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  • 1
    Publication Date: 2008-03-28
    Description: Clinical trials of small interfering RNA (siRNA) targeting vascular endothelial growth factor-A (VEGFA) or its receptor VEGFR1 (also called FLT1), in patients with blinding choroidal neovascularization (CNV) from age-related macular degeneration, are premised on gene silencing by means of intracellular RNA interference (RNAi). We show instead that CNV inhibition is a siRNA-class effect: 21-nucleotide or longer siRNAs targeting non-mammalian genes, non-expressed genes, non-genomic sequences, pro- and anti-angiogenic genes, and RNAi-incompetent siRNAs all suppressed CNV in mice comparably to siRNAs targeting Vegfa or Vegfr1 without off-target RNAi or interferon-alpha/beta activation. Non-targeted (against non-mammalian genes) and targeted (against Vegfa or Vegfr1) siRNA suppressed CNV via cell-surface toll-like receptor 3 (TLR3), its adaptor TRIF, and induction of interferon-gamma and interleukin-12. Non-targeted siRNA suppressed dermal neovascularization in mice as effectively as Vegfa siRNA. siRNA-induced inhibition of neovascularization required a minimum length of 21 nucleotides, a bridging necessity in a modelled 2:1 TLR3-RNA complex. Choroidal endothelial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular siRNA-induced cytotoxicity, facilitating individualized pharmacogenetic therapy. Multiple human endothelial cell types expressed surface TLR3, indicating that generic siRNAs might treat angiogenic disorders that affect 8% of the world's population, and that siRNAs might induce unanticipated vascular or immune effects.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642938/" 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/PMC2642938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kleinman, Mark E -- Yamada, Kiyoshi -- Takeda, Atsunobu -- Chandrasekaran, Vasu -- Nozaki, Miho -- Baffi, Judit Z -- Albuquerque, Romulo J C -- Yamasaki, Satoshi -- Itaya, Masahiro -- Pan, Yuzhen -- Appukuttan, Binoy -- Gibbs, Daniel -- Yang, Zhenglin -- Kariko, Katalin -- Ambati, Balamurali K -- Wilgus, Traci A -- DiPietro, Luisa A -- Sakurai, Eiji -- Zhang, Kang -- Smith, Justine R -- Taylor, Ethan W -- Ambati, Jayakrishna -- R01 EY015422/EY/NEI NIH HHS/ -- R01 EY015422-04/EY/NEI NIH HHS/ -- R01 EY018350/EY/NEI NIH HHS/ -- R01 EY018350-02/EY/NEI NIH HHS/ -- R01 EY018836/EY/NEI NIH HHS/ -- R01 EY018836-01/EY/NEI NIH HHS/ -- England -- Nature. 2008 Apr 3;452(7187):591-7. doi: 10.1038/nature06765. Epub 2008 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology, University of Kentucky, Lexington, Kentucky 40506, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368052" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Endothelial Cells/metabolism ; Genetic Therapy/*methods ; Humans ; Immunity, Innate/*immunology ; Interferon-gamma/immunology ; Interleukin-12/immunology ; Macular Degeneration/complications/genetics/therapy ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic/genetics/*immunology/*prevention & control/therapy ; RNA, Small Interfering/chemistry/genetics/*immunology/*metabolism ; Toll-Like Receptor 3/chemistry/genetics/*metabolism ; Vascular Endothelial Growth Factor A/genetics
    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: 2008-07-25
    Description: The endoplasmic reticulum is responsible for much of a cell's protein synthesis and folding, but it also has an important role in sensing cellular stress. Recently, it has been shown that the endoplasmic reticulum mediates a specific set of intracellular signalling pathways in response to the accumulation of unfolded or misfolded proteins, and these pathways are collectively known as the unfolded-protein response. New observations suggest that the unfolded-protein response can initiate inflammation, and the coupling of these responses in specialized cells and tissues is now thought to be fundamental in the pathogenesis of inflammatory diseases. The knowledge gained from this emerging field will aid in the development of therapies for modulating cellular stress and inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727659/" 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/PMC2727659/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Kezhong -- Kaufman, Randal J -- DK042394/DK/NIDDK NIH HHS/ -- HL052173/HL/NHLBI NIH HHS/ -- HL057346/HL/NHLBI NIH HHS/ -- P01 HL057346/HL/NHLBI NIH HHS/ -- P01 HL057346-100006/HL/NHLBI NIH HHS/ -- P01 HL057346-11A18575/HL/NHLBI NIH HHS/ -- R01 DK042394/DK/NIDDK NIH HHS/ -- R01 DK042394-09/DK/NIDDK NIH HHS/ -- R01 HL052173/HL/NHLBI NIH HHS/ -- R01 HL052173-11/HL/NHLBI NIH HHS/ -- R01 HL052173-12/HL/NHLBI NIH HHS/ -- R37 DK042394/DK/NIDDK NIH HHS/ -- R37 DK042394-10/DK/NIDDK NIH HHS/ -- R37 DK042394-11/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Jul 24;454(7203):455-62. doi: 10.1038/nature07203.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, The University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease ; Endoplasmic Reticulum/metabolism/*pathology ; Humans ; Inflammation/metabolism/*pathology ; JNK Mitogen-Activated Protein Kinases/metabolism ; NF-kappa B/metabolism ; Protein Folding ; Reactive Oxygen Species/metabolism
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  • 3
    Publication Date: 2008-01-25
    Description: Heterochromatin in eukaryotic genomes regulates diverse chromosomal processes including transcriptional silencing. However, in Schizosaccharomyces pombe RNA polymerase II (RNAPII) transcription of centromeric repeats is essential for RNA-interference-mediated heterochromatin assembly. Here we study heterochromatin dynamics during the cell cycle and its effect on RNAPII transcription. We describe a brief period during the S phase of the cell cycle in which RNAPII preferentially transcribes centromeric repeats. This period is enforced by heterochromatin, which restricts RNAPII accessibility at centromeric repeats for most of the cell cycle. RNAPII transcription during S phase is linked to loading of RNA interference and heterochromatin factors such as the Ago1 subunit of the RITS complex and the Clr4 methyltransferase complex subunit Rik1 (ref. 7). Moreover, Set2, an RNAPII-associated methyltransferase that methylates histone H3 lysine 36 at repeat loci during S phase, acts in a pathway parallel to Clr4 to promote heterochromatin assembly. We also show that phosphorylation of histone H3 serine 10 alters heterochromatin during mitosis, correlating with recruitment of condensin that affects silencing of centromeric repeats. Our analyses suggest at least two distinct modes of heterochromatin targeting to centromeric repeats, whereby RNAPII transcription of repeats and chromodomain proteins bound to methylated histone H3 lysine 9 mediate recruitment of silencing factors. Together, these processes probably facilitate heterochromatin maintenance through successive cell divisions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Ee Sin -- Zhang, Ke -- Nicolas, Estelle -- Cam, Hugh P -- Zofall, Martin -- Grewal, Shiv I S -- Intramural NIH HHS/ -- England -- Nature. 2008 Feb 7;451(7179):734-7. doi: 10.1038/nature06561. Epub 2008 Jan 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, National Cancer 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/18216783" target="_blank"〉PubMed〈/a〉
    Keywords: Argonaute Proteins ; Cell Cycle/*physiology ; Cell Cycle Proteins/metabolism ; Centromere/*genetics ; *Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/metabolism ; Gene Silencing ; Heterochromatin/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/chemistry/metabolism ; Methylation ; Methyltransferases/metabolism ; Phosphorylation ; RNA Polymerase II/metabolism ; RNA-Binding Proteins ; S Phase ; Schizosaccharomyces/*cytology/enzymology/*genetics ; Schizosaccharomyces pombe Proteins/metabolism ; *Transcription, Genetic
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  • 4
    Publication Date: 2009-08-21
    Description: Eukaryotic transcriptomes are characterized by widespread transcription of noncoding and antisense RNAs, which is linked to key chromosomal processes, such as chromatin remodelling, gene regulation and heterochromatin assembly. However, these transcripts can be deleterious, and their accumulation is suppressed by several mechanisms including degradation by the nuclear exosome. The mechanisms by which cells differentiate coding RNAs from transcripts targeted for degradation are not clear. Here we show that the variant histone H2A.Z, which is loaded preferentially at the 5' ends of genes by the Swr1 complex containing a JmjC domain protein, mediates suppression of antisense transcripts in the fission yeast Schizosaccharomyces pombe genome. H2A.Z is partially redundant in this regard with the Clr4 (known as SUV39H in mammals)-containing heterochromatin silencing complex that is also distributed at euchromatic loci, and with RNA interference component Argonaute (Ago1). Loss of Clr4 or Ago1 alone has little effect on antisense transcript levels, but cells lacking either of these factors and H2A.Z show markedly increased levels of antisense RNAs that are normally degraded by the exosome. These analyses suggest that as well as performing other functions, H2A.Z is a component of a genome indexing mechanism that cooperates with heterochromatin and RNAi factors to suppress read-through antisense transcripts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746258/" 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/PMC2746258/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zofall, Martin -- Fischer, Tamas -- Zhang, Ke -- Zhou, Ming -- Cui, Bowen -- Veenstra, Timothy D -- Grewal, Shiv I S -- N01-CO-12400/CO/NCI NIH HHS/ -- Z01 BC010523-04/Intramural NIH HHS/ -- England -- Nature. 2009 Sep 17;461(7262):419-22. doi: 10.1038/nature08321. Epub 2009 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, National Cancer 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/19693008" target="_blank"〉PubMed〈/a〉
    Keywords: Argonaute Proteins ; Cell Cycle Proteins/genetics/metabolism ; Exosomes/metabolism ; *Gene Expression Regulation, Fungal ; Heterochromatin/genetics/*metabolism ; Histones/deficiency/genetics/*metabolism ; Methyltransferases/deficiency/genetics/metabolism ; *RNA Interference ; RNA, Antisense/*antagonists & inhibitors/biosynthesis/*genetics ; RNA, Fungal/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins ; Schizosaccharomyces/*genetics/metabolism ; Schizosaccharomyces pombe Proteins/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2006-03-11
    Description: A biosynthetic approach was developed to control and probe cooperativity in multiunit biomotor assemblies by linking molecular motors to artificial protein scaffolds. This approach provides precise control over spatial and elastic coupling between motors. Cooperative interactions between monomeric kinesin-1 motors attached to protein scaffolds enhance hydrolysis activity and microtubule gliding velocity. However, these interactions are not influenced by changes in the elastic properties of the scaffold, distinguishing multimotor transport from that powered by unorganized monomeric motors. These results highlight the role of supramolecular architecture in determining mechanisms of collective transport.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diehl, Michael R -- Zhang, Kechun -- Lee, Heun Jin -- Tirrell, David A -- New York, N.Y. -- Science. 2006 Mar 10;311(5766):1468-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. diehl@rice.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16527982" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry ; Amino Acid Sequence ; Elasticity ; Elastin/chemistry ; Hydrolysis ; Kinesin/chemistry ; Microtubules/physiology ; Models, Biological ; Molecular Motor Proteins/*physiology ; Molecular Sequence Data ; Protein Engineering ; Protein Structure, Tertiary ; Proteins/chemistry/*physiology ; Recombinant Proteins/chemistry ; Structure-Activity Relationship
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2007-02-03
    Description: Acetylation of histone H3 lysine 56 (H3-K56) occurs in S phase, and cells lacking H3-K56 acetylation are sensitive to DNA-damaging agents. However, the histone acetyltransferase (HAT) that catalyzes global H3-K56 acetylation has not been found. Here we show that regulation of Ty1 transposition gene product 109 (Rtt109) is an H3-K56 HAT. Cells lacking Rtt109 or expressing rtt109 mutants with alterations at a conserved aspartate residue lose H3-K56 acetylation and exhibit increased sensitivity toward genotoxic agents, as well as elevated levels of spontaneous chromosome breaks. Thus, Rtt109, which shares no sequence homology with any other known HATs, is a unique HAT that acetylates H3-K56.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Junhong -- Zhou, Hui -- Horazdovsky, Bruce -- Zhang, Kangling -- Xu, Rui-Ming -- Zhang, Zhiguo -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):653-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272723" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Camptothecin/pharmacology ; Catalytic Domain ; Chromosome Breakage ; DNA Damage ; *DNA Replication ; Histone Acetyltransferases/chemistry/genetics/*metabolism ; Histones/*metabolism ; Hydroxyurea/pharmacology ; Lysine/*metabolism ; Methyl Methanesulfonate/pharmacology ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutagens/pharmacology ; Mutation ; Recombinant Proteins/metabolism ; S Phase ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Sequence Homology, Amino Acid
    Print ISSN: 0036-8075
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  • 7
    Publication Date: 2008-08-23
    Description: Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756290/" 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/PMC2756290/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Horwitz, Gregory A -- Zhang, Kangling -- McBrian, Matthew A -- Grunstein, Michael -- Kurdistani, Siavash K -- Berk, Arnold J -- CA25235/CA/NCI NIH HHS/ -- R37 CA025235/CA/NCI NIH HHS/ -- R37 CA025235-30/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1084-5. doi: 10.1126/science.1155544.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719283" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Adenovirus E1A Proteins/genetics/*metabolism ; Adenoviruses, Human/*metabolism ; Antigens, Polyomavirus Transforming/metabolism ; CREB-Binding Protein/metabolism ; *Cell Cycle ; Cell Line ; Cell Transformation, Viral ; Cells, Cultured ; HeLa Cells ; Histones/*metabolism ; Humans ; Lysine/metabolism ; Mutation ; p300-CBP Transcription Factors/metabolism
    Print ISSN: 0036-8075
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  • 8
    Publication Date: 2005-08-06
    Description: We describe a DNA sequencing technology in which a commonly available, inexpensive epifluorescence microscope is converted to rapid nonelectrophoretic DNA sequencing automation. We apply this technology to resequence an evolved strain of Escherichia coli at less than one error per million consensus bases. A cell-free, mate-paired library provided single DNA molecules that were amplified in parallel to 1-micrometer beads by emulsion polymerase chain reaction. Millions of beads were immobilized in a polyacrylamide gel and subjected to automated cycles of sequencing by ligation and four-color imaging. Cost per base was roughly one-ninth as much as that of conventional sequencing. Our protocols were implemented with off-the-shelf instrumentation and reagents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shendure, Jay -- Porreca, Gregory J -- Reppas, Nikos B -- Lin, Xiaoxia -- McCutcheon, John P -- Rosenbaum, Abraham M -- Wang, Michael D -- Zhang, Kun -- Mitra, Robi D -- Church, George M -- New York, N.Y. -- Science. 2005 Sep 9;309(5741):1728-32. Epub 2005 Aug 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. shendure@alumni.princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16081699" target="_blank"〉PubMed〈/a〉
    Keywords: Acrylic Resins ; Algorithms ; Automation ; Costs and Cost Analysis ; DNA Ligases/metabolism ; DNA Primers ; DNA, Bacterial/*genetics ; Escherichia coli/*genetics ; *Evolution, Molecular ; Fluorescent Dyes ; Gels ; Gene Library ; *Genome, Bacterial ; Microscopy, Fluorescence ; Microspheres ; Mutation ; Nucleic Acid Hybridization ; Point Mutation ; Polymerase Chain Reaction ; Sequence Analysis, DNA/economics/instrumentation/*methods
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  • 9
    Publication Date: 2006-10-21
    Description: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world and has a strong genetic predisposition. A locus at human chromosome 10q26 affects the risk of AMD, but the precise gene(s) have not been identified. We genotyped 581 AMD cases and 309 normal controls in a Caucasian cohort in Utah. We demonstrate that a single-nucleotide polymorphism, rs11200638, in the promoter region of HTRA1 is the most likely causal variant for AMD at 10q26 and is estimated to confer a population attributable risk of 49.3%. The HTRA1 gene encodes a secreted serine protease. Preliminary analysis of lymphocytes and retinal pigment epithelium from four AMD patients revealed that the risk allele was associated with elevated expression levels of HTRA1 mRNA and protein. We also found that drusen in the eyes of AMD patients were strongly immunolabeled with HTRA1 antibody. Together, these findings support a key role for HTRA1 in AMD susceptibility and identify a potential new pathway for AMD pathogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Zhenglin -- Camp, Nicola J -- Sun, Hui -- Tong, Zongzhong -- Gibbs, Daniel -- Cameron, D Joshua -- Chen, Haoyu -- Zhao, Yu -- Pearson, Erik -- Li, Xi -- Chien, Jeremy -- Dewan, Andrew -- Harmon, Jennifer -- Bernstein, Paul S -- Shridhar, Viji -- Zabriskie, Norman A -- Hoh, Josephine -- Howes, Kimberly -- Zhang, Kang -- CA98364/CA/NCI NIH HHS/ -- GCRC M01-RR00064/RR/NCRR NIH HHS/ -- P30EY014800/EY/NEI NIH HHS/ -- R01EY14428/EY/NEI NIH HHS/ -- R01EY14448/EY/NEI NIH HHS/ -- R01EY15771/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2006 Nov 10;314(5801):992-3. Epub 2006 Oct 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17053109" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aging ; Alleles ; Case-Control Studies ; Chromosomes, Human, Pair 10/genetics ; Cohort Studies ; European Continental Ancestry Group/genetics ; Female ; *Genetic Predisposition to Disease ; Genotype ; Homozygote ; Humans ; Lymphocytes/enzymology ; Macular Degeneration/*genetics ; Male ; Middle Aged ; Pigment Epithelium of Eye/enzymology ; *Polymorphism, Single Nucleotide ; *Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Retinal Drusen/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Serine Endopeptidases/analysis/*genetics/metabolism
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  • 10
    Publication Date: 2007-07-21
    Description: Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1991296/" 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/PMC1991296/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fellay, Jacques -- Shianna, Kevin V -- Ge, Dongliang -- Colombo, Sara -- Ledergerber, Bruno -- Weale, Mike -- Zhang, Kunlin -- Gumbs, Curtis -- Castagna, Antonella -- Cossarizza, Andrea -- Cozzi-Lepri, Alessandro -- De Luca, Andrea -- Easterbrook, Philippa -- Francioli, Patrick -- Mallal, Simon -- Martinez-Picado, Javier -- Miro, Jose M -- Obel, Niels -- Smith, Jason P -- Wyniger, Josiane -- Descombes, Patrick -- Antonarakis, Stylianos E -- Letvin, Norman L -- McMichael, Andrew J -- Haynes, Barton F -- Telenti, Amalio -- Goldstein, David B -- G0200585/Medical Research Council/United Kingdom -- MC_U137884177/Medical Research Council/United Kingdom -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-03/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 17;317(5840):944-7. Epub 2007 Jul 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Population Genomics and Pharmacogenetics, Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641165" target="_blank"〉PubMed〈/a〉
    Keywords: Cohort Studies ; DNA-Binding Proteins/genetics ; Disease Progression ; Female ; Genes, MHC Class I ; *Genome, Human ; HIV Infections/*genetics/immunology/therapy/*virology ; HIV-1/*physiology ; HLA-B Antigens/*genetics ; HLA-C Antigens/*genetics ; Haplotypes ; Humans ; Immediate-Early Proteins/genetics ; Major Histocompatibility Complex/*genetics ; Male ; Polymorphism, Single Nucleotide ; RNA, Untranslated ; Regression Analysis ; Viral Load
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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