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  • Binding Sites  (3)
  • Uncertainty  (3)
  • Nature Publishing Group (NPG)  (6)
  • Wiley
  • 1
    Publication Date: 2008-05-24
    Description: The RecA family of ATPases mediates homologous recombination, a reaction essential for maintaining genomic integrity and for generating genetic diversity. RecA, ATP and single-stranded DNA (ssDNA) form a helical filament that binds to double-stranded DNA (dsDNA), searches for homology, and then catalyses the exchange of the complementary strand, producing a new heteroduplex. Here we have solved the crystal structures of the Escherichia coli RecA-ssDNA and RecA-heteroduplex filaments. They show that ssDNA and ATP bind to RecA-RecA interfaces cooperatively, explaining the ATP dependency of DNA binding. The ATP gamma-phosphate is sensed across the RecA-RecA interface by two lysine residues that also stimulate ATP hydrolysis, providing a mechanism for DNA release. The DNA is underwound and stretched globally, but locally it adopts a B-DNA-like conformation that restricts the homology search to Watson-Crick-type base pairing. The complementary strand interacts primarily through base pairing, making heteroduplex formation strictly dependent on complementarity. The underwound, stretched filament conformation probably evolved to destabilize the donor duplex, freeing the complementary strand for homology sampling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Zhucheng -- Yang, Haijuan -- Pavletich, Nikola P -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 May 22;453(7194):489-4. doi: 10.1038/nature06971.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497818" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; DNA, Single-Stranded/chemistry/genetics/metabolism ; Escherichia coli/*enzymology/genetics ; Models, Molecular ; Nucleic Acid Conformation ; Nucleic Acid Heteroduplexes/chemistry/genetics/metabolism ; Protein Conformation ; Rec A Recombinases/*chemistry/*metabolism ; *Recombination, Genetic/genetics ; *Sequence Homology, Nucleic Acid
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-02-19
    Description: The deep-water Avalon biota (about 579 to 565 million years old) is often regarded as the earliest-known fossil assemblage with macroscopic and morphologically complex life forms. It has been proposed that the rise of the Avalon biota was triggered by the oxygenation of mid-Ediacaran deep oceans. Here we report a diverse assemblage of morphologically differentiated benthic macrofossils that were preserved largely in situ as carbonaceous compressions in black shales of the Ediacaran Lantian Formation (southern Anhui Province, South China). The Lantian biota, probably older than and taxonomically distinct from the Avalon biota, suggests that morphological diversification of macroscopic eukaryotes may have occurred in the early Ediacaran Period, perhaps shortly after the Marinoan glaciation, and that the redox history of Ediacaran oceans was more complex than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yuan, Xunlai -- Chen, Zhe -- Xiao, Shuhai -- Zhou, Chuanming -- Hua, Hong -- England -- Nature. 2011 Feb 17;470(7334):390-3. doi: 10.1038/nature09810.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology, Chinese Academy of Sciences, Nanjing 210008, China. xlyuan@nigpas.ac.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21331041" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; *Biota ; *Body Size ; China ; Eukaryota/*classification/cytology/isolation & purification ; *Fossils ; Geologic Sediments ; History, Ancient ; Oceans and Seas ; Oxidation-Reduction ; Phylogeny ; Uncertainty
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-06-19
    Description: Pacific Ocean western boundary currents and the interlinked equatorial Pacific circulation system were among the first currents of these types to be explored by pioneering oceanographers. The widely accepted but poorly quantified importance of these currents-in processes such as the El Nino/Southern Oscillation, the Pacific Decadal Oscillation and the Indonesian Throughflow-has triggered renewed interest. Ongoing efforts are seeking to understand the heat and mass balances of the equatorial Pacific, and possible changes associated with greenhouse-gas-induced climate change. Only a concerted international effort will close the observational, theoretical and technical gaps currently limiting a robust answer to these elusive questions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Dunxin -- Wu, Lixin -- Cai, Wenju -- Gupta, Alex Sen -- Ganachaud, Alexandre -- Qiu, Bo -- Gordon, Arnold L -- Lin, Xiaopei -- Chen, Zhaohui -- Hu, Shijian -- Wang, Guojian -- Wang, Qingye -- Sprintall, Janet -- Qu, Tangdong -- Kashino, Yuji -- Wang, Fan -- Kessler, William S -- England -- Nature. 2015 Jun 18;522(7556):299-308. doi: 10.1038/nature14504.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Ocean Circulation and Waves, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. ; Physical Oceanography Laboratory, Qingdao Collaborative Innovation Center of Marine Science and Technology, Ocean University of China, Qingdao 266003, China. ; 1] Physical Oceanography Laboratory, Qingdao Collaborative Innovation Center of Marine Science and Technology, Ocean University of China, Qingdao 266003, China [2] CSIRO Oceans and Atmosphere Flagship, Aspendale, Victoria 3195, Australia. ; Australian Research Council (ARC) Centre of Excellence for Climate System Science, Mathews Building, The University of New South Wales, Sydney 2052, Australia. ; Institut de Recherche pour le Developpement (IRD), UMR5566-LEGOS, UPS (OMP-PCA), 31400 Toulouse, France. ; Department of Oceanography, University of Hawaii at Manoa, 1000 Pope Road, Honolulu, Hawaii 96822, USA. ; Lamont-Doherty Earth Observatory, Earth Institute at Columbia University, Palisades, New York 10964, USA. ; CSIRO Oceans and Atmosphere Flagship, Aspendale, Victoria 3195, Australia. ; Scripps Institution of Oceanography, 9500 Gilman Drive, La Jolla, California 92037, USA. ; IPRC, Department of Oceanography, SOEST, University of Hawaii, Honolulu, Hawaii 96822, USA. ; Center for Earth Information Science and Technology, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) 3173-25 Showa-machi Kanazawa-ku, Yokohama 236-0001, Japan. ; NOAA/Pacific Marine Environmental Laboratory, Seattle, Washington 98115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26085269" target="_blank"〉PubMed〈/a〉
    Keywords: *Climate ; *Climate Change ; El Nino-Southern Oscillation ; Hot Temperature ; Pacific Ocean ; Uncertainty ; *Water Movements
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2012-10-12
    Description: Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptide- and lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the structure and chemistry within the antigen-binding cleft of MR1 is distinct from the MHC and CD1 families. MR1 is ideally suited to bind ligands originating from vitamin metabolites. The structure of MR1 in complex with 6-formyl pterin, a folic acid (vitamin B9) metabolite, shows the pterin ring sequestered within MR1. Furthermore, we characterize related MR1-restricted vitamin derivatives, originating from the bacterial riboflavin (vitamin B2) biosynthetic pathway, which specifically and potently activate MAIT cells. Accordingly, we show that metabolites of vitamin B represent a class of antigen that are presented by MR1 for MAIT-cell immunosurveillance. As many vitamin biosynthetic pathways are unique to bacteria and yeast, our data suggest that MAIT cells use these metabolites to detect microbial infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kjer-Nielsen, Lars -- Patel, Onisha -- Corbett, Alexandra J -- Le Nours, Jerome -- Meehan, Bronwyn -- Liu, Ligong -- Bhati, Mugdha -- Chen, Zhenjun -- Kostenko, Lyudmila -- Reantragoon, Rangsima -- Williamson, Nicholas A -- Purcell, Anthony W -- Dudek, Nadine L -- McConville, Malcolm J -- O'Hair, Richard A J -- Khairallah, George N -- Godfrey, Dale I -- Fairlie, David P -- Rossjohn, Jamie -- McCluskey, James -- England -- Nature. 2012 Nov 29;491(7426):717-23. doi: 10.1038/nature11605. Epub 2012 Oct 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23051753" target="_blank"〉PubMed〈/a〉
    Keywords: Antigen Presentation ; Bacterial Infections/immunology/microbiology ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Folic Acid/chemistry/immunology/*metabolism ; Histocompatibility Antigens/chemistry/immunology ; Histocompatibility Antigens Class I/*chemistry/*immunology/metabolism ; Humans ; Immunologic Surveillance/immunology ; Jurkat Cells ; Ligands ; Lymphocyte Activation ; Models, Molecular ; Protein Refolding/drug effects ; Pterins/*chemistry/*immunology/metabolism/pharmacology ; Salmonella/immunology/metabolism ; Salmonella Infections/immunology/microbiology ; Static Electricity ; T-Lymphocytes/*immunology ; beta 2-Microglobulin/immunology/metabolism
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    Electronic ISSN: 1476-4687
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  • 5
    Publication Date: 2012-06-23
    Description: Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T cells. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes. A growing number of immunologically based drug reactions, including abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens-Johnson syndrome (SJS), are associated with specific HLA alleles. However, little is known about the underlying mechanisms of these associations, including AHS, a prototypical HLA-associated drug reaction occurring exclusively in individuals with the common histocompatibility allele HLA-B*57:01, and with a relative risk of more than 1,000 (refs 6, 7). We show that unmodified abacavir binds non-covalently to HLA-B*57:01, lying across the bottom of the antigen-binding cleft and reaching into the F-pocket, where a carboxy-terminal tryptophan typically anchors peptides bound to HLA-B*57:01. Abacavir binds with exquisite specificity to HLA-B*57:01, changing the shape and chemistry of the antigen-binding cleft, thereby altering the repertoire of endogenous peptides that can bind HLA-B*57:01. In this way, abacavir guides the selection of new endogenous peptides, inducing a marked alteration in 'immunological self'. The resultant peptide-centric 'altered self' activates abacavir-specific T-cells, thereby driving polyclonal CD8 T-cell activation and a systemic reaction manifesting as AHS. We also show that carbamazepine, a widely used anti-epileptic drug associated with hypersensitivity reactions in HLA-B*15:02 individuals, binds to this allotype, producing alterations in the repertoire of presented self peptides. Our findings simultaneously highlight the importance of HLA polymorphism in the evolution of pharmacogenomics and provide a general mechanism for some of the growing number of HLA-linked hypersensitivities that involve small-molecule drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Illing, Patricia T -- Vivian, Julian P -- Dudek, Nadine L -- Kostenko, Lyudmila -- Chen, Zhenjun -- Bharadwaj, Mandvi -- Miles, John J -- Kjer-Nielsen, Lars -- Gras, Stephanie -- Williamson, Nicholas A -- Burrows, Scott R -- Purcell, Anthony W -- Rossjohn, Jamie -- McCluskey, James -- England -- Nature. 2012 Jun 28;486(7404):554-8. doi: 10.1038/nature11147.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722860" target="_blank"〉PubMed〈/a〉
    Keywords: Antigen Presentation/*drug effects ; Autoimmunity/*drug effects/*immunology ; Binding Sites ; Blood Donors ; CD8-Positive T-Lymphocytes/drug effects/immunology ; Carbamazepine/pharmacology ; Dideoxynucleosides/*pharmacology ; Drug Hypersensitivity ; HLA-B Antigens/chemistry/*immunology ; Humans ; Models, Molecular ; Protein Conformation ; Syndrome ; T-Lymphocytes/*drug effects/*immunology
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  • 6
    Publication Date: 2016-03-18
    Description: Knowledge of the contribution that individual countries have made to global radiative forcing is important to the implementation of the agreement on "common but differentiated responsibilities" reached by the United Nations Framework Convention on Climate Change. Over the past three decades, China has experienced rapid economic development, accompanied by increased emission of greenhouse gases, ozone precursors and aerosols, but the magnitude of the associated radiative forcing has remained unclear. Here we use a global coupled biogeochemistry-climate model and a chemistry and transport model to quantify China's present-day contribution to global radiative forcing due to well-mixed greenhouse gases, short-lived atmospheric climate forcers and land-use-induced regional surface albedo changes. We find that China contributes 10% +/- 4% of the current global radiative forcing. China's relative contribution to the positive (warming) component of global radiative forcing, mainly induced by well-mixed greenhouse gases and black carbon aerosols, is 12% +/- 2%. Its relative contribution to the negative (cooling) component is 15% +/- 6%, dominated by the effect of sulfate and nitrate aerosols. China's strongest contributions are 0.16 +/- 0.02 watts per square metre for CO2 from fossil fuel burning, 0.13 +/- 0.05 watts per square metre for CH4, -0.11 +/- 0.05 watts per square metre for sulfate aerosols, and 0.09 +/- 0.06 watts per square metre for black carbon aerosols. China's eventual goal of improving air quality will result in changes in radiative forcing in the coming years: a reduction of sulfur dioxide emissions would drive a faster future warming, unless offset by larger reductions of radiative forcing from well-mixed greenhouse gases and black carbon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Bengang -- Gasser, Thomas -- Ciais, Philippe -- Piao, Shilong -- Tao, Shu -- Balkanski, Yves -- Hauglustaine, Didier -- Boisier, Juan-Pablo -- Chen, Zhuo -- Huang, Mengtian -- Li, Laurent Zhaoxin -- Li, Yue -- Liu, Hongyan -- Liu, Junfeng -- Peng, Shushi -- Shen, Zehao -- Sun, Zhenzhong -- Wang, Rong -- Wang, Tao -- Yin, Guodong -- Yin, Yi -- Zeng, Hui -- Zeng, Zhenzhong -- Zhou, Feng -- England -- Nature. 2016 Mar 17;531(7594):357-61. doi: 10.1038/nature17165.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sino-French Institute for Earth System Science, Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. ; Jiangsu Center for Collaborative Innovation in Geographical Information Resource Development and Application, Nanjing, 210023, China. ; Laboratoire des Sciences du Climat et de l'Environnement, CEA-CNRS-UVSQ, 91191 Gif-sur-Yvette, France. ; Centre International de Recherche en Environnement et Developpement, CNRS-PontsParisTech-EHESS-AgroParisTech-CIRAD, 94736 Nogent-sur-Marne, France. ; Key Laboratory of Alpine Ecology and Biodiversity, Institute of Tibetan Plateau Research, Center for Excellence in Tibetan Earth Science, Chinese Academy of Sciences, Beijing 100085, China. ; Laboratoire de Meteorologie Dynamique, CNRS, Universite Pierre et Marie Curie-Paris 6, 75252 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26983540" target="_blank"〉PubMed〈/a〉
    Keywords: Aerosols/analysis/chemistry ; Air Pollution/*analysis ; Atmosphere/*chemistry ; Carbon Dioxide/analysis ; China ; Fossil Fuels ; *Greenhouse Effect ; Methane/analysis ; Soot/analysis ; Sulfates/analysis ; Sulfur Dioxide/analysis ; Uncertainty
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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