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  • 2005-2009  (1,157)
  • 1
    Publication Date: 2008-05-16
    Description: The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 (ref. 7) and H1N1 (ref. 8) viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Patrick J -- Haire, Lesley F -- Lin, Yi Pu -- Liu, Junfeng -- Russell, Rupert J -- Walker, Philip A -- Skehel, John J -- Martin, Stephen R -- Hay, Alan J -- Gamblin, Steven J -- MC_U117512711/Medical Research Council/United Kingdom -- MC_U117512723/Medical Research Council/United Kingdom -- MC_U117570592/Medical Research Council/United Kingdom -- MC_U117584222/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2008 Jun 26;453(7199):1258-61. doi: 10.1038/nature06956. Epub 2008 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480754" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; *Drug Resistance, Viral ; Enzyme Inhibitors/chemistry/metabolism/pharmacology ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects/enzymology/genetics ; Influenza A Virus, H5N1 Subtype/*drug effects/*enzymology/genetics ; Influenza, Human/virology ; Kinetics ; Models, Molecular ; Molecular Conformation ; Mutation/*genetics ; Neuraminidase/antagonists & inhibitors/*chemistry/*genetics/metabolism ; Oseltamivir/chemistry/metabolism/*pharmacology ; Protein Binding ; Zanamivir/pharmacology
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    Electronic ISSN: 1476-4687
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  • 2
    Publication Date: 2008-05-20
    Description: Non-human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non-human primate models of human diseases. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor impairment, cognitive deterioration and psychiatric disturbances followed by death within 10-15 years of the onset of the symptoms. HD is caused by the expansion of cytosine-adenine-guanine (CAG, translated into glutamine) trinucleotide repeats in the first exon of the human huntingtin (HTT) gene. Mutant HTT with expanded polyglutamine (polyQ) is widely expressed in the brain and peripheral tissues, but causes selective neurodegeneration that is most prominent in the striatum and cortex of the brain. Although rodent models of HD have been developed, these models do not satisfactorily parallel the brain changes and behavioural features observed in HD patients. Because of the close physiological, neurological and genetic similarities between humans and higher primates, monkeys can serve as very useful models for understanding human physiology and diseases. Here we report our progress in developing a transgenic model of HD in a rhesus macaque that expresses polyglutamine-expanded HTT. Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys. Additionally, the transgenic monkeys showed important clinical features of HD, including dystonia and chorea. A transgenic HD monkey model may open the way to understanding the underlying biology of HD better, and to the development of potential therapies. Moreover, our data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652570/" 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/PMC2652570/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Shang-Hsun -- Cheng, Pei-Hsun -- Banta, Heather -- Piotrowska-Nitsche, Karolina -- Yang, Jin-Jing -- Cheng, Eric C H -- Snyder, Brooke -- Larkin, Katherine -- Liu, Jun -- Orkin, Jack -- Fang, Zhi-Hui -- Smith, Yoland -- Bachevalier, Jocelyne -- Zola, Stuart M -- Li, Shi-Hua -- Li, Xiao-Jiang -- Chan, Anthony W S -- R01 AG019206/AG/NIA NIH HHS/ -- R01 AG019206-07/AG/NIA NIH HHS/ -- R01 NS036232/NS/NINDS NIH HHS/ -- R01 NS036232-09/NS/NINDS NIH HHS/ -- R01 NS041669/NS/NINDS NIH HHS/ -- R01 NS041669-07/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Jun 12;453(7197):921-4. doi: 10.1038/nature06975. Epub 2008 May 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18488016" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Animals, Newborn ; Brain/metabolism/pathology ; Chorea/genetics/physiopathology ; *Disease Models, Animal ; Dystonia/genetics/physiopathology ; Exons/genetics ; Female ; Humans ; Huntington Disease/*genetics/metabolism/pathology/*physiopathology ; Macaca mulatta/*genetics ; Male ; Nerve Tissue Proteins/*genetics/metabolism ; Nuclear Proteins/*genetics/metabolism ; Peptides/genetics/metabolism ; Pregnancy ; Survival Analysis ; Trinucleotide Repeat Expansion/*genetics
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2008-08-01
    Description: The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610422/" 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/PMC2610422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jun -- Bartesaghi, Alberto -- Borgnia, Mario J -- Sapiro, Guillermo -- Subramaniam, Sriram -- Z01 BC010825-01/Intramural NIH HHS/ -- England -- Nature. 2008 Sep 4;455(7209):109-13. doi: 10.1038/nature07159. Epub 2008 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18668044" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD4/chemistry/metabolism ; Cryoelectron Microscopy ; HIV Envelope Protein gp120/*chemistry/immunology/*metabolism ; HIV-1/*chemistry ; Immunoglobulin Fab Fragments/chemistry/immunology ; Models, Molecular ; Protein Binding ; Protein Structure, Quaternary ; Protein Subunits/chemistry/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2008-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Junguo -- Savenije, H H G -- England -- Nature. 2008 May 29;453(7195):587. doi: 10.1038/453587c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509419" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Commerce/*statistics & numerical data ; Crops, Agricultural/economics/*metabolism/*supply & distribution ; Food Supply/economics ; Soybeans ; Water/*metabolism ; Water Supply/*economics
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    Electronic ISSN: 1476-4687
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  • 5
    Publication Date: 2008-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Junguo -- Yang, Hong -- Savenije, H H G -- England -- Nature. 2008 Jul 24;454(7203):397. doi: 10.1038/454397a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650891" target="_blank"〉PubMed〈/a〉
    Keywords: China/epidemiology ; Diet/*statistics & numerical data/trends ; Food Supply/*statistics & numerical data ; Health Education ; Humans ; *Meat ; Water Supply/*statistics & numerical data
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  • 6
    Publication Date: 2009-05-16
    Description: When the packing fraction is increased sufficiently, loose particulates jam to form a rigid solid in which the constituents are no longer free to move. In typical granular materials and foams, the thermal energy is too small to produce structural rearrangements. In this zero-temperature (T = 0) limit, multiple diverging and vanishing length scales characterize the approach to a sharp jamming transition. However, because thermal motion becomes relevant when the particles are small enough, it is imperative to understand how these length scales evolve as the temperature is increased. Here we used both colloidal experiments and computer simulations to progress beyond the zero-temperature limit to track one of the key parameters-the overlap distance between neighbouring particles-which vanishes at the T = 0 jamming transition. We find that this structural feature retains a vestige of its T = 0 behaviour and evolves in an unusual manner, which has masked its appearance until now. It is evident as a function of packing fraction at fixed temperature, but not as a function of temperature at fixed packing fraction or pressure. Our results conclusively demonstrate that length scales associated with the T = 0 jamming transition persist in thermal systems, not only in simulations but also in laboratory experiments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Zexin -- Xu, Ning -- Chen, Daniel T N -- Yunker, Peter -- Alsayed, Ahmed M -- Aptowicz, Kevin B -- Habdas, Piotr -- Liu, Andrea J -- Nagel, Sidney R -- Yodh, Arjun G -- England -- Nature. 2009 May 14;459(7244):230-3. doi: 10.1038/nature07998.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. zexin@sas.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444211" target="_blank"〉PubMed〈/a〉
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  • 7
    Publication Date: 2008-11-26
    Description: Segregating hybrids and stable allopolyploids display morphological vigour, and Arabidopsis allotetraploids are larger than the parents Arabidopsis thaliana and Arabidopsis arenosa-the mechanisms for this are unknown. Circadian clocks mediate metabolic pathways and increase fitness in animals and plants. Here we report that epigenetic modifications of the circadian clock genes CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) and their reciprocal regulators TIMING OF CAB EXPRESSION 1 (TOC1) and GIGANTEA (GI) mediate expression changes in downstream genes and pathways. During the day, epigenetic repression of CCA1 and LHY induced the expression of TOC1, GI and downstream genes containing evening elements in chlorophyll and starch metabolic pathways in allotetraploids and F(1) hybrids, which produced more chlorophyll and starch than the parents in the same environment. Mutations in cca1 and cca1 lhy and the daily repression of cca1 by RNA interference (RNAi) in TOC1::cca1(RNAi) transgenic plants increased the expression of downstream genes and increased chlorophyll and starch content, whereas constitutively expressing CCA1 or ectopically expressing TOC1::CCA1 had the opposite effect. The causal effects of CCA1 on output traits suggest that hybrids and allopolyploids gain advantages from the control of circadian-mediated physiological and metabolic pathways, leading to growth vigour and increased biomass.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679702/" 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/PMC2679702/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ni, Zhongfu -- Kim, Eun-Deok -- Ha, Misook -- Lackey, Erika -- Liu, Jianxin -- Zhang, Yirong -- Sun, Qixin -- Chen, Z Jeffrey -- GM067015/GM/NIGMS NIH HHS/ -- R01 GM067015/GM/NIGMS NIH HHS/ -- R01 GM067015-04/GM/NIGMS NIH HHS/ -- R01 GM067015-05/GM/NIGMS NIH HHS/ -- R01 GM067015-06/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jan 15;457(7227):327-31. doi: 10.1038/nature07523. Epub 2008 Nov 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Molecular Cell and Developmental Biology, The University of Texas at Austin, One University Station, A-4800, Austin, Texas 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19029881" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/classification/*genetics/*growth & development ; Arabidopsis Proteins/genetics/metabolism ; Base Sequence ; Biological Clocks/genetics/physiology ; Chlorophyll/metabolism ; Chromatin/genetics ; Circadian Rhythm/genetics/*physiology ; DNA-Binding Proteins/genetics/metabolism ; Epigenesis, Genetic ; Gene Expression Regulation, Plant/genetics ; *Hybridization, Genetic ; Plants, Genetically Modified ; *Polyploidy ; Starch/biosynthesis ; Transcription Factors/genetics/metabolism
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  • 8
    Publication Date: 2009-05-01
    Description: Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities including a severe defect in stem cell self-renewal, alterations in thymocyte maturation and a shortened lifespan. Previous work has implicated de-repression of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of the Bmi1(-/-) phenotype. Here we demonstrate that cells derived from Bmi1(-/-) mice also have impaired mitochondrial function, a marked increase in the intracellular levels of reactive oxygen species and subsequent engagement of the DNA damage response pathway. Furthermore, many of the deficiencies normally observed in Bmi1(-/-) mice improve after either pharmacological treatment with the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that Bmi1 has an unexpected role in maintaining mitochondrial function and redox homeostasis and indicate that the Polycomb family of proteins can coordinately regulate cellular metabolism with stem and progenitor cell function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721521/" 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/PMC4721521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jie -- Cao, Liu -- Chen, Jichun -- Song, Shiwei -- Lee, In Hye -- Quijano, Celia -- Liu, Hongjun -- Keyvanfar, Keyvan -- Chen, Haoqian -- Cao, Long-Yue -- Ahn, Bong-Hyun -- Kumar, Neil G -- Rovira, Ilsa I -- Xu, Xiao-Ling -- van Lohuizen, Maarten -- Motoyama, Noboru -- Deng, Chu-Xia -- Finkel, Toren -- R00 AG032356/AG/NIA NIH HHS/ -- Z01 HL005012-11/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 May 21;459(7245):387-92. doi: 10.1038/nature08040. Epub 2009 Apr 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Translational Medicine Branch, National Heart Lung and Blood 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/19404261" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcysteine/pharmacology ; Animals ; Antioxidants/pharmacology ; Checkpoint Kinase 2 ; *DNA Damage/genetics ; Female ; Male ; Mice ; Mitochondria/*metabolism ; Nuclear Proteins/deficiency/genetics/*metabolism ; Oxidation-Reduction/drug effects ; Polycomb Repressive Complex 1 ; Protein-Serine-Threonine Kinases/deficiency/genetics ; Proto-Oncogene Proteins/deficiency/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Repressor Proteins/genetics/*metabolism ; Stem Cells/cytology/drug effects/metabolism ; Thymus Gland/cytology/drug effects
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  • 9
    Publication Date: 2008-11-11
    Description: A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3). Here we show that an improved T-cell-based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIV(MAC251) challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS-related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T-cell-based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614452/" 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/PMC2614452/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jinyan -- O'Brien, Kara L -- Lynch, Diana M -- Simmons, Nathaniel L -- La Porte, Annalena -- Riggs, Ambryice M -- Abbink, Peter -- Coffey, Rory T -- Grandpre, Lauren E -- Seaman, Michael S -- Landucci, Gary -- Forthal, Donald N -- Montefiori, David C -- Carville, Angela -- Mansfield, Keith G -- Havenga, Menzo J -- Pau, Maria G -- Goudsmit, Jaap -- Barouch, Dan H -- AI030034/AI/NIAID NIH HHS/ -- AI066305/AI/NIAID NIH HHS/ -- AI066924/AI/NIAID NIH HHS/ -- AI078526/AI/NIAID NIH HHS/ -- P51 RR000168/RR/NCRR NIH HHS/ -- P51 RR000168-446932/RR/NCRR NIH HHS/ -- P51 RR000168-455647/RR/NCRR NIH HHS/ -- P51 RR000168-466922/RR/NCRR NIH HHS/ -- R01 AI058727/AI/NIAID NIH HHS/ -- R01 AI058727-04/AI/NIAID NIH HHS/ -- R01 AI058727-05/AI/NIAID NIH HHS/ -- R01 AI066924/AI/NIAID NIH HHS/ -- R01 AI066924-02/AI/NIAID NIH HHS/ -- R01 AI066924-03/AI/NIAID NIH HHS/ -- RR000168/RR/NCRR NIH HHS/ -- U19 AI066305/AI/NIAID NIH HHS/ -- U19 AI066305-02/AI/NIAID NIH HHS/ -- U19 AI066305-020001/AI/NIAID NIH HHS/ -- U19 AI066305-03/AI/NIAID NIH HHS/ -- U19 AI066305-030001/AI/NIAID NIH HHS/ -- U19 AI066305-04/AI/NIAID NIH HHS/ -- U19 AI066305-040001/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI078526-01/AI/NIAID NIH HHS/ -- U19 AI078526-017546/AI/NIAID NIH HHS/ -- U19 AI078526-017549/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Jan 1;457(7225):87-91. doi: 10.1038/nature07469. Epub 2008 Nov 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18997770" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/genetics ; Animals ; Antibodies, Viral/immunology ; CD4-Positive T-Lymphocytes/*immunology ; HIV Infections/immunology/prevention & control ; Humans ; Macaca mulatta/*immunology/*virology ; Neutralization Tests ; SAIDS Vaccines/administration & dosage/*immunology ; Simian Acquired Immunodeficiency Syndrome/*immunology/mortality/prevention & ; control/virology ; Simian Immunodeficiency Virus/*immunology ; Vaccination ; Viral Load
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  • 10
    Publication Date: 2009-11-06
    Description: Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor alpha (ER-alpha) in the human genome. We found that most high-confidence remote ER-alpha-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-alpha functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774924/" 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/PMC2774924/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fullwood, Melissa J -- Liu, Mei Hui -- Pan, You Fu -- Liu, Jun -- Xu, Han -- Mohamed, Yusoff Bin -- Orlov, Yuriy L -- Velkov, Stoyan -- Ho, Andrea -- Mei, Poh Huay -- Chew, Elaine G Y -- Huang, Phillips Yao Hui -- Welboren, Willem-Jan -- Han, Yuyuan -- Ooi, Hong Sain -- Ariyaratne, Pramila N -- Vega, Vinsensius B -- Luo, Yanquan -- Tan, Peck Yean -- Choy, Pei Ye -- Wansa, K D Senali Abayratna -- Zhao, Bing -- Lim, Kar Sian -- Leow, Shi Chi -- Yow, Jit Sin -- Joseph, Roy -- Li, Haixia -- Desai, Kartiki V -- Thomsen, Jane S -- Lee, Yew Kok -- Karuturi, R Krishna Murthy -- Herve, Thoreau -- Bourque, Guillaume -- Stunnenberg, Hendrik G -- Ruan, Xiaoan -- Cacheux-Rataboul, Valere -- Sung, Wing-Kin -- Liu, Edison T -- Wei, Chia-Lin -- Cheung, Edwin -- Ruan, Yijun -- 1U54HG004557-01/HG/NHGRI NIH HHS/ -- R01 HG004456/HG/NHGRI NIH HHS/ -- R01 HG004456-01/HG/NHGRI NIH HHS/ -- R01 HG004456-02/HG/NHGRI NIH HHS/ -- R01 HG004456-03/HG/NHGRI NIH HHS/ -- R01HG003521-01/HG/NHGRI NIH HHS/ -- R01HG004456-01/HG/NHGRI NIH HHS/ -- U54 HG004557/HG/NHGRI NIH HHS/ -- U54 HG004557-01/HG/NHGRI NIH HHS/ -- U54 HG004557-02/HG/NHGRI NIH HHS/ -- U54 HG004557-03/HG/NHGRI NIH HHS/ -- U54 HG004557-04/HG/NHGRI NIH HHS/ -- England -- Nature. 2009 Nov 5;462(7269):58-64. doi: 10.1038/nature08497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890323" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Line ; Chromatin/*genetics/*metabolism ; Chromatin Immunoprecipitation ; Cross-Linking Reagents ; Estrogen Receptor alpha/*metabolism ; Formaldehyde ; Genome, Human/*genetics ; Humans ; Promoter Regions, Genetic/genetics ; Protein Binding ; Reproducibility of Results ; Sequence Analysis, DNA ; Transcription, Genetic ; Transcriptional Activation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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