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  • 1
    Publication Date: 2008-12-19
    Description: Nucleosome organization is critical for gene regulation. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers, competition with site-specific DNA-binding proteins, and the DNA sequence preferences of the nucleosomes themselves. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for approximately 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658732/" 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/PMC2658732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaplan, Noam -- Moore, Irene K -- Fondufe-Mittendorf, Yvonne -- Gossett, Andrea J -- Tillo, Desiree -- Field, Yair -- LeProust, Emily M -- Hughes, Timothy R -- Lieb, Jason D -- Widom, Jonathan -- Segal, Eran -- R01 CA119176/CA/NCI NIH HHS/ -- R01 CA119176-03/CA/NCI NIH HHS/ -- R01 GM054692/GM/NIGMS NIH HHS/ -- R01 GM054692-11/GM/NIGMS NIH HHS/ -- R01 GM058617/GM/NIGMS NIH HHS/ -- R01 GM058617-11/GM/NIGMS NIH HHS/ -- R01 GM072518/GM/NIGMS NIH HHS/ -- R01 GM072518-01A1/GM/NIGMS NIH HHS/ -- R01 GM072518-02/GM/NIGMS NIH HHS/ -- R01 GM072518-03/GM/NIGMS NIH HHS/ -- R01 GM072518-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Mar 19;458(7236):362-6. doi: 10.1038/nature07667. Epub 2008 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092803" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Caenorhabditis elegans/genetics ; Chickens ; Computational Biology ; Computer Simulation ; Eukaryotic Cells/*metabolism ; Genome, Fungal/*genetics ; Micrococcal Nuclease/metabolism ; Nucleosomes/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Saccharomyces cerevisiae/*genetics/growth & development ; Sequence Analysis, DNA ; Transcription Factors/metabolism
    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: 2008-07-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoegh-Guldberg, O -- Hughes, L -- McIntyre, S -- Lindenmayer, D B -- Parmesan, C -- Possingham, H P -- Thomas, C D -- New York, N.Y. -- Science. 2008 Jul 18;321(5887):345-6. doi: 10.1126/science.1157897.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Marine Studies, Australian Research Council Centre for Excellence in Reef Studies and the Coral Reef Targeted Research Project, University of Queensland, St Lucia, Queensland (QLD) 4072, Australia. oveh@uq.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18635780" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; Biodiversity ; *Climate ; *Conservation of Natural Resources ; Ecology/*methods ; *Ecosystem ; Extinction, Biological ; Geography ; Humans ; Population Dynamics ; Socioeconomic Factors
    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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  • 3
    Publication Date: 2008-05-31
    Description: Close relatedness has long been considered crucial to the evolution of eusociality. However, it has recently been suggested that close relatedness may be a consequence, rather than a cause, of eusociality. We tested this idea with a comparative analysis of female mating frequencies in 267 species of eusocial bees, wasps, and ants. We found that mating with a single male, which maximizes relatedness, is ancestral for all eight independent eusocial lineages that we investigated. Mating with multiple males is always derived. Furthermore, we found that high polyandry (〉2 effective mates) occurs only in lineages whose workers have lost reproductive totipotency. These results provide the first evidence that monogamy was critical in the evolution of eusociality, strongly supporting the prediction of inclusive fitness theory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, William O H -- Oldroyd, Benjamin P -- Beekman, Madeleine -- Ratnieks, Francis L W -- New York, N.Y. -- Science. 2008 May 30;320(5880):1213-6. doi: 10.1126/science.1156108.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Integrative and Comparative Biology, University of Leeds, Leeds, LS2 9JT, UK. w.o.h.hughes@leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18511689" target="_blank"〉PubMed〈/a〉
    Keywords: Altruism ; Animals ; Ants ; Bees ; *Biological Evolution ; Female ; Male ; Phylogeny ; *Sexual Behavior, Animal ; *Social Behavior ; Sociobiology ; Wasps
    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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  • 4
    Publication Date: 2008-01-19
    Description: The evolutionarily conserved Wnt/Wingless signal transduction pathway directs cell proliferation, cell fate, and cell death during development in metazoans and is inappropriately activated in several types of cancer. The majority of colorectal carcinomas contain truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor, a negative regulator of Wnt/Wingless signaling. Here, we demonstrate that Drosophila Apc homologs also have an activating role in both physiological and ectopic Wingless signaling. The Apc amino terminus is important for its activating function, whereas the beta-catenin binding sites are dispensable. Apc likely promotes Wingless transduction through down-regulation of Axin, a negative regulator of Wingless signaling. Given the evolutionary conservation of APC in Wnt signal transduction, an activating role may also be present in vertebrates with relevance to development and cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takacs, Carter M -- Baird, Jason R -- Hughes, Edward G -- Kent, Sierra S -- Benchabane, Hassina -- Paik, Raehum -- Ahmed, Yashi -- KO8CA078532/CA/NCI NIH HHS/ -- R01 CA105038/CA/NCI NIH HHS/ -- R01CA105038/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Jan 18;319(5861):333-6. doi: 10.1126/science.1151232.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and the Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03755, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202290" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Apoptosis ; Armadillo Domain Proteins/metabolism ; Axin Protein ; Binding Sites ; Cytoskeletal Proteins/chemistry/genetics/*metabolism ; Down-Regulation ; Drosophila/genetics/growth & development/*metabolism ; Drosophila Proteins/chemistry/genetics/*metabolism ; Genes, Insect ; Mutation ; Photoreceptor Cells, Invertebrate/cytology ; Proto-Oncogene Proteins/*metabolism ; *Signal Transduction ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/chemistry/genetics/*metabolism ; Wings, Animal/growth & development/metabolism ; Wnt1 Protein
    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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  • 5
    Publication Date: 2008-08-23
    Description: Many bacterial pathogens rely on a conserved membrane histidine sensor kinase, QseC, to respond to host adrenergic signaling molecules and bacterial signals in order to promote the expression of virulence factors. Using a high-throughput screen, we identified a small molecule, LED209, that inhibits the binding of signals to QseC, preventing its autophosphorylation and consequently inhibiting QseC-mediated activation of virulence gene expression. LED209 is not toxic and does not inhibit pathogen growth; however, this compound markedly inhibits the virulence of several pathogens in vitro and in vivo in animals. Inhibition of signaling offers a strategy for the development of broad-spectrum antimicrobial drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605406/" 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/PMC2605406/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rasko, David A -- Moreira, Cristiano G -- Li, De Run -- Reading, Nicola C -- Ritchie, Jennifer M -- Waldor, Matthew K -- Williams, Noelle -- Taussig, Ron -- Wei, Shuguang -- Roth, Michael -- Hughes, David T -- Huntley, Jason F -- Fina, Maggy W -- Falck, John R -- Sperandio, Vanessa -- P01 AI055637/AI/NIAID NIH HHS/ -- P01 AI055637-010005/AI/NIAID NIH HHS/ -- P01-AI055637-03/AI/NIAID NIH HHS/ -- R01 AI053067/AI/NIAID NIH HHS/ -- R01 AI053067-06/AI/NIAID NIH HHS/ -- R01 GM31278/GM/NIGMS NIH HHS/ -- R03 NS053582/NS/NINDS NIH HHS/ -- R03 NS053582-01/NS/NINDS NIH HHS/ -- R21 AI067827/AI/NIAID NIH HHS/ -- U01 AI077853/AI/NIAID NIH HHS/ -- U01 AI077853-01/AI/NIAID NIH HHS/ -- UO1-AI77853/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1078-80. doi: 10.1126/science.1160354.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719281" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/administration & dosage/*pharmacology/therapeutic use ; Enterohemorrhagic Escherichia coli/drug ; effects/genetics/metabolism/*pathogenicity ; Escherichia coli Infections/drug therapy ; Escherichia coli Proteins/antagonists & inhibitors/genetics/*metabolism ; Francisella tularensis/drug effects/genetics/metabolism/*pathogenicity ; Gene Expression Regulation, Bacterial/drug effects ; Gram-Negative Bacterial Infections/*drug therapy ; Mice ; Norepinephrine/metabolism ; Phosphorylation ; Protein Kinases/genetics/*metabolism ; Rabbits ; Salmonella Infections, Animal/drug therapy ; Salmonella typhimurium/drug effects/genetics/metabolism/*pathogenicity ; Signal Transduction/drug effects ; Small Molecule Libraries ; Sulfonamides/administration & dosage/chemistry/*pharmacology/therapeutic use ; Tularemia/drug therapy ; Virulence Factors/genetics
    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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