumenau/Santa Catarina 89030-000, Brazil. ; Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26331545" target="_blank"〉PubMed〈/a〉
    Keywords: Ecology/statistics & numerical data ; Ecosystem ; Forestry/statistics & numerical data ; *Forests ; *Geographic Mapping ; Population Density ; Reproducibility of Results ; Trees/*growth & development
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