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  • History, 21st Century  (61)
  • Chemistry
  • EARTH RESOURCES AND REMOTE SENSING
  • Magnetism
  • Polymer and Materials Science
  • Protein Binding
  • Nature Publishing Group (NPG)  (109)
  • 2010-2014  (109)
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  • 1
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-04-10
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ware, Jessica -- England -- Nature. 2012 Apr 5;484(7392):133.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22486001" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Biological Evolution ; Career Mobility ; *Classification ; Cooperative Behavior ; Financing, Organized ; Fossils ; Genome/genetics ; *Genomics/history ; History, 21st Century ; *Insects/anatomy & histology/genetics/physiology ; *Social Behavior ; Transcriptome/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 2
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-03-17
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolman, David -- England -- Nature. 2012 Mar 14;483(7389):260-3. doi: 10.1038/483260a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22422242" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adolescent ; Age Factors ; Animals ; Brain/*physiology/*physiopathology/surgery ; Cohort Studies ; Corpus Callosum/physiology/physiopathology/*surgery ; Epilepsy/history/surgery ; Female ; Functional Laterality/*physiology ; History, 20th Century ; History, 21st Century ; Humans ; Magnetic Resonance Imaging ; Male ; Morals ; Neurosciences/*history ; Seizures/history/surgery
    Print ISSN: 0028-0836
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 3
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-01-20
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, Stuart A -- Haselkorn, Robert -- England -- Nature. 2012 Jan 18;481(7381):266. doi: 10.1038/481266a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and the James Franck Institute, University of Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22258598" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Biochemistry/*history ; DNA/chemistry ; History, 20th Century ; History, 21st Century ; Polymers/chemistry ; Proteins/chemistry ; United States
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 4
    Publikationsdatum: 2012-10-23
    Beschreibung: The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex I (type-I NADH dehydrogenase (NDH-1), also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain. The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD(+) homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex I defects, particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics. Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone- and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQ(I) and UQ(II)) in Ndi1. NADH and UQ(I) can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQ(I) interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQ(I) complex to UQ(II). Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feng, Yue -- Li, Wenfei -- Li, Jian -- Wang, Jiawei -- Ge, Jingpeng -- Xu, Duo -- Liu, Yanjing -- Wu, Kaiqi -- Zeng, Qingyin -- Wu, Jia-Wei -- Tian, Changlin -- Zhou, Bing -- Yang, Maojun -- England -- Nature. 2012 Nov 15;491(7424):478-82. doi: 10.1038/nature11541. Epub 2012 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23086143" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray ; Electron Transport Complex I/*chemistry/isolation & purification/metabolism ; Mitochondria/*enzymology ; *Models, Molecular ; NAD/chemistry ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/chemistry/enzymology ; Saccharomyces cerevisiae Proteins/*chemistry/isolation & purification/metabolism ; Ubiquinone/chemistry
    Print ISSN: 0028-0836
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 5
    Publikationsdatum: 2012-08-04
    Beschreibung: One of the greatest sources of uncertainty for future climate predictions is the response of the global carbon cycle to climate change. Although approximately one-half of total CO(2) emissions is at present taken up by combined land and ocean carbon reservoirs, models predict a decline in future carbon uptake by these reservoirs, resulting in a positive carbon-climate feedback. Several recent studies suggest that rates of carbon uptake by the land and ocean have remained constant or declined in recent decades. Other work, however, has called into question the reported decline. Here we use global-scale atmospheric CO(2) measurements, CO(2) emission inventories and their full range of uncertainties to calculate changes in global CO(2) sources and sinks during the past 50 years. Our mass balance analysis shows that net global carbon uptake has increased significantly by about 0.05 billion tonnes of carbon per year and that global carbon uptake doubled, from 2.4 +/- 0.8 to 5.0 +/- 0.9 billion tonnes per year, between 1960 and 2010. Therefore, it is very unlikely that both land and ocean carbon sinks have decreased on a global scale. Since 1959, approximately 350 billion tonnes of carbon have been emitted by humans to the atmosphere, of which about 55 per cent has moved into the land and oceans. Thus, identifying the mechanisms and locations responsible for increasing global carbon uptake remains a critical challenge in constraining the modern global carbon budget and predicting future carbon-climate interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ballantyne, A P -- Alden, C B -- Miller, J B -- Tans, P P -- White, J W C -- England -- Nature. 2012 Aug 2;488(7409):70-2. doi: 10.1038/nature11299.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology, University of Colorado, Boulder, Colorado 80309, USA. apballantyne@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859203" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Atmosphere/*chemistry ; Carbon/analysis ; Carbon Dioxide/*analysis/history ; *Carbon Sequestration ; Climate Change/*statistics & numerical data ; History, 20th Century ; History, 21st Century ; Human Activities ; Models, Theoretical ; Oceans and Seas ; Seawater/*chemistry ; Time Factors ; Uncertainty
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 6
    Publikationsdatum: 2012-07-06
    Beschreibung: The lengths of human telomeres, which protect chromosome ends from degradation and end fusions, are crucial determinants of cell lifespan. During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in cancer cells, human telomerase binds the shelterin component TPP1 at telomeres during the S phase of the cell cycle, and adds ~60 nucleotides in a single round of extension, after which telomerase is turned off by unknown mechanisms. Here we show that the human CST (CTC1, STN1 and TEN1) complex, previously implicated in telomere protection and DNA metabolism, inhibits telomerase activity through primer sequestration and physical interaction with the protection of telomeres 1 (POT1)-TPP1 telomerase processivity factor. CST competes with POT1-TPP1 for telomeric DNA, and CST-telomeric-DNA binding increases during late S/G2 phase only on telomerase action, coinciding with telomerase shut-off. Depletion of CST allows excessive telomerase activity, promoting telomere elongation. We propose that through binding of the telomerase-extended telomere, CST limits telomerase action at individual telomeres to approximately one binding and extension event per cell cycle. Our findings define the sequence of events that occur to first enable and then terminate telomerase-mediated telomere elongation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Liuh-Yow -- Redon, Sophie -- Lingner, Joachim -- 232812/European Research Council/International -- England -- Nature. 2012 Aug 23;488(7412):540-4. doi: 10.1038/nature11269.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Federale de Lausanne, Station 19, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763445" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aminopeptidases/metabolism ; Base Sequence ; Cell Line, Tumor ; DNA/genetics/metabolism ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Electrophoretic Mobility Shift Assay ; Enzyme Assays ; G2 Phase ; HEK293 Cells ; Humans ; Longevity ; Multiprotein Complexes/chemistry/genetics/*metabolism ; Protein Binding ; S Phase ; Serine Proteases/metabolism ; Telomerase/*antagonists & inhibitors/metabolism ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/genetics/*metabolism
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    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 7
    Publikationsdatum: 2012-12-12
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rossant, Janet -- Mummery, Christine -- England -- Nature. 2012 Dec 6;492(7427):56. doi: 10.1038/492056a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222608" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult Stem Cells/*cytology ; Animals ; *Cellular Reprogramming ; Cloning, Organism/*history ; History, 20th Century ; History, 21st Century ; Humans ; *Medicine ; *Nobel Prize ; *Nuclear Transfer Techniques ; *Physiology ; Rejuvenation ; Sheep
    Print ISSN: 0028-0836
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 8
    Publikationsdatum: 2012-12-12
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roth, Bryan L -- Marshall, Fiona H -- England -- Nature. 2012 Dec 6;492(7427):57. doi: 10.1038/492057a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222609" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Biochemistry/history ; *Chemistry/history ; Drug Discovery/history ; High-Throughput Screening Assays/history ; History, 20th Century ; History, 21st Century ; Humans ; *Nobel Prize ; Receptors, G-Protein-Coupled/genetics/isolation & purification/*metabolism ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 9
    Publikationsdatum: 2012-07-06
    Beschreibung: It is possible that anthropogenic climate change will drive the Earth system into a qualitatively different state. Although different types of uncertainty limit our capacity to assess this risk, Earth system scientists are particularly concerned about tipping elements, large-scale components of the Earth system that can be switched into qualitatively different states by small perturbations. Despite growing evidence that tipping elements exist in the climate system, whether large-scale vegetation systems can tip into alternative states is poorly understood. Here we show that tropical grassland, savanna and forest ecosystems, areas large enough to have powerful impacts on the Earth system, are likely to shift to alternative states. Specifically, we show that increasing atmospheric CO2 concentration will force transitions to vegetation states characterized by higher biomass and/or woody-plant dominance. The timing of these critical transitions varies as a result of between-site variance in the rate of temperature increase, as well as a dependence on stochastic variation in fire severity and rainfall. We further show that the locations of bistable vegetation zones (zones where alternative vegetation states can exist) will shift as climate changes. We conclude that even though large-scale directional regime shifts in terrestrial ecosystems are likely, asynchrony in the timing of these shifts may serve to dampen, but not nullify, the shock that these changes may represent to the Earth system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Higgins, Steven I -- Scheiter, Simon -- England -- Nature. 2012 Aug 9;488(7410):209-12. doi: 10.1038/nature11238.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Physische Geographie, Goethe Universitat Frankfurt am Main, 60438 Frankfurt am Main, Germany. higgins@em.uni-frankfurt.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763447" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Africa ; Atmosphere/*chemistry ; Biomass ; Carbon/metabolism ; Carbon Dioxide/analysis/*metabolism ; Climate Change/*statistics & numerical data ; *Ecosystem ; Fires ; Geography ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Hot Temperature ; Models, Biological ; Photosynthesis/physiology ; Poaceae/growth & development/metabolism ; Probability ; Rain ; Stochastic Processes ; Time Factors ; Trees/*growth & development/metabolism ; Wood
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 10
    Publikationsdatum: 2012-03-27
    Beschreibung: In most eukaryotes, the progressive loss of chromosome-terminal DNA sequences is counteracted by the enzyme telomerase, a reverse transcriptase that uses part of an RNA subunit as template to synthesize telomeric repeats. Many cancer cells express high telomerase activity, and mutations in telomerase subunits are associated with degenerative syndromes including dyskeratosis congenita and aplastic anaemia. The therapeutic value of altering telomerase activity thus provides ample impetus to study the biogenesis and regulation of this enzyme in human cells and model systems. We have previously identified a precursor of the fission yeast telomerase RNA subunit (TER1) and demonstrated that the mature 3'-end is generated by the spliceosome in a single cleavage reaction akin to the first step of splicing. Directly upstream and partly overlapping with the spliceosomal cleavage site is a putative binding site for Sm proteins. Sm and like-Sm (LSm) proteins belong to an ancient family of RNA-binding proteins represented in all three domains of life. Members of this family form ring complexes on specific sets of target RNAs and have critical roles in their biogenesis, function and turnover. Here we demonstrate that the canonical Sm ring and the Lsm2-8 complex sequentially associate with fission yeast TER1. The Sm ring binds to the TER1 precursor, stimulates spliceosomal cleavage and promotes the hypermethylation of the 5'-cap by Tgs1. Sm proteins are then replaced by the Lsm2-8 complex, which promotes the association with the catalytic subunit and protects the mature 3'-end of TER1 from exonucleolytic degradation. Our findings define the sequence of events that occur during telomerase biogenesis and characterize roles for Sm and Lsm complexes as well as for the methylase Tgs1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326189/" 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/PMC3326189/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Wen -- Kannan, Ram -- Blanchette, Marco -- Baumann, Peter -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 25;484(7393):260-4. doi: 10.1038/nature10924.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Kansas City, Missouri 64110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22446625" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Base Sequence ; Chromosomes, Fungal/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Methyltransferases/metabolism ; Multiprotein Complexes/chemistry/*metabolism ; Protein Binding ; RNA/*biosynthesis/genetics ; RNA Splicing ; RNA, Fungal/genetics/metabolism ; RNA-Binding Proteins/*metabolism ; Schizosaccharomyces/enzymology/*genetics/*metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; Spliceosomes/*metabolism ; Telomerase/*biosynthesis/genetics ; Telomere/genetics/metabolism ; tRNA Methyltransferases/metabolism
    Print ISSN: 0028-0836
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 11
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-11-07
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barley, Shanta -- England -- Nature. 2012 Nov 1;491(7422):24-6. doi: 10.1038/491024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128207" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Developed Countries ; Eritrea ; *Federal Government ; History, 20th Century ; History, 21st Century ; Hospitals/statistics & numerical data ; Human Rights/statistics & numerical data ; Humans ; *International Cooperation ; Medicine/*organization & administration ; Missouri ; Physicians/supply & distribution ; Public Health/statistics & numerical data ; Schools, Medical/history/manpower/organization & administration ; Science/manpower/*organization & administration
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 12
    Publikationsdatum: 2012-12-04
    Beschreibung: Mechanisms of protein recognition have been extensively studied for single-domain proteins, but are less well characterized for dynamic multidomain systems. Ubiquitin chains represent a biologically important multidomain system that requires recognition by structurally diverse ubiquitin-interacting proteins. Ubiquitin chain conformations in isolation are often different from conformations observed in ubiquitin-interacting protein complexes, indicating either great dynamic flexibility or extensive chain remodelling upon binding. Using single-molecule fluorescence resonance energy transfer, we show that Lys 63-, Lys 48- and Met 1-linked diubiquitin exist in several distinct conformational states in solution. Lys 63- and Met 1-linked diubiquitin adopt extended 'open' and more compact 'closed' conformations, and ubiquitin-binding domains and deubiquitinases (DUBs) select pre-existing conformations. By contrast, Lys 48-linked diubiquitin adopts predominantly compact conformations. DUBs directly recognize existing conformations, but may also remodel ubiquitin chains to hydrolyse the isopeptide bond. Disruption of the Lys 48-diubiquitin interface changes conformational dynamics and affects DUB activity. Hence, conformational equilibria in ubiquitin chains provide an additional layer of regulation in the ubiquitin system, and distinct conformations observed in differently linked polyubiquitin may contribute to the specificity of ubiquitin-interacting proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605796/" 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/PMC3605796/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ye, Yu -- Blaser, Georg -- Horrocks, Mathew H -- Ruedas-Rama, Maria J -- Ibrahim, Shehu -- Zhukov, Alexander A -- Orte, Angel -- Klenerman, David -- Jackson, Sophie E -- Komander, David -- 092096/Wellcome Trust/United Kingdom -- BB/F00219X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_U105192732/Medical Research Council/United Kingdom -- U.1051.03.019.00001.01(92732)/Medical Research Council/United Kingdom -- U105192732/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2012 Dec 13;492(7428):266-70. doi: 10.1038/nature11722. Epub 2012 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Protein and Nucleic Acids Chemistry, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23201676" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Fluorescence Resonance Energy Transfer ; *Models, Molecular ; Protein Binding ; Protein Structure, Tertiary ; Ubiquitin/*chemistry/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 13
    Publikationsdatum: 2012-05-04
    Beschreibung: The mTOR complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses. mTORC1 regulates messenger RNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in mouse cells acutely treated with the mTOR inhibitor Torin 1, which, unlike rapamycin, fully inhibits mTORC1 (ref. 2). Our data reveal a surprisingly simple model of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs that are specifically regulated by mTORC1 consists almost entirely of transcripts with established 5' terminal oligopyrimidine (TOP) motifs, or, like Hsp90ab1 and Ybx1, with previously unrecognized TOP or related TOP-like motifs that we identified. We find no evidence to support proposals that mTORC1 preferentially regulates mRNAs with increased 5' untranslated region length or complexity. mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown. Remarkably, loss of just the 4E-BP family of translational repressors, arguably the best characterized mTORC1 substrates, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin 1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. Our results clarify the translational program controlled by mTORC1 and identify 4E-BPs and eIF4G1 as its master effectors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347774/" 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/PMC3347774/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thoreen, Carson C -- Chantranupong, Lynne -- Keys, Heather R -- Wang, Tim -- Gray, Nathanael S -- Sabatini, David M -- CA103866/CA/NCI NIH HHS/ -- CA129105/CA/NCI NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R01 CA103866-08/CA/NCI NIH HHS/ -- R01 CA129105/CA/NCI NIH HHS/ -- R01 CA129105-05/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 May 2;485(7396):109-13. doi: 10.1038/nature11083.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana Farber Cancer Institute, 250 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22552098" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 5' Untranslated Regions/genetics ; Animals ; Base Sequence ; Cell Line, Tumor ; Eukaryotic Initiation Factor-4E/metabolism ; Eukaryotic Initiation Factor-4G/metabolism ; *Gene Expression Regulation/drug effects ; Humans ; Male ; Mice ; *Models, Biological ; Multiprotein Complexes ; Naphthyridines/pharmacology ; Nucleotide Motifs ; Phosphorylation ; Prostatic Neoplasms/genetics/pathology ; Protein Binding ; *Protein Biosynthesis/drug effects ; Proteins/antagonists & inhibitors/*metabolism ; RNA, Messenger/genetics/metabolism ; Ribosomes/metabolism ; TOR Serine-Threonine Kinases
    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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  • 14
    Publikationsdatum: 2012-11-13
    Beschreibung: Chromatin-remodelling complexes (CRCs) mobilize nucleosomes to mediate the access of DNA-binding factors to their sites in vivo. These CRCs contain a catalytic subunit that bears an ATPase/DNA-translocase domain and flanking regions that bind nucleosomal epitopes. A central question is whether and how these flanking regions regulate ATP hydrolysis or the coupling of hydrolysis to DNA translocation, to affect nucleosome-sliding efficiency. ISWI-family CRCs contain the protein ISWI, which uses its ATPase/DNA-translocase domain to pump DNA around the histone octamer to enable sliding. ISWI is positively regulated by two 'activating' nucleosomal epitopes: the 'basic patch' on the histone H4 tail, and extranucleosomal (linker) DNA. Previous work defined the HAND-SANT-SLIDE (HSS) domain at the ISWI carboxy terminus that binds linker DNA, needed for ISWI activity. Here we define two new, conserved and separate regulatory regions on Drosophila ISWI, termed AutoN and NegC, which negatively regulate ATP hydrolysis (AutoN) or the coupling of ATP hydrolysis to productive DNA translocation (NegC). The two aforementioned nucleosomal epitopes promote remodelling indirectly by preventing the negative regulation of AutoN and NegC. Notably, mutation or removal of AutoN and NegC enables marked nucleosome sliding without the H4 basic patch or extranucleosomal DNA, or the HSS domain, conferring on ISWI the biochemical attributes normally associated with SWI/SNF-family ATPases. Thus, the ISWI ATPase catalytic core is an intrinsically active DNA translocase that conducts nucleosome sliding, onto which selective 'inhibition-of-inhibition' modules are placed, to help ensure that remodelling occurs only in the presence of proper nucleosomal epitopes. This supports a general concept for the specialization of chromatin-remodelling ATPases, in which specific regulatory modules adapt an ancient active DNA translocase to conduct particular tasks only on the appropriate chromatin landscape.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631562/" 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/PMC3631562/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clapier, Cedric R -- Cairns, Bradley R -- CA042014/CA/NCI NIH HHS/ -- GM60415/GM/NIGMS NIH HHS/ -- R01 GM060415/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Dec 13;492(7428):280-4. doi: 10.1038/nature11625. Epub 2012 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. cedric.clapier@hci.utah.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23143334" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine Triphosphatases/chemistry/*genetics/*metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Chromatin Assembly and Disassembly ; Drosophila Proteins/chemistry/genetics/metabolism ; Drosophila melanogaster/enzymology/*genetics/*metabolism ; Epitopes/*metabolism ; *Gene Expression Regulation ; Hydrolysis ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Nucleosomes/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Regulatory Sequences, Nucleic Acid/genetics ; Sequence Alignment ; Transcription Factors/chemistry/*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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  • 15
    Publikationsdatum: 2012-11-13
    Beschreibung: Mutations in the gene encoding NLRP3 cause a spectrum of autoinflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS). NLRP3 is a key component of one of several distinct cytoplasmic multiprotein complexes (inflammasomes) that mediate the maturation of the proinflammatory cytokine interleukin-1beta (IL-1beta) by activating caspase-1. Although several models for inflammasome activation, such as K(+) efflux, generation of reactive oxygen species and lysosomal destabilization, have been proposed, the precise molecular mechanism of NLRP3 inflammasome activation, as well as the mechanism by which CAPS-associated mutations activate NLRP3, remain to be elucidated. Here we show that the murine calcium-sensing receptor (CASR) activates the NLRP3 inflammasome, mediated by increased intracellular Ca(2+) and decreased cellular cyclic AMP (cAMP). Ca(2+) or other CASR agonists activate the NLRP3 inflammasome in the absence of exogenous ATP, whereas knockdown of CASR reduces inflammasome activation in response to known NLRP3 activators. CASR activates the NLRP3 inflammasome through phospholipase C, which catalyses inositol-1,4,5-trisphosphate production and thereby induces release of Ca(2+) from endoplasmic reticulum stores. The increased cytoplasmic Ca(2+) promotes the assembly of inflammasome components, and intracellular Ca(2+) is required for spontaneous inflammasome activity in cells from patients with CAPS. CASR stimulation also results in reduced intracellular cAMP, which independently activates the NLRP3 inflammasome. cAMP binds to NLRP3 directly to inhibit inflammasome assembly, and downregulation of cAMP relieves this inhibition. The binding affinity of cAMP for CAPS-associated mutant NLRP3 is substantially lower than for wild-type NLRP3, and the uncontrolled mature IL-1beta production from CAPS patients' peripheral blood mononuclear cells is attenuated by increasing cAMP. Taken together, these findings indicate that Ca(2+) and cAMP are two key molecular regulators of the NLRP3 inflammasome that have critical roles in the molecular pathogenesis of CAPS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175565/" 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/PMC4175565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Geun-Shik -- Subramanian, Naeha -- Kim, Andrew I -- Aksentijevich, Ivona -- Goldbach-Mansky, Raphaela -- Sacks, David B -- Germain, Ronald N -- Kastner, Daniel L -- Chae, Jae Jin -- Z99 HG999999/Intramural NIH HHS/ -- England -- Nature. 2012 Dec 6;492(7427):123-7. doi: 10.1038/nature11588. Epub 2012 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Inflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23143333" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine Triphosphate/metabolism ; Animals ; Calcium/*metabolism ; *Calcium Signaling ; Carrier Proteins/genetics/*metabolism ; Cryopyrin-Associated Periodic Syndromes/etiology/genetics/metabolism ; Cyclic AMP/*metabolism ; Endoplasmic Reticulum/metabolism ; Gene Knockdown Techniques ; Humans ; Inflammasomes/*metabolism ; Inositol 1,4,5-Trisphosphate/metabolism ; Interleukin-1beta/biosynthesis/metabolism ; Leukocytes, Mononuclear/metabolism ; Mice ; Protein Binding ; Receptors, Calcium-Sensing/*metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Type C Phospholipases/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    Publikationsdatum: 2012-02-14
    Beschreibung: Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is characterized by tumorigenesis in multiple endocrine organs. Menin interacts with many proteins and is involved in a variety of cellular processes. Menin binds the JUN family transcription factor JUND and inhibits its transcriptional activity. Several MEN1 missense mutations disrupt the menin-JUND interaction, suggesting a correlation between the tumour-suppressor function of menin and its suppression of JUND-activated transcription. Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 methyltransferase, and functions as an oncogenic cofactor to upregulate gene transcription and promote MLL1-fusion-protein-induced leukaemogenesis. A recent report on the tethering of MLL1 to chromatin binding factor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adaptor coordinating the functions of multiple proteins. Despite its importance, how menin interacts with many distinct partners and regulates their functions remains poorly understood. Here we present the crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer. These structures show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983792/" 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/PMC3983792/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Jing -- Gurung, Buddha -- Wan, Bingbing -- Matkar, Smita -- Veniaminova, Natalia A -- Wan, Ke -- Merchant, Juanita L -- Hua, Xianxin -- Lei, Ming -- GM083015-01/GM/NIGMS NIH HHS/ -- R01 DK085121/DK/NIDDK NIH HHS/ -- R01-DK085121/DK/NIDDK NIH HHS/ -- R37 DK045729/DK/NIDDK NIH HHS/ -- R37-DK45729/DK/NIDDK NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 12;482(7386):542-6. doi: 10.1038/nature10806.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22327296" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Binding Sites ; Chromatin/metabolism ; Crystallography, X-Ray ; Fibroblasts ; HEK293 Cells ; Histone-Lysine N-Methyltransferase ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Myeloid-Lymphoid Leukemia Protein/chemistry/*metabolism ; Phosphorylation ; Protein Binding ; Protein Multimerization ; Proto-Oncogene Proteins/*chemistry/*metabolism ; Proto-Oncogene Proteins c-jun/chemistry/*metabolism ; Structure-Activity Relationship ; *Transcription, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
    Publikationsdatum: 2012-11-16
    Beschreibung: Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes approximately 98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Jinghe -- Ofek, Gilad -- Laub, Leo -- Louder, Mark K -- Doria-Rose, Nicole A -- Longo, Nancy S -- Imamichi, Hiromi -- Bailer, Robert T -- Chakrabarti, Bimal -- Sharma, Shailendra K -- Alam, S Munir -- Wang, Tao -- Yang, Yongping -- Zhang, Baoshan -- Migueles, Stephen A -- Wyatt, Richard -- Haynes, Barton F -- Kwong, Peter D -- Mascola, John R -- Connors, Mark -- HSN261200800001E/PHS HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Nov 15;491(7424):406-12. doi: 10.1038/nature11544. Epub 2012 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23151583" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Substitution ; Antibodies, Neutralizing/chemistry/*metabolism ; Antibody Specificity ; Cells, Cultured ; HEK293 Cells ; HIV Antibodies/chemistry/isolation & purification/*metabolism ; HIV Envelope Protein gp41/chemistry/*immunology ; HIV-1/*physiology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Tertiary
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 18
    Publikationsdatum: 2012-10-23
    Beschreibung: Calcium ions (Ca(2+)) have an important role as secondary messengers in numerous signal transduction processes, and cells invest much energy in controlling and maintaining a steep gradient between intracellular ( approximately 0.1-micromolar) and extracellular ( approximately 2-millimolar) Ca(2+) concentrations. Calmodulin-stimulated calcium pumps, which include the plasma-membrane Ca(2+)-ATPases (PMCAs), are key regulators of intracellular Ca(2+) in eukaryotes. They contain a unique amino- or carboxy-terminal regulatory domain responsible for autoinhibition, and binding of calcium-loaded calmodulin to this domain releases autoinhibition and activates the pump. However, the structural basis for the activation mechanism is unknown and a key remaining question is how calmodulin-mediated PMCA regulation can cover both basal Ca(2+) levels in the nanomolar range as well as micromolar-range Ca(2+) transients generated by cell stimulation. Here we present an integrated study combining the determination of the high-resolution crystal structure of a PMCA regulatory-domain/calmodulin complex with in vivo characterization and biochemical, biophysical and bioinformatics data that provide mechanistic insights into a two-step PMCA activation mechanism mediated by calcium-loaded calmodulin. The structure shows the entire PMCA regulatory domain and reveals an unexpected 2:1 stoichiometry with two calcium-loaded calmodulin molecules binding to different sites on a long helix. A multifaceted characterization of the role of both sites leads to a general structural model for calmodulin-mediated regulation of PMCAs that allows stringent, highly responsive control of intracellular calcium in eukaryotes, making it possible to maintain a stable, basal level at a threshold Ca(2+) concentration, where steep activation occurs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tidow, Henning -- Poulsen, Lisbeth R -- Andreeva, Antonina -- Knudsen, Michael -- Hein, Kim L -- Wiuf, Carsten -- Palmgren, Michael G -- Nissen, Poul -- MC_U105192716/Medical Research Council/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):468-72. doi: 10.1038/nature11539. Epub 2012 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Aarhus University, Gustav Wieds Vej 10c, DK-8000 Aarhus C, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23086147" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Arabidopsis/chemistry/enzymology/*metabolism ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Binding Sites ; Calcium/*metabolism ; Calcium-Transporting ATPases/*chemistry/genetics/*metabolism ; Calmodulin/*chemistry/metabolism ; Enzyme Activation ; Eukaryota/*metabolism ; Intracellular Space/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Tertiary ; Sequence Alignment
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 19
    Publikationsdatum: 2012-08-03
    Beschreibung: Motor axons receive retrograde signals from skeletal muscle that are essential for the differentiation and stabilization of motor nerve terminals. Identification of these retrograde signals has proved elusive, but their production by muscle depends on the receptor tyrosine kinase, MuSK (muscle, skeletal receptor tyrosine-protein kinase), and Lrp4 (low-density lipoprotein receptor (LDLR)-related protein 4), an LDLR family member that forms a complex with MuSK, binds neural agrin and stimulates MuSK kinase activity. Here we show that Lrp4 also functions as a direct muscle-derived retrograde signal for early steps in presynaptic differentiation. We demonstrate that Lrp4 is necessary, independent of MuSK activation, for presynaptic differentiation in vivo, and we show that Lrp4 binds to motor axons and induces clustering of synaptic-vesicle and active-zone proteins. Thus, Lrp4 acts bidirectionally and coordinates synapse formation by binding agrin, activating MuSK and stimulating postsynaptic differentiation, and functioning in turn as a muscle-derived retrograde signal that is necessary and sufficient for presynaptic differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448831/" 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/PMC3448831/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yumoto, Norihiro -- Kim, Natalie -- Burden, Steven J -- 5 P30CA16087-31/CA/NCI NIH HHS/ -- NS36193/NS/NINDS NIH HHS/ -- R01 NS036193/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Sep 20;489(7416):438-42. doi: 10.1038/nature11348. Epub 2012 Aug 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Program, Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, New York, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22854782" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amyotrophic Lateral Sclerosis ; Animals ; *Cell Differentiation ; Cells, Cultured ; Coculture Techniques ; Diaphragm ; Mice ; Motor Neurons/metabolism ; Muscle, Skeletal/cytology/*innervation/metabolism ; Neural Tube/cytology/metabolism ; Neuromuscular Junction/*cytology/*metabolism ; Presynaptic Terminals/*metabolism ; Protein Binding ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, LDL/*metabolism ; Sarcopenia ; *Signal Transduction ; Synapsins/metabolism ; Tissue Culture Techniques
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 20
    Publikationsdatum: 2012-04-14
    Beschreibung: Dynamic access to genetic information is central to organismal development and environmental response. Consequently, genomic processes must be regulated by mechanisms that alter genome function relatively rapidly. Conventional chromatin immunoprecipitation (ChIP) experiments measure transcription factor occupancy, but give no indication of kinetics and are poor predictors of transcription factor function at a given locus. To measure transcription-factor-binding dynamics across the genome, we performed competition ChIP (refs 6, 7) with a sequence-specific Saccharomyces cerevisiae transcription factor, Rap1 (ref. 8). Rap1-binding dynamics and Rap1 occupancy were only weakly correlated (R(2) = 0.14), but binding dynamics were more strongly linked to function than occupancy. Long Rap1 residence was coupled to transcriptional activation, whereas fast binding turnover, which we refer to as 'treadmilling', was linked to low transcriptional output. Thus, DNA-binding events that seem identical by conventional ChIP may have different underlying modes of interaction that lead to opposing functional outcomes. We propose that transcription factor binding turnover is a major point of regulation in determining the functional consequences of transcription factor binding, and is mediated mainly by control of competition between transcription factors and nucleosomes. Our model predicts a clutch-like mechanism that rapidly engages a treadmilling transcription factor into a stable binding state, or vice versa, to modulate transcription factor function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341663/" 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/PMC3341663/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lickwar, Colin R -- Mueller, Florian -- Hanlon, Sean E -- McNally, James G -- Lieb, Jason D -- R01 GM072518/GM/NIGMS NIH HHS/ -- R01 GM072518-05/GM/NIGMS NIH HHS/ -- R01-GM072518/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Apr 11;484(7393):251-5. doi: 10.1038/nature10985.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3280, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22498630" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Base Sequence ; Binding Sites ; Binding, Competitive ; Chromatin Immunoprecipitation ; DNA, Fungal/genetics/*metabolism ; Gene Expression Regulation, Fungal ; *Genome, Fungal ; Histone Acetyltransferases/metabolism ; *Models, Biological ; Nucleosomes/genetics/metabolism ; Protein Binding ; RNA Polymerase II/metabolism ; RNA, Messenger/biosynthesis/genetics ; Saccharomyces cerevisiae/classification/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Telomere-Binding Proteins/*metabolism ; Time Factors ; Transcription Factors/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 21
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    Unbekannt
    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-06-09
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Jun 6;486(7401):19. doi: 10.1038/486019a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678261" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Biodiversity ; Brazil ; *Congresses as Topic/history ; *Conservation of Natural Resources/economics/history/legislation & ; jurisprudence/trends ; Developing Countries/economics ; *Environmental Policy/economics/history/legislation & jurisprudence/trends ; History, 20th Century ; History, 21st Century ; *International Cooperation/history/legislation & jurisprudence
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 22
    Publikationsdatum: 2012-04-14
    Beschreibung: Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean. These links are extensive, influencing a range of climate processes such as hurricane activity and African Sahel and Amazonian droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations. A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures, but climate models have so far failed to reproduce these interactions and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860-2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910-1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol-cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol-cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Booth, Ben B B -- Dunstone, Nick J -- Halloran, Paul R -- Andrews, Timothy -- Bellouin, Nicolas -- England -- Nature. 2012 Apr 4;484(7393):228-32. doi: 10.1038/nature10946.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Met Office Hadley Centre, FitzRoy Road, Exeter EX1 3PB, UK. ben.booth@metoffice.gov.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22498628" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Aerosols ; Atlantic Ocean ; *Climate ; Droughts ; Global Warming/*statistics & numerical data ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Human Activities ; Radiation ; Seawater ; Temperature ; Volcanic Eruptions ; Water Movements
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  • 23
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-12-22
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Udovicic, Frank -- England -- Nature. 2012 Dec 20;492(7429):356. doi: 10.1038/492356a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257870" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Botany ; History, 20th Century ; History, 21st Century ; International Cooperation ; *Language/history ; Research Report/*standards ; *Terminology as Topic ; Translations
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  • 24
    Publikationsdatum: 2012-10-02
    Beschreibung: The genome-wide identification of pairs of interacting proteins is an important step in the elucidation of cell regulatory mechanisms. Much of our present knowledge derives from high-throughput techniques such as the yeast two-hybrid assay and affinity purification, as well as from manual curation of experiments on individual systems. A variety of computational approaches based, for example, on sequence homology, gene co-expression and phylogenetic profiles, have also been developed for the genome-wide inference of protein-protein interactions (PPIs). Yet comparative studies suggest that the development of accurate and complete repertoires of PPIs is still in its early stages. Here we show that three-dimensional structural information can be used to predict PPIs with an accuracy and coverage that are superior to predictions based on non-structural evidence. Moreover, an algorithm, termed PrePPI, which combines structural information with other functional clues, is comparable in accuracy to high-throughput experiments, yielding over 30,000 high-confidence interactions for yeast and over 300,000 for human. Experimental tests of a number of predictions demonstrate the ability of the PrePPI algorithm to identify unexpected PPIs of considerable biological interest. The surprising effectiveness of three-dimensional structural information can be attributed to the use of homology models combined with the exploitation of both close and remote geometric relationships between proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482288/" 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/PMC3482288/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Qiangfeng Cliff -- Petrey, Donald -- Deng, Lei -- Qiang, Li -- Shi, Yu -- Thu, Chan Aye -- Bisikirska, Brygida -- Lefebvre, Celine -- Accili, Domenico -- Hunter, Tony -- Maniatis, Tom -- Califano, Andrea -- Honig, Barry -- CA082683/CA/NCI NIH HHS/ -- CA121852/CA/NCI NIH HHS/ -- DK057539/DK/NIDDK NIH HHS/ -- GM030518/GM/NIGMS NIH HHS/ -- GM094597/GM/NIGMS NIH HHS/ -- R01 CA082683/CA/NCI NIH HHS/ -- R01 DK057539/DK/NIDDK NIH HHS/ -- R01 GM030518/GM/NIGMS NIH HHS/ -- R01 NS043915/NS/NINDS NIH HHS/ -- R01NS043915/NS/NINDS NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 GM094597/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Oct 25;490(7421):556-60. doi: 10.1038/nature11503. Epub 2012 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023127" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Algorithms ; Animals ; Bayes Theorem ; Brain/metabolism ; Cadherins/metabolism ; High-Throughput Screening Assays ; Humans ; Matrix Attachment Region Binding Proteins/metabolism ; Mice ; Models, Molecular ; PPAR gamma/metabolism ; Phylogeny ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping/*methods ; *Protein Interaction Maps ; Protein Kinases/chemistry/metabolism ; Proteins/*chemistry/*metabolism ; Proteome/chemistry/metabolism ; Proteomics/*methods ; ROC Curve ; Reproducibility of Results ; Saccharomyces cerevisiae/chemistry/metabolism ; Suppressor of Cytokine Signaling Proteins/metabolism ; Transcription Factors/metabolism
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  • 25
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-10-19
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Noorden, Richard -- England -- Nature. 2012 Oct 18;490(7420):320. doi: 10.1038/490320a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23075956" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Arrestins/chemistry/history/metabolism ; Cell Communication ; *Drug Discovery/history ; History, 20th Century ; History, 21st Century ; *Nobel Prize ; Receptors, Adrenergic, beta-2/chemistry/history/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/chemistry/history/*metabolism ; *Signal Transduction
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  • 26
    Publikationsdatum: 2012-10-23
    Beschreibung: The differentiation of several T- and B-cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodelling. Here we report that promyelocytic leukaemia zinc finger (PLZF), the BTB-zinc finger (BTB-ZF) transcription factor directing the innate-like effector program of natural killer T-cell thymocytes, is prominently associated with cullin 3 (CUL3), an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding. PLZF transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex. Furthermore, PLZF expression results in selective ubiquitination changes of several components of this complex. CUL3 was also found associated with the BTB-ZF transcription factor BCL6, which directs the germinal-centre B cell and follicular T-helper cell programs. Conditional CUL3 deletion in mice demonstrated an essential role for CUL3 in the development of PLZF- and BCL6-dependent lineages. We conclude that distinct lineage-specific BTB-ZF transcription factors recruit CUL3 to alter the ubiquitination pattern of their associated chromatin-modifying complex. We propose that this new function is essential to direct the differentiation of several T- and B-cell effector programs, and may also be involved in the oncogenic role of PLZF and BCL6 in leukaemias and lymphomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504649/" 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/PMC3504649/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathew, Rebecca -- Seiler, Michael P -- Scanlon, Seth T -- Mao, Ai-ping -- Constantinides, Michael G -- Bertozzi-Villa, Clara -- Singer, Jeffrey D -- Bendelac, Albert -- 5R01GM082940/GM/NIGMS NIH HHS/ -- P30 DK042086/DK/NIDDK NIH HHS/ -- R01 AI038339/AI/NIAID NIH HHS/ -- R01 GM082940/GM/NIGMS NIH HHS/ -- R01AI038339/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Nov 22;491(7425):618-21. doi: 10.1038/nature11548. Epub 2012 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Committee on Immunology, Department of Pathology, The Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23086144" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; B-Lymphocytes/cytology/*metabolism ; Cell Differentiation ; Cell Line ; Cullin Proteins/chemistry/genetics/*metabolism ; DNA-Binding Proteins/metabolism ; Kruppel-Like Transcription Factors/*metabolism ; Mice ; Protein Binding ; Protein Transport ; T-Lymphocytes/cytology/*metabolism ; Ubiquitination ; *Zinc Fingers
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  • 27
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-12-12
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Helen -- England -- Nature. 2012 Dec 6;492(7427):17. doi: 10.1038/492017a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222583" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Climate Change ; *Federal Government ; History, 20th Century ; History, 21st Century ; Patents as Topic/legislation & jurisprudence ; Science/economics/*legislation & jurisprudence ; Texas ; United States ; United States Environmental Protection Agency
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  • 28
    Publikationsdatum: 2012-03-16
    Beschreibung: Viral infection is commonly associated with virus-driven hijacking of host proteins. Here we describe a novel mechanism by which influenza virus affects host cells through the interaction of influenza non-structural protein 1 (NS1) with the infected cell epigenome. We show that the NS1 protein of influenza A H3N2 subtype possesses a histone-like sequence (histone mimic) that is used by the virus to target the human PAF1 transcription elongation complex (hPAF1C). We demonstrate that binding of NS1 to hPAF1C depends on the NS1 histone mimic and results in suppression of hPAF1C-mediated transcriptional elongation. Furthermore, human PAF1 has a crucial role in the antiviral response. Loss of hPAF1C binding by NS1 attenuates influenza infection, whereas hPAF1C deficiency reduces antiviral gene expression and renders cells more susceptible to viruses. We propose that the histone mimic in NS1 enables the influenza virus to affect inducible gene expression selectively, thus contributing to suppression of the antiviral response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598589/" 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/PMC3598589/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marazzi, Ivan -- Ho, Jessica S Y -- Kim, Jaehoon -- Manicassamy, Balaji -- Dewell, Scott -- Albrecht, Randy A -- Seibert, Chris W -- Schaefer, Uwe -- Jeffrey, Kate L -- Prinjha, Rab K -- Lee, Kevin -- Garcia-Sastre, Adolfo -- Roeder, Robert G -- Tarakhovsky, Alexander -- 1K99AI095320-01/AI/NIAID NIH HHS/ -- CA129325/CA/NCI NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- R01 CA129325/CA/NCI NIH HHS/ -- R01AI046954/AI/NIAID NIH HHS/ -- R01AI068058/AI/NIAID NIH HHS/ -- U19AI083025/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Mar 14;483(7390):428-33. doi: 10.1038/nature10892.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. imarazzi@rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22419161" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; *Gene Expression Regulation/immunology ; Histones/chemistry/*metabolism ; Humans ; Influenza A Virus, H3N2 Subtype/genetics/*metabolism/pathogenicity ; Influenza, Human/*genetics/*immunology/pathology/virology ; *Molecular Mimicry ; Molecular Sequence Data ; Nuclear Proteins/antagonists & inhibitors/metabolism ; Protein Binding ; Transcription, Genetic/immunology ; Viral Nonstructural Proteins/chemistry/*metabolism
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  • 29
    Publikationsdatum: 2012-08-24
    Beschreibung: After methane, ethane is the most abundant hydrocarbon in the remote atmosphere. It is a precursor to tropospheric ozone and it influences the atmosphere's oxidative capacity through its reaction with the hydroxyl radical, ethane's primary atmospheric sink. Here we present the longest continuous record of global atmospheric ethane levels. We show that global ethane emission rates decreased from 14.3 to 11.3 teragrams per year, or by 21 per cent, from 1984 to 2010. We attribute this to decreasing fugitive emissions from ethane's fossil fuel source--most probably decreased venting and flaring of natural gas in oil fields--rather than a decline in its other major sources, biofuel use and biomass burning. Ethane's major emission sources are shared with methane, and recent studies have disagreed on whether reduced fossil fuel or microbial emissions have caused methane's atmospheric growth rate to slow. Our findings suggest that reduced fugitive fossil fuel emissions account for at least 10-21 teragrams per year (30-70 per cent) of the decrease in methane's global emissions, significantly contributing to methane's slowing atmospheric growth rate since the mid-1980s.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simpson, Isobel J -- Sulbaek Andersen, Mads P -- Meinardi, Simone -- Bruhwiler, Lori -- Blake, Nicola J -- Helmig, Detlev -- Rowland, F Sherwood -- Blake, Donald R -- England -- Nature. 2012 Aug 23;488(7412):490-4. doi: 10.1038/nature11342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California-Irvine, Irvine, California 92697, USA. isimpson@uci.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22914166" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Atmosphere/*chemistry ; Biofuels/utilization ; Biomass ; Ethane/*analysis/*chemistry/history ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Methane/*analysis/*chemistry/history ; Natural Gas/utilization ; Oil and Gas Fields ; Ozone/chemistry ; Wetlands
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 30
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-02-24
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waldrop, M Mitchell -- England -- Nature. 2012 Feb 22;482(7386):456-8. doi: 10.1038/482456a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358809" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Brain/*physiology ; Cognition/physiology ; *Computer Simulation ; European Union ; History, 20th Century ; History, 21st Century ; Humans ; Internationality ; *Models, Neurological ; Neurosciences/economics/history/trends ; Switzerland
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 31
    Publikationsdatum: 2012-12-04
    Beschreibung: Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high messenger RNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a range of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25-nucleotide 'TINCR box' motif that is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyse TINCR binding capacity to approximately 9,400 human recombinant proteins revealed direct binding of TINCR RNA to the staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay, however, did not have differentiation effects. Instead, the TINCR-STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through lncRNA binding to differentiation mRNAs to ensure their expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674581/" 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/PMC3674581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kretz, Markus -- Siprashvili, Zurab -- Chu, Ci -- Webster, Dan E -- Zehnder, Ashley -- Qu, Kun -- Lee, Carolyn S -- Flockhart, Ross J -- Groff, Abigail F -- Chow, Jennifer -- Johnston, Danielle -- Kim, Grace E -- Spitale, Robert C -- Flynn, Ryan A -- Zheng, Grace X Y -- Aiyer, Subhadra -- Raj, Arjun -- Rinn, John L -- Chang, Howard Y -- Khavari, Paul A -- AR49737/AR/NIAMS NIH HHS/ -- DP2 OD008514/OD/NIH HHS/ -- P30 CA124435/CA/NCI NIH HHS/ -- R01 AR049737/AR/NIAMS NIH HHS/ -- R01 HG004361/HG/NHGRI NIH HHS/ -- R01-HG004361/HG/NHGRI NIH HHS/ -- T32 AR007422/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jan 10;493(7431):231-5. doi: 10.1038/nature11661. Epub 2012 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23201690" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Base Sequence ; Cell Differentiation/*genetics ; Cells, Cultured ; Cytoskeletal Proteins/metabolism ; Epidermis/*cytology/*metabolism ; Gene Expression Regulation ; High-Throughput Screening Assays ; Humans ; Keratinocytes ; Mutation ; Nucleotide Motifs/genetics ; Protein Binding ; RNA Stability/genetics ; RNA, Long Noncoding/*genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/metabolism ; Skin Diseases/genetics
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  • 32
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-08-04
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2012 Aug 2;488(7409):24-6. doi: 10.1038/488024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859185" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Archives ; Conflict (Psychology) ; Databases, Factual ; Employment/statistics & numerical data/trends ; Epidemics/statistics & numerical data ; Food Chain ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; *Models, Theoretical ; *Periodicity ; Politics ; Social Change/*history ; Statistics as Topic ; Violence/history/prevention & control/trends
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  • 33
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-10-06
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bynum, William -- England -- Nature. 2012 Oct 4;490(7418):31-2. doi: 10.1038/490031a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College London, UK. w.bynum@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23038449" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Chemistry/history ; Dogs ; England ; Genetics/history ; Germany ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Laboratories/*history/*standards/trends ; Molecular Biology/*history/standards ; New York ; *Nobel Prize ; Personality ; Physics/history ; Physiology/history ; Russia
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 34
    Publikationsdatum: 2012-05-25
    Beschreibung: Bacterial ribosomes stalled at the 3' end of malfunctioning messenger RNAs can be rescued by transfer-messenger RNA (tmRNA)-mediated trans-translation. The SmpB protein forms a complex with the tmRNA, and the transfer-RNA-like domain (TLD) of the tmRNA then enters the A site of the ribosome. Subsequently, the TLD-SmpB module is translocated to the P site, a process that is facilitated by the elongation factor EF-G, and translation is switched to the mRNA-like domain (MLD) of the tmRNA. Accurate loading of the MLD into the mRNA path is an unusual initiation mechanism. Despite various snapshots of different ribosome-tmRNA complexes at low to intermediate resolution, it is unclear how the large, highly structured tmRNA is translocated and how the MLD is loaded. Here we present a cryo-electron microscopy reconstruction of a fusidic-acid-stalled ribosomal 70S-tmRNA-SmpB-EF-G complex (carrying both of the large ligands, that is, EF-G and tmRNA) at 8.3 A resolution. This post-translocational intermediate (TI(POST)) presents the TLD-SmpB module in an intrasubunit ap/P hybrid site and a tRNA(fMet) in an intrasubunit pe/E hybrid site. Conformational changes in the ribosome and tmRNA occur in the intersubunit space and on the solvent side. The key underlying event is a unique extra-large swivel movement of the 30S head, which is crucial for both tmRNA-SmpB translocation and MLD loading, thereby coupling translocation to MLD loading. This mechanism exemplifies the versatile, dynamic nature of the ribosome, and it shows that the conformational modes of the ribosome that normally drive canonical translation can also be used in a modified form to facilitate more complex tasks in specialized non-canonical pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramrath, David J F -- Yamamoto, Hiroshi -- Rother, Kristian -- Wittek, Daniela -- Pech, Markus -- Mielke, Thorsten -- Loerke, Justus -- Scheerer, Patrick -- Ivanov, Pavel -- Teraoka, Yoshika -- Shpanchenko, Olga -- Nierhaus, Knud H -- Spahn, Christian M T -- England -- Nature. 2012 May 6;485(7399):526-9. doi: 10.1038/nature11006.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Medizinische Physik und Biophysik, Charite - Universitatsmedizin Berlin, Ziegelstrasse 5-9, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22622583" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Base Sequence ; Cryoelectron Microscopy ; Escherichia coli/*chemistry ; Fusidic Acid/metabolism ; Ligands ; Models, Molecular ; Nucleic Acid Conformation ; Peptide Elongation Factor G/chemistry/*metabolism/ultrastructure ; Protein Binding ; *Protein Biosynthesis ; Protein Conformation ; RNA, Bacterial/*chemistry/genetics/*metabolism/ultrastructure ; RNA-Binding Proteins/chemistry/*metabolism/ultrastructure ; Ribosome Subunits/chemistry/genetics/metabolism/ultrastructure ; Ribosomes/chemistry/genetics/*metabolism/ultrastructure
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 35
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-10-27
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMichael, Andrew -- Chantler, Cyril -- England -- Nature. 2012 Oct 25;490(7421):487. doi: 10.1038/490487c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099395" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Awards and Prizes ; Biomedical Research/*history ; Fellowships and Scholarships/*history ; Great Britain ; History, 20th Century ; History, 21st Century ; *Nobel Prize
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 36
    Publikationsdatum: 2012-08-17
    Beschreibung: The South Pacific convergence zone (SPCZ) is the Southern Hemisphere's most expansive and persistent rain band, extending from the equatorial western Pacific Ocean southeastward towards French Polynesia. Owing to its strong rainfall gradient, a small displacement in the position of the SPCZ causes drastic changes to hydroclimatic conditions and the frequency of extreme weather events--such as droughts, floods and tropical cyclones--experienced by vulnerable island countries in the region. The SPCZ position varies from its climatological mean location with the El Nino/Southern Oscillation (ENSO), moving a few degrees northward during moderate El Nino events and southward during La Nina events. During strong El Nino events, however, the SPCZ undergoes an extreme swing--by up to ten degrees of latitude toward the Equator--and collapses to a more zonally oriented structure with commensurately severe weather impacts. Understanding changes in the characteristics of the SPCZ in a changing climate is therefore of broad scientific and socioeconomic interest. Here we present climate modelling evidence for a near doubling in the occurrences of zonal SPCZ events between the periods 1891-1990 and 1991-2090 in response to greenhouse warming, even in the absence of a consensus on how ENSO will change. We estimate the increase in zonal SPCZ events from an aggregation of the climate models in the Coupled Model Intercomparison Project phases 3 and 5 (CMIP3 and CMIP5) multi-model database that are able to simulate such events. The change is caused by a projected enhanced equatorial warming in the Pacific and may lead to more frequent occurrences of extreme events across the Pacific island nations most affected by zonal SPCZ events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cai, Wenju -- Lengaigne, Matthieu -- Borlace, Simon -- Collins, Matthew -- Cowan, Tim -- McPhaden, Michael J -- Timmermann, Axel -- Power, Scott -- Brown, Josephine -- Menkes, Christophe -- Ngari, Arona -- Vincent, Emmanuel M -- Widlansky, Matthew J -- England -- Nature. 2012 Aug 16;488(7411):365-9. doi: 10.1038/nature11358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CSIRO Marine and Atmospheric Research, Aspendale, Victoria 3195, Australia. wenju.cai@csiro.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895343" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Databases, Factual ; El Nino-Southern Oscillation/history ; Global Warming/economics/history/*statistics & numerical data ; Greenhouse Effect/economics/history/*statistics & numerical data ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Models, Theoretical ; Pacific Ocean ; Rain ; Socioeconomic Factors
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 37
    Publikationsdatum: 2012-10-27
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kring, David A -- Burns, Jack O -- Bussey, D Ben J -- England -- Nature. 2012 Oct 25;490(7421):487. doi: 10.1038/490487d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099396" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Astronauts/history/trends ; *Extraterrestrial Environment ; History, 20th Century ; History, 21st Century ; Mars ; Meteoroids ; Minor Planets ; *Moon ; Robotics ; Space Flight/instrumentation/*trends
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 38
    Publikationsdatum: 2012-03-03
    Beschreibung: Ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers such as SUMO (also known as Smt3 in Saccharomyces cerevisiae) mediate signal transduction through post-translational modification of substrate proteins in pathways that control differentiation, apoptosis and the cell cycle, and responses to stress such as the DNA damage response. In yeast, the proliferating cell nuclear antigen PCNA (also known as Pol30) is modified by ubiquitin in response to DNA damage and by SUMO during S phase. Whereas Ub-PCNA can signal for recruitment of translesion DNA polymerases, SUMO-PCNA signals for recruitment of the anti-recombinogenic DNA helicase Srs2. It remains unclear how receptors such as Srs2 specifically recognize substrates after conjugation to Ub and Ubls. Here we show, through structural, biochemical and functional studies, that the Srs2 carboxy-terminal domain harbours tandem receptor motifs that interact independently with PCNA and SUMO and that both motifs are required to recognize SUMO-PCNA specifically. The mechanism presented is pertinent to understanding how other receptors specifically recognize Ub- and Ubl-modified substrates to facilitate signal transduction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306252/" 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/PMC3306252/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Armstrong, Anthony A -- Mohideen, Firaz -- Lima, Christopher D -- F32 GM086066/GM/NIGMS NIH HHS/ -- F32 GM086066-01/GM/NIGMS NIH HHS/ -- F32 GM086066-02/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- P41RR012408/RR/NCRR NIH HHS/ -- R01 GM065872/GM/NIGMS NIH HHS/ -- R01 GM065872-08/GM/NIGMS NIH HHS/ -- R01 GM065872-09/GM/NIGMS NIH HHS/ -- R01 GM065872-10/GM/NIGMS NIH HHS/ -- R01 GM065872-11/GM/NIGMS NIH HHS/ -- R01 GM065872-12/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2012 Feb 29;483(7387):59-63. doi: 10.1038/nature10883.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22382979" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Motifs ; Antigens, Nuclear/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA Helicases/*chemistry/*metabolism ; Methylation ; Models, Molecular ; Proliferating Cell Nuclear Antigen/chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/*chemistry/genetics/growth & development ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism ; Small Ubiquitin-Related Modifier Proteins/chemistry/*metabolism ; Structure-Activity Relationship ; *Sumoylation
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 39
    Publikationsdatum: 2012-03-20
    Beschreibung: The basic unit of skeletal muscle in all metazoans is the multinucleate myofibre, within which individual nuclei are regularly positioned. The molecular machinery responsible for myonuclear positioning is not known. Improperly positioned nuclei are a hallmark of numerous diseases of muscle, including centronuclear myopathies, but it is unclear whether correct nuclear positioning is necessary for muscle function. Here we identify the microtubule-associated protein ensconsin (Ens)/microtubule-associated protein 7 (MAP7) and kinesin heavy chain (Khc)/Kif5b as essential, evolutionarily conserved regulators of myonuclear positioning in Drosophila and cultured mammalian myotubes. We find that these proteins interact physically and that expression of the Kif5b motor domain fused to the MAP7 microtubule-binding domain rescues nuclear positioning defects in MAP7-depleted cells. This suggests that MAP7 links Kif5b to the microtubule cytoskeleton to promote nuclear positioning. Finally, we show that myonuclear positioning is physiologically important. Drosophila ens mutant larvae have decreased locomotion and incorrect myonuclear positioning, and these phenotypes are rescued by muscle-specific expression of Ens. We conclude that improper nuclear positioning contributes to muscle dysfunction in a cell-autonomous fashion.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321085/" 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/PMC3321085/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Metzger, Thomas -- Gache, Vincent -- Xu, Mu -- Cadot, Bruno -- Folker, Eric S -- Richardson, Brian E -- Gomes, Edgar R -- Baylies, Mary K -- GM056989/GM/NIGMS NIH HHS/ -- GM0781318/GM/NIGMS NIH HHS/ -- R01 GM056989/GM/NIGMS NIH HHS/ -- R01 GM056989-09/GM/NIGMS NIH HHS/ -- R01 GM078318/GM/NIGMS NIH HHS/ -- R01 GM078318-04/GM/NIGMS NIH HHS/ -- T32 BM008539/BM/FDA HHS/ -- England -- Nature. 2012 Mar 18;484(7392):120-4. doi: 10.1038/nature10914.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Developmental Biology, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22425998" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Compartmentation/genetics ; Cell Line ; Cell Nucleus/*metabolism ; Cell Polarity/genetics ; Cells, Cultured ; Drosophila melanogaster/cytology/genetics/growth & development ; Kinesin/chemistry/deficiency/genetics/*metabolism ; Larva/cytology/genetics/metabolism ; Locomotion/genetics/physiology ; Mice ; Microtubule-Associated Proteins/chemistry/genetics/*metabolism ; Microtubules/metabolism ; Muscle Fibers, Skeletal/cytology/metabolism ; Muscle, Skeletal/*cytology/*physiology ; Organ Specificity ; Phenotype ; Protein Binding ; Protein Structure, Tertiary
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 40
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    Unbekannt
    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-03-31
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Evans, Ronald -- England -- Nature. 2012 Mar 28;483(7391):542. doi: 10.1038/483542a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute, La Jolla, California 92037, USA. evans@salk.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460892" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Corticotropin-Releasing Hormone/chemistry/history/isolation & purification ; History, 20th Century ; History, 21st Century ; Humans ; Neuroendocrinology/*history ; Nobel Prize ; Thyrotropin-Releasing Hormone/history
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 41
    facet.materialart.
    Unbekannt
    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-11-30
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Nov 29;491(7426):653. doi: 10.1038/491653a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23192125" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Carbon Footprint/economics/*legislation & jurisprudence/statistics & numerical ; data ; China ; Climate Change/*statistics & numerical data ; Developed Countries ; Developing Countries ; Environmental Policy/history/*legislation & jurisprudence/*trends ; Global Warming/history/legislation & jurisprudence/prevention & ; control/statistics & numerical data ; History, 20th Century ; History, 21st Century ; International Cooperation/*legislation & jurisprudence ; Japan
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 42
    Publikationsdatum: 2012-01-13
    Beschreibung: The proteasome is the major ATP-dependent protease in eukaryotic cells, but limited structural information restricts a mechanistic understanding of its activities. The proteasome regulatory particle, consisting of the lid and base subcomplexes, recognizes and processes polyubiquitinated substrates. Here we used electron microscopy and a new heterologous expression system for the lid to delineate the complete subunit architecture of the regulatory particle from yeast. Our studies reveal the spatial arrangement of ubiquitin receptors, deubiquitinating enzymes and the protein unfolding machinery at subnanometre resolution, outlining the substrate's path to degradation. Unexpectedly, the ATPase subunits within the base unfoldase are arranged in a spiral staircase, providing insight into potential mechanisms for substrate translocation through the central pore. Large conformational rearrangements of the lid upon holoenzyme formation suggest allosteric regulation of deubiquitination. We provide a structural basis for the ability of the proteasome to degrade a diverse set of substrates and thus regulate vital cellular processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285539/" 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/PMC3285539/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lander, Gabriel C -- Estrin, Eric -- Matyskiela, Mary E -- Bashore, Charlene -- Nogales, Eva -- Martin, Andreas -- R01 GM094497/GM/NIGMS NIH HHS/ -- R01 GM094497-01A1/GM/NIGMS NIH HHS/ -- R01-GM094497-01A1/GM/NIGMS NIH HHS/ -- RR017573/RR/NCRR NIH HHS/ -- T32 GM007232/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 11;482(7384):186-91. doi: 10.1038/nature10774.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237024" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism ; Binding Sites ; Endopeptidases/metabolism ; Escherichia coli/metabolism ; Holoenzymes/chemistry/genetics/metabolism ; Models, Molecular ; Proteasome Endopeptidase Complex/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Conformation ; Protein Subunits/*chemistry/genetics/*metabolism ; Recombinant Proteins/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Ubiquitin/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 43
    Publikationsdatum: 2012-08-17
    Beschreibung: Access to clean, affordable and reliable energy has been a cornerstone of the world's increasing prosperity and economic growth since the beginning of the industrial revolution. Our use of energy in the twenty-first century must also be sustainable. Solar and water-based energy generation, and engineering of microbes to produce biofuels are a few examples of the alternatives. This Perspective puts these opportunities into a larger context by relating them to a number of aspects in the transportation and electricity generation sectors. It also provides a snapshot of the current energy landscape and discusses several research and development opportunities and pathways that could lead to a prosperous, sustainable and secure energy future for the world.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chu, Steven -- Majumdar, Arun -- England -- Nature. 2012 Aug 16;488(7411):294-303. doi: 10.1038/nature11475.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Department of Energy, 1000 Independence Avenue SW, Washington DC 20585, USA. the.secretary@hq.doe.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895334" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Conservation of Energy Resources/statistics & numerical data/*trends ; Electricity ; Energy-Generating Resources/economics/history/statistics & numerical data ; Friction ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Horses/physiology ; Motor Vehicles ; Renewable Energy/economics/*statistics & numerical data ; Transportation/statistics & numerical data ; United States
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 44
    Publikationsdatum: 2012-10-30
    Beschreibung: Human chromosome ends are capped by shelterin, a protein complex that protects the natural ends from being recognized as sites of DNA damage and also regulates the telomere-replicating enzyme, telomerase. Shelterin includes the heterodimeric POT1-TPP1 protein, which binds the telomeric single-stranded DNA tail. TPP1 has been implicated both in recruiting telomerase to telomeres and in stimulating telomerase processivity (the addition of multiple DNA repeats after a single primer-binding event). Determining the mechanisms of these activities has been difficult, especially because genetic perturbations also tend to affect the essential chromosome end-protection function of TPP1 (refs 15-17). Here we identify separation-of-function mutants of human TPP1 that retain full telomere-capping function in vitro and in vivo, yet are defective in binding human telomerase. The seven separation-of-function mutations map to a patch of amino acids on the surface of TPP1, the TEL patch, that both recruits telomerase to telomeres and promotes high-processivity DNA synthesis, indicating that these two activities are manifestations of the same molecular interaction. Given that the interaction between telomerase and TPP1 is required for telomerase function in vivo, the TEL patch of TPP1 provides a new target for anticancer drug development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521872/" 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/PMC3521872/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nandakumar, Jayakrishnan -- Bell, Caitlin F -- Weidenfeld, Ina -- Zaug, Arthur J -- Leinwand, Leslie A -- Cech, Thomas R -- K99 CA167644/CA/NCI NIH HHS/ -- K99CA167644/CA/NCI NIH HHS/ -- R01 GM029090/GM/NIGMS NIH HHS/ -- R01 GM099705/GM/NIGMS NIH HHS/ -- R01GM099705/GM/NIGMS NIH HHS/ -- R01GM29090/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Dec 13;492(7428):285-9. doi: 10.1038/nature11648. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Colorado BioFrontiers Institute, Boulder, Colorado 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103865" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Cell Line ; HEK293 Cells ; HeLa Cells ; Humans ; Models, Molecular ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; Telomerase/*metabolism ; Telomere/genetics/*metabolism ; Telomere-Binding Proteins/chemistry/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 45
    Publikationsdatum: 2012-11-30
    Beschreibung: A new data set of middle- and upper-stratospheric temperatures based on reprocessing of satellite radiances provides a view of stratospheric climate change during the period 1979-2005 that is strikingly different from that provided by earlier data sets. The new data call into question our understanding of observed stratospheric temperature trends and our ability to test simulations of the stratospheric response to emissions of greenhouse gases and ozone-depleting substances. Here we highlight the important issues raised by the new data and suggest how the climate science community can resolve them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, David W J -- Seidel, Dian J -- Randel, William J -- Zou, Cheng-Zhi -- Butler, Amy H -- Mears, Carl -- Osso, Albert -- Long, Craig -- Lin, Roger -- England -- Nature. 2012 Nov 29;491(7426):692-7. doi: 10.1038/nature11579.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atmospheric Science, Colorado State University, Fort Collins, Colorado 80523, USA. davet@atmos.colostate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23192146" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Altitude ; *Atmosphere/analysis ; Climate ; Global Warming/history/statistics & numerical data ; History, 20th Century ; History, 21st Century ; Human Activities ; Models, Theoretical ; Spacecraft ; *Temperature ; Time Factors ; *Uncertainty
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 46
    Publikationsdatum: 2012-12-04
    Beschreibung: Although initially viewed as unregulated, increasing evidence suggests that cellular necrosis often proceeds through a specific molecular program. In particular, death ligands such as tumour necrosis factor (TNF)-alpha activate necrosis by stimulating the formation of a complex containing receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Relatively little is known regarding how this complex formation is regulated. Here, we show that the NAD-dependent deacetylase SIRT2 binds constitutively to RIP3 and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. Furthermore, genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha. We further demonstrate that RIP1 is a critical target of SIRT2-dependent deacetylation. Using gain- and loss-of-function mutants, we demonstrate that acetylation of RIP1 lysine 530 modulates RIP1-RIP3 complex formation and TNF-alpha-stimulated necrosis. In the setting of ischaemia-reperfusion injury, RIP1 is deacetylated in a SIRT2-dependent fashion. Furthermore, the hearts of Sirt2(-/-) mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischaemic injury. Taken together, these results implicate SIRT2 as an important regulator of programmed necrosis and indicate that inhibitors of this deacetylase may constitute a novel approach to protect against necrotic injuries, including ischaemic stroke and myocardial infarction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narayan, Nisha -- Lee, In Hye -- Borenstein, Ronen -- Sun, Junhui -- Wong, Renee -- Tong, Guang -- Fergusson, Maria M -- Liu, Jie -- Rovira, Ilsa I -- Cheng, Hwei-Ling -- Wang, Guanghui -- Gucek, Marjan -- Lombard, David -- Alt, Fredrick W -- Sack, Michael N -- Murphy, Elizabeth -- Cao, Liu -- Finkel, Toren -- Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Dec 13;492(7428):199-204. doi: 10.1038/nature11700. Epub 2012 Nov 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Medicine, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23201684" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylation ; Animals ; Cell Line ; Female ; HEK293 Cells ; HeLa Cells ; Humans ; Jurkat Cells ; Male ; Mice ; Necrosis/*enzymology ; Nuclear Pore Complex Proteins/metabolism ; Protein Binding ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Sirtuin 2/*genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 47
    Publikationsdatum: 2012-12-22
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heuer, Rolf-Dieter -- Rosenzweig, Cynthia -- Steltzner, Adam -- Blanpain, Cedric -- Iorns, Elizabeth -- Wang, Jun -- Handelsman, Jo -- Gowers, Tim -- De Bernardinis, Bernardo -- Fouchier, Ron -- England -- Nature. 2012 Dec 20;492(7429):335-43. doi: 10.1038/492335a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257862" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Access to Information ; Animals ; Bioterrorism/prevention & control ; Climate Change ; Disaster Planning/history ; Earthquakes/statistics & numerical data ; Forecasting ; Genomics ; History, 20th Century ; History, 21st Century ; Humans ; Influenza A Virus, H5N1 Subtype/genetics/pathogenicity ; Influenza, Human/transmission/virology ; Mars ; Neoplastic Stem Cells/cytology ; New York City ; Physics/history ; Publishing/economics ; Reproducibility of Results ; *Research/economics/standards/statistics & numerical data ; Security Measures ; Sexism/psychology/statistics & numerical data ; Space Flight/history/instrumentation
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 48
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-06-07
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bialik, Mayim -- England -- Nature. 2012 May 31;485(7400):669.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22670263" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Drama/history ; *Education, Graduate/history ; History, 21st Century ; Los Angeles ; Maternal Behavior/psychology ; *Neurosciences/education ; *Research Personnel/education/psychology ; *Television/history
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 49
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-06-09
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- Gilbert, Natasha -- England -- Nature. 2012 Jun 6;486(7401):20-3. doi: 10.1038/486020a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678262" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Biodiversity ; Brazil ; Carbon Dioxide/analysis ; *Congresses as Topic/history/trends ; Conservation of Natural Resources/economics/history/*statistics & numerical data ; Desert Climate/adverse effects ; Developed Countries/economics/statistics & numerical data ; Developing Countries/economics/statistics & numerical data ; *Environmental Policy/economics/history/legislation & jurisprudence/trends ; Extinction, Biological ; History, 20th Century ; History, 21st Century ; *International Cooperation/history ; Ozone/history ; Politics ; Renewable Energy/economics/statistics & numerical data ; United Nations
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 50
    Publikationsdatum: 2012-06-16
    Beschreibung: Salicylic acid (SA) is a plant immune signal produced after pathogen challenge to induce systemic acquired resistance. It is the only major plant hormone for which the receptor has not been firmly identified. Systemic acquired resistance in Arabidopsis requires the transcription cofactor nonexpresser of PR genes 1 (NPR1), the degradation of which acts as a molecular switch. Here we show that the NPR1 paralogues NPR3 and NPR4 are SA receptors that bind SA with different affinities. NPR3 and NPR4 function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the Arabidopsis npr3 npr4 double mutant accumulates higher levels of NPR1, and is insensitive to induction of systemic acquired resistance. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376392/" 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/PMC3376392/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, Zheng Qing -- Yan, Shunping -- Saleh, Abdelaty -- Wang, Wei -- Ruble, James -- Oka, Nodoka -- Mohan, Rajinikanth -- Spoel, Steven H -- Tada, Yasuomi -- Zheng, Ning -- Dong, Xinnian -- CA107134/CA/NCI NIH HHS/ -- GM069594-05/GM/NIGMS NIH HHS/ -- R01 CA107134/CA/NCI NIH HHS/ -- R01 GM069594/GM/NIGMS NIH HHS/ -- T32 GM008268/GM/NIGMS NIH HHS/ -- T32GM008268-23/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 May 16;486(7402):228-32. doi: 10.1038/nature11162.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Department of Biology, PO Box 90338, Duke University, Durham, North Carolina 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22699612" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Arabidopsis/*genetics/immunology/*metabolism ; Arabidopsis Proteins/genetics/metabolism ; Mutation ; Protein Binding ; Salicylic Acid/*metabolism ; *Signal Transduction ; Two-Hybrid System Techniques ; Ubiquitin-Protein Ligases/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 51
    Publikationsdatum: 2012-03-20
    Beschreibung: Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of approximately 50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of approximately 50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345284/" 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/PMC3345284/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hong, Weizhe -- Mosca, Timothy J -- Luo, Liqun -- 5T32 NS007280/NS/NINDS NIH HHS/ -- HD007249/HD/NICHD NIH HHS/ -- R01 DC-005982/DC/NIDCD NIH HHS/ -- R01 DC005982/DC/NIDCD NIH HHS/ -- R01 DC005982-10/DC/NIDCD NIH HHS/ -- T32 HD007249/HD/NICHD NIH HHS/ -- T32 HD007249-28/HD/NICHD NIH HHS/ -- T32 NS007280/NS/NINDS NIH HHS/ -- T32 NS007280-25/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 18;484(7393):201-7. doi: 10.1038/nature10926.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22425994" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Axons/metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*cytology/*metabolism ; Olfactory Pathways/*physiology ; Olfactory Receptor Neurons/metabolism ; Protein Binding ; RNA Interference ; Receptors, Cell Surface/*metabolism ; Smell/physiology ; Synapses/*metabolism ; Tenascin/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 52
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-06-09
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Jun 6;486(7401):5. doi: 10.1038/486005a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678243" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Conservation of Natural Resources/history/legislation & jurisprudence/statistics ; & numerical data ; Earth (Planet) ; Environmental Policy/history/*legislation & jurisprudence ; Forestry/history/statistics & numerical data ; History, 20th Century ; History, 21st Century ; *International Cooperation ; *Leadership ; Politics
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 53
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-06-05
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 May 30;485(7400):547-8. doi: 10.1038/485547b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22660278" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Child ; Disease Eradication/economics/history/*statistics & numerical data ; Global Health/economics/*statistics & numerical data ; History, 20th Century ; History, 21st Century ; Humans ; Poliomyelitis/economics/*epidemiology/history ; Poliovirus Vaccines/administration & dosage/economics ; Vaccination
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 54
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-02-18
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trivedi, Bijal P -- England -- Nature. 2012 Feb 15;482(7385):294-6. doi: 10.1038/482294a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22337030" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alzheimer Disease/drug therapy/metabolism/prevention & control ; Amyloid beta-Peptides/metabolism ; Animals ; *Biological Evolution ; Clinical Trials as Topic ; Drosophila Proteins/deficiency/genetics/metabolism ; Drosophila melanogaster/genetics/metabolism ; Genetic Variation/genetics ; HSP90 Heat-Shock Proteins/antagonists & inhibitors/*metabolism ; Heat-Shock Proteins/deficiency/genetics/metabolism ; Heat-Shock Response/physiology ; History, 20th Century ; History, 21st Century ; Humans ; Models, Biological ; Neoplasms/drug therapy/metabolism ; Peptide Termination Factors/metabolism ; Prions/chemistry/*metabolism ; Protein Folding ; Saccharomyces cerevisiae/genetics/growth & development/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 55
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-10-19
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Samant, Rahul S -- Workman, Paul -- England -- Nature. 2012 Oct 18;490(7420):351-2. doi: 10.1038/490351a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23075983" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Enzyme Stability ; HSP90 Heat-Shock Proteins/antagonists & inhibitors/*metabolism ; Luminescent Measurements ; Protein Binding ; Protein Interaction Mapping ; *Protein Interaction Maps ; Substrate Specificity
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 56
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-01-10
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hopkins, Nancy -- England -- Nature. 2012 Jan 4;481(7379):13. doi: 10.1038/481013a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22222731" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; *Prejudice ; Research Personnel/history/psychology/*statistics & numerical data ; Science/*manpower/standards ; Sex Characteristics ; Women's Rights/*history
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 57
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-04-28
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Apr 25;484(7395):416. doi: 10.1038/484416a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22538562" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Bloodletting/history ; Conservation of Natural Resources/*methods ; Endangered Species ; Hirudin Therapy/history/utilization ; History, 19th Century ; History, 21st Century ; History, Ancient ; Humans ; Leeches/*metabolism ; Leeching/adverse effects/history/utilization
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 58
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-01-13
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lok, Corie -- England -- Nature. 2012 Jan 11;481(7380):130-3. doi: 10.1038/481130a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237089" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Biotechnology/ethics/history/*trends ; Blindness/pathology/surgery/therapy ; Clinical Trials as Topic/trends ; Cloning, Organism/ethics/history ; Embryo Research/ethics/history ; Embryonic Stem Cells/*transplantation ; History, 21st Century ; Humans ; Rats ; Retinal Pigment Epithelium/cytology/transplantation ; *Stem Cell Research/ethics/history ; United States ; United States Food and Drug Administration
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 59
    Publikationsdatum: 2012-08-31
    Beschreibung: Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palike, Heiko -- Lyle, Mitchell W -- Nishi, Hiroshi -- Raffi, Isabella -- Ridgwell, Andy -- Gamage, Kusali -- Klaus, Adam -- Acton, Gary -- Anderson, Louise -- Backman, Jan -- Baldauf, Jack -- Beltran, Catherine -- Bohaty, Steven M -- Bown, Paul -- Busch, William -- Channell, Jim E T -- Chun, Cecily O J -- Delaney, Margaret -- Dewangan, Pawan -- Dunkley Jones, Tom -- Edgar, Kirsty M -- Evans, Helen -- Fitch, Peter -- Foster, Gavin L -- Gussone, Nikolaus -- Hasegawa, Hitoshi -- Hathorne, Ed C -- Hayashi, Hiroki -- Herrle, Jens O -- Holbourn, Ann -- Hovan, Steve -- Hyeong, Kiseong -- Iijima, Koichi -- Ito, Takashi -- Kamikuri, Shin-ichi -- Kimoto, Katsunori -- Kuroda, Junichiro -- Leon-Rodriguez, Lizette -- Malinverno, Alberto -- Moore, Ted C Jr -- Murphy, Brandon H -- Murphy, Daniel P -- Nakamura, Hideto -- Ogane, Kaoru -- Ohneiser, Christian -- Richter, Carl -- Robinson, Rebecca -- Rohling, Eelco J -- Romero, Oscar -- Sawada, Ken -- Scher, Howie -- Schneider, Leah -- Sluijs, Appy -- Takata, Hiroyuki -- Tian, Jun -- Tsujimoto, Akira -- Wade, Bridget S -- Westerhold, Thomas -- Wilkens, Roy -- Williams, Trevor -- Wilson, Paul A -- Yamamoto, Yuhji -- Yamamoto, Shinya -- Yamazaki, Toshitsugu -- Zeebe, Richard E -- England -- Nature. 2012 Aug 30;488(7413):609-14. doi: 10.1038/nature11360.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ocean and Earth Science, National Oceanography Centre Southampton, University of Southampton, Waterfront Campus, European Way, Southampton SO14 3ZH, UK. hpaelike@marum.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22932385" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Altitude ; Atmosphere/chemistry ; Calcium Carbonate/*analysis ; *Carbon Cycle ; Carbon Dioxide/analysis ; Diatoms/metabolism ; Foraminifera/metabolism ; Geologic Sediments/chemistry ; Global Warming/history/statistics & numerical data ; History, 21st Century ; History, Ancient ; Marine Biology ; Oxygen/metabolism ; Pacific Ocean ; Seawater/*chemistry ; Temperature
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 60
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-10-27
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sansom, Mark -- England -- Nature. 2012 Oct 25;490(7421):488. doi: 10.1038/490488a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. mark.sansom@bioch.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099399" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Biochemistry/history ; Biophysics/*history ; Crystallography, X-Ray/*history ; Glycogen Phosphorylase/chemistry/history ; Great Britain ; History, 20th Century ; History, 21st Century ; Muramidase/chemistry/history
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 61
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-12-22
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Noorden, Richard -- England -- Nature. 2012 Dec 20;492(7429):324-7. doi: 10.1038/492324a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257860" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Drug Approval ; Drug Industry/economics ; Economic Recession ; Encyclopedias as Topic ; Food, Genetically Modified/standards ; Genetics ; Global Warming ; History, 21st Century ; Humans ; Influenza A Virus, H5N1 Subtype/genetics/pathogenicity ; Mars ; Nuclear Energy ; Physics ; Science/*history ; Space Flight/instrumentation ; Transportation/legislation & jurisprudence
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 62
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-12-22
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, David -- Moreno, Jonathan -- England -- Nature. 2012 Dec 20;492(7429):345-7. doi: 10.1038/492345a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. dikaiser@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257863" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Bioterrorism/prevention & control ; DNA, Recombinant/history ; Ferrets/virology ; Genetic Engineering/history/legislation & jurisprudence/standards ; History, 20th Century ; History, 21st Century ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/*pathogenicity ; Influenza, Human/epidemiology/*transmission/*virology ; Nuclear Warfare/history/legislation & jurisprudence ; Risk Assessment ; Security Measures/*history/*standards
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 63
    Publikationsdatum: 2012-05-19
    Beschreibung: Evolution of the mammalian sex chromosomes has resulted in a heterologous X and Y pair, where the Y chromosome has lost most of its genes. Hence, there is a need for X-linked gene dosage compensation between XY males and XX females. In placental mammals, this is achieved by random inactivation of one X chromosome in all female somatic cells. Upregulation of Xist transcription on the future inactive X chromosome acts against Tsix antisense transcription, and spreading of Xist RNA in cis triggers epigenetic changes leading to X-chromosome inactivation. Previously, we have shown that the X-encoded E3 ubiquitin ligase RNF12 is upregulated in differentiating mouse embryonic stem cells and activates Xist transcription and X-chromosome inactivation. Here we identify the pluripotency factor REX1 as a key target of RNF12 in the mechanism of X-chromosome inactivation. RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. Using chromatin immunoprecipitation sequencing, REX1 binding sites were detected in Xist and Tsix regulatory regions. Overexpression of REX1 in female embryonic stem cells was found to inhibit Xist transcription and X-chromosome inactivation, whereas male Rex1(+/-) embryonic stem cells showed ectopic X-chromosome inactivation. From this, we propose that RNF12 causes REX1 breakdown through dose-dependent catalysis, thereby representing an important pathway to initiate X-chromosome inactivation. Rex1 and Xist are present only in placental mammals, which points to co-evolution of these two genes and X-chromosome inactivation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gontan, Cristina -- Achame, Eskeatnaf Mulugeta -- Demmers, Jeroen -- Barakat, Tahsin Stefan -- Rentmeester, Eveline -- van IJcken, Wilfred -- Grootegoed, J Anton -- Gribnau, Joost -- England -- Nature. 2012 Apr 29;485(7398):386-90. doi: 10.1038/nature11070.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Reproduction and Development, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22596162" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Binding Sites ; Embryonic Stem Cells/metabolism ; Female ; Gene Expression Regulation ; Male ; Mice ; Molecular Sequence Data ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; Transcription Factors/deficiency/genetics/*metabolism ; Transcription, Genetic ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitination ; X Chromosome/*genetics ; *X Chromosome Inactivation
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 64
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    Unbekannt
    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-06-29
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2012 Jun 27;486(7404):460-2. doi: 10.1038/486460a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22739294" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Developmental Biology/history ; *Evolution, Molecular ; History, 20th Century ; History, 21st Century ; Humans ; Invertebrates/genetics ; Mammals/genetics ; MicroRNAs/*analysis/*genetics ; *Phylogeny
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 65
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    Unbekannt
    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-04-14
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prather, Michael J -- Blake, Donald R -- England -- Nature. 2012 Apr 11;484(7393):168. doi: 10.1038/484168a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, Irvine, California, USA. mprather@uci.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22498618" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Chemistry/*history ; Chlorofluorocarbons/analysis/*chemistry ; Ecology/history ; Environmental Policy/history ; History, 20th Century ; History, 21st Century ; Nobel Prize ; Ozone/*analysis/*chemistry ; Petroleum Pollution ; United States
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 66
    Publikationsdatum: 2012-04-17
    Beschreibung: Effective targeted cancer therapeutic development depends upon distinguishing disease-associated 'driver' mutations, which have causative roles in malignancy pathogenesis, from 'passenger' mutations, which are dispensable for cancer initiation and maintenance. Translational studies of clinically active targeted therapeutics can definitively discriminate driver from passenger lesions and provide valuable insights into human cancer biology. Activating internal tandem duplication (ITD) mutations in FLT3 (FLT3-ITD) are detected in approximately 20% of acute myeloid leukaemia (AML) patients and are associated with a poor prognosis. Abundant scientific and clinical evidence, including the lack of convincing clinical activity of early FLT3 inhibitors, suggests that FLT3-ITD probably represents a passenger lesion. Here we report point mutations at three residues within the kinase domain of FLT3-ITD that confer substantial in vitro resistance to AC220 (quizartinib), an active investigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET; evolution of AC220-resistant substitutions at two of these amino acid positions was observed in eight of eight FLT3-ITD-positive AML patients with acquired resistance to AC220. Our findings demonstrate that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML. AC220-resistant FLT3 kinase domain mutants represent high-value targets for future FLT3 inhibitor development efforts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390926/" 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/PMC3390926/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Catherine C -- Wang, Qi -- Chin, Chen-Shan -- Salerno, Sara -- Damon, Lauren E -- Levis, Mark J -- Perl, Alexander E -- Travers, Kevin J -- Wang, Susana -- Hunt, Jeremy P -- Zarrinkar, Patrick P -- Schadt, Eric E -- Kasarskis, Andrew -- Kuriyan, John -- Shah, Neil P -- P50 CA100632/CA/NCI NIH HHS/ -- P50 CA100632-06/CA/NCI NIH HHS/ -- R01 CA12886/CA/NCI NIH HHS/ -- R01 CA128864/CA/NCI NIH HHS/ -- R01 CA166616/CA/NCI NIH HHS/ -- England -- Nature. 2012 Apr 15;485(7397):260-3. doi: 10.1038/nature11016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology/Oncology, University of California, San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22504184" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Benzothiazoles/pharmacology/*therapeutic use ; Cell Line, Tumor ; DNA Mutational Analysis ; Drug Resistance, Neoplasm/genetics ; Humans ; Leukemia, Myeloid, Acute/*drug therapy/*genetics/metabolism ; Models, Molecular ; Molecular Structure ; *Molecular Targeted Therapy ; Mutation/*genetics ; Phenylurea Compounds/pharmacology/*therapeutic use ; Protein Binding ; Protein Structure, Tertiary/genetics ; Recurrence ; Reproducibility of Results ; fms-Like Tyrosine Kinase 3/*antagonists & inhibitors/*genetics/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 67
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-02-10
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walter, Matthew -- England -- Nature. 2012 Feb 8;482(7384):148-52. doi: 10.1038/482148a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318585" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult ; Aged, 80 and over ; Biomedical Research/ethics/history ; Child ; Female ; Gonorrhea/epidemiology/history ; Guatemala/epidemiology ; History, 20th Century ; History, 21st Century ; Human Experimentation/*ethics/*history/statistics & numerical data ; Humans ; Male ; Military Personnel/statistics & numerical data ; Military Science/ethics/history ; Sex Workers/statistics & numerical data ; Sexually Transmitted Diseases/epidemiology/*history/prevention & control ; Syphilis/epidemiology/history ; United States/epidemiology
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 68
    Publikationsdatum: 2012-03-16
    Beschreibung: Fifty per cent of the genome is discontinuously replicated on the lagging strand as Okazaki fragments. Eukaryotic Okazaki fragments remain poorly characterized and, because nucleosomes are rapidly deposited on nascent DNA, Okazaki fragment processing and nucleosome assembly potentially affect one another. Here we show that ligation-competent Okazaki fragments in Saccharomyces cerevisiae are sized according to the nucleosome repeat. Using deep sequencing, we demonstrate that ligation junctions preferentially occur near nucleosome midpoints rather than in internucleosomal linker regions. Disrupting chromatin assembly or lagging-strand polymerase processivity affects both the size and the distribution of Okazaki fragments, suggesting a role for nascent chromatin, assembled immediately after the passage of the replication fork, in the termination of Okazaki fragment synthesis. Our studies represent the first high-resolution analysis--to our knowledge--of eukaryotic Okazaki fragments in vivo, and reveal the interconnection between lagging-strand synthesis and chromatin assembly.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490407/" 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/PMC3490407/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Duncan J -- Whitehouse, Iestyn -- P30 CA008748/CA/NCI NIH HHS/ -- R01 GM102253/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 14;483(7390):434-8. doi: 10.1038/nature10895.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22419157" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Chromatin Assembly and Disassembly/*physiology ; DNA/*biosynthesis/genetics/metabolism ; DNA Ligases/deficiency/metabolism ; DNA Polymerase III/metabolism ; *DNA Replication ; DNA-Binding Proteins/metabolism ; High-Throughput Nucleotide Sequencing ; Nucleosomes/genetics/*metabolism ; Protein Binding ; Saccharomyces cerevisiae/enzymology/*genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription Factors/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 69
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-09-11
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Kerri -- England -- Nature. 2012 Sep 6;489(7414):22-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22962704" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Beak ; Birds/anatomy & histology/*classification ; China ; Dinosaurs/anatomy & histology/*classification/physiology ; Expeditions ; Feathers/anatomy & histology/physiology ; *Fossils ; History, 20th Century ; History, 21st Century ; Museums ; Paleontology/*history/standards ; Peer Review, Research/standards ; *Phylogeny
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 70
    Publikationsdatum: 2012-11-20
    Beschreibung: There is a recognized need to anticipate tipping points, or critical transitions, in social-ecological systems. Studies of mathematical and experimental systems have shown that systems may 'wobble' before a critical transition. Such early warning signals may be due to the phenomenon of critical slowing down, which causes a system to recover slowly from small impacts, or to a flickering phenomenon, which causes a system to switch back and forth between alternative states in response to relatively large impacts. Such signals for transitions in social-ecological systems have rarely been observed, not the least because high-resolution time series are normally required. Here we combine empirical data from a lake-catchment system with a mathematical model and show that flickering can be detected from sparse data. We show how rising variance coupled to decreasing autocorrelation and skewness started 10-30 years before the transition to eutrophic lake conditions in both the empirical records and the model output, a finding that is consistent with flickering rather than critical slowing down. Our results suggest that if environmental regimes are sufficiently affected by large external impacts that flickering is induced, then early warning signals of transitions in modern social-ecological systems may be stronger, and hence easier to identify, than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Rong -- Dearing, John A -- Langdon, Peter G -- Zhang, Enlou -- Yang, Xiangdong -- Dakos, Vasilis -- Scheffer, Marten -- 268732/European Research Council/International -- England -- Nature. 2012 Dec 20;492(7429):419-22. doi: 10.1038/nature11655. Epub 2012 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Palaeoecological Laboratory, Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23160492" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): China ; Diatoms/isolation & purification ; *Eutrophication ; Forecasting/*methods ; Geologic Sediments/analysis/chemistry ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Lakes/chemistry ; Phosphorus/analysis ; Time Factors
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 71
    Publikationsdatum: 2012-12-12
    Beschreibung: Ten eleven translocation (TET) enzymes, including TET1, TET2 and TET3, convert 5-methylcytosine to 5-hydroxymethylcytosine and regulate gene transcription. However, the molecular mechanism by which TET family enzymes regulate gene transcription remains elusive. Using protein affinity purification, here we search for functional partners of TET proteins, and find that TET2 and TET3 associate with O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT), an enzyme that by itself catalyses the addition of O-GlcNAc onto serine and threonine residues (O-GlcNAcylation) in vivo. TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription start sites. Downregulation of TET2 reduces the amount of histone 2B Ser 112 GlcNAc marks in vivo, which are associated with gene transcription regulation. Taken together, these results reveal a TET2-dependent O-GlcNAcylation of chromatin. The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684361/" 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/PMC3684361/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Qiang -- Chen, Yibin -- Bian, Chunjing -- Fujiki, Ryoji -- Yu, Xiaochun -- CA130899/CA/NCI NIH HHS/ -- CA132755/CA/NCI NIH HHS/ -- P30 DK034933/DK/NIDDK NIH HHS/ -- R01 CA130899/CA/NCI NIH HHS/ -- R01 CA132755/CA/NCI NIH HHS/ -- England -- Nature. 2013 Jan 24;493(7433):561-4. doi: 10.1038/nature11742. Epub 2012 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222540" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Biocatalysis ; Chromatin/chemistry/metabolism ; DNA-Binding Proteins/*metabolism ; Epigenesis, Genetic ; Glycosylation ; Histones/*chemistry/*metabolism ; Humans ; N-Acetylglucosaminyltransferases/*metabolism ; Protein Binding ; Proto-Oncogene Proteins/*metabolism ; Serine/metabolism ; Transcription Initiation Site ; *Transcription, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 72
    Publikationsdatum: 2012-11-20
    Beschreibung: In response to genotoxic stress, a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint (DDC) signalling pathway positively contributes to genome maintenance. Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest, cells must tightly regulate the activity of the kinases involved in this pathway. Despite their importance, the mechanisms for monitoring and modulating DDC signalling are not fully understood. Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae. On replication stress, cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53, whereas activation of the upstream DDC kinase Mec1 remains normal. An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A, two positive regulators of Rad9-dependent Rad53 activation. A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107. We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions. Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536934/" 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/PMC3536934/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ohouo, Patrice Y -- Bastos de Oliveira, Francisco M -- Liu, Yi -- Ma, Chu Jian -- Smolka, Marcus B -- F31 GM093588/GM/NIGMS NIH HHS/ -- F31-GM093588/GM/NIGMS NIH HHS/ -- R01 GM097272/GM/NIGMS NIH HHS/ -- R01-GM097272/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jan 3;493(7430):120-4. doi: 10.1038/nature11658. Epub 2012 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23160493" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Binding, Competitive ; Cell Cycle Checkpoints/*physiology ; Cell Cycle Proteins/antagonists & inhibitors/deficiency/genetics/*metabolism ; Checkpoint Kinase 2 ; DNA Damage/drug effects ; DNA Repair/drug effects/*physiology ; DNA Replication/drug effects ; Endodeoxyribonucleases/deficiency/metabolism ; Enzyme Activation ; Histones/chemistry/genetics/metabolism ; Hydroxyurea/pharmacology ; Intracellular Signaling Peptides and Proteins/metabolism ; Mutation ; Nuclear Proteins/deficiency/metabolism ; Phosphorylation ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Saccharomyces cerevisiae/*cytology/drug effects/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Signal Transduction ; Stress, Physiological/drug effects
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 73
    Publikationsdatum: 2012-11-28
    Beschreibung: DNA double-strand break repair is critical for cell viability and involves highly coordinated pathways to restore DNA integrity at the lesion. An early event during homology-dependent repair is resection of the break to generate progressively longer 3' single-strand tails that are used to identify suitable templates for repair. Sister chromatids provide near-perfect sequence homology and are therefore the preferred templates during homologous recombination. To provide a bias for the use of sisters as donors, cohesin--the complex that tethers sister chromatids together--is recruited to the break to enforce physical proximity. Here we show that DNA breaks promote dissociation of cohesin loaded during the previous S phase in budding yeast, and that damage-induced dissociation of cohesin requires separase, the protease that dissolves cohesion in anaphase. Moreover, a separase-resistant allele of the gene coding for the alpha-kleisin subunit of cohesin, Mcd1 (also known as Scc1), reduces double-strand break resection and compromises the efficiency of repair even when loaded during DNA damage. We conclude that post-replicative DNA repair involves cohesin dissociation by separase to promote accessibility to repair factors during the coordinated cellular response to restore DNA integrity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McAleenan, Alexandra -- Clemente-Blanco, Andres -- Cordon-Preciado, Violeta -- Sen, Nicholas -- Esteras, Miguel -- Jarmuz, Adam -- Aragon, Luis -- MC_U120074328/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2013 Jan 10;493(7431):250-4. doi: 10.1038/nature11630. Epub 2012 Nov 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23178808" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alleles ; Anaphase ; Cell Cycle Proteins/*chemistry/genetics/*metabolism ; Chromatin Immunoprecipitation ; Chromosomal Proteins, Non-Histone/*chemistry/genetics/*metabolism ; DNA Breaks, Double-Stranded ; *DNA Repair ; *DNA Replication ; Endopeptidases/*metabolism ; G2 Phase ; Metaphase ; Protein Binding ; Protein Stability ; Protein Subunits/chemistry/metabolism ; S Phase ; Saccharomyces cerevisiae/cytology/enzymology/genetics/*physiology ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Separase
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 74
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-03-02
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dunn, Barbara -- England -- Nature. 2012 Feb 29;483(7387):S2-6. doi: 10.1038/483S2a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cancer Prevention, US National Cancer Institute, USA. dunnb@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22378123" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Diet ; History, 18th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Male ; Molecular Targeted Therapy ; *Neoplasms/etiology/history/prevention & control/therapy ; Neoplastic Stem Cells/metabolism/pathology ; Porifera/cytology/genetics
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 75
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-08-24
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKee, Maggie -- England -- Nature. 2012 Aug 23;488(7412):460. doi: 10.1038/488460a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉maggieqmckee@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22914157" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Astronauts/*history/psychology ; Atmosphere/chemistry ; Exobiology/economics ; History, 20th Century ; History, 21st Century ; Mars ; Physics/history ; Prejudice ; Space Flight/economics/history ; Tennis ; United States ; United States National Aeronautics and Space Administration/economics/history ; Women's Rights/*history
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 76
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-04-28
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitfield, John -- England -- Nature. 2012 Apr 25;484(7395):436-8. doi: 10.1038/484436a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22538583" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Biological Specimen Banks/history/statistics & numerical data ; Botany/history/*manpower/trends ; *Classification/methods ; Employment/statistics & numerical data/trends ; Expeditions/history ; Genetic Markers ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Internationality ; Plants/*classification/genetics ; *Research Personnel/history ; Tropical Climate
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 77
    Publikationsdatum: 2012-03-01
    Beschreibung: Histones are ubiquitinated in response to DNA double-strand breaks (DSB), promoting recruitment of repair proteins to chromatin. UBC13 (also known as UBE2N) is a ubiquitin-conjugating enzyme (E2) that heterodimerizes with UEV1A (also known as UBE2V1) and synthesizes K63-linked polyubiquitin (K63Ub) chains at DSB sites in concert with the ubiquitin ligase (E3), RNF168 (ref. 3). K63Ub synthesis is regulated in a non-canonical manner by the deubiquitinating enzyme, OTUB1 (OTU domain-containing ubiquitin aldehyde-binding protein 1), which binds preferentially to the UBC13 approximately Ub thiolester. Residues amino-terminal to the OTU domain, which had been implicated in ubiquitin binding, are required for binding to UBC13 approximately Ub and inhibition of K63Ub synthesis. Here we describe structural and biochemical studies elucidating how OTUB1 inhibits UBC13 and other E2 enzymes. We unexpectedly find that OTUB1 binding to UBC13 approximately Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13 approximately Ub, while at the same time disrupting interactions with UEV1A in a manner that depends on the OTUB1 N terminus. Crystal structures of an OTUB1-UBC13 complex and of OTUB1 bound to ubiquitin aldehyde and a chemical UBC13 approximately Ub conjugate show that binding of free ubiquitin to OTUB1 triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N terminus, thus promoting binding of the conjugated donor ubiquitin in UBC13 approximately Ub to OTUB1. The donor ubiquitin thus cannot interact with the E2 enzyme, which has been shown to be important for ubiquitin transfer. The N-terminal helix of OTUB1 is positioned to interfere with UEV1A binding to UBC13, as well as with attack on the thiolester by an acceptor ubiquitin, thereby inhibiting K63Ub synthesis. OTUB1 binding also occludes the RING E3 binding site on UBC13, thus providing a further component of inhibition. The general features of the inhibition mechanism explain how OTUB1 inhibits other E2 enzymes in a non-catalytic manner.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319311/" 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/PMC3319311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wiener, Reuven -- Zhang, Xiangbin -- Wang, Tao -- Wolberger, Cynthia -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 22;483(7391):618-22. doi: 10.1038/nature10911.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22367539" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Allosteric Regulation ; Amino Acid Sequence ; Animals ; Binding Sites ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism ; Cysteine Endopeptidases/chemistry/genetics/*metabolism ; DNA Damage ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Tertiary ; Ubiquitin/*antagonists & inhibitors/metabolism ; Ubiquitin-Conjugating Enzymes/antagonists & ; inhibitors/chemistry/genetics/metabolism ; *Ubiquitination ; Ubiquitins/chemistry/metabolism
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  • 78
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-09-14
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinberger, Sharon -- England -- Nature. 2012 Sep 13;489(7415):198-200. doi: 10.1038/489198a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22972277" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): History, 20th Century ; History, 21st Century ; Human Experimentation ; Humans ; Microwaves/*adverse effects ; Military Science/history/*methods ; United States ; *Weapons/history
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  • 79
    Publikationsdatum: 2012-09-04
    Beschreibung: Macromolecular assemblies involving membrane proteins (MPs) serve vital biological roles and are prime drug targets in a variety of diseases. Large-scale affinity purification studies of soluble-protein complexes have been accomplished for diverse model organisms, but no global characterization of MP-complex membership has been described so far. Here we report a complete survey of 1,590 putative integral, peripheral and lipid-anchored MPs from Saccharomyces cerevisiae, which were affinity purified in the presence of non-denaturing detergents. The identities of the co-purifying proteins were determined by tandem mass spectrometry and subsequently used to derive a high-confidence physical interaction map encompassing 1,726 membrane protein-protein interactions and 501 putative heteromeric complexes associated with the various cellular membrane systems. Our analysis reveals unexpected physical associations underlying the membrane biology of eukaryotes and delineates the global topological landscape of the membrane interactome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Babu, Mohan -- Vlasblom, James -- Pu, Shuye -- Guo, Xinghua -- Graham, Chris -- Bean, Bjorn D M -- Burston, Helen E -- Vizeacoumar, Franco J -- Snider, Jamie -- Phanse, Sadhna -- Fong, Vincent -- Tam, Yuen Yi C -- Davey, Michael -- Hnatshak, Olha -- Bajaj, Navgeet -- Chandran, Shamanta -- Punna, Thanuja -- Christopolous, Constantine -- Wong, Victoria -- Yu, Analyn -- Zhong, Gouqing -- Li, Joyce -- Stagljar, Igor -- Conibear, Elizabeth -- Wodak, Shoshana J -- Emili, Andrew -- Greenblatt, Jack F -- MOP 81156/Canadian Institutes of Health Research/Canada -- MOP 64394/Canadian Institutes of Health Research/Canada -- MOP 82940/Canadian Institutes of Health Research/Canada -- England -- Nature. 2012 Sep 27;489(7417):585-9. doi: 10.1038/nature11354. Epub 2012 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, Donnelly Centre, 160 College Street, University of Toronto, Toronto, Ontario M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22940862" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Cell Membrane/chemistry/metabolism ; Chitin Synthase/metabolism ; Detergents ; Endoplasmic Reticulum/metabolism ; Golgi Apparatus/metabolism ; Mass Spectrometry ; Membrane Proteins/analysis/chemistry/*metabolism ; Protein Binding ; Protein Interaction Mapping ; *Protein Interaction Maps ; Proteome/analysis/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/analysis/chemistry/*metabolism
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  • 80
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-10-19
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haroche, Serge -- England -- Nature. 2012 Oct 18;490(7420):311. doi: 10.1038/490311a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecole Normale Superieure, Paris, France. serge.haroche@lkb.ens.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23075943" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): France ; History, 20th Century ; History, 21st Century ; *Nobel Prize ; Physics/*economics/history ; Research Support as Topic/*organization & administration ; Time Factors
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  • 81
    Publikationsdatum: 2012-11-09
    Beschreibung: Studies of bacteriophage Mu transposition paved the way for understanding retroviral integration and V(D)J recombination as well as many other DNA transposition reactions. Here we report the structure of the Mu transpososome--Mu transposase (MuA) in complex with bacteriophage DNA ends and target DNA--determined from data that extend anisotropically to 5.2 A, 5.2 A and 3.7 A resolution, in conjunction with previously determined structures of individual domains. The highly intertwined structure illustrates why chemical activity depends on formation of the synaptic complex, and reveals that individual domains have different roles when bound to different sites. The structure also provides explanations for the increased stability of the final product complex and for its preferential recognition by the ATP-dependent unfoldase ClpX. Although MuA and many other recombinases share a structurally conserved 'DDE' catalytic domain, comparisons among the limited set of available complex structures indicate that some conserved features, such as catalysis in trans and target DNA bending, arose through convergent evolution because they are important for function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536463/" 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/PMC3536463/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Montano, Sherwin P -- Pigli, Ying Z -- Rice, Phoebe A -- GM086826/GM/NIGMS NIH HHS/ -- R01 GM086826/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Nov 15;491(7424):413-7. doi: 10.1038/nature11602. Epub 2012 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23135398" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bacteriophage mu/classification/*enzymology ; DNA, Viral/chemistry ; *Evolution, Molecular ; Models, Molecular ; Protein Binding ; Protein Structure, Tertiary ; Recombinases/*chemistry/*metabolism ; Transposases/*chemistry/metabolism
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  • 82
    Publikationsdatum: 2012-09-25
    Beschreibung: The ATP-binding cassette (ABC) transporter BtuCD mediates the uptake of vitamin B(12) across the inner membrane of Escherichia coli. Previous structures have shown the conformations of apo states, but the transport mechanism has remained unclear. Here we report the 3.5 A crystal structure of the transporter-binding protein complex BtuCD-BtuF (BtuCD-F) trapped in an beta-gamma-imidoadenosine 5'-phosphate (AMP-PNP)-bound intermediate state. Although the ABC domains (BtuD subunits) form the expected closed sandwich dimer, the membrane-spanning BtuC subunits adopt a new conformation, with the central translocation pathway sealed by a previously unrecognized cytoplasmic gate. A fully enclosed cavity is thus formed approximately halfway across the membrane. It is large enough to accommodate a vitamin B(12) molecule, and radioligand trapping showed that liposome-reconstituted BtuCD-F indeed contains bound B(12) in the presence of AMP-PNP. In combination with engineered disulphide crosslinking and functional assays, our data suggest an unexpected peristaltic transport mechanism that is distinct from those observed in other ABC transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korkhov, Vladimir M -- Mireku, Samantha A -- Locher, Kaspar P -- England -- Nature. 2012 Oct 18;490(7420):367-72. doi: 10.1038/nature11442. Epub 2012 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology and Biophysics, ETH Zurich, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23000901" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): ATP-Binding Cassette Transporters/*chemistry/genetics/metabolism ; Adenosine Triphosphatases/chemistry/metabolism ; Adenosine Triphosphate/metabolism ; Adenylyl Imidodiphosphate/chemistry/*metabolism ; Amino Acid Sequence ; Crystallography, X-Ray ; Cytoplasm/metabolism ; Disulfides/chemistry/metabolism ; Escherichia coli/*chemistry/genetics ; Escherichia coli Proteins/*chemistry/genetics/metabolism ; Magnesium/metabolism ; Models, Biological ; Models, Molecular ; Mutant Proteins/chemistry/genetics/metabolism ; Mutation ; Periplasmic Binding Proteins/*chemistry/genetics/metabolism ; Protein Binding ; Protein Conformation ; Protein Subunits/chemistry/genetics/metabolism ; Structure-Activity Relationship ; Vitamin B 12/chemistry/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 83
    Publikationsdatum: 2012-02-07
    Beschreibung: Dynamic variations in the structure of chromatin influence virtually all DNA-related processes in eukaryotes and are controlled in part by post-translational modifications of histones. One such modification, the acetylation of lysine 56 (H3K56ac) in the amino-terminal alpha-helix (alphaN) of histone H3, has been implicated in the regulation of nucleosome assembly during DNA replication and repair, and nucleosome disassembly during gene transcription. In Saccharomyces cerevisiae, the histone chaperone Rtt106 contributes to the deposition of newly synthesized H3K56ac-carrying H3-H4 complex on replicating DNA, but it is unclear how Rtt106 binds H3-H4 and specifically recognizes H3K56ac as there is no apparent acetylated lysine reader domain in Rtt106. Here, we show that two domains of Rtt106 are involved in a combinatorial recognition of H3-H4. An N-terminal domain homodimerizes and interacts with H3-H4 independently of acetylation while a double pleckstrin-homology (PH) domain binds the K56-containing region of H3. Affinity is markedly enhanced upon acetylation of K56, an effect that is probably due to increased conformational entropy of the alphaN helix of H3. Our data support a mode of interaction where the N-terminal homodimeric domain of Rtt106 intercalates between the two H3-H4 components of the (H3-H4)(2) tetramer while two double PH domains in the Rtt106 dimer interact with each of the two H3K56ac sites in (H3-H4)(2). We show that the Rtt106-(H3-H4)(2) interaction is important for gene silencing and the DNA damage response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439842/" 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/PMC3439842/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Dan -- Hu, Qi -- Li, Qing -- Thompson, James R -- Cui, Gaofeng -- Fazly, Ahmed -- Davies, Brian A -- Botuyan, Maria Victoria -- Zhang, Zhiguo -- Mer, Georges -- P50 CA108961/CA/NCI NIH HHS/ -- R01 CA132878/CA/NCI NIH HHS/ -- R01 CA132878-04/CA/NCI NIH HHS/ -- R01 GM072719/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Feb 5;483(7387):104-7. doi: 10.1038/nature10861.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22307274" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylation ; Animals ; Binding Sites ; Crystallography, X-Ray ; DNA Damage ; Gene Silencing ; Genomic Instability ; Histones/*chemistry/*metabolism ; Lysine/analogs & derivatives/chemistry/metabolism ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Chaperones/*chemistry/genetics/*metabolism ; Mutation/genetics ; Pliability ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/*chemistry ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; Structure-Activity Relationship ; Substrate Specificity ; Xenopus laevis
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 84
    Publikationsdatum: 2012-08-24
    Beschreibung: Rapid warming over the past 50 years on the Antarctic Peninsula is associated with the collapse of a number of ice shelves and accelerating glacier mass loss. In contrast, warming has been comparatively modest over West Antarctica and significant changes have not been observed over most of East Antarctica, suggesting that the ice-core palaeoclimate records available from these areas may not be representative of the climate history of the Antarctic Peninsula. Here we show that the Antarctic Peninsula experienced an early-Holocene warm period followed by stable temperatures, from about 9,200 to 2,500 years ago, that were similar to modern-day levels. Our temperature estimates are based on an ice-core record of deuterium variations from James Ross Island, off the northeastern tip of the Antarctic Peninsula. We find that the late-Holocene development of ice shelves near James Ross Island was coincident with pronounced cooling from 2,500 to 600 years ago. This cooling was part of a millennial-scale climate excursion with opposing anomalies on the eastern and western sides of the Antarctic Peninsula. Although warming of the northeastern Antarctic Peninsula began around 600 years ago, the high rate of warming over the past century is unusual (but not unprecedented) in the context of natural climate variability over the past two millennia. The connection shown here between past temperature and ice-shelf stability suggests that warming for several centuries rendered ice shelves on the northeastern Antarctic Peninsula vulnerable to collapse. Continued warming to temperatures that now exceed the stable conditions of most of the Holocene epoch is likely to cause ice-shelf instability to encroach farther southward along the Antarctic Peninsula.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mulvaney, Robert -- Abram, Nerilie J -- Hindmarsh, Richard C A -- Arrowsmith, Carol -- Fleet, Louise -- Triest, Jack -- Sime, Louise C -- Alemany, Olivier -- Foord, Susan -- England -- Nature. 2012 Sep 6;489(7414):141-4. doi: 10.1038/nature11391.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉British Antarctic Survey, Natural Environment Research Council, Cambridge CB3 0ET, UK. rmu@bas.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22914090" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Antarctic Regions ; Geography ; Geologic Sediments/chemistry ; Global Warming/history/*statistics & numerical data ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; *Ice Cover ; Oceans and Seas ; Seawater/analysis ; Temperature
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 85
    Publikationsdatum: 2012-01-06
    Beschreibung: Oestrogen receptor-alpha (ER) is the defining and driving transcription factor in the majority of breast cancers and its target genes dictate cell growth and endocrine response, yet genomic understanding of ER function has been restricted to model systems. Here we map genome-wide ER-binding events, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), in primary breast cancers from patients with different clinical outcomes and in distant ER-positive metastases. We find that drug-resistant cancers still recruit ER to the chromatin, but that ER binding is a dynamic process, with the acquisition of unique ER-binding regions in tumours from patients that are likely to relapse. The acquired ER regulatory regions associated with poor clinical outcome observed in primary tumours reveal gene signatures that predict clinical outcome in ER-positive disease exclusively. We find that the differential ER-binding programme observed in tumours from patients with poor outcome is not due to the selection of a rare subpopulation of cells, but is due to the FOXA1-mediated reprogramming of ER binding on a rapid timescale. The parallel redistribution of ER and FOXA1 binding events in drug-resistant cellular contexts is supported by histological co-expression of ER and FOXA1 in metastatic samples. By establishing transcription-factor mapping in primary tumour material, we show that there is plasticity in ER-binding capacity, with distinct combinations of cis-regulatory elements linked with the different clinical outcomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272464/" 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/PMC3272464/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ross-Innes, Caryn S -- Stark, Rory -- Teschendorff, Andrew E -- Holmes, Kelly A -- Ali, H Raza -- Dunning, Mark J -- Brown, Gordon D -- Gojis, Ondrej -- Ellis, Ian O -- Green, Andrew R -- Ali, Simak -- Chin, Suet-Feung -- Palmieri, Carlo -- Caldas, Carlos -- Carroll, Jason S -- A10178/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2012 Jan 4;481(7381):389-93. doi: 10.1038/nature10730.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22217937" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Base Sequence ; Breast Neoplasms/*diagnosis/drug therapy/*genetics/pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/drug effects/genetics ; Female ; *Gene Expression Regulation, Neoplastic/drug effects ; Hepatocyte Nuclear Factor 3-alpha/metabolism ; Humans ; Neoplasm Metastasis/genetics ; Prognosis ; Protein Binding ; Receptors, Estrogen/*metabolism ; Regulatory Sequences, Nucleic Acid/genetics ; Survival Analysis ; Tamoxifen/pharmacology/therapeutic use ; Treatment Outcome
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 86
    Publikationsdatum: 2012-12-04
    Beschreibung: The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573685/" 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/PMC3573685/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rollauer, Sarah E -- Tarry, Michael J -- Graham, James E -- Jaaskelainen, Mari -- Jager, Franziska -- Johnson, Steven -- Krehenbrink, Martin -- Liu, Sai-Man -- Lukey, Michael J -- Marcoux, Julien -- McDowell, Melanie A -- Rodriguez, Fernanda -- Roversi, Pietro -- Stansfeld, Phillip J -- Robinson, Carol V -- Sansom, Mark S P -- Palmer, Tracy -- Hogbom, Martin -- Berks, Ben C -- Lea, Susan M -- 083599/Wellcome Trust/United Kingdom -- 088150/Wellcome Trust/United Kingdom -- 092970/Wellcome Trust/United Kingdom -- 092970MA/Wellcome Trust/United Kingdom -- BB/1019855/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E023347/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F02150X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I019855/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0900888/Medical Research Council/United Kingdom -- G0900888(92020)/Medical Research Council/United Kingdom -- G100164/Medical Research Council/United Kingdom -- G1001640/Medical Research Council/United Kingdom -- G1001640/1/Medical Research Council/United Kingdom -- England -- Nature. 2012 Dec 13;492(7428):210-4. doi: 10.1038/nature11683. Epub 2012 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23201679" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Binding Sites ; Escherichia coli/genetics ; Gram-Negative Bacteria/*chemistry/genetics/*metabolism ; Membrane Transport Proteins/*chemistry/metabolism ; *Models, Molecular ; Protein Binding ; Protein Sorting Signals ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry/genetics
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 87
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-11-09
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, John Meurig -- England -- Nature. 2012 Nov 8;491(7423):186-7. doi: 10.1038/491186a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB2 3QZ, UK. jmt2@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23135450" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Crystallography, X-Ray/*history ; Great Britain ; History, 20th Century ; History, 21st Century ; Nobel Prize
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 88
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-08-24
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhong, Weimin -- Wu, Hao -- Li, Linheng -- England -- Nature. 2012 Aug 23;488(7412):459. doi: 10.1038/488459a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22914156" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adolescent ; Adolescent Development ; *Awards and Prizes ; China/ethnology ; Doping in Sports ; Female ; *Gold ; History, 20th Century ; History, 21st Century ; Humans ; Internationality ; London ; Male ; Numismatics ; Performance-Enhancing Substances ; Swimming/*physiology ; Time Factors
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 89
    Publikationsdatum: 2012-02-24
    Beschreibung: Ribosome-driven protein biosynthesis is comprised of four phases: initiation, elongation, termination and recycling. In bacteria, ribosome recycling requires ribosome recycling factor and elongation factor G, and several structures of bacterial recycling complexes have been determined. In the eukaryotic and archaeal kingdoms, however, recycling involves the ABC-type ATPase ABCE1 and little is known about its structural basis. Here we present cryo-electron microscopy reconstructions of eukaryotic and archaeal ribosome recycling complexes containing ABCE1 and the termination factor paralogue Pelota. These structures reveal the overall binding mode of ABCE1 to be similar to canonical translation factors. Moreover, the iron-sulphur cluster domain of ABCE1 interacts with and stabilizes Pelota in a conformation that reaches towards the peptidyl transferase centre, thus explaining how ABCE1 may stimulate peptide-release activity of canonical termination factors. Using the mechanochemical properties of ABCE1, a conserved mechanism in archaea and eukaryotes is suggested that couples translation termination to recycling, and eventually to re-initiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becker, Thomas -- Franckenberg, Sibylle -- Wickles, Stephan -- Shoemaker, Christopher J -- Anger, Andreas M -- Armache, Jean-Paul -- Sieber, Heidemarie -- Ungewickell, Charlotte -- Berninghausen, Otto -- Daberkow, Ingo -- Karcher, Annette -- Thomm, Michael -- Hopfner, Karl-Peter -- Green, Rachel -- Beckmann, Roland -- U19 AI083025/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 22;482(7386):501-6. doi: 10.1038/nature10829.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Center and Center for integrated Protein Science Munich, Department of Biochemistry, University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany. becker@lmb.uni-muenchen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358840" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): ATP-Binding Cassette Transporters/chemistry/metabolism ; Cell Cycle Proteins/chemistry/metabolism ; Cryoelectron Microscopy ; Endoribonucleases/chemistry/metabolism ; *Evolution, Molecular ; Iron-Sulfur Proteins/chemistry/metabolism ; Models, Molecular ; Movement ; Multiprotein Complexes/chemistry/metabolism ; Nuclear Proteins/chemistry/metabolism ; Peptide Termination Factors/chemistry/metabolism ; Protein Binding ; Protein Stability ; Protein Structure, Tertiary ; Pyrococcus furiosus/*chemistry/metabolism ; Ribosomes/*chemistry/*metabolism/ultrastructure ; Saccharomyces cerevisiae/*chemistry/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 90
    Publikationsdatum: 2012-05-25
    Beschreibung: Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes. However, the lineage of the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI-catalysed conversion of chalcones to chiral (S)-flavanones is a committed step in the production of plant flavonoids, compounds that contribute to attraction, defence and development. CHI operates near the diffusion limit with stereospecific control. Although associated primarily with plants, the CHI fold occurs in several other eukaryotic lineages and in some bacteria. Here we report crystal structures, ligand-binding properties and in vivo functional characterization of a non-catalytic CHI-fold family from plants. Arabidopsis thaliana contains five actively transcribed genes encoding CHI-fold proteins, three of which additionally encode amino-terminal chloroplast-transit sequences. These three CHI-fold proteins localize to plastids, the site of de novo fatty-acid biosynthesis in plant cells. Furthermore, their expression profiles correlate with those of core fatty-acid biosynthetic enzymes, with maximal expression occurring in seeds and coinciding with increased fatty-acid storage in the developing embryo. In vitro, these proteins are fatty-acid-binding proteins (FAPs). FAP knockout A. thaliana plants show elevated alpha-linolenic acid levels and marked reproductive defects, including aberrant seed formation. Notably, the FAP discovery defines the adaptive evolution of a stereospecific and catalytically 'perfected' enzyme from a non-enzymatic ancestor over a defined period of plant evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880581/" 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/PMC3880581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ngaki, Micheline N -- Louie, Gordon V -- Philippe, Ryan N -- Manning, Gerard -- Pojer, Florence -- Bowman, Marianne E -- Li, Ling -- Larsen, Elise -- Wurtele, Eve Syrkin -- Noel, Joseph P -- CA14195/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 May 13;485(7399):530-3. doi: 10.1038/nature11009.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, Iowa 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22622584" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Arabidopsis/*chemistry/enzymology/genetics/growth & development ; Arabidopsis Proteins/chemistry/genetics/metabolism ; *Biocatalysis ; Crystallography, X-Ray ; *Evolution, Molecular ; Fatty Acid-Binding Proteins/chemistry/deficiency/genetics/metabolism ; Fatty Acids/*metabolism ; Intramolecular Lyases/*chemistry/deficiency/genetics/*metabolism ; Ligands ; Models, Molecular ; Phenotype ; Protein Binding ; *Protein Folding ; Stereoisomerism ; alpha-Linolenic Acid/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 91
    Publikationsdatum: 2012-06-23
    Beschreibung: MicroRNAs (miRNAs) comprise a large family of small RNA molecules that post-transcriptionally regulate gene expression in many biological pathways. Most miRNAs are derived from long primary transcripts that undergo processing by Drosha to produce ~65-nucleotide precursors that are then cleaved by Dicer, resulting in the mature 22-nucleotide forms. Serving as guides in Argonaute protein complexes, mature miRNAs use imperfect base pairing to recognize sequences in messenger RNA transcripts, leading to translational repression and destabilization of the target messenger RNAs. Here we show that the miRNA complex also targets and regulates non-coding RNAs that serve as substrates for the miRNA-processing pathway. We found that the Argonaute protein in Caenorhabditis elegans, ALG-1, binds to a specific site at the 3' end of let-7 miRNA primary transcripts and promotes downstream processing events. This interaction is mediated by mature let-7 miRNA through a conserved complementary site in its own primary transcript, thus creating a positive-feedback loop. We further show that ALG-1 associates with let-7 primary transcripts in nuclear fractions. Argonaute also binds let-7 primary transcripts in human cells, demonstrating that the miRNA pathway targets non-coding RNAs in addition to protein-coding messenger RNAs across species. Moreover, our studies in C. elegans reveal a novel role for Argonaute in promoting biogenesis of a targeted transcript, expanding the functions of the miRNA pathway in gene regulation. This discovery of autoregulation of let-7 biogenesis establishes a new mechanism for controlling miRNA expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387326/" 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/PMC3387326/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zisoulis, Dimitrios G -- Kai, Zoya S -- Chang, Roger K -- Pasquinelli, Amy E -- GM071654/GM/NIGMS NIH HHS/ -- R01 GM071654/GM/NIGMS NIH HHS/ -- R01 GM071654-09/GM/NIGMS NIH HHS/ -- T32 CA009523/CA/NCI NIH HHS/ -- England -- Nature. 2012 Jun 28;486(7404):541-4. doi: 10.1038/nature11134.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, University of California, San Diego, La Jolla, California 92093-0349, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722835" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Base Pairing ; Base Sequence ; Binding Sites ; Caenorhabditis elegans/classification/cytology/*genetics/*metabolism ; Caenorhabditis elegans Proteins/*metabolism ; Cell Nucleus/genetics/metabolism ; Feedback, Physiological ; *Gene Expression Regulation ; MicroRNAs/*biosynthesis/*genetics/metabolism ; Protein Binding ; RNA Processing, Post-Transcriptional ; RNA, Messenger/biosynthesis/genetics/metabolism ; RNA-Binding Proteins/*metabolism ; Transcription, Genetic
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 92
    Publikationsdatum: 2012-02-10
    Beschreibung: First identified as histone-modifying proteins, lysine acetyltransferases (KATs) and deacetylases (KDACs) antagonize each other through modification of the side chains of lysine residues in histone proteins. Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Here we dissect the functional specificity of 12 critical human KDACs using a genome-wide synthetic lethality screen in cultured human cells. The genetic interaction profiles revealed enzyme-substrate relationships between individual KDACs and many important substrates governing a wide array of biological processes including metabolism, development and cell cycle progression. We further confirmed that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277212/" 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/PMC3277212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Yu-yi -- Kiihl, Samara -- Suhail, Yasir -- Liu, Shang-Yun -- Chou, Yi-hsuan -- Kuang, Zheng -- Lu, Jin-ying -- Khor, Chin Ni -- Lin, Chi-Long -- Bader, Joel S -- Irizarry, Rafael -- Boeke, Jef D -- U54 RR 020839/RR/NCRR NIH HHS/ -- U54 RR020839/RR/NCRR NIH HHS/ -- U54 RR020839-09/RR/NCRR NIH HHS/ -- England -- Nature. 2012 Feb 8;482(7384):251-5. doi: 10.1038/nature10804.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. yuyilin@ntu.edu.tw〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318606" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): AMP-Activated Protein Kinases/chemistry/genetics/*metabolism ; Acetylation ; Biocatalysis ; Catalytic Domain ; Cell Cycle ; Cell Line ; Cell Line, Tumor ; Histone Deacetylase 1/genetics/*metabolism ; Humans ; Lysine/*metabolism ; Phosphorylation ; Protein Binding ; Protein-Serine-Threonine Kinases/metabolism ; RNA Interference ; Substrate Specificity ; p300-CBP Transcription Factors/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-11-30
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2012 Nov 29;491(7426):656-8. doi: 10.1038/491656a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23192127" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Carbon Dioxide/analysis/supply & distribution ; Carbon Footprint/legislation & jurisprudence/*statistics & numerical data ; China ; Conservation of Natural Resources/statistics & numerical data ; Developed Countries/economics/history/statistics & numerical data ; Developing Countries/economics/history/statistics & numerical data ; Economic Recession ; Environmental Policy/economics/*history/legislation & jurisprudence ; Fossil Fuels/economics/supply & distribution/utilization ; Global Warming/*legislation & jurisprudence/prevention & control/*statistics & ; numerical data ; History, 20th Century ; History, 21st Century ; International Cooperation/*history/legislation & jurisprudence ; Japan
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-09-29
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2012 Sep 27;489(7417):481-2. doi: 10.1038/489481a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23018940" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Analgesics, Opioid/analysis ; *Chemistry/history ; Drug and Narcotic Control/history/*legislation & jurisprudence ; History, 21st Century ; Human Rights/history/*legislation & jurisprudence ; Papaver/chemistry ; *Politics ; *Prisoners/history ; *Research Personnel/history ; Russia ; Seeds/chemistry
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 95
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-05-25
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 May 23;485(7399):415-6. doi: 10.1038/485415b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22622529" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Chernobyl Nuclear Accident ; History, 20th Century ; History, 21st Century ; Humans ; Japan ; Neoplasms, Radiation-Induced/epidemiology ; Nuclear Weapons/history ; *Radiation Monitoring/history ; Radioactive Fallout/adverse effects/analysis/statistics & numerical data ; *Radioactive Hazard Release/history ; Ussr ; United States
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 96
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-08-17
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiermeier, Quirin -- England -- Nature. 2012 Aug 16;488(7411):272-4. doi: 10.1038/488272a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895317" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Africa ; Archaeology ; *Desert Climate ; *Ecosystem ; Expeditions/*history/trends ; Geography ; Geologic Sediments/chemistry ; Geology/*history ; Germany ; History, 20th Century ; History, 21st Century ; History, Ancient ; Lakes/chemistry
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 97
    Publikationsdatum: 2012-12-14
    Beschreibung: At the end of cell division, cytokinesis splits the cytoplasm of nascent daughter cells and partitions segregated sister genomes. To coordinate cell division with chromosome segregation, the mitotic spindle controls cytokinetic events at the cell envelope. The spindle midzone stimulates the actomyosin-driven contraction of the cleavage furrow, which proceeds until the formation of a microtubule-rich intercellular bridge with the midbody at its centre. The midbody directs the final membrane abscission reaction and has been proposed to attach the cleavage furrow to the intercellular bridge. How the mitotic spindle is connected to the plasma membrane during cytokinesis is not understood. Here we identify a plasma membrane tethering activity in the centralspindlin protein complex, a conserved component of the spindle midzone and midbody. We demonstrate that the C1 domain of the centralspindlin subunit MgcRacGAP associates with the plasma membrane by interacting with polyanionic phosphoinositide lipids. Using X-ray crystallography we determine the structure of this atypical C1 domain. Mutations in the hydrophobic cap and in basic residues of the C1 domain of MgcRacGAP prevent association of the protein with the plasma membrane, and abrogate cytokinesis in human and chicken cells. Artificial membrane tethering of centralspindlin restores cell division in the absence of the C1 domain of MgcRacGAP. Although C1 domain function is dispensable for the formation of the midzone and midbody, it promotes contractility and is required for the attachment of the plasma membrane to the midbody, a long-postulated function of this organelle. Our analysis suggests that centralspindlin links the mitotic spindle to the plasma membrane to secure the final cut during cytokinesis in animal cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lekomtsev, Sergey -- Su, Kuan-Chung -- Pye, Valerie E -- Blight, Ken -- Sundaramoorthy, Sriramkumar -- Takaki, Tohru -- Collinson, Lucy M -- Cherepanov, Peter -- Divecha, Nullin -- Petronczki, Mark -- Cancer Research UK/United Kingdom -- England -- Nature. 2012 Dec 13;492(7428):276-9. doi: 10.1038/nature11773.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235882" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Membrane/*metabolism ; Cytokinesis/genetics/*radiation effects ; GTPase-Activating Proteins/chemistry/genetics/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Microtubule-Associated Proteins/chemistry/genetics/*metabolism ; Microtubules/chemistry/metabolism ; Models, Molecular ; Protein Binding ; Protein Kinase C-alpha/metabolism ; Protein Structure, Tertiary ; Protein Transport/drug effects ; Spindle Apparatus/*metabolism ; Tetradecanoylphorbol Acetate/analogs & derivatives/pharmacology
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    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2012-03-02
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, James -- England -- Nature. 2012 Feb 29;483(7387):S8-10. doi: 10.1038/483S8a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Boston University, USA. jcollins@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22378128" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Bioengineering/trends ; DNA Restriction Enzymes/metabolism ; Genetic Code/genetics ; Genetic Engineering/history ; History, 20th Century ; History, 21st Century ; Humans ; *Synthetic Biology/ethics/methods/trends
    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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  • 99
    Publikationsdatum: 2012-09-21
    Beschreibung: The AP1 transcription factor Batf3 is required for homeostatic development of CD8alpha(+) classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3-independent pathway in mice for CD8alpha(+) dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-gamma. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf, which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482832/" 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/PMC3482832/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tussiwand, Roxane -- Lee, Wan-Ling -- Murphy, Theresa L -- Mashayekhi, Mona -- KC, Wumesh -- Albring, Jorn C -- Satpathy, Ansuman T -- Rotondo, Jeffrey A -- Edelson, Brian T -- Kretzer, Nicole M -- Wu, Xiaodi -- Weiss, Leslie A -- Glasmacher, Elke -- Li, Peng -- Liao, Wei -- Behnke, Michael -- Lam, Samuel S K -- Aurthur, Cora T -- Leonard, Warren J -- Singh, Harinder -- Stallings, Christina L -- Sibley, L David -- Schreiber, Robert D -- Murphy, Kenneth M -- AI076427-02/AI/NIAID NIH HHS/ -- P30 CA91842/CA/NCI NIH HHS/ -- R01 AI036629/AI/NIAID NIH HHS/ -- R01 AI076427/AI/NIAID NIH HHS/ -- R01 CA043059/CA/NCI NIH HHS/ -- T32 AI007163/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Oct 25;490(7421):502-7. doi: 10.1038/nature11531. Epub 2012 Sep 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22992524" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigen Presentation ; Antigens, CD/metabolism ; Antigens, CD8/immunology/metabolism ; Basic-Leucine Zipper Transcription ; Factors/chemistry/deficiency/genetics/*metabolism ; CD4-Positive T-Lymphocytes/cytology/immunology ; CTLA-4 Antigen/metabolism ; Cell Differentiation ; Cell Line, Tumor ; Cell Lineage ; Dendritic Cells/*cytology/immunology/*metabolism ; Female ; Fibrosarcoma/immunology/metabolism/pathology ; Gene Expression Regulation ; Integrin alpha Chains/metabolism ; Interferon Regulatory Factors/deficiency/genetics/*metabolism ; Interleukin-10/metabolism ; Interleukin-12/immunology/metabolism ; Leucine Zippers ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Oncogene Protein p65(gag-jun)/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins/deficiency/genetics ; T-Lymphocytes, Helper-Inducer/cytology/immunology/metabolism ; Toxoplasma/immunology
    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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  • 100
    Publikationsdatum: 2012-07-18
    Beschreibung: How the interplay between protein structure and internal dynamics regulates protein function is poorly understood. Often, ligand binding, post-translational modifications and mutations modify protein activity in a manner that is not possible to rationalize solely on the basis of structural data. It is likely that changes in the internal motions of proteins have a major role in regulating protein activity, but the nature of their contributions remains elusive, especially in quantitative terms. Here we show that changes in conformational entropy can determine whether protein-ligand interactions will occur, even among protein complexes with identical binding interfaces. We have used NMR spectroscopy to determine the changes in structure and internal dynamics that are elicited by the binding of DNA to several variants of the catabolite activator protein (CAP) that differentially populate the inactive and active DNA-binding domain states. We found that the CAP variants have markedly different affinities for DNA, despite the CAP-DNA-binding interfaces being essentially identical in the various complexes. Combined with thermodynamic data, the results show that conformational entropy changes can inhibit the binding of CAP variants that are structurally poised for optimal DNA binding or can stimulate the binding activity of CAP variants that only transiently populate the DNA-binding-domain active state. Collectively, the data show how changes in fast internal dynamics (conformational entropy) and slow internal dynamics (energetically excited conformational states) can regulate binding activity in a way that cannot be predicted on the basis of the protein's ground-state structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tzeng, Shiou-Ru -- Kalodimos, Charalampos G -- England -- Nature. 2012 Aug 9;488(7410):236-40. doi: 10.1038/nature11271.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry & Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22801505" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Binding Sites ; Cyclic AMP Receptor Protein/*chemistry/genetics/*metabolism ; DNA/chemistry/metabolism ; *Entropy ; Models, Molecular ; Motion ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Structure, Tertiary ; Time Factors
    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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