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  • Models, Biological  (118)
  • Nature Publishing Group (NPG)  (118)
  • Institute of Physics
  • PANGAEA
  • 2020-2024
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  • 2010-2014  (88)
  • 2005-2009  (30)
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  • 2010-2014  (88)
  • 2005-2009  (30)
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  • 1
    Publikationsdatum: 2010-07-20
    Beschreibung: Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912966/" 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/PMC2912966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Robert A -- Wright, Karen D -- Poppleton, Helen -- Mohankumar, Kumarasamypet M -- Finkelstein, David -- Pounds, Stanley B -- Rand, Vikki -- Leary, Sarah E S -- White, Elsie -- Eden, Christopher -- Hogg, Twala -- Northcott, Paul -- Mack, Stephen -- Neale, Geoffrey -- Wang, Yong-Dong -- Coyle, Beth -- Atkinson, Jennifer -- DeWire, Mariko -- Kranenburg, Tanya A -- Gillespie, Yancey -- Allen, Jeffrey C -- Merchant, Thomas -- Boop, Fredrick A -- Sanford, Robert A -- Gajjar, Amar -- Ellison, David W -- Taylor, Michael D -- Grundy, Richard G -- Gilbertson, Richard J -- P01 CA096832/CA/NCI NIH HHS/ -- P01 CA096832-06A18120/CA/NCI NIH HHS/ -- P01 CA096832-078120/CA/NCI NIH HHS/ -- P01CA96832/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30 CA021765-319030/CA/NCI NIH HHS/ -- P30CA021765/CA/NCI NIH HHS/ -- R01 CA129541/CA/NCI NIH HHS/ -- R01 CA129541-01/CA/NCI NIH HHS/ -- R01 CA129541-02/CA/NCI NIH HHS/ -- R01 CA129541-03/CA/NCI NIH HHS/ -- R01 CA129541-04/CA/NCI NIH HHS/ -- R01CA129541/CA/NCI NIH HHS/ -- T32 CA070089/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jul 29;466(7306):632-6. doi: 10.1038/nature09173. Epub 2010 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20639864" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Cell Compartmentation ; Central Nervous System/cytology/growth & development ; Central Nervous System Neoplasms/classification/genetics/pathology ; *Disease Models, Animal ; Ependymoma/classification/*genetics/*pathology ; Gene Deletion ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, p16 ; *Genomics ; Humans ; Mice ; Models, Biological ; Mutation/*genetics ; Polymorphism, Single Nucleotide/genetics ; Receptor, EphB2/genetics/metabolism ; Species Specificity ; Stem Cells/cytology/metabolism ; Synapses/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2013-07-05
    Beschreibung: We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087036/" 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/PMC4087036/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galagan, James E -- Minch, Kyle -- Peterson, Matthew -- Lyubetskaya, Anna -- Azizi, Elham -- Sweet, Linsday -- Gomes, Antonio -- Rustad, Tige -- Dolganov, Gregory -- Glotova, Irina -- Abeel, Thomas -- Mahwinney, Chris -- Kennedy, Adam D -- Allard, Rene -- Brabant, William -- Krueger, Andrew -- Jaini, Suma -- Honda, Brent -- Yu, Wen-Han -- Hickey, Mark J -- Zucker, Jeremy -- Garay, Christopher -- Weiner, Brian -- Sisk, Peter -- Stolte, Christian -- Winkler, Jessica K -- Van de Peer, Yves -- Iazzetti, Paul -- Camacho, Diogo -- Dreyfuss, Jonathan -- Liu, Yang -- Dorhoi, Anca -- Mollenkopf, Hans-Joachim -- Drogaris, Paul -- Lamontagne, Julie -- Zhou, Yiyong -- Piquenot, Julie -- Park, Sang Tae -- Raman, Sahadevan -- Kaufmann, Stefan H E -- Mohney, Robert P -- Chelsky, Daniel -- Moody, D Branch -- Sherman, David R -- Schoolnik, Gary K -- HHSN272200800059C/AI/NIAID NIH HHS/ -- HHSN272200800059C/PHS HHS/ -- R01 AI 071155/AI/NIAID NIH HHS/ -- R01 AI071155/AI/NIAID NIH HHS/ -- U19 AI 076217/AI/NIAID NIH HHS/ -- U19 AI076217/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):178-83. doi: 10.1038/nature12337. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA. jgalag@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823726" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adaptation, Physiological ; Anoxia/*genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Binding Sites ; Chromatin Immunoprecipitation ; Gene Expression Profiling ; *Gene Regulatory Networks/genetics ; Genomics ; Lipid Metabolism/genetics ; Metabolic Networks and Pathways/*genetics ; Models, Biological ; Mycobacterium tuberculosis/drug effects/*genetics/*metabolism/physiology ; Oxygen/pharmacology ; Proteolysis ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Sequence Analysis, DNA ; Transcription Factors/genetics/metabolism ; Tuberculosis/metabolism/microbiology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2013-11-29
    Beschreibung: Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940870/" 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/PMC3940870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNamara, Case W -- Lee, Marcus C S -- Lim, Chek Shik -- Lim, Siau Hoi -- Roland, Jason -- Nagle, Advait -- Simon, Oliver -- Yeung, Bryan K S -- Chatterjee, Arnab K -- McCormack, Susan L -- Manary, Micah J -- Zeeman, Anne-Marie -- Dechering, Koen J -- Kumar, T R Santha -- Henrich, Philipp P -- Gagaring, Kerstin -- Ibanez, Maureen -- Kato, Nobutaka -- Kuhen, Kelli L -- Fischli, Christoph -- Rottmann, Matthias -- Plouffe, David M -- Bursulaya, Badry -- Meister, Stephan -- Rameh, Lucia -- Trappe, Joerg -- Haasen, Dorothea -- Timmerman, Martijn -- Sauerwein, Robert W -- Suwanarusk, Rossarin -- Russell, Bruce -- Renia, Laurent -- Nosten, Francois -- Tully, David C -- Kocken, Clemens H M -- Glynne, Richard J -- Bodenreider, Christophe -- Fidock, David A -- Diagana, Thierry T -- Winzeler, Elizabeth A -- 078285/Wellcome Trust/United Kingdom -- 089275/Wellcome Trust/United Kingdom -- 090534/Wellcome Trust/United Kingdom -- 096157/Wellcome Trust/United Kingdom -- R01 AI079709/AI/NIAID NIH HHS/ -- R01 AI085584/AI/NIAID NIH HHS/ -- R01 AI090141/AI/NIAID NIH HHS/ -- R01 AI103058/AI/NIAID NIH HHS/ -- R01079709/PHS HHS/ -- R01085584/PHS HHS/ -- R01AI090141/AI/NIAID NIH HHS/ -- WT078285/Wellcome Trust/United Kingdom -- WT096157/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Dec 12;504(7479):248-53. doi: 10.1038/nature12782. Epub 2013 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2]. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2]. ; Novartis Institutes for Tropical Disease, 138670 Singapore. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Parasitology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands. ; TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands. ; Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA. ; Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland. ; 1] Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland [2] University of Basel, CH-4003 Basel, Switzerland. ; Department of Medicine, School of Medicine, Boston University, Boston, Massachusetts 02118, USA. ; Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. ; 1] TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands [2] Department of Medical Microbiology, Radboud University, Nijmegen Medical CentrePO Box 9101, 6500 HB Nijmegen, The Netherlands. ; Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore. ; 1] Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore [2] Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 117545 Singapore. ; 1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK [2] Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2] Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA. ; 1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2] Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24284631" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 1-Phosphatidylinositol 4-Kinase/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cytokinesis/drug effects ; Drug Resistance/drug effects/genetics ; Fatty Acids/metabolism ; Female ; Hepatocytes/parasitology ; Humans ; Imidazoles/metabolism/pharmacology ; Life Cycle Stages/drug effects ; Macaca mulatta ; Malaria/*drug therapy/*parasitology ; Male ; Models, Biological ; Models, Molecular ; Phosphatidylinositol Phosphates/metabolism ; Plasmodium/classification/*drug effects/*enzymology/growth & development ; Pyrazoles/metabolism/pharmacology ; Quinoxalines/metabolism/pharmacology ; Reproducibility of Results ; Schizonts/cytology/drug effects ; rab GTP-Binding Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Publikationsdatum: 2010-08-06
    Beschreibung: Sponges are an ancient group of animals that diverged from other metazoans over 600 million years ago. Here we present the draft genome sequence of Amphimedon queenslandica, a demosponge from the Great Barrier Reef, and show that it is remarkably similar to other animal genomes in content, structure and organization. Comparative analysis enabled by the sequencing of the sponge genome reveals genomic events linked to the origin and early evolution of animals, including the appearance, expansion and diversification of pan-metazoan transcription factor, signalling pathway and structural genes. This diverse 'toolkit' of genes correlates with critical aspects of all metazoan body plans, and comprises cell cycle control and growth, development, somatic- and germ-cell specification, cell adhesion, innate immunity and allorecognition. Notably, many of the genes associated with the emergence of animals are also implicated in cancer, which arises from defects in basic processes associated with metazoan multicellularity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130542/" 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/PMC3130542/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Srivastava, Mansi -- Simakov, Oleg -- Chapman, Jarrod -- Fahey, Bryony -- Gauthier, Marie E A -- Mitros, Therese -- Richards, Gemma S -- Conaco, Cecilia -- Dacre, Michael -- Hellsten, Uffe -- Larroux, Claire -- Putnam, Nicholas H -- Stanke, Mario -- Adamska, Maja -- Darling, Aaron -- Degnan, Sandie M -- Oakley, Todd H -- Plachetzki, David C -- Zhai, Yufeng -- Adamski, Marcin -- Calcino, Andrew -- Cummins, Scott F -- Goodstein, David M -- Harris, Christina -- Jackson, Daniel J -- Leys, Sally P -- Shu, Shengqiang -- Woodcroft, Ben J -- Vervoort, Michel -- Kosik, Kenneth S -- Manning, Gerard -- Degnan, Bernard M -- Rokhsar, Daniel S -- R01 HG004164/HG/NHGRI NIH HHS/ -- R01 HG004164-03/HG/NHGRI NIH HHS/ -- R01 HG004164-04/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):720-6. doi: 10.1038/nature09201.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Integrative Genomics and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. mansi@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686567" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Apoptosis/genetics ; Cell Adhesion/genetics ; Cell Cycle/genetics ; Cell Polarity/genetics ; Cell Proliferation ; *Evolution, Molecular ; Genes/genetics ; Genome/*genetics ; Genomics ; Humans ; Immunity, Innate/genetics ; Models, Biological ; Neurons/metabolism ; Phosphotransferases/chemistry/genetics ; Phylogeny ; Porifera/anatomy & histology/cytology/*genetics/immunology ; Sequence Analysis, DNA ; Signal Transduction/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 2011-12-23
    Beschreibung: Restriction factors, such as the retroviral complementary DNA deaminase APOBEC3G, are cellular proteins that dominantly block virus replication. The AIDS virus, human immunodeficiency virus type 1 (HIV-1), produces the accessory factor Vif, which counteracts the host's antiviral defence by hijacking a ubiquitin ligase complex, containing CUL5, ELOC, ELOB and a RING-box protein, and targeting APOBEC3G for degradation. Here we reveal, using an affinity tag/purification mass spectrometry approach, that Vif additionally recruits the transcription cofactor CBF-beta to this ubiquitin ligase complex. CBF-beta, which normally functions in concert with RUNX DNA binding proteins, allows the reconstitution of a recombinant six-protein assembly that elicits specific polyubiquitination activity with APOBEC3G, but not the related deaminase APOBEC3A. Using RNA knockdown and genetic complementation studies, we also demonstrate that CBF-beta is required for Vif-mediated degradation of APOBEC3G and therefore for preserving HIV-1 infectivity. Finally, simian immunodeficiency virus (SIV) Vif also binds to and requires CBF-beta to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-beta-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310910/" 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/PMC3310910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jager, Stefanie -- Kim, Dong Young -- Hultquist, Judd F -- Shindo, Keisuke -- LaRue, Rebecca S -- Kwon, Eunju -- Li, Ming -- Anderson, Brett D -- Yen, Linda -- Stanley, David -- Mahon, Cathal -- Kane, Joshua -- Franks-Skiba, Kathy -- Cimermancic, Peter -- Burlingame, Alma -- Sali, Andrej -- Craik, Charles S -- Harris, Reuben S -- Gross, John D -- Krogan, Nevan J -- P01 AI090935/AI/NIAID NIH HHS/ -- P01 GM091743/GM/NIGMS NIH HHS/ -- P41 GM103481/GM/NIGMS NIH HHS/ -- P41RR001614/RR/NCRR NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- P50 GM082250/GM/NIGMS NIH HHS/ -- P50 GM082250-05/GM/NIGMS NIH HHS/ -- P50GM081879/GM/NIGMS NIH HHS/ -- R01 AI064046/AI/NIAID NIH HHS/ -- T32 AI083196/AI/NIAID NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- England -- Nature. 2011 Dec 21;481(7381):371-5. doi: 10.1038/nature10693.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22190037" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Affinity Labels ; Animals ; Core Binding Factor beta Subunit/*metabolism ; Cullin Proteins/metabolism ; Cytidine Deaminase/*metabolism ; Gene Knockdown Techniques ; Gene Products, vif/*metabolism ; Genetic Complementation Test ; HEK293 Cells ; HIV Infections/*metabolism/*virology ; HIV-1/*physiology ; Host-Pathogen Interactions ; Humans ; Jurkat Cells ; Macaca mulatta/metabolism/virology ; Mass Spectrometry ; Models, Biological ; Protein Binding ; Proteolysis ; Simian Immunodeficiency Virus/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitination ; Virus Replication ; vif Gene Products, Human Immunodeficiency Virus/*metabolism
    Print ISSN: 0028-0836
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Publikationsdatum: 2009-02-20
    Beschreibung: The response of terrestrial vegetation to a globally changing environment is central to predictions of future levels of atmospheric carbon dioxide. The role of tropical forests is critical because they are carbon-dense and highly productive. Inventory plots across Amazonia show that old-growth forests have increased in carbon storage over recent decades, but the response of one-third of the world's tropical forests in Africa is largely unknown owing to an absence of spatially extensive observation networks. Here we report data from a ten-country network of long-term monitoring plots in African tropical forests. We find that across 79 plots (163 ha) above-ground carbon storage in live trees increased by 0.63 Mg C ha(-1) yr(-1) between 1968 and 2007 (95% confidence interval (CI), 0.22-0.94; mean interval, 1987-96). Extrapolation to unmeasured forest components (live roots, small trees, necromass) and scaling to the continent implies a total increase in carbon storage in African tropical forest trees of 0.34 Pg C yr(-1) (CI, 0.15-0.43). These reported changes in carbon storage are similar to those reported for Amazonian forests per unit area, providing evidence that increasing carbon storage in old-growth forests is a pan-tropical phenomenon. Indeed, combining all standardized inventory data from this study and from tropical America and Asia together yields a comparable figure of 0.49 Mg C ha(-1) yr(-1) (n = 156; 562 ha; CI, 0.29-0.66; mean interval, 1987-97). This indicates a carbon sink of 1.3 Pg C yr(-1) (CI, 0.8-1.6) across all tropical forests during recent decades. Taxon-specific analyses of African inventory and other data suggest that widespread changes in resource availability, such as increasing atmospheric carbon dioxide concentrations, may be the cause of the increase in carbon stocks, as some theory and models predict.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, Simon L -- Lopez-Gonzalez, Gabriela -- Sonke, Bonaventure -- Affum-Baffoe, Kofi -- Baker, Timothy R -- Ojo, Lucas O -- Phillips, Oliver L -- Reitsma, Jan M -- White, Lee -- Comiskey, James A -- Djuikouo K, Marie-Noel -- Ewango, Corneille E N -- Feldpausch, Ted R -- Hamilton, Alan C -- Gloor, Manuel -- Hart, Terese -- Hladik, Annette -- Lloyd, Jon -- Lovett, Jon C -- Makana, Jean-Remy -- Malhi, Yadvinder -- Mbago, Frank M -- Ndangalasi, Henry J -- Peacock, Julie -- Peh, Kelvin S-H -- Sheil, Douglas -- Sunderland, Terry -- Swaine, Michael D -- Taplin, James -- Taylor, David -- Thomas, Sean C -- Votere, Raymond -- Woll, Hannsjorg -- England -- Nature. 2009 Feb 19;457(7232):1003-6. doi: 10.1038/nature07771.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Earth and Biosphere Institute, School of Geography, University of Leeds, Leeds LS2 9JT, UK. s.l.lewis@leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225523" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Africa ; Atmosphere/chemistry ; Biomass ; Carbon/analysis/*metabolism ; Carbon Dioxide/analysis/metabolism ; Models, Biological ; Trees/anatomy & histology/chemistry/growth & development/*metabolism ; *Tropical Climate ; Wilderness ; Wood/analysis/chemistry
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Publikationsdatum: 2010-05-28
    Beschreibung: Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease. Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum. Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines. Here we present the complete sequences of a primary lung tumour (60x coverage) and adjacent normal tissue (46x). Comparing the two genomes, we identify a wide variety of somatic variations, including 〉50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, William -- Jiang, Zhaoshi -- Liu, Jinfeng -- Haverty, Peter M -- Guan, Yinghui -- Stinson, Jeremy -- Yue, Peng -- Zhang, Yan -- Pant, Krishna P -- Bhatt, Deepali -- Ha, Connie -- Johnson, Stephanie -- Kennemer, Michael I -- Mohan, Sankar -- Nazarenko, Igor -- Watanabe, Colin -- Sparks, Andrew B -- Shames, David S -- Gentleman, Robert -- de Sauvage, Frederic J -- Stern, Howard -- Pandita, Ajay -- Ballinger, Dennis G -- Drmanac, Radoje -- Modrusan, Zora -- Seshagiri, Somasekar -- Zhang, Zemin -- England -- Nature. 2010 May 27;465(7297):473-7. doi: 10.1038/nature09004.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20505728" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Carcinoma, Non-Small-Cell Lung/*genetics ; DNA Mutational Analysis ; Genome, Human/*genetics ; Humans ; Lung Neoplasms/*genetics ; Male ; Middle Aged ; Models, Biological ; Point Mutation/*genetics ; Selection, Genetic/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Publikationsdatum: 2014-01-17
    Beschreibung: Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephenson, N L -- Das, A J -- Condit, R -- Russo, S E -- Baker, P J -- Beckman, N G -- Coomes, D A -- Lines, E R -- Morris, W K -- Ruger, N -- Alvarez, E -- Blundo, C -- Bunyavejchewin, S -- Chuyong, G -- Davies, S J -- Duque, A -- Ewango, C N -- Flores, O -- Franklin, J F -- Grau, H R -- Hao, Z -- Harmon, M E -- Hubbell, S P -- Kenfack, D -- Lin, Y -- Makana, J-R -- Malizia, A -- Malizia, L R -- Pabst, R J -- Pongpattananurak, N -- Su, S-H -- Sun, I-F -- Tan, S -- Thomas, D -- van Mantgem, P J -- Wang, X -- Wiser, S K -- Zavala, M A -- England -- Nature. 2014 Mar 6;507(7490):90-3. doi: 10.1038/nature12914. Epub 2014 Jan 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Geological Survey, Western Ecological Research Center, Three Rivers, California 93271, USA. ; Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama. ; School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588, USA. ; Department of Forest and Ecosystem Science, University of Melbourne, Victoria 3121, Australia. ; 1] School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588, USA [2] Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio 43210, USA (N.G.B.); German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, 04103 Leipzig, Germany (N.R.). ; Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, UK. ; Department of Geography, University College London, London WC1E 6BT, UK. ; School of Botany, University of Melbourne, Victoria 3010, Australia. ; 1] Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama [2] Spezielle Botanik und Funktionelle Biodiversitat, Universitat Leipzig, 04103 Leipzig, Germany [3] Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio 43210, USA (N.G.B.); German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, 04103 Leipzig, Germany (N.R.). ; Jardin Botanico de Medellin, Calle 73, No. 51D-14, Medellin, Colombia. ; Instituto de Ecologia Regional, Universidad Nacional de Tucuman, 4107 Yerba Buena, Tucuman, Argentina. ; Research Office, Department of National Parks, Wildlife and Plant Conservation, Bangkok 10900, Thailand. ; Department of Botany and Plant Physiology, Buea, Southwest Province, Cameroon. ; Smithsonian Institution Global Earth Observatory-Center for Tropical Forest Science, Smithsonian Institution, PO Box 37012, Washington, DC 20013, USA. ; Universidad Nacional de Colombia, Departamento de Ciencias Forestales, Medellin, Colombia. ; Wildlife Conservation Society, Kinshasa/Gombe, Democratic Republic of the Congo. ; Unite Mixte de Recherche-Peuplements Vegetaux et Bioagresseurs en Milieu Tropical, Universite de la Reunion/CIRAD, 97410 Saint Pierre, France. ; School of Environmental and Forest Sciences, University of Washington, Seattle, Washington 98195, USA. ; State Key Laboratory of Forest and Soil Ecology, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110164, China. ; Department of Forest Ecosystems and Society, Oregon State University, Corvallis, Oregon 97331, USA. ; 1] Smithsonian Tropical Research Institute, Apartado 0843-03092, Balboa, Republic of Panama [2] Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA. ; Department of Life Science, Tunghai University, Taichung City 40704, Taiwan. ; Facultad de Ciencias Agrarias, Universidad Nacional de Jujuy, 4600 San Salvador de Jujuy, Argentina. ; Faculty of Forestry, Kasetsart University, ChatuChak Bangkok 10900, Thailand. ; Taiwan Forestry Research Institute, Taipei 10066, Taiwan. ; Department of Natural Resources and Environmental Studies, National Dong Hwa University, Hualien 97401, Taiwan. ; Sarawak Forestry Department, Kuching, Sarawak 93660, Malaysia. ; Department of Botany and Plant Pathology, Oregon State University, Corvallis, Oregon 97331, USA. ; US Geological Survey, Western Ecological Research Center, Arcata, California 95521, USA. ; Landcare Research, PO Box 40, Lincoln 7640, New Zealand. ; Forest Ecology and Restoration Group, Department of Life Sciences, University of Alcala, Alcala de Henares, 28805 Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24429523" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aging/metabolism ; Biomass ; *Body Size ; Carbon/*metabolism ; *Carbon Cycle ; Climate ; Geography ; Models, Biological ; Plant Leaves/growth & development/metabolism ; Sample Size ; Species Specificity ; Time Factors ; Trees/*anatomy & histology/classification/growth & development/*metabolism ; Tropical Climate
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2014-02-07
    Beschreibung: The seasonality of sunlight and rainfall regulates net primary production in tropical forests. Previous studies have suggested that light is more limiting than water for tropical forest productivity, consistent with greening of Amazon forests during the dry season in satellite data. We evaluated four potential mechanisms for the seasonal green-up phenomenon, including increases in leaf area or leaf reflectance, using a sophisticated radiative transfer model and independent satellite observations from lidar and optical sensors. Here we show that the apparent green up of Amazon forests in optical remote sensing data resulted from seasonal changes in near-infrared reflectance, an artefact of variations in sun-sensor geometry. Correcting this bidirectional reflectance effect eliminated seasonal changes in surface reflectance, consistent with independent lidar observations and model simulations with unchanging canopy properties. The stability of Amazon forest structure and reflectance over seasonal timescales challenges the paradigm of light-limited net primary production in Amazon forests and enhanced forest growth during drought conditions. Correcting optical remote sensing data for artefacts of sun-sensor geometry is essential to isolate the response of global vegetation to seasonal and interannual climate variability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morton, Douglas C -- Nagol, Jyoteshwar -- Carabajal, Claudia C -- Rosette, Jacqueline -- Palace, Michael -- Cook, Bruce D -- Vermote, Eric F -- Harding, David J -- North, Peter R J -- England -- Nature. 2014 Feb 13;506(7487):221-4. doi: 10.1038/nature13006. Epub 2014 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA. ; 1] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [2] Global Land Cover Facility, College Park, Maryland 20740, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] Sigma Space Corporation, Lantham, Maryland 20706, USA. ; 1] NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, USA [2] University of Maryland, College Park, Department of Geographical Sciences, College Park, Maryland 20742, USA [3] Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK. ; Earth System Research Center, University of New Hampshire, Durham, New Hampshire 03824, USA. ; Swansea University, Department of Geography, Singleton Park, Swansea SA2 8PP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499816" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Artifacts ; Brazil ; Color ; *Droughts ; Ecosystem ; Fresh Water/analysis ; Models, Biological ; Photosynthesis ; Pigmentation/*physiology ; Plant Leaves/anatomy & histology/growth & development/*physiology ; Rain ; Satellite Imagery ; *Seasons ; *Sunlight ; Trees/anatomy & histology/growth & development/*physiology ; *Tropical Climate
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Publikationsdatum: 2011-02-04
    Beschreibung: Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression. Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGFbeta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753179/" 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/PMC3753179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Zhihu -- Wu, Chang-Jiun -- Chu, Gerald C -- Xiao, Yonghong -- Ho, Dennis -- Zhang, Jingfang -- Perry, Samuel R -- Labrot, Emma S -- Wu, Xiaoqiu -- Lis, Rosina -- Hoshida, Yujin -- Hiller, David -- Hu, Baoli -- Jiang, Shan -- Zheng, Hongwu -- Stegh, Alexander H -- Scott, Kenneth L -- Signoretti, Sabina -- Bardeesy, Nabeel -- Wang, Y Alan -- Hill, David E -- Golub, Todd R -- Stampfer, Meir J -- Wong, Wing H -- Loda, Massimo -- Mucci, Lorelei -- Chin, Lynda -- DePinho, Ronald A -- P50 CA090381/CA/NCI NIH HHS/ -- P50 CA090381-08/CA/NCI NIH HHS/ -- P50 CA90381/CA/NCI NIH HHS/ -- R01 5R01CA136578/CA/NCI NIH HHS/ -- R01 CA131945/CA/NCI NIH HHS/ -- R01CA131945/CA/NCI NIH HHS/ -- R01CA141298/CA/NCI NIH HHS/ -- U01-CA84313/CA/NCI NIH HHS/ -- England -- Nature. 2011 Feb 10;470(7333):269-73. doi: 10.1038/nature09677. Epub 2011 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21289624" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; *Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor/physiology ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Mice ; Mice, Transgenic ; Models, Biological ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/*pathology ; Osteopontin/genetics/metabolism ; PTEN Phosphohydrolase/deficiency/genetics ; Penetrance ; Prognosis ; Prostate/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/diagnosis/genetics/*pathology ; Smad4 Protein/deficiency/genetics/*metabolism ; Transforming Growth Factor beta
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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