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  • 2005-2009  (35)
  • 1975-1979  (26)
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  • 1
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    Origins and functional impact of copy number variation in the human genome (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-10-09
    Description: Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330748/" 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/PMC3330748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Donald F -- Pinto, Dalila -- Redon, Richard -- Feuk, Lars -- Gokcumen, Omer -- Zhang, Yujun -- Aerts, Jan -- Andrews, T Daniel -- Barnes, Chris -- Campbell, Peter -- Fitzgerald, Tomas -- Hu, Min -- Ihm, Chun Hwa -- Kristiansson, Kati -- Macarthur, Daniel G -- Macdonald, Jeffrey R -- Onyiah, Ifejinelo -- Pang, Andy Wing Chun -- Robson, Sam -- Stirrups, Kathy -- Valsesia, Armand -- Walter, Klaudia -- Wei, John -- Wellcome Trust Case Control Consortium -- Tyler-Smith, Chris -- Carter, Nigel P -- Lee, Charles -- Scherer, Stephen W -- Hurles, Matthew E -- 077006/Z/05/Z/Wellcome Trust/United Kingdom -- 077008/Wellcome Trust/United Kingdom -- 077009/Wellcome Trust/United Kingdom -- 077014/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- GM081533/GM/NIGMS NIH HHS/ -- HG004221/HG/NHGRI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Apr 1;464(7289):704-12. doi: 10.1038/nature08516. Epub 2009 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812545" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/genetics ; DNA Copy Number Variations/*genetics ; Gene Duplication ; Genetic Predisposition to Disease/*genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genotype ; Haplotypes/genetics ; Humans ; Mutagenesis/*genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Towards responsible use of cognitive-enhancing drugs by the healthy (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-12-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greely, Henry -- Sahakian, Barbara -- Harris, John -- Kessler, Ronald C -- Gazzaniga, Michael -- Campbell, Philip -- Farah, Martha J -- England -- Nature. 2008 Dec 11;456(7223):702-5. doi: 10.1038/456702a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford Law School, Crown Quadrangle, 559 Nathan Abbott Way, Stanford, California 94305-8610, USA. hgreely@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19060880" target="_blank"〉PubMed〈/a〉
    Keywords: Attention/drug effects ; *Bioethical Issues ; Brain/*drug effects ; Drug and Narcotic Control/*legislation & jurisprudence ; Health Policy ; Humans ; Memory/drug effects ; Nootropic Agents/administration & dosage/*pharmacology/*therapeutic use ; Risk Assessment
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Sarcolemma-localized nNOS is required to maintain activity after mild exercise (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-10-28
    Description: Many neuromuscular conditions are characterized by an exaggerated exercise-induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients, and some patients experience severe fatigue without any demonstrable somatic disease. Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown. With no treatment available, this form of inactivity is a major determinant of disability. Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS-null mice do not have muscle pathology and have no loss of muscle-specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction-induced signalling from sarcolemma-localized nNOS, which decreases cGMP-mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588643/" 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/PMC2588643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kobayashi, Yvonne M -- Rader, Erik P -- Crawford, Robert W -- Iyengar, Nikhil K -- Thedens, Daniel R -- Faulkner, John A -- Parikh, Swapnesh V -- Weiss, Robert M -- Chamberlain, Jeffrey S -- Moore, Steven A -- Campbell, Kevin P -- F32 AR048742-01/AR/NIAMS NIH HHS/ -- F32 AR048742-02/AR/NIAMS NIH HHS/ -- K26 RR017369/RR/NCRR NIH HHS/ -- K26 RR017369-01A1/RR/NCRR NIH HHS/ -- K26 RR017369-02/RR/NCRR NIH HHS/ -- K26 RR017369-03/RR/NCRR NIH HHS/ -- K26 RR017369-04/RR/NCRR NIH HHS/ -- K26 RR017369-05/RR/NCRR NIH HHS/ -- R01 AG033610/AG/NIA NIH HHS/ -- R01 AR051199/AR/NIAMS NIH HHS/ -- R01 AR051199-01/AR/NIAMS NIH HHS/ -- T32 HL007121/HL/NHLBI NIH HHS/ -- T32 HL007121-26/HL/NHLBI NIH HHS/ -- T32 HL007121-27/HL/NHLBI NIH HHS/ -- U54 NS053672/NS/NINDS NIH HHS/ -- U54 NS053672-01/NS/NINDS NIH HHS/ -- U54 NS053672-02/NS/NINDS NIH HHS/ -- U54 NS053672-02S1/NS/NINDS NIH HHS/ -- U54 NS053672-03/NS/NINDS NIH HHS/ -- U54 NS053672-04/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Nov 27;456(7221):511-5. doi: 10.1038/nature07414. Epub 2008 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, Iowa 52242-1101, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18953332" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cyclic GMP/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; *Disease Models, Animal ; Edema/drug therapy/etiology/prevention & control ; Enzyme Activation ; Exercise/*physiology ; Fatigue/pathology/*physiopathology ; Hemodynamics/drug effects ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Muscle, Skeletal/blood supply/cytology/enzymology/physiopathology ; Muscular Diseases/enzymology/pathology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type I/deficiency/genetics/*metabolism ; Phosphodiesterase 5 Inhibitors ; Protein Transport ; Sarcolemma/*enzymology ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Maddox by his successor (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Campbell, Philip -- England -- Nature. 2009 Apr 23;458(7241):985-6. doi: 10.1038/458985a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396137" target="_blank"〉PubMed〈/a〉
    Keywords: *Editorial Policies ; Greenhouse Effect ; History, 20th Century ; *Peer Review, Research/methods ; Periodicals as Topic/*history
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    John Maddox 1925-2009 (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Campbell, Philip -- England -- Nature. 2009 Apr 16;458(7240):807. doi: 10.1038/458807a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19378388" target="_blank"〉PubMed〈/a〉
    Keywords: Editorial Policies ; History, 20th Century ; Journalism/*history ; Peer Review, Research ; Periodicals as Topic/*history
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Electronic Resource
    Electronic Resource
    Sequential extraction procedure for the speciation of particulate trace metals (1979)
    s.l. : American Chemical Society
    Analytical chemistry 51 (1979), S. 844-851 
    Details
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ac50043a017
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  • 7
    Electronic Resource
    Electronic Resource
    Critical evaluation of the copper(II) solubilization method for the determination of the complexation capacity of natural waters (1977)
    s.l. : American Chemical Society
    Analytical chemistry 49 (1977), S. 2358-2363 
    Details
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ac50022a057
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  • 8
    Electronic Resource
    Electronic Resource
    Histidine nutrition and genotype affect cataract development in Atlantic salmon, Salmo salar L. (2005)
    Oxford, UK : Blackwell Science Ltd
    Journal of fish diseases 28 (2005), S. 0 
    Details
    ISSN: 1365-2761
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The aim of this study was to investigate effects of dietary levels of histidine (His) and iron (Fe) on cataract development in two strains of Atlantic salmon monitored through parr-smolt transformation. Three experimental diets were fed: (i) a control diet (CD) with 110 mg kg−1 Fe and 11.7 g kg−1 His; (ii) CD supplemented with crystalline His to a level of 18 g kg−1 (HD); and (iii) HD with added iron up to 220 mg kg−1 (HID). A cross-over design, with two feeding periods was used. A 6-week freshwater (FW) period was followed by a 20-week period, of which the first three were in FW and the following 17 weeks in sea water (SW). Fish were sampled for weighing, cataract assessment and tissue analysis at five time points. Cataracts developed in all groups in SW, but scores were lower in those fed high His diets (P 〈 0.05). This effect was most pronounced when HD or HID was given in SW, but was also observed when these diets were given in FW only. Histidine supplementation had a positive effect on growth performance and feed conversion ratio (P 〈 0.05), whereas this did not occur when iron was added. Groups fed HD or HID had higher lens levels of His and N-acetyl histidine (NAH), the latter showing a marked increase post-smoltification (P 〈 0.05). The HD or HID groups also showed higher muscle concentrations of the His dipeptide anserine (P 〈 0.05). There was a strong genetic influence on cataract development in the CD groups (P 〈 0.001), not associated with tissue levels of His or NAH. The role of His and His-related compounds in cataractogenesis is discussed in relation to tissue buffering, osmoregulation and antioxidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2761.2005.00640.x
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  • 9
    Electronic Resource
    Electronic Resource
    Dietary histidine affects lens protein turnover and synthesis of N-acetylhistidine in Atlantic salmon (Salmo salar L.) undergoing parr–smolt transformation (2005)
    Oxford, UK : Blackwell Science Ltd
    Aquaculture nutrition 11 (2005), S. 0 
    Details
    ISSN: 1365-2095
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: This study was conducted to investigate protein synthesis rates and metabolism of histidine (His)-derivatives in lenses of Atlantic salmon (Salmo salar L.) of different dietary His background during parr–smolt transformation. Two populations of Atlantic salmon parr of equal origin were established in freshwater (FW), 3 months prior to transfer to seawater (SW). The populations were fed either a control diet (CD) containing 8.9 g kg−1 His or the same diet added crystalline His to a total level of 14.2 g kg−1 (HD). On the basis of these two populations, 14C His force-feeding studies were performed; in FW 3 weeks prior to sea transfer and in SW 6 weeks after transfer. The studies were conducted by force-feeding the respective diets enriched with 14C labelled His, with subsequent measurements of incorporation of 14C His into lens free amino acid pool, as well as into lens proteins and other free His pool fractions. The latter included the major lens imidazole N-acetylhistidine (NAH). Lens concentrations of His and NAH were clearly influenced by dietary His history, both in parr and smolt. The lens His and NAH concentrations in the CD population were considerably lower in SW than in FW, while in the HD group the His level was equal and the NAH level 50% higher in SW than in FW. Fractional synthesis rate for NAH, KS (NAH), in FW was 8.2 and 4.2 μmol g−1 day−1 for fish in the CD and HD populations, respectively. The corresponding KS (NAH) values in SW were 5.1 and 33.0 μmol g−1 day−1. Our data show that free His is rapidly converted to NAH in the lens, and that NAH seems to have a very high turnover, especially in salmon reared in SW. Fractional synthesis rate for lens proteins, KS (PROTEIN), ranged between 1.8 and 17.3% day−1 (182 and 2791 μg g−1 day−1, respectively), and was generally higher in SW than in FW (P 〈 0.01). In SW, KS (PROTEIN) was highest in fish in the HD population (P 〈 0.05), whereas lens protein retention in the HD group was significantly lower than the CD group (P = 0.01). In a second model assuming that His from lens NAH is available for protein synthesis, calculated values of KS (PROTEIN) ranged between 0.17% day−1 (17.6 μg g−1 day−1) and 0.48% day−1 (70.2 μg g−1 day−1). Cataract scores recorded in the His populations at a later point (day 204), showed that the CD fish had significantly higher mean cataract scores than individuals in the HD population (P 〈 0.01), confirming that low levels of lens His and NAH are associated with cataract development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2095.2005.00362.x
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  • 10
    Electronic Resource
    Electronic Resource
    An Lyt differentiated thymocyte subpopulation detected by flow microfluorometry (1979)
    [s.l.] : Nature Publishing Group
    Nature 277 (1979), S. 478-480 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1 Normal or cortisone-resistant thymocytes from 3-5-month C57BL/6 (B6) or appropriate B6/Ly congeneic mice were treated with anti-Lyt antisera and fluorescent goat anti-mouse immunoglobulin (Fl-GAMlg). CRT were obtained 36-40 h after intraperitoneal administration of 0.25 nig cortisone acetate ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/277478a0
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