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  • Base Sequence
  • American Association for the Advancement of Science (AAAS)  (143)
  • Nature Publishing Group (NPG)  (35)
  • American Association of Petroleum Geologists (AAPG)
  • 2005-2009  (178)
Collection
Publisher
  • American Association for the Advancement of Science (AAAS)  (143)
  • Nature Publishing Group (NPG)  (35)
  • American Association of Petroleum Geologists (AAPG)
Years
Year
  • 1
    Publication Date: 2009-10-30
    Description: The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanism: one that involves the formation of hydrogen bonds with specific bases, primarily in the major groove, and one involving sequence-dependent deformations of the DNA helix. By comprehensively analysing the three-dimensional structures of protein-DNA complexes, here we show that the binding of arginine residues to narrow minor grooves is a widely used mode for protein-DNA recognition. This readout mechanism exploits the phenomenon that narrow minor grooves strongly enhance the negative electrostatic potential of the DNA. The nucleosome core particle offers a prominent example of this effect. Minor-groove narrowing is often associated with the presence of A-tracts, AT-rich sequences that exclude the flexible TpA step. These findings indicate that the ability to detect local variations in DNA shape and electrostatic potential is a general mechanism that enables proteins to use information in the minor groove, which otherwise offers few opportunities for the formation of base-specific hydrogen bonds, to achieve DNA-binding specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793086/" 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/PMC2793086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohs, Remo -- West, Sean M -- Sosinsky, Alona -- Liu, Peng -- Mann, Richard S -- Honig, Barry -- GM54510/GM/NIGMS NIH HHS/ -- R01 GM030518/GM/NIGMS NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 CA121852-05/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Oct 29;461(7268):1248-53. doi: 10.1038/nature08473.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biophysics, Columbia University, 1130 Saint Nicholas Avenue, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865164" target="_blank"〉PubMed〈/a〉
    Keywords: AT Rich Sequence/genetics ; Animals ; Arginine/metabolism ; Base Sequence ; DNA/*chemistry/genetics/*metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Databases, Factual ; Hydrogen Bonding ; Lysine ; *Nucleic Acid Conformation ; Nucleosomes/chemistry/metabolism ; Protein Binding ; Saccharomyces cerevisiae ; Static Electricity
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  • 2
    Publication Date: 2009-09-04
    Description: We live in a macroscopic three-dimensional (3D) world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires a bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter. The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: a motif that has a robust 3D structure, dominant affinity interactions between parts of the motif when it self-associates, and predictable structures for these affinity interactions. Fulfilling these three criteria to produce a 3D periodic system is not easy, but should readily be achieved with well-structured branched DNA motifs tailed by sticky ends. Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so; the helically repeating nature of DNA facilitates the construction of a periodic array. It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter. Here we report the crystal structure at 4 A resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle. The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764300/" 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/PMC2764300/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Jianping -- Birktoft, Jens J -- Chen, Yi -- Wang, Tong -- Sha, Ruojie -- Constantinou, Pamela E -- Ginell, Stephan L -- Mao, Chengde -- Seeman, Nadrian C -- 1R21EB007472/EB/NIBIB NIH HHS/ -- R21 EB007472/EB/NIBIB NIH HHS/ -- R21 EB007472-03/EB/NIBIB NIH HHS/ -- England -- Nature. 2009 Sep 3;461(7260):74-7. doi: 10.1038/nature08274.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, New York University, New York 10003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19727196" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Crystallization ; Crystallography, X-Ray ; DNA/*chemistry/genetics ; *Drug Design ; Molecular Sequence Data ; *Nucleic Acid Conformation
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  • 3
    Publication Date: 2009-02-03
    Description: There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (〉95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified approximately 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFkappaB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754849/" 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/PMC2754849/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guttman, Mitchell -- Amit, Ido -- Garber, Manuel -- French, Courtney -- Lin, Michael F -- Feldser, David -- Huarte, Maite -- Zuk, Or -- Carey, Bryce W -- Cassady, John P -- Cabili, Moran N -- Jaenisch, Rudolf -- Mikkelsen, Tarjei S -- Jacks, Tyler -- Hacohen, Nir -- Bernstein, Bradley E -- Kellis, Manolis -- Regev, Aviv -- Rinn, John L -- Lander, Eric S -- DP1 OD003958/OD/NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG004037-02/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-05/HG/NHGRI NIH HHS/ -- England -- Nature. 2009 Mar 12;458(7235):223-7. doi: 10.1038/nature07672. Epub 2009 Feb 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19182780" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cells, Cultured ; Chromatin/*genetics ; *Conserved Sequence/genetics ; DNA, Intergenic ; Exons/genetics ; Mammals/*genetics ; Mice ; Promoter Regions, Genetic/genetics ; RNA/*genetics ; Reproducibility of Results ; Transcription Factors/metabolism
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  • 4
    Publication Date: 2009-07-22
    Description: Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(+/+) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanada, Masashi -- Suzuki, Takahiro -- Shih, Lee-Yung -- Otsu, Makoto -- Kato, Motohiro -- Yamazaki, Satoshi -- Tamura, Azusa -- Honda, Hiroaki -- Sakata-Yanagimoto, Mamiko -- Kumano, Keiki -- Oda, Hideaki -- Yamagata, Tetsuya -- Takita, Junko -- Gotoh, Noriko -- Nakazaki, Kumi -- Kawamata, Norihiko -- Onodera, Masafumi -- Nobuyoshi, Masaharu -- Hayashi, Yasuhide -- Harada, Hiroshi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Hiraku -- Ozawa, Keiya -- Omine, Mitsuhiro -- Hirai, Hisamaru -- Nakauchi, Hiromitsu -- Koeffler, H Phillip -- Ogawa, Seishi -- 2R01CA026038-30/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):904-8. doi: 10.1038/nature08240. Epub 2009 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19620960" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosomes, Human, Pair 11/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Leukemia, Myeloid/*genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/*metabolism ; Mutation ; NIH 3T3 Cells ; Neoplasm Transplantation ; Oncogenes/genetics ; Phosphorylation ; Protein Conformation ; Proto-Oncogene Proteins c-cbl/antagonists & ; inhibitors/chemistry/deficiency/*genetics/*metabolism ; Ubiquitination ; Uniparental Disomy/genetics ; ras Proteins/genetics/metabolism
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  • 5
    Publication Date: 2009-10-23
    Description: Maturation of precursor transfer RNA (pre-tRNA) includes excision of the 5' leader and 3' trailer sequences, removal of introns and addition of the CCA terminus. Nucleotide modifications are incorporated at different stages of tRNA processing, after the RNA molecule adopts the proper conformation. In bacteria, tRNA(Ile2) lysidine synthetase (TilS) modifies cytidine into lysidine (L; 2-lysyl-cytidine) at the first anticodon of tRNA(Ile2) (refs 4-9). This modification switches tRNA(Ile2) from a methionine-specific to an isoleucine-specific tRNA. However, the aminoacylation of tRNA(Ile2) by methionyl-tRNA synthetase (MetRS), before the modification by TilS, might lead to the misincorporation of methionine in response to isoleucine codons. The mechanism used by bacteria to avoid this pitfall is unknown. Here we show that the TilS enzyme specifically recognizes and modifies tRNA(Ile2) in its precursor form, thereby avoiding translation errors. We identified the lysidine modification in pre-tRNA(Ile2) isolated from RNase-E-deficient Escherichia coli and did not detect mature tRNA(Ile2) lacking this modification. Our kinetic analyses revealed that TilS can modify both types of RNA molecule with comparable efficiencies. X-ray crystallography and mutational analyses revealed that TilS specifically recognizes the entire L-shape structure in pre-tRNA(Ile2) through extensive interactions coupled with sequential domain movements. Our results demonstrate how TilS prevents the recognition of tRNA(Ile2) by MetRS and achieves high specificity for its substrate. These two key points form the basis for maintaining the fidelity of isoleucine codon translation in bacteria. Our findings also provide a rationale for the necessity of incorporating specific modifications at the precursor level during tRNA biogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakanishi, Kotaro -- Bonnefond, Luc -- Kimura, Satoshi -- Suzuki, Tsutomu -- Ishitani, Ryuichiro -- Nureki, Osamu -- England -- Nature. 2009 Oct 22;461(7267):1144-8. doi: 10.1038/nature08474.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Kanagawa 225-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19847269" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/*chemistry/genetics/*metabolism ; Apoproteins/genetics/metabolism ; Bacillus subtilis ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Escherichia coli ; Geobacillus ; Kinetics ; Lysine/analogs & derivatives/metabolism ; Mass Spectrometry ; Models, Molecular ; Molecular Sequence Data ; *Protein Biosynthesis ; Pyrimidine Nucleosides/metabolism ; RNA, Transfer, Ile/genetics/metabolism ; Substrate Specificity
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  • 6
    Publication Date: 2009-05-01
    Description: An efficient method for making directed DNA sequence modifications to plant genes (gene targeting) is at present lacking, thereby frustrating efforts to dissect plant gene function and engineer crop plants that better meet the world's burgeoning need for food, fibre and fuel. Zinc-finger nucleases (ZFNs)-enzymes engineered to create DNA double-strand breaks at specific loci-are potent stimulators of gene targeting; for example, they can be used to precisely modify engineered reporter genes in plants. Here we demonstrate high-frequency ZFN-stimulated gene targeting at endogenous plant genes, namely the tobacco acetolactate synthase genes (ALS SuRA and SuRB), for which specific mutations are known to confer resistance to imidazolinone and sulphonylurea herbicides. Herbicide-resistance mutations were introduced into SuR loci by ZFN-mediated gene targeting at frequencies exceeding 2% of transformed cells for mutations as far as 1.3 kilobases from the ZFN cleavage site. More than 40% of recombinant plants had modifications in multiple SuR alleles. The observed high frequency of gene targeting indicates that it is now possible to efficiently make targeted sequence changes in endogenous plant genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743854/" 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/PMC2743854/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Townsend, Jeffrey A -- Wright, David A -- Winfrey, Ronnie J -- Fu, Fengli -- Maeder, Morgan L -- Joung, J Keith -- Voytas, Daniel F -- DP1 OD006862/OD/NIH HHS/ -- R01 GM069906/GM/NIGMS NIH HHS/ -- R01 GM069906-01A1/GM/NIGMS NIH HHS/ -- R01 GM069906-02/GM/NIGMS NIH HHS/ -- R01 GM069906-02S1/GM/NIGMS NIH HHS/ -- R01 GM069906-03/GM/NIGMS NIH HHS/ -- R01 GM069906-04/GM/NIGMS NIH HHS/ -- R01 GM069906-05/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 May 21;459(7245):442-5. doi: 10.1038/nature07845. Epub 2009 Apr 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Development & Cell Biology, Iowa State University, Ames, Iowa 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19404258" target="_blank"〉PubMed〈/a〉
    Keywords: Acetolactate Synthase/genetics ; Alleles ; Amino Acid Sequence ; Base Sequence ; Deoxyribonucleases/chemistry/genetics/*metabolism ; Food, Genetically Modified ; Gene Targeting/*methods ; Genes, Plant/*genetics ; Herbicide Resistance/genetics ; Herbicides/pharmacology ; Molecular Sequence Data ; Plants, Genetically Modified ; *Protein Engineering ; Recombination, Genetic/genetics ; Tobacco/drug effects/enzymology/*genetics ; Transformation, Genetic ; *Zinc Fingers
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  • 7
    Publication Date: 2009-07-10
    Description: Single-walled carbon nanotubes (SWNTs) are a family of molecules that have the same cylindrical shape but different chiralities. Many fundamental studies and technological applications of SWNTs require a population of tubes with identical chirality that current syntheses cannot provide. The SWNT sorting problem-that is, separation of a synthetic mixture of tubes into individual single-chirality components-has attracted considerable attention in recent years. Intense efforts so far have focused largely on, and resulted in solutions for, a weaker version of the sorting problem: metal/semiconductor separation. A systematic and general method to purify each and every single-chirality species of the same electronic type from the synthetic mixture of SWNTs is highly desirable, but the task has proven to be insurmountable to date. Here we report such a method, which allows purification of all 12 major single-chirality semiconducting species from a synthetic mixture, with sufficient yield for both fundamental studies and application development. We have designed an effective search of a DNA library of approximately 10(60) in size, and have identified more than 20 short DNA sequences, each of which recognizes and enables chromatographic purification of a particular nanotube species from the synthetic mixture. Recognition sequences exhibit a periodic purine-pyrimidines pattern, which can undergo hydrogen-bonding to form a two-dimensional sheet, and fold selectively on nanotubes into a well-ordered three-dimensional barrel. We propose that the ordered two-dimensional sheet and three-dimensional barrel provide the structural basis for the observed DNA recognition of SWNTs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tu, Xiaomin -- Manohar, Suresh -- Jagota, Anand -- Zheng, Ming -- England -- Nature. 2009 Jul 9;460(7252):250-3. doi: 10.1038/nature08116.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DuPont Central Research and Development, Wilmington, Delaware 19880, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587767" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chemical Fractionation/*methods ; DNA/*chemistry/genetics ; Gene Library ; Models, Molecular ; Nanotubes, Carbon/*chemistry ; Nucleic Acid Conformation ; Sensitivity and Specificity ; Spectrophotometry ; Substrate Specificity
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  • 8
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    Nature Publishing Group (NPG)
    Publication Date: 2009-10-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tullius, Tom -- England -- Nature. 2009 Oct 29;461(7268):1225-6. doi: 10.1038/4611225a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865161" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA/*chemistry/genetics/*metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Humans ; *Nucleic Acid Conformation ; Protein Binding
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  • 9
    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hersam, Mark C -- England -- Nature. 2009 Jul 9;460(7252):186-7. doi: 10.1038/460186a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587756" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Base Sequence ; Chemical Fractionation/*methods ; DNA/*chemistry/genetics ; Nanotubes, Carbon/*chemistry ; Nucleic Acid Conformation ; Sensitivity and Specificity
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  • 10
    Publication Date: 2009-12-04
    Description: Estimates of the total number of bacterial species indicate that existing DNA sequence databases carry only a tiny fraction of the total amount of DNA sequence space represented by this division of life. Indeed, environmental DNA samples have been shown to encode many previously unknown classes of proteins and RNAs. Bioinformatics searches of genomic DNA from bacteria commonly identify new noncoding RNAs (ncRNAs) such as riboswitches. In rare instances, RNAs that exhibit more extensive sequence and structural conservation across a wide range of bacteria are encountered. Given that large structured RNAs are known to carry out complex biochemical functions such as protein synthesis and RNA processing reactions, identifying more RNAs of great size and intricate structure is likely to reveal additional biochemical functions that can be achieved by RNA. We applied an updated computational pipeline to discover ncRNAs that rival the known large ribozymes in size and structural complexity or that are among the most abundant RNAs in bacteria that encode them. These RNAs would have been difficult or impossible to detect without examining environmental DNA sequences, indicating that numerous RNAs with extraordinary size, structural complexity, or other exceptional characteristics remain to be discovered in unexplored sequence space.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140389/" 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/PMC4140389/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinberg, Zasha -- Perreault, Jonathan -- Meyer, Michelle M -- Breaker, Ronald R -- P01 GM022778/GM/NIGMS NIH HHS/ -- RR19895-02/RR/NCRR NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Dec 3;462(7273):656-9. doi: 10.1038/nature08586.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, New Haven, Connecticut 06520-8103, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956260" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*genetics/metabolism ; Base Sequence ; Gene Expression Regulation, Bacterial ; Genome, Bacterial/*genetics ; *Genomics ; Molecular Sequence Data ; *Nucleic Acid Conformation ; RNA, Bacterial/*chemistry/*genetics ; RNA, Untranslated/chemistry/*genetics
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  • 11
    Publication Date: 2009-01-13
    Description: Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours, have recently been described in common solid tumours. Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to 're-discover' the BCR-ABL1 (ref. 10) gene fusion in a chronic myelogenous leukaemia cell line and the TMPRSS2-ERG gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725402/" 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/PMC2725402/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maher, Christopher A -- Kumar-Sinha, Chandan -- Cao, Xuhong -- Kalyana-Sundaram, Shanker -- Han, Bo -- Jing, Xiaojun -- Sam, Lee -- Barrette, Terrence -- Palanisamy, Nallasivam -- Chinnaiyan, Arul M -- R01 CA132874/CA/NCI NIH HHS/ -- R01 CA132874-01A1/CA/NCI NIH HHS/ -- U01 CA111275/CA/NCI NIH HHS/ -- U01 CA111275-04/CA/NCI NIH HHS/ -- U54 DA 021519/DA/NIDA NIH HHS/ -- England -- Nature. 2009 Mar 5;458(7234):97-101. doi: 10.1038/nature07638. Epub 2009 Jan 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Michigan Center for Translational Pathology, Ann Arbor, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19136943" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line, Tumor ; Fusion Proteins, bcr-abl/analysis/genetics ; Gene Expression Profiling/*methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Male ; Molecular Sequence Data ; Neoplasms/*genetics ; Oncogene Proteins, Fusion/*analysis/*genetics ; Prostatic Neoplasms/genetics ; Sequence Analysis, DNA/instrumentation/*methods
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    Electronic ISSN: 1476-4687
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  • 12
    Publication Date: 2009-03-17
    Description: The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained-double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than did regions identified solely on the basis of nucleotide sequence. These results support the idea that the molecular shape of DNA is under selection and can identify evolutionary history.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749491/" 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/PMC2749491/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Stephen C J -- Hansen, Loren -- Abaan, Hatice Ozel -- Tullius, Thomas D -- Margulies, Elliott H -- R01 HG003541/HG/NHGRI NIH HHS/ -- R01 HG003541-03/HG/NHGRI NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):389-92. doi: 10.1126/science.1169050. Epub 2009 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics Program, Boston University, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286520" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Motifs ; Base Sequence ; Binding Sites ; Conserved Sequence ; DNA/*chemistry/genetics ; Deoxyribonuclease I/metabolism ; Early Growth Response Protein 1/genetics/metabolism ; Evolution, Molecular ; *Genome, Human ; Humans ; Mutant Proteins/metabolism ; Nucleic Acid Conformation ; Phenotype ; Polymorphism, Single Nucleotide ; Selection, Genetic
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  • 13
    Publication Date: 2009-12-08
    Description: Hepatitis delta virus (HDV) and cytoplasmic polyadenylation element-binding protein 3 (CPEB3) ribozymes form a family of self-cleaving RNAs characterized by a conserved nested double-pseudoknot and minimal sequence conservation. Secondary structure-based searches were used to identify sequences capable of forming this fold, and their self-cleavage activity was confirmed in vitro. Active sequences were uncovered in several marine organisms, two nematodes, an arthropod, a bacterium, and an insect virus, often in multiple sequence families and copies. Sequence searches based on identified ribozymes showed that plants, fungi, and a unicellular eukaryote also harbor the ribozymes. In Anopheles gambiae, the ribozymes were found differentially expressed and self-cleaved at basic developmental stages. Our results indicate that HDV-like ribozymes are abundant in nature and suggest that self-cleaving RNAs may play a variety of biological roles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159031/" 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/PMC3159031/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Webb, Chiu-Ho T -- Riccitelli, Nathan J -- Ruminski, Dana J -- Luptak, Andrej -- R01 GM094929/GM/NIGMS NIH HHS/ -- R01 GM094929-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):953. doi: 10.1126/science.1178084.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965505" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/enzymology/*genetics/growth & development ; Base Sequence ; Catalysis ; Eukaryota/enzymology/*genetics ; Expressed Sequence Tags ; Hepatitis Delta Virus/enzymology/genetics ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Catalytic/*chemistry/*metabolism
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  • 14
    Publication Date: 2009-05-09
    Description: Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism's antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086368/" 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/PMC3086368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinstein, Joshua A -- Jiang, Ning -- White, Richard A 3rd -- Fisher, Daniel S -- Quake, Stephen R -- DP1 OD000251/OD/NIH HHS/ -- DP1 OD000251-04/OD/NIH HHS/ -- DP1 OD000251-05/OD/NIH HHS/ -- DP1 OD000251-06/OD/NIH HHS/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):807-10. doi: 10.1126/science.1170020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Program, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423829" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/genetics ; Antibody Diversity ; Base Sequence ; Complementarity Determining Regions/*genetics ; Computational Biology ; Female ; Gene Library ; *Genes, Immunoglobulin Heavy Chain ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Joining Region/genetics ; Immunoglobulin M/*genetics ; Male ; Molecular Sequence Data ; Recombination, Genetic ; Sequence Analysis, DNA ; VDJ Exons ; Zebrafish/genetics/*immunology
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  • 15
    Publication Date: 2009-03-03
    Description: Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in maintaining small RNA-associated gene silencing. Curiously, the eudicot Arabidopsis thaliana is not affected when either function is lost. By use of mutation selection and positional cloning, we showed that the largest subunit of the presumed maize Pol IV is involved in paramutation, an inherited epigenetic change facilitated by an interaction between two alleles, as well as normal maize development. Bioinformatics analyses and nuclear run-on transcription assays indicate that Pol IV does not engage in the efficient RNA synthesis typical of the three major eukaryotic DNA-dependent RNA polymerases. These results indicate that Pol IV employs abnormal RNA polymerase activities to achieve genome-wide silencing and that its absence affects both maize development and heritable epigenetic changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erhard, Karl F Jr -- Stonaker, Jennifer L -- Parkinson, Susan E -- Lim, Jana P -- Hale, Christopher J -- Hollick, Jay B -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1201-5. doi: 10.1126/science.1164508.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, 111 Koshland Hall, University of California, Berkeley, CA 94720-3102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251626" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Computational Biology ; DNA-Directed RNA Polymerases/chemistry/genetics/*metabolism ; *Epigenesis, Genetic ; Gene Silencing ; Genes, Plant ; Molecular Sequence Data ; *Mutation ; Phylogeny ; Protein Subunits/chemistry/genetics/metabolism ; RNA, Plant/genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; Transcription, Genetic ; Zea mays/*enzymology/*genetics/growth & development
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  • 16
    Publication Date: 2009-04-18
    Description: Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777810/" 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/PMC2777810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meijsing, Sebastiaan H -- Pufall, Miles A -- So, Alex Y -- Bates, Darren L -- Chen, Lin -- Yamamoto, Keith R -- GM08537/GM/NIGMS NIH HHS/ -- R01 CA020535/CA/NCI NIH HHS/ -- R01 CA020535-31/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):407-10. doi: 10.1126/science.1164265.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372434" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Crystallography, X-Ray ; DNA/*chemistry/*metabolism ; Humans ; Ligands ; Models, Molecular ; Mutation ; Protein Conformation ; Protein Isoforms/chemistry/metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, Glucocorticoid/chemistry/genetics/*metabolism ; Transcriptional Activation
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  • 17
    Publication Date: 2009-12-08
    Description: Primordial organisms of the putative RNA world would have required polymerase ribozymes able to replicate RNA. Known ribozymes with polymerase activity best approximating that needed for RNA replication contain at their catalytic core the class I RNA ligase, an artificial ribozyme with a catalytic rate among the fastest of known ribozymes. Here we present the 3.0 angstrom crystal structure of this ligase. The architecture resembles a tripod, its three legs converging near the ligation junction. Interacting with this tripod scaffold through a series of 10 minor-groove interactions (including two A-minor triads) is the unpaired segment that contributes to and organizes the active site. A cytosine nucleobase and two backbone phosphates abut the ligation junction; their location suggests a model for catalysis resembling that of proteinaceous polymerases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978776/" 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/PMC3978776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shechner, David M -- Grant, Robert A -- Bagby, Sarah C -- Koldobskaya, Yelena -- Piccirilli, Joseph A -- Bartel, David P -- GM61835/GM/NIGMS NIH HHS/ -- R01 GM061835/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1271-5. doi: 10.1126/science.1174676.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965478" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalysis ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/chemistry/metabolism ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Magnesium/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Polynucleotide Ligases/chemistry/metabolism ; RNA, Catalytic/*chemistry/metabolism ; Ribonucleotides/chemistry/metabolism
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  • 18
    Publication Date: 2009-05-16
    Description: Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905877/" 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/PMC2905877/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Badis, Gwenael -- Berger, Michael F -- Philippakis, Anthony A -- Talukder, Shaheynoor -- Gehrke, Andrew R -- Jaeger, Savina A -- Chan, Esther T -- Metzler, Genita -- Vedenko, Anastasia -- Chen, Xiaoyu -- Kuznetsov, Hanna -- Wang, Chi-Fong -- Coburn, David -- Newburger, Daniel E -- Morris, Quaid -- Hughes, Timothy R -- Bulyk, Martha L -- R01 HG003985/HG/NHGRI NIH HHS/ -- R01 HG003985-01/HG/NHGRI NIH HHS/ -- R01 HG003985-02/HG/NHGRI NIH HHS/ -- R01 HG003985-03/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1720-3. doi: 10.1126/science.1162327. Epub 2009 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443739" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/chemistry/*metabolism ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Mice ; Protein Array Analysis ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Transcription Factors/*chemistry/*metabolism
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  • 19
    Publication Date: 2009-09-12
    Description: Miniature inverted repeat transposable elements (MITEs) are widespread in eukaryotic genomes, where they can attain high copy numbers despite a lack of coding capacity. However, little is known about how they originate and amplify. We performed a genome-wide screen of functional interactions between Stowaway MITEs and potential transposases in the rice genome and identified a transpositionally active MITE that possesses key properties that enhance transposition. Although not directly related to its autonomous element, the MITE has less affinity for the transposase than does the autonomous element but lacks a motif repressing transposition in the autonomous element. The MITE contains internal sequences that enhance transposition. These findings suggest that MITEs achieve high transposition activity by scavenging transposases encoded by distantly related and self-restrained autonomous elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Guojun -- Nagel, Dawn Holligan -- Feschotte, Cedric -- Hancock, C Nathan -- Wessler, Susan R -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1391-4. doi: 10.1126/science.1175688.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, University of Georgia, Athens, GA 30602, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745152" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA Transposable Elements ; *Genome, Plant ; Inverted Repeat Sequences ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oryza/*genetics/metabolism ; Transposases/genetics/*metabolism
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  • 20
    Publication Date: 2009-12-08
    Description: Although the nematode Caenorhabditis elegans produces self-fertile hermaphrodites, it descended from a male/female species, so hermaphroditism provides a model for the origin of novel traits. In the related species C. remanei, which has only male and female sexes, lowering the activity of tra-2 by RNA interference created XX animals that made spermatids as well as oocytes, but their spermatids could not activate without the addition of male seminal fluid. However, by lowering the expression of both tra-2 and swm-1, a gene that regulates sperm activation in C. elegans, we produced XX animals with active sperm that were self-fertile. Thus, the evolution of hermaphroditism in Caenorhabditis probably required two steps: a mutation in the sex-determination pathway that caused XX spermatogenesis and a mutation that allowed these spermatids to self-activate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldi, Chris -- Cho, Soochin -- Ellis, Ronald E -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):1002-5. doi: 10.1126/science.1176013.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Caenorhabditis/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Crosses, Genetic ; Disorders of Sex Development/genetics ; Female ; Genes, Helminth ; Germ Cells/physiology ; Male ; Membrane Proteins/genetics/physiology ; Molecular Sequence Data ; *Mutation ; Oogenesis ; Ovulation ; Phylogeny ; Reproduction ; Selection, Genetic ; Sex Determination Processes ; Spermatids/physiology ; Spermatogenesis
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  • 21
    Publication Date: 2009-07-25
    Description: The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831805/" 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/PMC2831805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geurts, Aron M -- Cost, Gregory J -- Freyvert, Yevgeniy -- Zeitler, Bryan -- Miller, Jeffrey C -- Choi, Vivian M -- Jenkins, Shirin S -- Wood, Adam -- Cui, Xiaoxia -- Meng, Xiangdong -- Vincent, Anna -- Lam, Stephen -- Michalkiewicz, Mieczyslaw -- Schilling, Rebecca -- Foeckler, Jamie -- Kalloway, Shawn -- Weiler, Hartmut -- Menoret, Severine -- Anegon, Ignacio -- Davis, Gregory D -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Jacob, Howard J -- Buelow, Roland -- 5P01HL082798-03/HL/NHLBI NIH HHS/ -- 5U01HL066579-08/HL/NHLBI NIH HHS/ -- P01 HL082798/HL/NHLBI NIH HHS/ -- P01 HL082798-03/HL/NHLBI NIH HHS/ -- U01 HL066579/HL/NHLBI NIH HHS/ -- U01 HL066579-08/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):433. doi: 10.1126/science.1172447.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Dna ; Embryo, Mammalian ; Endodeoxyribonucleases/genetics/*metabolism ; Feasibility Studies ; Female ; *Gene Knockout Techniques ; Green Fluorescent Proteins ; Immunoglobulin M/*genetics ; Male ; *Microinjections ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; RNA, Messenger ; Rats ; *Zinc Fingers/genetics ; rab GTP-Binding Proteins/*genetics
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  • 22
    Publication Date: 2009-01-20
    Description: Combining biomolecular function with integrated circuit technology could usher in a new era of biologically enabled electronics. A key challenge has been coupling different molecular functions to specific chip locations for communication with the circuit. We used spatially confined electric fields to assemble different populations of DNA-coated nanowires to desired positions with an accuracy that enabled postassembly fabrication of contacts to each individual nanowire, with high yield and without loss of DNA function. This combination of off-chip synthesis and biofunctionalization with high-density, heterogeneous assembly and integration at the individual nanowire level points to new ways of incorporating biological functionality with silicon electronics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837912/" 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/PMC2837912/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morrow, Thomas J -- Li, Mingwei -- Kim, Jaekyun -- Mayer, Theresa S -- Keating, Christine D -- R01 EB000268/EB/NIBIB NIH HHS/ -- R01 EB000268-08/EB/NIBIB NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):352. doi: 10.1126/science.1165921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150837" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA/chemistry ; Electricity ; Electronics/*instrumentation/methods ; Nanotechnology/methods ; *Nanowires/chemistry ; Oligodeoxyribonucleotides/chemistry
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  • 23
    Publication Date: 2009-12-08
    Description: We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnable, Patrick S -- Ware, Doreen -- Fulton, Robert S -- Stein, Joshua C -- Wei, Fusheng -- Pasternak, Shiran -- Liang, Chengzhi -- Zhang, Jianwei -- Fulton, Lucinda -- Graves, Tina A -- Minx, Patrick -- Reily, Amy Denise -- Courtney, Laura -- Kruchowski, Scott S -- Tomlinson, Chad -- Strong, Cindy -- Delehaunty, Kim -- Fronick, Catrina -- Courtney, Bill -- Rock, Susan M -- Belter, Eddie -- Du, Feiyu -- Kim, Kyung -- Abbott, Rachel M -- Cotton, Marc -- Levy, Andy -- Marchetto, Pamela -- Ochoa, Kerri -- Jackson, Stephanie M -- Gillam, Barbara -- Chen, Weizu -- Yan, Le -- Higginbotham, Jamey -- Cardenas, Marco -- Waligorski, Jason -- Applebaum, Elizabeth -- Phelps, Lindsey -- Falcone, Jason -- Kanchi, Krishna -- Thane, Thynn -- Scimone, Adam -- Thane, Nay -- Henke, Jessica -- Wang, Tom -- Ruppert, Jessica -- Shah, Neha -- Rotter, Kelsi -- Hodges, Jennifer -- Ingenthron, Elizabeth -- Cordes, Matt -- Kohlberg, Sara -- Sgro, Jennifer -- Delgado, Brandon -- Mead, Kelly -- Chinwalla, Asif -- Leonard, Shawn -- Crouse, Kevin -- Collura, Kristi -- Kudrna, Dave -- Currie, Jennifer -- He, Ruifeng -- Angelova, Angelina -- Rajasekar, Shanmugam -- Mueller, Teri -- Lomeli, Rene -- Scara, Gabriel -- Ko, Ara -- Delaney, Krista -- Wissotski, Marina -- Lopez, Georgina -- Campos, David -- Braidotti, Michele -- Ashley, Elizabeth -- Golser, Wolfgang -- Kim, HyeRan -- Lee, Seunghee -- Lin, Jinke -- Dujmic, Zeljko -- Kim, Woojin -- Talag, Jayson -- Zuccolo, Andrea -- Fan, Chuanzhu -- Sebastian, Aswathy -- Kramer, Melissa -- Spiegel, Lori -- Nascimento, Lidia -- Zutavern, Theresa -- Miller, Beth -- Ambroise, Claude -- Muller, Stephanie -- Spooner, Will -- Narechania, Apurva -- Ren, Liya -- Wei, Sharon -- Kumari, Sunita -- Faga, Ben -- Levy, Michael J -- McMahan, Linda -- Van Buren, Peter -- Vaughn, Matthew W -- Ying, Kai -- Yeh, Cheng-Ting -- Emrich, Scott J -- Jia, Yi -- Kalyanaraman, Ananth -- Hsia, An-Ping -- Barbazuk, W Brad -- Baucom, Regina S -- Brutnell, Thomas P -- Carpita, Nicholas C -- Chaparro, Cristian -- Chia, Jer-Ming -- Deragon, Jean-Marc -- Estill, James C -- Fu, Yan -- Jeddeloh, Jeffrey A -- Han, Yujun -- Lee, Hyeran -- Li, Pinghua -- Lisch, Damon R -- Liu, Sanzhen -- Liu, Zhijie -- Nagel, Dawn Holligan -- McCann, Maureen C -- SanMiguel, Phillip -- Myers, Alan M -- Nettleton, Dan -- Nguyen, John -- Penning, Bryan W -- Ponnala, Lalit -- Schneider, Kevin L -- Schwartz, David C -- Sharma, Anupma -- Soderlund, Carol -- Springer, Nathan M -- Sun, Qi -- Wang, Hao -- Waterman, Michael -- Westerman, Richard -- Wolfgruber, Thomas K -- Yang, Lixing -- Yu, Yeisoo -- Zhang, Lifang -- Zhou, Shiguo -- Zhu, Qihui -- Bennetzen, Jeffrey L -- Dawe, R Kelly -- Jiang, Jiming -- Jiang, Ning -- Presting, Gernot G -- Wessler, Susan R -- Aluru, Srinivas -- Martienssen, Robert A -- Clifton, Sandra W -- McCombie, W Richard -- Wing, Rod A -- Wilson, Richard K -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1112-5. doi: 10.1126/science.1178534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Plant Genomics, Iowa State University, Ames, IA 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965430" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Centromere/genetics ; Chromosome Mapping ; Chromosomes, Plant/genetics ; Crops, Agricultural/genetics ; DNA Copy Number Variations ; DNA Methylation ; DNA Transposable Elements ; DNA, Plant/genetics ; Genes, Plant ; *Genetic Variation ; *Genome, Plant ; Inbreeding ; MicroRNAs/genetics ; Molecular Sequence Data ; Ploidies ; RNA, Plant/genetics ; Recombination, Genetic ; Retroelements ; *Sequence Analysis, DNA ; Zea mays/*genetics
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  • 24
    Publication Date: 2009-06-13
    Description: Several classes of nucleic acid analogs have been reported, but no synthetic informational polymer has yet proven responsive to selection pressures under enzyme-free conditions. Here, we introduce an oligomer family that efficiently self-assembles by means of reversible covalent anchoring of nucleobase recognition units onto simple oligo-dipeptide backbones [thioester peptide nucleic acids (tPNAs)] and undergoes dynamic sequence modification in response to changing templates in solution. The oligomers specifically self-pair with complementary tPNA strands and cross-pair with RNA and DNA in Watson-Crick fashion. Thus, tPNA combines base-pairing interactions with the side-chain functionalities of typical peptides and proteins. These characteristics might prove advantageous for the design or selection of catalytic constructs or biomaterials that are capable of dynamic sequence repair and adaptation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ura, Yasuyuki -- Beierle, John M -- Leman, Luke J -- Orgel, Leslie E -- Ghadiri, M Reza -- New York, N.Y. -- Science. 2009 Jul 3;325(5936):73-7. doi: 10.1126/science.1174577. Epub 2009 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19520909" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/chemistry ; Amino Acids/chemistry ; Base Pairing ; Base Sequence ; Biotinylation ; DNA/*chemistry ; Dipeptides/chemistry ; Models, Molecular ; Molecular Structure ; Nucleic Acid Conformation ; Oligonucleotides/chemistry ; Peptide Nucleic Acids/*chemistry ; Peptides/chemistry ; RNA/chemistry
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  • 25
    Publication Date: 2009-04-11
    Description: In vertebrates, the readily apparent left/right (L/R) anatomical asymmetries of the internal organs can be traced to molecular events initiated at or near the time of gastrulation. However, the earliest steps of this process do not seem to be universally conserved. In particular, how this axis is first defined in chicks has remained problematic. Here we show that asymmetric cell rearrangements take place within chick embryos, creating a leftward movement of cells around the node. It is the relative displacement of cells expressing sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8) that is responsible for establishing their asymmetric expression patterns. The creation of asymmetric expression domains as a passive effect of cell movements represents an alternative strategy for breaking L/R symmetry in gene activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993078/" 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/PMC2993078/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gros, Jerome -- Feistel, Kerstin -- Viebahn, Christoph -- Blum, Martin -- Tabin, Clifford J -- R01 HD045499/HD/NICHD NIH HHS/ -- R01 HD045499-06/HD/NICHD NIH HHS/ -- R01-HD045499/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):941-4. doi: 10.1126/science.1172478. Epub 2009 Apr 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Body Patterning ; *Cell Movement ; Chick Embryo ; Fibroblast Growth Factor 8/genetics ; *Gastrulation ; *Gene Expression ; Gene Expression Profiling ; Hedgehog Proteins/genetics ; Molecular Sequence Data ; Organizers, Embryonic/*cytology/embryology/*metabolism ; Primitive Streak/*cytology/embryology/metabolism ; Swine/embryology ; Tissue Culture Techniques
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  • 26
    Publication Date: 2009-12-08
    Description: To study basic principles of transcriptome organization in bacteria, we analyzed one of the smallest self-replicating organisms, Mycoplasma pneumoniae. We combined strand-specific tiling arrays, complemented by transcriptome sequencing, with more than 252 spotted arrays. We detected 117 previously undescribed, mostly noncoding transcripts, 89 of them in antisense configuration to known genes. We identified 341 operons, of which 139 are polycistronic; almost half of the latter show decaying expression in a staircase-like manner. Under various conditions, operons could be divided into 447 smaller transcriptional units, resulting in many alternative transcripts. Frequent antisense transcripts, alternative transcripts, and multiple regulators per gene imply a highly dynamic transcriptome, more similar to that of eukaryotes than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guell, Marc -- van Noort, Vera -- Yus, Eva -- Chen, Wei-Hua -- Leigh-Bell, Justine -- Michalodimitrakis, Konstantinos -- Yamada, Takuji -- Arumugam, Manimozhiyan -- Doerks, Tobias -- Kuhner, Sebastian -- Rode, Michaela -- Suyama, Mikita -- Schmidt, Sabine -- Gavin, Anne-Claude -- Bork, Peer -- Serrano, Luis -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1268-71. doi: 10.1126/science.1176951.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation (CRG), Universitat Pompeu Fabra, Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965477" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; *Genome, Bacterial ; Molecular Sequence Data ; Mycoplasma pneumoniae/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Operon ; RNA, Antisense/genetics/metabolism ; RNA, Bacterial/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Untranslated/analysis/*genetics ; *Transcription, Genetic
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉King, David G -- Kashi, Yechezkel -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):229-30. doi: 10.1126/science.326_229.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, Southern Illinois University, Carbondale, IL 62901, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815757" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; DNA/chemistry/*genetics ; Evolution, Molecular ; Mutation ; *Repetitive Sequences, Nucleic Acid
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Otterstrom, Jason J -- van Oijen, Antoine M -- R01 GM077248/GM/NIGMS NIH HHS/ -- R01 GM077248-03/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):547-8. doi: 10.1126/science.1177311.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644099" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalytic Domain ; DNA/chemistry/*metabolism ; Diffusion ; Nucleosomes/*metabolism ; Optical Tweezers ; RNA Polymerase II/chemistry/*metabolism ; RNA, Messenger/metabolism ; Templates, Genetic ; *Transcription, Genetic
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  • 29
    Publication Date: 2009-07-18
    Description: Selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA). O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) catalyzes the final step of selenocysteine formation by a poorly understood tRNA-dependent mechanism. The crystal structure of human tRNA(Sec) in complex with SepSecS, phosphoserine, and thiophosphate, together with in vivo and in vitro enzyme assays, supports a pyridoxal phosphate-dependent mechanism of Sec-tRNA(Sec) formation. Two tRNA(Sec) molecules, with a fold distinct from other canonical tRNAs, bind to each SepSecS tetramer through their 13-base pair acceptor-TPsiC arm (where Psi indicates pseudouridine). The tRNA binding is likely to induce a conformational change in the enzyme's active site that allows a phosphoserine covalently attached to tRNA(Sec), but not free phosphoserine, to be oriented properly for the reaction to occur.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857584/" 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/PMC2857584/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palioura, Sotiria -- Sherrer, R Lynn -- Steitz, Thomas A -- Soll, Dieter -- Simonovic, Miljan -- R01 GM022854/GM/NIGMS NIH HHS/ -- R01 GM022854-33/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):321-5. doi: 10.1126/science.1173755.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608919" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/*chemistry/*metabolism ; Base Sequence ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phosphates/chemistry/metabolism ; Phosphoserine/chemistry/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; RNA, Transfer, Amino Acid-Specific/*chemistry/*metabolism ; RNA, Transfer, Amino Acyl/*metabolism ; Selenocysteine/*biosynthesis/genetics
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  • 30
    Publication Date: 2009-08-08
    Description: Pathogens can use DNA recombination to promote antigenic variation (Av) of surface structures to avoid immune detection. We identified a cis-acting DNA sequence near the antigenically variable pilin locus of the human pathogen, Neisseria gonorrhoeae. This 16-base pair guanine (G)-rich sequence was required for pilin Av and formed a guanine quartet (G4) structure in vitro. Individual mutations that disrupted the structure also blocked pilin Av and prevented nicks required for recombination from occurring within the G4 region. A compound that binds and stabilizes G4 structures also inhibited pilin Av and prevented nicks from occurring on the G-rich strand. This site constitutes a recombination initiation sequence/structure that directs gene conversion to a specific chromosomal locus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803317/" 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/PMC2803317/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cahoon, Laty A -- Seifert, H Steven -- R01 AI044239/AI/NIAID NIH HHS/ -- R01 AI044239-08/AI/NIAID NIH HHS/ -- R01 AI044239-09/AI/NIAID NIH HHS/ -- R01 AI044239-10/AI/NIAID NIH HHS/ -- R01 AI055977/AI/NIAID NIH HHS/ -- R01 AI055977-03/AI/NIAID NIH HHS/ -- R01 AI055977-04/AI/NIAID NIH HHS/ -- R01 AI055977-05/AI/NIAID NIH HHS/ -- R01AI044239/AI/NIAID NIH HHS/ -- R01AI055977/AI/NIAID NIH HHS/ -- R37 AI033493/AI/NIAID NIH HHS/ -- R37 AI033493-14/AI/NIAID NIH HHS/ -- R37 AI033493-15/AI/NIAID NIH HHS/ -- R37 AI033493-16/AI/NIAID NIH HHS/ -- R37AI033493/AI/NIAID NIH HHS/ -- T32GM08061/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):764-7. doi: 10.1126/science.1175653.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661435" target="_blank"〉PubMed〈/a〉
    Keywords: *Antigenic Variation ; Base Pairing ; Base Sequence ; DNA Damage ; DNA, Bacterial/chemistry/*genetics ; Fimbriae Proteins/chemistry/*genetics/*immunology ; Fimbriae, Bacterial ; Gene Conversion ; Guanine/chemistry ; Mesoporphyrins/metabolism/pharmacology ; Neisseria gonorrhoeae/*genetics/growth & development/*immunology ; Oligodeoxyribonucleotides/chemistry ; Recombination, Genetic
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  • 31
    Publication Date: 2009-02-14
    Description: Infection by human rhinovirus (HRV) is a major cause of upper and lower respiratory tract disease worldwide and displays considerable phenotypic variation. We examined diversity by completing the genome sequences for all known serotypes (n = 99). Superimposition of capsid crystal structure and optimal-energy RNA configurations established alignments and phylogeny. These revealed conserved motifs; clade-specific diversity, including a potential newly identified species (HRV-D); mutations in field isolates; and recombination. In analogy with poliovirus, a hypervariable 5' untranslated region tract may affect virulence. A configuration consistent with nonscanning internal ribosome entry was found in all HRVs and may account for rapid translation. The data density from complete sequences of the reference HRVs provided high resolution for this degree of modeling and serves as a platform for full genome-based epidemiologic studies and antiviral or vaccine development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923423/" 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/PMC3923423/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palmenberg, Ann C -- Spiro, David -- Kuzmickas, Ryan -- Wang, Shiliang -- Djikeng, Appolinaire -- Rathe, Jennifer A -- Fraser-Liggett, Claire M -- Liggett, Stephen B -- R01 HL091490/HL/NHLBI NIH HHS/ -- U19 AI070503/AI/NIAID NIH HHS/ -- U19-AI070503/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):55-9. doi: 10.1126/science.1165557. Epub 2009 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular Virology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213880" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; 5' Untranslated Regions ; Base Composition ; Base Sequence ; Codon, Terminator ; *Evolution, Molecular ; *Genome, Viral ; Humans ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Open Reading Frames ; Phylogeny ; Picornaviridae Infections/virology ; Polyproteins/biosynthesis/chemistry/genetics ; RNA, Viral/chemistry/*genetics ; Recombination, Genetic ; Respiratory Tract Infections/virology ; Rhinovirus/classification/*genetics/ultrastructure ; Sequence Alignment ; Sequence Analysis, RNA ; Serotyping ; Viral Proteins/biosynthesis/chemistry/genetics
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):664. doi: 10.1126/science.325_664.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661393" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Patents as Topic ; *Phylogeny ; *Sequence Analysis, DNA ; United States
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sherman, William -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):46-7. doi: 10.1126/science.1172136.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Functional Nanomaterials, Brookhaven National Laboratory, Upton, NY 11973, USA. wsherman@bnl.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342576" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA/chemistry ; Furocoumarins/chemistry ; Hot Temperature ; Nanotechnology/*methods ; Nucleic Acid Conformation ; Nucleic Acid Denaturation ; Nucleic Acid Hybridization ; Ultraviolet Rays
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feuillet, Catherine -- Eversole, Kellye -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1071-2. doi: 10.1126/science.1183463.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UMR INRA-UBP, Genetique, Diversite et Ecophysiologie des Cereales, 63100 Clermont-Ferrand, France. catherine.feuillet@clermont.inra.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965417" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chromosome Mapping ; Crops, Agricultural/genetics ; Genes, Plant ; Genetic Variation ; *Genome, Plant ; Haplotypes ; Hybrid Vigor ; Hybridization, Genetic ; *Sequence Analysis, DNA ; Zea mays/*genetics/physiology
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  • 35
    Publication Date: 2009-04-25
    Description: The script of the ancient Indus civilization remains undeciphered. The hypothesis that the script encodes language has recently been questioned. Here, we present evidence for the linguistic hypothesis by showing that the script's conditional entropy is closer to those of natural languages than various types of nonlinguistic systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rao, Rajesh P N -- Yadav, Nisha -- Vahia, Mayank N -- Joglekar, Hrishikesh -- Adhikari, R -- Mahadevan, Iravatham -- New York, N.Y. -- Science. 2009 May 29;324(5931):1165. doi: 10.1126/science.1170391. Epub 2009 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA. rao@cs.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19389998" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Chromosomes, Human, Pair 2/genetics ; Escherichia coli Proteins/chemistry ; History, Ancient ; Humans ; India ; Language ; Linguistics/*history ; Pakistan ; Programming Languages ; Writing/*history
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  • 36
    Publication Date: 2009-11-11
    Description: Genetic changes contributing to phenotypic differences within or between species have been identified for a handful of traits, but the relationship between alleles underlying intraspecific polymorphism and interspecific divergence is largely unknown. We found that noncoding changes in the tan gene, as well as changes linked to the ebony gene, contribute to pigmentation divergence between closely related Drosophila species. Moreover, we found that alleles linked to tan and ebony fixed in one Drosophila species also contribute to variation within another species, and that multiple genotypes underlie similar phenotypes even within the same population. These alleles appear to predate speciation, which suggests that standing genetic variation present in the common ancestor gave rise to both intraspecific polymorphism and interspecific divergence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wittkopp, Patricia J -- Stewart, Emma E -- Arnold, Lisa L -- Neidert, Adam H -- Haerum, Belinda K -- Thompson, Elizabeth M -- Akhras, Saleh -- Smith-Winberry, Gabriel -- Shefner, Laura -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):540-4. doi: 10.1126/science.1176980.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA. wittkopp@umich.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900891" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Animals, Genetically Modified ; Base Sequence ; Chromosomal Proteins, Non-Histone/*genetics/metabolism ; Crosses, Genetic ; DNA-Binding Proteins/*genetics/metabolism ; Drosophila/classification/*genetics/growth & development/metabolism ; Drosophila Proteins/*genetics/metabolism ; Female ; Gene Expression ; Gene Expression Regulation ; Genes, Insect ; Genetic Speciation ; Genotype ; Introns ; Male ; Molecular Sequence Data ; Phenotype ; Pigmentation/*genetics ; *Polymorphism, Genetic ; Quantitative Trait Loci ; Species Specificity
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Guanyang -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1672; author reply 1672. doi: 10.1126/science.323.5922.1672.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325099" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Biodiversity ; *Biological Specimen Banks ; Databases, Factual ; *Databases, Nucleic Acid ; National Library of Medicine (U.S.) ; *Natural History ; United States
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monroe, Don -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):142-3. doi: 10.1126/science.325_142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589978" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Conserved Sequence ; DNA/*genetics/metabolism ; DNA, Intergenic/genetics ; DNA-Binding Proteins/metabolism ; Evolution, Molecular ; Genes, Essential ; *Genome, Human ; Humans ; Mice ; Mutation ; RNA/genetics ; Regulatory Sequences, Nucleic Acid
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-11-26
    Description: TAL effectors of plant pathogenic bacteria in the genus Xanthomonas bind host DNA and activate genes that contribute to disease or turn on defense. Target specificity depends on an effector-variable number of typically 34 amino acid repeats, but the mechanism of recognition is not understood. We show that a repeat-variable pair of residues specifies the nucleotides in the target site, one pair to one nucleotide, with no apparent context dependence. Our finding represents a previously unknown mechanism for protein-DNA recognition that explains TAL effector specificity, enables target site prediction, and opens prospects for use of TAL effectors in research and biotechnology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moscou, Matthew J -- Bogdanove, Adam J -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1501. doi: 10.1126/science.1178817. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology and Bioinformatics and Computational Biology Program, Iowa State University, Ames, IA 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933106" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry/metabolism ; Base Sequence ; Computational Biology ; DNA, Plant/chemistry/genetics/*metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Molecular Sequence Data ; Nucleotides/metabolism ; Oryza/*genetics/microbiology ; Promoter Regions, Genetic ; Protein Array Analysis ; Repetitive Sequences, Amino Acid ; *Transcriptional Activation ; Xanthomonas/*metabolism/pathogenicity
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  • 40
    Publication Date: 2009-01-20
    Description: Retroviruses have the potential to acquire host cell-derived genetic material during reverse transcription and can integrate into the genomes of larger, more complex DNA viruses. In contrast, RNA viruses were believed not to integrate into the host's genome under any circumstances. We found that illegitimate recombination between an exogenous nonretroviral RNA virus, lymphocytic choriomeningitis virus, and the endogenous intracisternal A-type particle (IAP) retrotransposon occurred and led to reverse transcription of exogenous viral RNA. The resulting complementary DNA was integrated into the host's genome with an IAP element. Thus, RNA viruses should be closely scrutinized for any capacity to interact with endogenous retroviral elements before their approval for therapeutic use in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geuking, Markus B -- Weber, Jacqueline -- Dewannieux, Marie -- Gorelik, Elieser -- Heidmann, Thierry -- Hengartner, Hans -- Zinkernagel, Rolf M -- Hangartner, Lars -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):393-6. doi: 10.1126/science.1167375.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. geuking@mcmaster.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arenaviridae Infections/virology ; Base Sequence ; Cell Line ; DNA, Complementary/*genetics ; Genes, Intracisternal A-Particle/*genetics ; Glycoproteins/genetics ; Humans ; Lymphocytic choriomeningitis virus/*genetics ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Polymerase Chain Reaction ; RNA, Viral/*genetics ; *Recombination, Genetic ; *Reverse Transcription ; Transfection ; Viral Proteins/genetics ; *Virus Integration
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  • 41
    Publication Date: 2009-05-30
    Description: Adenosine-to-inosine (A-to-I) RNA editing leads to transcriptome diversity and is important for normal brain function. To date, only a handful of functional sites have been identified in mammals. We developed an unbiased assay to screen more than 36,000 computationally predicted nonrepetitive A-to-I sites using massively parallel target capture and DNA sequencing. A comprehensive set of several hundred human RNA editing sites was detected by comparing genomic DNA with RNAs from seven tissues of a single individual. Specificity of our profiling was supported by observations of enrichment with known features of targets of adenosine deaminases acting on RNA (ADAR) and validation by means of capillary sequencing. This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing-related human diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Jin Billy -- Levanon, Erez Y -- Yoon, Jung-Ki -- Aach, John -- Xie, Bin -- Leproust, Emily -- Zhang, Kun -- Gao, Yuan -- Church, George M -- New York, N.Y. -- Science. 2009 May 29;324(5931):1210-3. doi: 10.1126/science.1170995.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478186" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/metabolism ; Adrenal Glands/metabolism ; Alu Elements ; Animals ; Base Sequence ; Brain/*metabolism ; DNA/*genetics ; DNA, Complementary ; *Genome, Human ; Humans ; Intestine, Small/metabolism ; Mice ; *RNA Editing ; RNA, Double-Stranded/chemistry/genetics/metabolism ; RNA, Messenger/chemistry/genetics/*metabolism ; RNA-Binding Proteins ; Sequence Analysis, DNA
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  • 42
    Publication Date: 2009-12-08
    Description: Rates and mechanisms of intron gain and loss have traditionally been inferred from alignments of highly conserved genes sampled from phylogenetically distant taxa. We report a population-genomic approach that detected 24 discordant intron/exon boundaries between the whole-genome sequences of two Daphnia pulex isolates. Sequencing of presence/absence loci across a collection of D. pulex isolates and outgroup Daphnia species shows that most polymorphisms are a consequence of recent gains, with parallel gains often occurring at the same locations in independent allelic lineages. More than half of the recent gains are associated with short sequence repeats, suggesting an origin via repair of staggered double-strand breaks. By comparing the allele-frequency spectrum of intron-gain alleles with that for derived single-base substitutions, we also provide evidence that newly arisen introns are intrinsically deleterious and tend to accumulate in population-genetic settings where random genetic drift is a relatively strong force.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878872/" 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/PMC3878872/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Wenli -- Tucker, Abraham E -- Sung, Way -- Thomas, W Kelley -- Lynch, Michael -- R01 GM036827/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1260-2. doi: 10.1126/science.1179302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Indiana University, Bloomington, IN 47405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965475" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Computational Biology ; DNA Breaks, Double-Stranded ; DNA Repair ; Daphnia/*genetics ; Exons ; *Genome ; *Introns ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Repetitive Sequences, Nucleic Acid ; Time Factors
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  • 43
    Publication Date: 2009-01-10
    Description: Strict one-to-one correspondence between codons and amino acids is thought to be an essential feature of the genetic code. However, we report that one codon can code for two different amino acids with the choice of the inserted amino acid determined by a specific 3' untranslated region structure and location of the dual-function codon within the messenger RNA (mRNA). We found that the codon UGA specifies insertion of selenocysteine and cysteine in the ciliate Euplotes crassus, that the dual use of this codon can occur even within the same gene, and that the structural arrangements of Euplotes mRNA preserve location-dependent dual function of UGA when expressed in mammalian cells. Thus, the genetic code supports the use of one codon to code for multiple amino acids.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088105/" 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/PMC3088105/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turanov, Anton A -- Lobanov, Alexey V -- Fomenko, Dmitri E -- Morrison, Hilary G -- Sogin, Mitchell L -- Klobutcher, Lawrence A -- Hatfield, Dolph L -- Gladyshev, Vadim N -- AI058054/AI/NIAID NIH HHS/ -- GM061603/GM/NIGMS NIH HHS/ -- GM065204/GM/NIGMS NIH HHS/ -- R01 GM061603/GM/NIGMS NIH HHS/ -- R01 GM061603-04S2/GM/NIGMS NIH HHS/ -- ZIA BC010767-03/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):259-61. doi: 10.1126/science.1164748.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131629" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Codon/*genetics ; Codon, Terminator/*genetics ; Cysteine/*genetics/metabolism ; Euplotes/chemistry/*genetics ; *Genetic Code ; Humans ; Molecular Sequence Data ; Mutation ; Protozoan Proteins/biosynthesis/chemistry/genetics ; RNA, Protozoan/genetics/metabolism ; RNA, Transfer, Amino Acid-Specific/chemistry/genetics ; RNA, Transfer, Cys/chemistry/genetics ; Recombinant Fusion Proteins/metabolism ; Selenocysteine/*genetics/metabolism ; Selenoproteins/biosynthesis/chemistry/*genetics
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  • 44
    Publication Date: 2009-08-08
    Description: Protein synthesis involves the accurate attachment of amino acids to their matching transfer RNA (tRNA) molecules. Mistranslating the amino acids serine or glycine for alanine is prevented by the function of independent but collaborative aminoacylation and editing domains of alanyl-tRNA synthetases (AlaRSs). We show that the C-Ala domain plays a key role in AlaRS function. The C-Ala domain is universally tethered to the editing domain both in AlaRS and in many homologous free-standing editing proteins. Crystal structure and functional analyses showed that C-Ala forms an ancient single-stranded nucleic acid binding motif that promotes cooperative binding of both aminoacylation and editing domains to tRNA(Ala). In addition, C-Ala may have played an essential role in the evolution of AlaRSs by coupling aminoacylation to editing to prevent mistranslation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559334/" 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/PMC4559334/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Min -- Chong, Yeeting E -- Beebe, Kirk -- Shapiro, Ryan -- Yang, Xiang-Lei -- Schimmel, Paul -- GM 15539/GM/NIGMS NIH HHS/ -- R01 GM015539/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):744-7. doi: 10.1126/science.1174343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661429" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine-tRNA Ligase/*chemistry/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Bacteria/enzymology ; Base Sequence ; Crystallography, X-Ray ; Escherichia coli Proteins/chemistry/metabolism ; Evolution, Molecular ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Bacterial/chemistry/metabolism ; RNA, Transfer, Ala/*chemistry/*metabolism ; RNA, Transfer, Amino Acyl/chemistry/metabolism ; *Transfer RNA Aminoacylation
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  • 45
    Publication Date: 2009-09-19
    Description: Retroviruses can leave a "fossil record" in their hosts' genomes in the form of endogenous retroviruses. Foamy viruses, complex retroviruses that infect mammals, have been notably absent from this record. We have found an endogenous foamy virus within the genomes of sloths and show that foamy viruses were infecting mammals more than 100 million years ago and codiverged with their hosts across an entire geological era. Our analysis highlights the role of evolutionary constraint in maintaining viral genome structure and indicates that accessory genes and mammalian mechanisms of innate immunity are the products of macroevolutionary conflict played out over a geological time scale.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katzourakis, Aris -- Gifford, Robert J -- Tristem, Michael -- Gilbert, M Thomas P -- Pybus, Oliver G -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1512. doi: 10.1126/science.1174149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zoology Department, University of Oxford, Oxford OX1 3PS, UK. aris.katzourakis@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762636" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Endogenous Retroviruses/classification/*genetics ; *Evolution, Molecular ; Genome ; Genome, Viral ; Immunity, Innate ; Molecular Sequence Data ; Phylogeny ; Retroviridae Infections/veterinary/virology ; Sloths/classification/*genetics/immunology/*virology ; Spumavirus/classification/*genetics ; Time
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  • 46
    Publication Date: 2009-03-07
    Description: Genome-wide association studies (GWASs) are regularly used to map genomic regions contributing to common human diseases, but they often do not identify the precise causative genes and sequence variants. To identify causative type 1 diabetes (T1D) variants, we resequenced exons and splice sites of 10 candidate genes in pools of DNA from 480 patients and 480 controls and tested their disease association in over 30,000 participants. We discovered four rare variants that lowered T1D risk independently of each other (odds ratio = 0.51 to 0.74; P = 1.3 x 10(-3) to 2.1 x 10(-16)) in IFIH1 (interferon induced with helicase C domain 1), a gene located in a region previously associated with T1D by GWASs. These variants are predicted to alter the expression and structure of IFIH1 [MDA5 (melanoma differentiation-associated protein 5)], a cytoplasmic helicase that mediates induction of interferon response to viral RNA. This finding firmly establishes the role of IFIH1 in T1D and demonstrates that resequencing studies can pinpoint disease-causing genes in genomic regions initially identified by GWASs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707798/" 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/PMC2707798/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nejentsev, Sergey -- Walker, Neil -- Riches, David -- Egholm, Michael -- Todd, John A -- 061858/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):387-9. doi: 10.1126/science.1167728. Epub 2009 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK. sn262@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19264985" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Case-Control Studies ; Codon, Nonsense ; DEAD-box RNA Helicases/chemistry/*genetics/metabolism ; Diabetes Mellitus, Type 1/*genetics ; Gene Frequency ; *Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Linkage Disequilibrium ; Molecular Sequence Data ; *Polymorphism, Single Nucleotide ; RNA Splice Sites ; Risk ; Risk Factors ; Sequence Analysis, DNA
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  • 47
    Publication Date: 2009-10-10
    Description: Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lombardi, Vincent C -- Ruscetti, Francis W -- Das Gupta, Jaydip -- Pfost, Max A -- Hagen, Kathryn S -- Peterson, Daniel L -- Ruscetti, Sandra K -- Bagni, Rachel K -- Petrow-Sadowski, Cari -- Gold, Bert -- Dean, Michael -- Silverman, Robert H -- Mikovits, Judy A -- CA104943/CA/NCI NIH HHS/ -- HHSN26120080001E/PHS HHS/ -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):585-9. doi: 10.1126/science.1179052. Epub 2009 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whittemore Peterson Institute, Reno, NV 89557, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815723" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/blood ; B-Lymphocytes/immunology/virology ; Base Sequence ; Cell Line ; Cell Line, Tumor ; Coculture Techniques ; DNA/genetics ; Fatigue Syndrome, Chronic/*virology ; Gammaretrovirus/genetics/immunology/*isolation & purification/physiology ; Gene Products, env/analysis ; Gene Products, gag/analysis ; Genome, Viral ; Humans ; Leukocytes, Mononuclear/*virology ; Lymphocyte Activation ; Male ; Mice ; Molecular Sequence Data ; Prostatic Neoplasms/virology ; Retroviridae Infections/epidemiology/transmission/*virology ; T-Lymphocytes/immunology/virology ; Tumor Virus Infections/epidemiology/transmission/*virology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 48
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, Claire -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):526. doi: 10.1126/science.325_526.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644082" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA Primers ; DNA, Chloroplast/*genetics ; *Genes, Plant ; Genetic Markers ; Plants/*classification/*genetics
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  • 49
    Publication Date: 2009-09-12
    Description: Methylation of ribosomal RNA (rRNA) is required for optimal protein synthesis. Multiple 2'-O-ribose methylations are carried out by box C/D guide ribonucleoproteins [small ribonucleoproteins (sRNPs) and small nucleolar ribonucleoproteins (snoRNPs)], which are conserved from archaea to eukaryotes. Methylation is dictated by base pairing between the specific guide RNA component of the sRNP or snoRNP and the target rRNA. We determined the structure of a reconstituted and catalytically active box C/D sRNP from the archaeon Methanocaldococcus jannaschii by single-particle electron microscopy. We found that archaeal box C/D sRNPs unexpectedly formed a dimeric structure with an alternative organization of their RNA and protein components that challenges the conventional view of their architecture. Mutational analysis demonstrated that this di-sRNP structure was relevant for the enzymatic function of archaeal box C/D sRNPs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975540/" 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/PMC2975540/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bleichert, Franziska -- Gagnon, Keith T -- Brown, Bernard A 2nd -- Maxwell, E Stuart -- Leschziner, Andres E -- Unger, Vinzenz M -- Baserga, Susan J -- R01 GM052581/GM/NIGMS NIH HHS/ -- R01 GM052581-15/GM/NIGMS NIH HHS/ -- R01GM52581/GM/NIGMS NIH HHS/ -- R01GM69699/GM/NIGMS NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1384-7. doi: 10.1126/science.1176099.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745151" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeal Proteins/*chemistry/metabolism/ultrastructure ; Base Sequence ; Chromosomal Proteins, Non-Histone/*chemistry ; Methanococcales/*chemistry ; Microscopy, Electron ; Models, Molecular ; Molecular Weight ; Nucleic Acid Conformation ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; RNA, Archaeal/*chemistry/ultrastructure ; Ribonucleoproteins/*chemistry/metabolism/ultrastructure
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  • 50
    Publication Date: 2009-11-26
    Description: The pathogenicity of many bacteria depends on the injection of effector proteins via type III secretion into eukaryotic cells in order to manipulate cellular processes. TAL (transcription activator-like) effectors from plant pathogenic Xanthomonas are important virulence factors that act as transcriptional activators in the plant cell nucleus, where they directly bind to DNA via a central domain of tandem repeats. Here, we show how target DNA specificity of TAL effectors is encoded. Two hypervariable amino acid residues in each repeat recognize one base pair in the target DNA. Recognition sequences of TAL effectors were predicted and experimentally confirmed. The modular protein architecture enabled the construction of artificial effectors with new specificities. Our study describes the functionality of a distinct type of DNA binding domain and allows the design of DNA binding domains for biotechnology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boch, Jens -- Scholze, Heidi -- Schornack, Sebastian -- Landgraf, Angelika -- Hahn, Simone -- Kay, Sabine -- Lahaye, Thomas -- Nickstadt, Anja -- Bonas, Ulla -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1509-12. doi: 10.1126/science.1178811. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Institute of Biology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 10, D-06099 Halle (Saale) Germany. jens.boch@genetik.uni-halle.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933107" target="_blank"〉PubMed〈/a〉
    Keywords: *Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/genetics ; Bacterial Proteins/chemistry/metabolism ; Base Pairing ; Base Sequence ; Biotechnology ; Capsicum/genetics ; DNA, Plant/*chemistry/*metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Genes, Plant ; Models, Biological ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Binding ; Repetitive Sequences, Amino Acid ; Tobacco/genetics ; Transcription Factors/chemistry/metabolism ; *Transcriptional Activation ; Xanthomonas/*metabolism/pathogenicity
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 51
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-04
    Description: A substantial challenge in engineering molecular motors is designing mechanisms to coordinate the motion between multiple domains of the motor so as to bias random thermal motion. For bipedal motors, this challenge takes the form of coordinating the movement of the biped's legs so that they can move in a synchronized fashion. To address this problem, we have constructed an autonomous DNA bipedal walker that coordinates the action of its two legs by cyclically catalyzing the hybridization of metastable DNA fuel strands. This process leads to a chemically ratcheted walk along a directionally polar DNA track. By covalently cross-linking aliquots of the walker to its track in successive walking states, we demonstrate that this Brownian motor can complete a full walking cycle on a track whose length could be extended for longer walks. We believe that this study helps to uncover principles behind the design of unidirectional devices that can function without intervention. This device should be able to fulfill roles that entail the performance of useful mechanical work on the nanometer scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470906/" 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/PMC3470906/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Omabegho, Tosan -- Sha, Ruojie -- Seeman, Nadrian C -- R37 GM029554/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):67-71. doi: 10.1126/science.1170336.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342582" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA/*chemistry ; DNA, Single-Stranded/*chemistry ; Furocoumarins/chemistry ; Inverted Repeat Sequences ; Nanotechnology/methods ; Nucleic Acid Conformation ; Nucleic Acid Denaturation ; Nucleic Acid Hybridization ; Ultraviolet Rays
    Print ISSN: 0036-8075
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  • 52
    Publication Date: 2009-05-23
    Description: Integrons are found in the genome of hundreds of environmental bacteria but are mainly known for their role in the capture and spread of antibiotic resistance determinants among Gram-negative pathogens. We report a direct link between this system and the ubiquitous SOS response. We found that LexA controlled expression of most integron integrases and consequently regulated cassette recombination. This regulatory coupling enhanced the potential for cassette swapping and capture in cells under stress, while minimizing cassette rearrangements or loss in constant environments. This finding exposes integrons as integrated adaptive systems and has implications for antibiotic treatment policies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guerin, Emilie -- Cambray, Guillaume -- Sanchez-Alberola, Neus -- Campoy, Susana -- Erill, Ivan -- Da Re, Sandra -- Gonzalez-Zorn, Bruno -- Barbe, Jordi -- Ploy, Marie-Cecile -- Mazel, Didier -- New York, N.Y. -- Science. 2009 May 22;324(5930):1034. doi: 10.1126/science.1172914.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universite de Limoges, Faculte de Medecine, EA3175, INSERM, Equipe Avenir, 87000 Limoges, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19460999" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/metabolism ; Base Sequence ; Binding Sites ; Drug Resistance, Bacterial/genetics ; Escherichia coli/*genetics/metabolism ; Gene Expression Regulation, Bacterial ; Integrases/genetics ; Integrons/*genetics ; Molecular Sequence Data ; Promoter Regions, Genetic ; *Recombination, Genetic ; *SOS Response (Genetics) ; Serine Endopeptidases/metabolism ; Vibrio cholerae/*genetics/metabolism
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  • 53
    Publication Date: 2009-09-26
    Description: Metabolic plasticity, which largely relies on the creation of new genes, is an essential feature of plant adaptation and speciation and has led to the evolution of large gene families. A typical example is provided by the diversification of the cytochrome P450 enzymes in plants. We describe here a retroposition, neofunctionalization, and duplication sequence that, via selective and local amino acid replacement, led to the evolution of a novel phenolic pathway in Brassicaceae. This pathway involves a cascade of six successive hydroxylations by two partially redundant cytochromes P450, leading to the formation of N1,N5-di(hydroxyferuloyl)-N10-sinapoylspermidine, a major pollen constituent and so-far-overlooked player in phenylpropanoid metabolism. This example shows how positive Darwinian selection can favor structured clusters of nonsynonymous substitutions that are needed for the transition of enzymes to new functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuno, Michiyo -- Compagnon, Vincent -- Schoch, Guillaume A -- Schmitt, Martine -- Debayle, Delphine -- Bassard, Jean-Etienne -- Pollet, Brigitte -- Hehn, Alain -- Heintz, Dimitri -- Ullmann, Pascaline -- Lapierre, Catherine -- Bernier, Francois -- Ehlting, Jurgen -- Werck-Reichhart, Daniele -- New York, N.Y. -- Science. 2009 Sep 25;325(5948):1688-92. doi: 10.1126/science.1174095.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Biologie Moleculaire des Plantes, CNRS-UPR2357, Universite de Strasbourg, 28 Rue Goethe, 67083 Strasbourg Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779199" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/metabolism ; Base Sequence ; Brassica napus/genetics/growth & development/metabolism ; Brassicaceae/genetics/growth & development/*metabolism ; Cytochrome P-450 Enzyme System/chemistry/genetics/*metabolism ; *Evolution, Molecular ; Gene Duplication ; Hydroxylation ; Metabolic Networks and Pathways ; Methylation ; Models, Molecular ; Molecular Sequence Data ; Plant Proteins/chemistry/genetics/metabolism ; Pollen/*growth & development/metabolism ; RNA Interference ; Retroelements ; Selection, Genetic ; Spermidine/*analogs & derivatives/metabolism
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  • 54
    Publication Date: 2009-11-07
    Description: Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drmanac, Radoje -- Sparks, Andrew B -- Callow, Matthew J -- Halpern, Aaron L -- Burns, Norman L -- Kermani, Bahram G -- Carnevali, Paolo -- Nazarenko, Igor -- Nilsen, Geoffrey B -- Yeung, George -- Dahl, Fredrik -- Fernandez, Andres -- Staker, Bryan -- Pant, Krishna P -- Baccash, Jonathan -- Borcherding, Adam P -- Brownley, Anushka -- Cedeno, Ryan -- Chen, Linsu -- Chernikoff, Dan -- Cheung, Alex -- Chirita, Razvan -- Curson, Benjamin -- Ebert, Jessica C -- Hacker, Coleen R -- Hartlage, Robert -- Hauser, Brian -- Huang, Steve -- Jiang, Yuan -- Karpinchyk, Vitali -- Koenig, Mark -- Kong, Calvin -- Landers, Tom -- Le, Catherine -- Liu, Jia -- McBride, Celeste E -- Morenzoni, Matt -- Morey, Robert E -- Mutch, Karl -- Perazich, Helena -- Perry, Kimberly -- Peters, Brock A -- Peterson, Joe -- Pethiyagoda, Charit L -- Pothuraju, Kaliprasad -- Richter, Claudia -- Rosenbaum, Abraham M -- Roy, Shaunak -- Shafto, Jay -- Sharanhovich, Uladzislau -- Shannon, Karen W -- Sheppy, Conrad G -- Sun, Michel -- Thakuria, Joseph V -- Tran, Anne -- Vu, Dylan -- Zaranek, Alexander Wait -- Wu, Xiaodi -- Drmanac, Snezana -- Oliphant, Arnold R -- Banyai, William C -- Martin, Bruce -- Ballinger, Dennis G -- Church, George M -- Reid, Clifford A -- New York, N.Y. -- Science. 2010 Jan 1;327(5961):78-81. doi: 10.1126/science.1181498. Epub 2009 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, CA 94043, USA. rdrmanac@completegenomics.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892942" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Computational Biology ; Costs and Cost Analysis ; DNA/*chemistry/genetics ; Databases, Nucleic Acid ; *Genome, Human ; Genomic Library ; Genotype ; Haplotypes ; Human Genome Project ; Humans ; Male ; *Microarray Analysis ; Nanostructures ; Nanotechnology ; Nucleic Acid Amplification Techniques ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/economics/instrumentation/*methods/standards ; Software
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  • 55
    Publication Date: 2008-02-19
    Description: Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences. Recent genomic studies in Arabidopsis thaliana have revealed that many endogenous genes are methylated either within their promoters or within their transcribed regions, and that gene methylation is highly correlated with transcription levels. However, plants have different types of methylation controlled by different genetic pathways, and detailed information on the methylation status of each cytosine in any given genome is lacking. To this end, we generated a map at single-base-pair resolution of methylated cytosines for Arabidopsis, by combining bisulphite treatment of genomic DNA with ultra-high-throughput sequencing using the Illumina 1G Genome Analyser and Solexa sequencing technology. This approach, termed BS-Seq, unlike previous microarray-based methods, allows one to sensitively measure cytosine methylation on a genome-wide scale within specific sequence contexts. Here we describe methylation on previously inaccessible components of the genome and analyse the DNA methylation sequence composition and distribution. We also describe the effect of various DNA methylation mutants on genome-wide methylation patterns, and demonstrate that our newly developed library construction and computational methods can be applied to large genomes such as that of mouse.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377394/" 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/PMC2377394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cokus, Shawn J -- Feng, Suhua -- Zhang, Xiaoyu -- Chen, Zugen -- Merriman, Barry -- Haudenschild, Christian D -- Pradhan, Sriharsa -- Nelson, Stanley F -- Pellegrini, Matteo -- Jacobsen, Steven E -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 13;452(7184):215-9. doi: 10.1038/nature06745. Epub 2008 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18278030" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Arabidopsis/*genetics ; Base Sequence ; Computational Biology ; Cytosine/metabolism ; *DNA Methylation ; Gene Expression Regulation, Plant/genetics ; Gene Library ; Genome, Plant/*genetics ; Mice ; Mutation/genetics ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; Sulfites/*metabolism ; Uracil/metabolism
    Print ISSN: 0028-0836
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  • 56
    Publication Date: 2008-11-04
    Description: Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing, 86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3' untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593745/" 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/PMC2593745/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Eric T -- Sandberg, Rickard -- Luo, Shujun -- Khrebtukova, Irina -- Zhang, Lu -- Mayr, Christine -- Kingsmore, Stephen F -- Schroth, Gary P -- Burge, Christopher B -- R01 GM085319/GM/NIGMS NIH HHS/ -- R01 GM085319-01/GM/NIGMS NIH HHS/ -- R01 HG002439/HG/NHGRI NIH HHS/ -- R01 HG002439-07/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Nov 27;456(7221):470-6. doi: 10.1038/nature07509.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18978772" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/*genetics ; Base Sequence ; Cell Line ; Exons/genetics ; *Gene Expression Profiling ; Humans ; Open Reading Frames/genetics ; Organ Specificity ; Polyadenylation ; Protein Isoforms/*genetics ; RNA, Messenger/*analysis/*genetics ; RNA-Binding Proteins/metabolism ; Repressor Proteins/metabolism
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  • 57
    Publication Date: 2008-12-19
    Description: Here we report on a 3.0 A crystal structure of a ternary complex of wild-type Thermus thermophilus argonaute bound to a 5'-phosphorylated 21-nucleotide guide DNA and a 20-nucleotide target RNA containing cleavage-preventing mismatches at the 10-11 step. The seed segment (positions 2 to 8) adopts an A-helical-like Watson-Crick paired duplex, with both ends of the guide strand anchored in the complex. An arginine, inserted between guide-strand bases 10 and 11 in the binary complex, locking it in an inactive conformation, is released on ternary complex formation. The nucleic-acid-binding channel between the PAZ- and PIWI-containing lobes of argonaute widens on formation of a more open ternary complex. The relationship of structure to function was established by determining cleavage activity of ternary complexes containing position-dependent base mismatch, bulge and 2'-O-methyl modifications. Consistent with the geometry of the ternary complex, bulges residing in the seed segments of the target, but not the guide strand, were better accommodated and their complexes were catalytically active.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765400/" 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/PMC2765400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yanli -- Juranek, Stefan -- Li, Haitao -- Sheng, Gang -- Tuschl, Thomas -- Patel, Dinshaw J -- R01 AI068776/AI/NIAID NIH HHS/ -- R01 AI068776-02/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):921-6. doi: 10.1038/nature07666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial-Sloan Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092929" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics/*metabolism ; Base Pair Mismatch ; Base Pairing ; Base Sequence ; Crystallography, X-Ray ; DNA/chemistry/genetics/*metabolism ; Methylation ; Models, Molecular ; Phosphorylation ; Protein Conformation ; RNA/chemistry/genetics/*metabolism ; RNA Interference ; RNA-Induced Silencing Complex/*chemistry/genetics/*metabolism ; Substrate Specificity ; Thermus thermophilus/*chemistry
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  • 58
    Publication Date: 2008-01-19
    Description: Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism cannot be efficiently predicted solely on the basis of sequence motifs. In multicellular eukaryotes, long introns are recognized through exon definition and most genes produce multiple mRNA variants through alternative splicing. The nonsense-mediated mRNA decay (NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals. Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaillon, Olivier -- Bouhouche, Khaled -- Gout, Jean-Francois -- Aury, Jean-Marc -- Noel, Benjamin -- Saudemont, Baptiste -- Nowacki, Mariusz -- Serrano, Vincent -- Porcel, Betina M -- Segurens, Beatrice -- Le Mouel, Anne -- Lepere, Gersende -- Schachter, Vincent -- Betermier, Mireille -- Cohen, Jean -- Wincker, Patrick -- Sperling, Linda -- Duret, Laurent -- Meyer, Eric -- England -- Nature. 2008 Jan 17;451(7176):359-62. doi: 10.1038/nature06495.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genoscope (CEA), 2 rue Gaston Cremieux CP5706, 91057 Evry, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202663" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Animals ; Base Sequence ; Codon, Terminator/genetics ; Computational Biology ; Eukaryotic Cells/*metabolism ; Expressed Sequence Tags ; Genes, Protozoan/genetics ; Introns/*genetics ; Molecular Sequence Data ; Paramecium/*genetics ; *Protein Biosynthesis ; Protozoan Proteins/genetics/metabolism ; RNA Interference ; RNA Stability ; RNA, Protozoan/genetics/metabolism
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  • 59
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-05-03
    Description: The universality of ribonuclease P (RNase P), the ribonucleoprotein essential for transfer RNA (tRNA) 5' maturation, is challenged in the archaeon Nanoarchaeum equitans. Neither extensive computational analysis of the genome nor biochemical tests in cell extracts revealed the existence of this enzyme. Here we show that the conserved placement of its tRNA gene promoters allows the synthesis of leaderless tRNAs, whose presence was verified by the observation of 5' triphosphorylated mature tRNA species. Initiation of tRNA gene transcription requires a purine, which coincides with the finding that tRNAs with a cytosine in position 1 display unusually extended 5' termini with an extra purine residue. These tRNAs were shown to be substrates for their cognate aminoacyl-tRNA synthetases. These findings demonstrate how nature can cope with the loss of the universal and supposedly ancient RNase P through genomic rearrangement at tRNA genes under the pressure of genome condensation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Randau, Lennart -- Schroder, Imke -- Soll, Dieter -- England -- Nature. 2008 May 1;453(7191):120-3. doi: 10.1038/nature06833.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18451863" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/metabolism ; Aminoacylation ; Base Sequence ; *Evolution, Molecular ; Gene Deletion ; Genes, Archaeal/*genetics ; Models, Biological ; Molecular Sequence Data ; Nanoarchaeota/cytology/enzymology/*genetics ; Phosphorylation ; Promoter Regions, Genetic/*genetics ; RNA, Archaeal/*genetics/metabolism ; RNA, Transfer/*genetics/metabolism ; Ribonuclease P/*deficiency/metabolism ; Substrate Specificity ; Transcription, Genetic/genetics
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  • 60
    Publication Date: 2008-10-03
    Description: In bilaterian animals, such as humans, flies and worms, hundreds of microRNAs (miRNAs), some conserved throughout bilaterian evolution, collectively regulate a substantial fraction of the transcriptome. In addition to miRNAs, other bilaterian small RNAs, known as Piwi-interacting RNAs (piRNAs), protect the genome from transposons. Here we identify small RNAs from animal phyla that diverged before the emergence of the Bilateria. The cnidarian Nematostella vectensis (starlet sea anemone), a close relative to the Bilateria, possesses an extensive repertoire of miRNA genes, two classes of piRNAs and a complement of proteins specific to small-RNA biology comparable to that of humans. The poriferan Amphimedon queenslandica (sponge), one of the simplest animals and a distant relative of the Bilateria, also possesses miRNAs, both classes of piRNAs and a full complement of the small-RNA machinery. Animal miRNA evolution seems to have been relatively dynamic, with precursor sizes and mature miRNA sequences differing greatly between poriferans, cnidarians and bilaterians. Nonetheless, miRNAs and piRNAs have been available as classes of riboregulators to shape gene expression throughout the evolution and radiation of animal phyla.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837422/" 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/PMC3837422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimson, Andrew -- Srivastava, Mansi -- Fahey, Bryony -- Woodcroft, Ben J -- Chiang, H Rosaria -- King, Nicole -- Degnan, Bernard M -- Rokhsar, Daniel S -- Bartel, David P -- R01 GM067031/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 30;455(7217):1193-7. doi: 10.1038/nature07415. Epub 2008 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18830242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Eukaryotic Cells/metabolism ; *Evolution, Molecular ; Gene Expression Regulation ; Humans ; MicroRNAs/*genetics ; Phylogeny ; RNA, Small Interfering/*genetics ; Sea Anemones/*genetics ; Sequence Analysis
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  • 61
    Publication Date: 2008-06-13
    Description: In modern organisms, protein enzymes are solely responsible for the aminoacylation of transfer RNA. However, the evolution of protein synthesis in the RNA world required RNAs capable of catalysing this reaction. Ribozymes that aminoacylate RNA by using activated amino acids have been discovered through selection in vitro. Flexizyme is a 45-nucleotide ribozyme capable of charging tRNA in trans with various activated l-phenylalanine derivatives. In addition to a more than 10(5) rate enhancement and more than 10(4)-fold discrimination against some non-cognate amino acids, this ribozyme achieves good regioselectivity: of all the hydroxyl groups of a tRNA, it exclusively aminoacylates the terminal 3'-OH. Here we report the 2.8-A resolution structure of flexizyme fused to a substrate RNA. Together with randomization of ribozyme core residues and reselection, this structure shows that very few nucleotides are needed for the aminoacylation of specific tRNAs. Although it primarily recognizes tRNA through base-pairing with the CCA terminus of the tRNA molecule, flexizyme makes numerous local interactions to position the acceptor end of tRNA precisely. A comparison of two crystallographically independent flexizyme conformations, only one of which appears capable of binding activated phenylalanine, suggests that this ribozyme may achieve enhanced specificity by coupling active-site folding to tRNA docking. Such a mechanism would be reminiscent of the mutually induced fit of tRNA and protein employed by some aminoacyl-tRNA synthetases to increase specificity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xiao, Hong -- Murakami, Hiroshi -- Suga, Hiroaki -- Ferre-D'Amare, Adrian R -- England -- Nature. 2008 Jul 17;454(7202):358-61. doi: 10.1038/nature07033. Epub 2008 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548004" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/chemistry/metabolism ; Base Sequence ; Binding Sites ; Escherichia coli/enzymology ; Models, Molecular ; Nucleic Acid Conformation ; Protein Folding ; Protein Structure, Tertiary ; RNA, Catalytic/chemistry/genetics/*metabolism ; RNA, Transfer/chemistry/genetics/*metabolism ; *Transfer RNA Aminoacylation
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  • 62
    Publication Date: 2008-12-05
    Description: Telomeres cap the ends of chromosomes and provide a means to complete replication. The DNA portion of telomeres is synthesized by the enzyme telomerase using part of an RNA subunit as a template for reverse transcription. How the mature 3' end of telomerase RNA is generated has so far remained elusive. Here we show that in Schizosaccharomyces pombe telomerase RNA transcripts must be processed to generate functional telomerase. Characterization of the maturation pathway uncovered an unexpected role for the spliceosome, which normally catalyses splicing of pre-messenger RNA. The first spliceosomal cleavage reaction generates the mature 3' end of telomerase RNA (TER1, the functional RNA encoded by the ter1(+) gene), releasing the active form of the RNA without exon ligation. Blocking the first step or permitting completion of splicing generates inactive forms of TER1 and causes progressive telomere shortening. We establish that 3' end processing of TER1 is critical for telomerase function and describe a previously unknown mechanism for RNA maturation that uses the ability of the spliceosome to mediate site-specific cleavage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Box, Jessica A -- Bunch, Jeremy T -- Tang, Wen -- Baumann, Peter -- England -- Nature. 2008 Dec 18;456(7224):910-4. doi: 10.1038/nature07584. Epub 2008 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052544" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chromosomes, Fungal/genetics/metabolism ; Introns/genetics ; RNA/genetics/*metabolism ; RNA Splicing/genetics ; RNA Stability ; RNA, Fungal/genetics/metabolism ; RNA, Small Nuclear/genetics/metabolism ; Schizosaccharomyces/*enzymology/*genetics ; Spliceosomes/*metabolism ; Telomerase/genetics/*metabolism ; Telomere/genetics ; snRNP Core Proteins/metabolism
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  • 63
    Publication Date: 2008-03-04
    Description: In stratified epithelial tissues, homeostasis relies on the self-renewing capacity of stem cells located within the innermost basal layer. As basal cells become suprabasal, they lose proliferative potential and embark on a terminal differentiation programme. Here, we show that microRNA-203 is induced in the skin concomitantly with stratification and differentiation. By altering miR-203's spatiotemporal expression in vivo, we show that miR-203 promotes epidermal differentiation by restricting proliferative potential and inducing cell-cycle exit. We identify p63 as one of the conserved targets of miR-203 across vertebrates. Notably, p63 is an essential regulator of stem-cell maintenance in stratified epithelial tissues. We show that miR-203 directly represses the expression of p63: it fails to switch off suprabasally when either Dicer1 or miR-203 is absent and it becomes repressed basally when miR-203 is prematurely expressed. Our findings suggest that miR-203 defines a molecular boundary between proliferative basal progenitors and terminally differentiating suprabasal cells, ensuring proper identity of neighbouring layers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346711/" 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/PMC4346711/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yi, Rui -- Poy, Matthew N -- Stoffel, Markus -- Fuchs, Elaine -- R01 AR050452/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 13;452(7184):225-9. doi: 10.1038/nature06642. Epub 2008 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, The Rockefeller University, New York City, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18311128" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Animals ; Base Sequence ; Cell Cycle ; *Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Computational Biology ; Epidermis/cytology/metabolism ; Gene Expression Regulation ; Humans ; Keratinocytes/cytology/metabolism ; Mice ; Mice, Knockout ; MicroRNAs/antagonists & inhibitors/genetics/*metabolism ; Skin/*cytology/*metabolism ; Stem Cells/*cytology ; Zebrafish/genetics
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  • 64
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zanette, Damian -- England -- Nature. 2008 Jun 19;453(7198):988-9. doi: 10.1038/453988a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Statistical and Interdisciplinary Physics Group of Centro Atomico Bariloche.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563138" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Linguistics ; *Models, Statistical ; *Music
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  • 65
    Publication Date: 2008-08-30
    Description: Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672043/" 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/PMC2672043/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mosse, Yael P -- Laudenslager, Marci -- Longo, Luca -- Cole, Kristina A -- Wood, Andrew -- Attiyeh, Edward F -- Laquaglia, Michael J -- Sennett, Rachel -- Lynch, Jill E -- Perri, Patrizia -- Laureys, Genevieve -- Speleman, Frank -- Kim, Cecilia -- Hou, Cuiping -- Hakonarson, Hakon -- Torkamani, Ali -- Schork, Nicholas J -- Brodeur, Garrett M -- Tonini, Gian P -- Rappaport, Eric -- Devoto, Marcella -- Maris, John M -- K08 CA111733/CA/NCI NIH HHS/ -- K08 CA111733-04/CA/NCI NIH HHS/ -- K08-111733/PHS HHS/ -- R01 CA078545/CA/NCI NIH HHS/ -- R01 CA078545-09/CA/NCI NIH HHS/ -- R01 CA124709/CA/NCI NIH HHS/ -- R01-CA78454/CA/NCI NIH HHS/ -- R01-CA87847/CA/NCI NIH HHS/ -- U10 CA098543/CA/NCI NIH HHS/ -- U10 CA098543-06/CA/NCI NIH HHS/ -- England -- Nature. 2008 Oct 16;455(7215):930-5. doi: 10.1038/nature07261. Epub 2008 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18724359" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line, Tumor ; Child ; Chromosomes, Human, Pair 2/genetics ; Female ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/genetics ; Humans ; Male ; Models, Molecular ; Molecular Sequence Data ; Mutation/*genetics ; Neuroblastoma/*enzymology/*genetics ; Pedigree ; Phosphorylation ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry/deficiency/*genetics ; Receptor Protein-Tyrosine Kinases
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  • 66
    Publication Date: 2008-02-12
    Description: Cells with loss of BRCA2 function are defective in homologous recombination (HR) and are highly sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP), which provides the basis for a new therapeutic approach. Here we show that resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. We derived PARP-inhibitor-resistant (PIR) clones from the human CAPAN1 pancreatic cancer cell line, which carries the protein-truncating c.6174delT frameshift mutation. PIR clones could form DNA-damage-induced RAD51 nuclear foci and were able to limit genotoxin-induced genomic instability, both hallmarks of a competent HR pathway. New BRCA2 isoforms were expressed in the resistant lines as a result of intragenic deletion of the c.6174delT mutation and restoration of the open reading frame (ORF). Reconstitution of BRCA2-deficient cells with these revertant BRCA2 alleles rescued PARP inhibitor sensitivity and HR deficiency. Most of the deletions in BRCA2 were associated with small tracts of homology, and possibly arose from error-prone repair caused by BRCA2 deficiency. Similar ORF-restoring mutations were present in carboplatin-resistant ovarian tumours from c.6174delT mutation carriers. These observations have implications for understanding drug resistance in BRCA mutation carriers as well as in defining functionally important domains within BRCA2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Edwards, Stacey L -- Brough, Rachel -- Lord, Christopher J -- Natrajan, Rachael -- Vatcheva, Radost -- Levine, Douglas A -- Boyd, Jeff -- Reis-Filho, Jorge S -- Ashworth, Alan -- A8363/Cancer Research UK/United Kingdom -- England -- Nature. 2008 Feb 28;451(7182):1111-5. doi: 10.1038/nature06548. Epub 2008 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18264088" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Alleles ; Amino Acid Sequence ; BRCA2 Protein/deficiency/genetics ; Base Sequence ; Carboplatin/pharmacology ; Cell Line, Tumor ; Chromosome Aberrations/chemically induced ; Drug Resistance, Neoplasm/*drug effects/*genetics ; Female ; Fluorobenzenes/pharmacology ; Gene Expression Regulation, Neoplastic ; *Genes, BRCA2 ; Humans ; Middle Aged ; Mitomycin/pharmacology ; Molecular Sequence Data ; Mutation/genetics ; Open Reading Frames/genetics ; Ovarian Neoplasms/drug therapy/genetics ; Pancreatic Neoplasms/drug therapy/genetics/pathology ; Phthalazines/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors ; Recombination, Genetic/genetics ; Sequence Deletion/*genetics
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  • 67
    Publication Date: 2008-09-06
    Description: Maintenance methylation of hemimethylated CpG dinucleotides at DNA replication forks is the key to faithful mitotic inheritance of genomic methylation patterns. UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for maintenance methylation by interacting with DNA nucleotide methyltransferase 1 (DNMT1), the maintenance methyltransferase, and with hemimethylated CpG, the substrate for DNMT1 (refs 1 and 2). Here we present the crystal structure of the SET and RING-associated (SRA) domain of mouse UHRF1 in complex with DNA containing a hemimethylated CpG site. The DNA is contacted in both the major and minor grooves by two loops that penetrate into the middle of the DNA helix. The 5-methylcytosine has flipped completely out of the DNA helix and is positioned in a binding pocket with planar stacking contacts, Watson-Crick polar hydrogen bonds and van der Waals interactions specific for 5-methylcytosine. Hence, UHRF1 contains a previously unknown DNA-binding module and is the first example of a non-enzymatic, sequence-specific DNA-binding protein domain to use the base flipping mechanism to interact with DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2602803/" 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/PMC2602803/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hashimoto, Hideharu -- Horton, John R -- Zhang, Xing -- Bostick, Magnolia -- Jacobsen, Steven E -- Cheng, Xiaodong -- CA1263022/CA/NCI NIH HHS/ -- GM049245/GM/NIGMS NIH HHS/ -- GM060398/GM/NIGMS NIH HHS/ -- R01 GM049245/GM/NIGMS NIH HHS/ -- R01 GM049245-15/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 9;455(7214):826-9. doi: 10.1038/nature07280. Epub 2008 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772888" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/*metabolism ; Animals ; Base Sequence ; CpG Islands/genetics ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; *DNA Methylation ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Mice ; Models, Molecular ; Molecular Conformation ; Nuclear Proteins/*chemistry/*metabolism ; Protein Binding ; Protein Structure, Tertiary
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  • 68
    Publication Date: 2008-06-20
    Description: Quorum sensing is a term used to describe cell-to-cell communication that allows cell-density-dependent gene expression. Many bacteria use acyl-homoserine lactone (acyl-HSL) synthases to generate fatty acyl-HSL quorum-sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. Here we show that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl-HSL synthase to produce p-coumaroyl-HSL by using environmental p-coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl-HSL receptors that responds to p-coumaroyl-HSL to regulate global gene expression. We also found that p-coumaroyl-HSL is made by other bacteria including Bradyrhizobium sp. and Silicibacter pomeroyi. This discovery extends the range of possibilities for acyl-HSL quorum sensing and raises fundamental questions about quorum sensing within the context of environmental signalling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schaefer, Amy L -- Greenberg, E P -- Oliver, Colin M -- Oda, Yasuhiro -- Huang, Jean J -- Bittan-Banin, Gili -- Peres, Caroline M -- Schmidt, Silke -- Juhaszova, Katarina -- Sufrin, Janice R -- Harwood, Caroline S -- England -- Nature. 2008 Jul 31;454(7204):595-9. doi: 10.1038/nature07088. Epub 2008 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Washington, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563084" target="_blank"〉PubMed〈/a〉
    Keywords: 4-Butyrolactone/*analogs & derivatives/chemistry/metabolism ; Bacterial Proteins/genetics/isolation & purification/*metabolism ; Base Sequence ; Biological Assay ; Coumaric Acids/*metabolism ; Gene Expression Regulation, Bacterial ; *Quorum Sensing ; Regulon ; Rhodopseudomonas/enzymology/genetics/*growth & development/*metabolism ; Sequence Alignment ; *Signal Transduction
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  • 69
    Publication Date: 2008-07-04
    Description: Herpesviruses are characterized by their ability to maintain life-long latent infections in their animal hosts. However, the mechanisms that allow establishment and maintenance of the latent state remain poorly understood. Herpes simplex virus 1 (HSV-1) establishes latency in neurons of sensory ganglia, where the only abundant viral gene product is a non-coding RNA, the latency associated transcript (LAT). Here we show that LAT functions as a primary microRNA (miRNA) precursor that encodes four distinct miRNAs in HSV-1 infected cells. One of these miRNAs, miR-H2-3p, is transcribed in an antisense orientation to ICP0-a viral immediate-early transcriptional activator that is important for productive HSV-1 replication and thought to have a role in reactivation from latency. We show that miR-H2-3p is able to reduce ICP0 protein expression, but does not significantly affect ICP0 messenger RNA levels. We also identified a fifth HSV-1 miRNA in latently infected trigeminal ganglia, miR-H6, which derives from a previously unknown transcript distinct from LAT. miR-H6 shows extended seed complementarity to the mRNA encoding a second HSV-1 transcription factor, ICP4, and inhibits expression of ICP4, which is required for expression of most HSV-1 genes during productive infection. These results may explain the reported ability of LAT to promote latency. Thus, HSV-1 expresses at least two primary miRNA precursors in latently infected neurons that may facilitate the establishment and maintenance of viral latency by post-transcriptionally regulating viral gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666538/" 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/PMC2666538/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Umbach, Jennifer Lin -- Kramer, Martha F -- Jurak, Igor -- Karnowski, Heather W -- Coen, Donald M -- Cullen, Bryan R -- R01 AI067968/AI/NIAID NIH HHS/ -- R01 AI067968-02/AI/NIAID NIH HHS/ -- R01 AI067968-03/AI/NIAID NIH HHS/ -- T32 CA009111/CA/NCI NIH HHS/ -- England -- Nature. 2008 Aug 7;454(7205):780-3. doi: 10.1038/nature07103. Epub 2008 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Down-Regulation ; *Gene Expression Regulation, Viral ; Genome, Viral/genetics ; Herpesvirus 1, Human/*genetics/physiology ; Humans ; Immediate-Early Proteins/biosynthesis/genetics ; Male ; Mice ; MicroRNAs/*genetics/*metabolism ; RNA Processing, Post-Transcriptional ; RNA, Messenger/genetics/metabolism ; RNA, Viral/*genetics/*metabolism ; Ubiquitin-Protein Ligases/biosynthesis/genetics ; Virus Latency/*genetics/physiology
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  • 70
    Publication Date: 2008-03-14
    Description: DNA is renowned for its double helix structure and the base pairing that enables the recognition and highly selective binding of complementary DNA strands. These features, and the ability to create DNA strands with any desired sequence of bases, have led to the use of DNA rationally to design various nanostructures and even execute molecular computations. Of the wide range of self-assembled DNA nanostructures reported, most are one- or two-dimensional. Examples of three-dimensional DNA structures include cubes, truncated octahedra, octohedra and tetrahedra, which are all comprised of many different DNA strands with unique sequences. When aiming for large structures, the need to synthesize large numbers (hundreds) of unique DNA strands poses a challenging design problem. Here, we demonstrate a simple solution to this problem: the design of basic DNA building units in such a way that many copies of identical units assemble into larger three-dimensional structures. We test this hierarchical self-assembly concept with DNA molecules that form three-point-star motifs, or tiles. By controlling the flexibility and concentration of the tiles, the one-pot assembly yields tetrahedra, dodecahedra or buckyballs that are tens of nanometres in size and comprised of four, twenty or sixty individual tiles, respectively. We expect that our assembly strategy can be adapted to allow the fabrication of a range of relatively complex three-dimensional structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Yu -- Ye, Tao -- Su, Min -- Zhang, Chuan -- Ribbe, Alexander E -- Jiang, Wen -- Mao, Chengde -- England -- Nature. 2008 Mar 13;452(7184):198-201. doi: 10.1038/nature06597.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18337818" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cryoelectron Microscopy ; DNA/*chemistry/genetics/ultrastructure ; Fullerenes/chemistry ; Microscopy, Atomic Force ; Molecular Sequence Data ; Nanostructures/*chemistry/ultrastructure ; *Nucleic Acid Conformation ; Pliability
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  • 71
    Publication Date: 2008-05-23
    Description: Efficient translation initiation and optimal stability of most eukaryotic messenger RNAs depends on the formation of a closed-loop structure and the resulting synergistic interplay between the 5' m(7)G cap and the 3' poly(A) tail. Evidence of eIF4G and Pab1 interaction supports the notion of a closed-loop mRNP, but the mechanistic events that lead to its formation and maintenance are still unknown. Here we use toeprinting and polysome profiling assays to delineate ribosome positioning at initiator AUG codons and ribosome-mRNA association, respectively, and find that two distinct stable (resistant to cap analogue) closed-loop structures are formed during initiation in yeast cell-free extracts. The integrity of both forms requires the mRNA cap and poly(A) tail, as well as eIF4E, eIF4G, Pab1 and eIF3, and is dependent on the length of both the mRNA and the poly(A) tail. Formation of the first structure requires the 48S ribosomal complex, whereas the second requires an 80S ribosome and the termination factors eRF3/Sup35 and eRF1/Sup45. The involvement of the termination factors is independent of a termination event.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587346/" 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/PMC2587346/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amrani, Nadia -- Ghosh, Shubhendu -- Mangus, David A -- Jacobson, Allan -- R37 GM027757/GM/NIGMS NIH HHS/ -- R37 GM027757-26/GM/NIGMS NIH HHS/ -- R37 GM027757-27/GM/NIGMS NIH HHS/ -- R37 GM027757-28/GM/NIGMS NIH HHS/ -- R37 GM027757-29/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Jun 26;453(7199):1276-80. doi: 10.1038/nature06974. Epub 2008 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0122, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18496529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Codon, Initiator/genetics ; Cycloheximide/pharmacology ; Eukaryotic Initiation Factor-4G/metabolism ; Peptide Termination Factors/genetics/metabolism ; Poly(A)-Binding Proteins/metabolism ; Polyribosomes/genetics/metabolism ; Prions/metabolism ; *Protein Biosynthesis ; RNA Caps/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Ribonucleoproteins/*chemistry/genetics/*metabolism ; Ribosomal Proteins/chemistry/genetics/*metabolism ; Ribosomes/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism
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  • 72
    Publication Date: 2008-12-02
    Description: Nuclear receptors are multi-domain transcription factors that bind to DNA elements from which they regulate gene expression. The peroxisome proliferator-activated receptors (PPARs) form heterodimers with the retinoid X receptor (RXR), and PPAR-gamma has been intensively studied as a drug target because of its link to insulin sensitization. Previous structural studies have focused on isolated DNA or ligand-binding segments, with no demonstration of how multiple domains cooperate to modulate receptor properties. Here we present structures of intact PPAR-gamma and RXR-alpha as a heterodimer bound to DNA, ligands and coactivator peptides. PPAR-gamma and RXR-alpha form a non-symmetric complex, allowing the ligand-binding domain (LBD) of PPAR-gamma to contact multiple domains in both proteins. Three interfaces link PPAR-gamma and RXR-alpha, including some that are DNA dependent. The PPAR-gamma LBD cooperates with both DNA-binding domains (DBDs) to enhance response-element binding. The A/B segments are highly dynamic, lacking folded substructures despite their gene-activation properties.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743566/" 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/PMC2743566/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chandra, Vikas -- Huang, Pengxiang -- Hamuro, Yoshitomo -- Raghuram, Srilatha -- Wang, Yongjun -- Burris, Thomas P -- Rastinejad, Fraydoon -- R01 GM055217/GM/NIGMS NIH HHS/ -- R01 GM055217-11/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Nov 20;456(7220):350-6. doi: 10.1038/nature07413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, and Center for Molecular Design, University of Virginia Health System, 1300 Jefferson Park Avenue, Charlottesville, Virginia 22908-0735, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19043829" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Base Sequence ; DNA/chemistry/genetics/*metabolism ; Humans ; Ligands ; Models, Molecular ; Multiprotein Complexes/*chemistry/*metabolism ; PPAR gamma/*chemistry/*metabolism ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Response Elements/genetics ; Retinoid X Receptor alpha/*chemistry/*metabolism
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  • 73
    Publication Date: 2008-09-06
    Description: DNA methylation of CpG dinucleotides is an important epigenetic modification of mammalian genomes and is essential for the regulation of chromatin structure, of gene expression and of genome stability. Differences in DNA methylation patterns underlie a wide range of biological processes, such as genomic imprinting, inactivation of the X chromosome, embryogenesis, and carcinogenesis. Inheritance of the epigenetic methylation pattern is mediated by the enzyme DNA methyltransferase 1 (Dnmt1), which methylates newly synthesized CpG sequences during DNA replication, depending on the methylation status of the template strands. The protein UHRF1 (also known as Np95 and ICBP90) recognizes hemi-methylation sites via a SET and RING-associated (SRA) domain and directs Dnmt1 to these sites. Here we report the crystal structures of the SRA domain in free and hemi-methylated DNA-bound states. The SRA domain folds into a globular structure with a basic concave surface formed by highly conserved residues. Binding of DNA to the concave surface causes a loop and an amino-terminal tail of the SRA domain to fold into DNA interfaces at the major and minor grooves of the methylation site. In contrast to fully methylated CpG sites recognized by the methyl-CpG-binding domain, the methylcytosine base at the hemi-methylated site is flipped out of the DNA helix in the SRA-DNA complex and fits tightly into a protein pocket on the concave surface. The complex structure suggests that the successive flip out of the pre-existing methylated cytosine and the target cytosine to be methylated is associated with the coordinated transfer of the hemi-methylated CpG site from UHRF1 to Dnmt1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arita, Kyohei -- Ariyoshi, Mariko -- Tochio, Hidehito -- Nakamura, Yusuke -- Shirakawa, Masahiro -- England -- Nature. 2008 Oct 9;455(7214):818-21. doi: 10.1038/nature07249. Epub 2008 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772891" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Base Sequence ; Conserved Sequence ; CpG Islands/genetics ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; DNA (Cytosine-5-)-Methyltransferase/metabolism ; *DNA Methylation ; Mice ; Models, Biological ; Models, Molecular ; Molecular Conformation ; Nuclear Proteins/*chemistry/*metabolism ; Protein Binding ; Protein Structure, Tertiary
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  • 74
    Publication Date: 2008-03-07
    Description: The classical RNA secondary structure model considers A.U and G.C Watson-Crick as well as G.U wobble base pairs. Here we substitute it for a new one, in which sets of nucleotide cyclic motifs define RNA structures. This model allows us to unify all base pairing energetic contributions in an effective scoring function to tackle the problem of RNA folding. We show how pipelining two computer algorithms based on nucleotide cyclic motifs, MC-Fold and MC-Sym, reproduces a series of experimentally determined RNA three-dimensional structures from the sequence. This demonstrates how crucial the consideration of all base-pairing interactions is in filling the gap between sequence and structure. We use the pipeline to define rules of precursor microRNA folding in double helices, despite the presence of a number of presumed mismatches and bulges, and to propose a new model of the human immunodeficiency virus-1 -1 frame-shifting element.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parisien, Marc -- Major, Francois -- England -- Nature. 2008 Mar 6;452(7183):51-5. doi: 10.1038/nature06684.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Immunology and Cancer, Department of Computer Science and Operations Research, Universite de Montreal, PO Box 6128, Downtown Station, Montreal, Quebec H3C 3J7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18322526" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Base Pairing ; Base Sequence ; *Computational Biology ; Frameshifting, Ribosomal ; Genes, gag/genetics ; Genes, pol/genetics ; HIV-1/genetics ; Humans ; MicroRNAs/chemistry/metabolism ; Models, Genetic ; Models, Molecular ; Molecular Sequence Data ; *Nucleic Acid Conformation ; RNA/*chemistry/*genetics ; RNA Precursors/chemistry/metabolism ; RNA, Viral/chemistry/genetics/metabolism ; *Software ; Thermodynamics
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  • 75
    Publication Date: 2008-02-01
    Description: It was first shown more than ten years ago that DNA oligonucleotides can be attached to gold nanoparticles rationally to direct the formation of larger assemblies. Since then, oligonucleotide-functionalized nanoparticles have been developed into powerful diagnostic tools for nucleic acids and proteins, and into intracellular probes and gene regulators. In contrast, the conceptually simple yet powerful idea that functionalized nanoparticles might serve as basic building blocks that can be rationally assembled through programmable base-pairing interactions into highly ordered macroscopic materials remains poorly developed. So far, the approach has mainly resulted in polymerization, with modest control over the placement of, the periodicity in, and the distance between particles within the assembled material. That is, most of the materials obtained thus far are best classified as amorphous polymers, although a few examples of colloidal crystal formation exist. Here, we demonstrate that DNA can be used to control the crystallization of nanoparticle-oligonucleotide conjugates to the extent that different DNA sequences guide the assembly of the same type of inorganic nanoparticle into different crystalline states. We show that the choice of DNA sequences attached to the nanoparticle building blocks, the DNA linking molecules and the absence or presence of a non-bonding single-base flexor can be adjusted so that gold nanoparticles assemble into micrometre-sized face-centred-cubic or body-centred-cubic crystal structures. Our findings thus clearly demonstrate that synthetically programmable colloidal crystallization is possible, and that a single-component system can be directed to form different structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Sung Yong -- Lytton-Jean, Abigail K R -- Lee, Byeongdu -- Weigand, Steven -- Schatz, George C -- Mirkin, Chad A -- England -- Nature. 2008 Jan 31;451(7178):553-6. doi: 10.1038/nature06508.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235497" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Colloids/chemistry ; Crystallization/*methods ; DNA/*chemistry/genetics ; Gold/chemistry ; Metal Nanoparticles/*chemistry ; Scattering, Radiation ; Thermodynamics ; X-Ray Diffraction
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  • 76
    Publication Date: 2008-01-04
    Description: The establishment of complex expression patterns at precise times and locations is key to metazoan development, yet a mechanistic understanding of the underlying transcription control networks is still missing. Here we describe a novel thermodynamic model that computes expression patterns as a function of cis-regulatory sequence and of the binding-site preferences and expression of participating transcription factors. We apply this model to the segmentation gene network of Drosophila melanogaster and find that it predicts expression patterns of cis-regulatory modules with remarkable accuracy, demonstrating that positional information is encoded in the regulatory sequence and input factor distribution. Our analysis reveals that both strong and weaker binding sites contribute, leading to high occupancy of the module DNA, and conferring robustness against mutation; short-range homotypic clustering of weaker sites facilitates cooperative binding, which is necessary to sharpen the patterns. Our computational framework is generally applicable to most protein-DNA interaction systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Segal, Eran -- Raveh-Sadka, Tali -- Schroeder, Mark -- Unnerstall, Ulrich -- Gaul, Ulrike -- England -- Nature. 2008 Jan 31;451(7178):535-40. doi: 10.1038/nature06496. Epub 2008 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. eran@weizmann.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172436" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Site ; Animals ; Base Sequence ; Body Patterning/genetics ; Computational Biology ; DNA/genetics/metabolism ; Drosophila melanogaster/*embryology/*genetics ; Gene Expression Regulation, Developmental/*genetics ; *Models, Genetic ; Reproducibility of Results ; Response Elements/*genetics ; Thermodynamics ; Transcription Factors/metabolism
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  • 77
    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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  • 78
    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
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  • 79
    Publication Date: 2008-01-26
    Description: We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibson, Daniel G -- Benders, Gwynedd A -- Andrews-Pfannkoch, Cynthia -- Denisova, Evgeniya A -- Baden-Tillson, Holly -- Zaveri, Jayshree -- Stockwell, Timothy B -- Brownley, Anushka -- Thomas, David W -- Algire, Mikkel A -- Merryman, Chuck -- Young, Lei -- Noskov, Vladimir N -- Glass, John I -- Venter, J Craig -- Hutchison, Clyde A 3rd -- Smith, Hamilton O -- New York, N.Y. -- Science. 2008 Feb 29;319(5867):1215-20. doi: 10.1126/science.1151721. Epub 2008 Jan 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉J. Craig Venter Institute, Rockville, MD 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18218864" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chromosomes, Artificial, Bacterial ; Chromosomes, Artificial, Yeast ; *Cloning, Molecular ; DNA, Bacterial/*chemical synthesis ; DNA, Recombinant ; Escherichia coli/genetics ; Genetic Vectors ; *Genome, Bacterial ; Genomics/*methods ; Mycoplasma genitalium/*genetics ; Oligodeoxyribonucleotides/chemical synthesis ; Plasmids ; Recombination, Genetic ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, DNA ; Transformation, Genetic
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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-02-16
    Description: Cadherin-mediated cell adhesion and signaling is essential for metazoan development and yet is absent from all other multicellular organisms. We found cadherin genes at numbers similar to those observed in complex metazoans in one of the closest single-celled relatives of metazoans, the choanoflagellate Monosiga brevicollis. Because the evolution of metazoans from a single-celled ancestor required novel cell adhesion and signaling mechanisms, the discovery of diverse cadherins in choanoflagellates suggests that cadherins may have contributed to metazoan origins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abedin, Monika -- King, Nicole -- New York, N.Y. -- Science. 2008 Feb 15;319(5865):946-8. doi: 10.1126/science.1151084.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology and Center for Integrative Genomics, University of California at Berkeley, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276888" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Cadherins/*chemistry/*genetics/physiology ; Cell Adhesion ; Ciona intestinalis/chemistry ; Cnidaria/chemistry ; Drosophila melanogaster/chemistry ; Eukaryota/*chemistry ; Eukaryotic Cells/*chemistry/physiology ; Mice ; Molecular Sequence Data ; Protein Structure, Tertiary ; Repetitive Sequences, Amino Acid ; Signal Transduction ; Tyrosine/metabolism ; src Homology Domains
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  • 81
    Publication Date: 2008-12-20
    Description: Horizontal gene transfer (HGT) in bacteria and archaea occurs through phage transduction, transformation, or conjugation, and the latter is particularly important for the spread of antibiotic resistance. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci confer sequence-directed immunity against phages. A clinical isolate of Staphylococcus epidermidis harbors a CRISPR spacer that matches the nickase gene present in nearly all staphylococcal conjugative plasmids. Here we show that CRISPR interference prevents conjugation and plasmid transformation in S. epidermidis. Insertion of a self-splicing intron into nickase blocks interference despite the reconstitution of the target sequence in the spliced mRNA, which indicates that the interference machinery targets DNA directly. We conclude that CRISPR loci counteract multiple routes of HGT and can limit the spread of antibiotic resistance in pathogenic bacteria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695655/" 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/PMC2695655/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marraffini, Luciano A -- Sontheimer, Erik J -- GM072830/GM/NIGMS NIH HHS/ -- R01 GM072830/GM/NIGMS NIH HHS/ -- R01 GM072830-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Dec 19;322(5909):1843-5. doi: 10.1126/science.1165771.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19095942" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Conjugation, Genetic ; DNA, Bacterial/*genetics/metabolism ; Deoxyribonuclease I/genetics/metabolism ; *Gene Silencing ; *Gene Transfer, Horizontal ; Plasmids/genetics ; RNA Splicing ; RNA, Bacterial/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid/*genetics ; Staphylococcus Phages/genetics ; Staphylococcus aureus/genetics ; Staphylococcus epidermidis/*genetics ; *Transformation, Bacterial
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  • 82
    Publication Date: 2008-01-19
    Description: Dietary vitamin A deficiency causes eye disease in 40 million children each year and places 140 to 250 million at risk for health disorders. Many children in sub-Saharan Africa subsist on maize-based diets. Maize displays considerable natural variation for carotenoid composition, including vitamin A precursors alpha-carotene, beta-carotene, and beta-cryptoxanthin. Through association analysis, linkage mapping, expression analysis, and mutagenesis, we show that variation at the lycopene epsilon cyclase (lcyE) locus alters flux down alpha-carotene versus beta-carotene branches of the carotenoid pathway. Four natural lcyE polymorphisms explained 58% of the variation in these two branches and a threefold difference in provitamin A compounds. Selection of favorable lcyE alleles with inexpensive molecular markers will now enable developing-country breeders to more effectively produce maize grain with higher provitamin A levels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933658/" 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/PMC2933658/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harjes, Carlos E -- Rocheford, Torbert R -- Bai, Ling -- Brutnell, Thomas P -- Kandianis, Catherine Bermudez -- Sowinski, Stephen G -- Stapleton, Ann E -- Vallabhaneni, Ratnakar -- Williams, Mark -- Wurtzel, Eleanore T -- Yan, Jianbing -- Buckler, Edward S -- S06-GM08225/GM/NIGMS NIH HHS/ -- SC1 GM081160/GM/NIGMS NIH HHS/ -- SC1 GM081160-01/GM/NIGMS NIH HHS/ -- SC1 GM081160-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jan 18;319(5861):330-3. doi: 10.1126/science.1150255.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genomic Diversity, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202289" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Breeding ; Carotenoids/*analysis/metabolism ; Crosses, Genetic ; Cryptoxanthins ; Gene Expression Regulation, Plant ; *Genetic Variation ; Haplotypes ; Intramolecular Lyases/*genetics/metabolism ; Molecular Sequence Data ; Mutagenesis ; Nutritive Value ; Polymorphism, Genetic ; Quantitative Trait Loci ; Xanthophylls/analysis/metabolism ; Zea mays/chemistry/enzymology/*genetics ; beta Carotene/analysis/metabolism
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  • 83
    Publication Date: 2008-05-24
    Description: Viruses shape microbial community structure and function by altering the fitness of their hosts and by promoting genetic exchange. The complexity of most natural ecosystems has precluded detailed studies of virus-host interactions. We reconstructed virus and host bacterial and archaeal genome sequences from community genomic data from two natural acidophilic biofilms. Viruses were matched to their hosts by analyzing spacer sequences that occur among clustered regularly interspaced short palindromic repeats (CRISPRs) that are a hallmark of virus resistance. Virus population genomic analyses provided evidence that extensive recombination shuffles sequence motifs sufficiently to evade CRISPR spacers. Only the most recently acquired spacers match coexisting viruses, which suggests that community stability is achieved by rapid but compensatory shifts in host resistance levels and virus population structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andersson, Anders F -- Banfield, Jillian F -- New York, N.Y. -- Science. 2008 May 23;320(5879):1047-50. doi: 10.1126/science.1157358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Earth and Planetary Science and Environmental Science, Policy, and Management, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497291" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Archaea/*genetics/physiology/*virology ; Archaeal Viruses/genetics/*physiology ; Bacteria/*genetics/*virology ; Bacterial Physiological Phenomena ; Bacteriophages/genetics/*physiology ; Base Sequence ; Biofilms ; DNA, Intergenic ; Ecosystem ; Genome, Archaeal ; Genome, Bacterial ; Genome, Viral ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Recombination, Genetic ; *Repetitive Sequences, Nucleic Acid ; Thermoplasmales/genetics/physiology/virology ; Viral Proteins/chemistry/genetics/physiology
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  • 84
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-01-26
    Description: The statistical methods applied to the analysis of genomic data do not account for uncertainty in the sequence alignment. Indeed, the alignment is treated as an observation, and all of the subsequent inferences depend on the alignment being correct. This may not have been too problematic for many phylogenetic studies, in which the gene is carefully chosen for, among other things, ease of alignment. However, in a comparative genomics study, the same statistical methods are applied repeatedly on thousands of genes, many of which will be difficult to align. Using genomic data from seven yeast species, we show that uncertainty in the alignment can lead to several problems, including different alignment methods resulting in different conclusions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, Karen M -- Suchard, Marc A -- Huelsenbeck, John P -- GM-069801/GM/NIGMS NIH HHS/ -- R01 GM069801/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jan 25;319(5862):473-6. doi: 10.1126/science.1151532.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Ecology, Behavior and Evolution, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18218900" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Sequence ; Base Sequence ; Computational Biology ; Evolution, Molecular ; *Genome, Fungal ; *Genomics ; Models, Statistical ; Monte Carlo Method ; Open Reading Frames ; Phylogeny ; Saccharomyces/*genetics ; Selection, Genetic ; Sequence Alignment/*methods ; Software ; Uncertainty
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  • 85
    Publication Date: 2008-09-06
    Description: Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658639/" 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/PMC2658639/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prabhakar, Shyam -- Visel, Axel -- Akiyama, Jennifer A -- Shoukry, Malak -- Lewis, Keith D -- Holt, Amy -- Plajzer-Frick, Ingrid -- Morrison, Harris -- Fitzpatrick, David R -- Afzal, Veena -- Pennacchio, Len A -- Rubin, Edward M -- Noonan, James P -- 1-F32-GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367-02/GM/NIGMS NIH HHS/ -- HG003988/HG/NHGRI NIH HHS/ -- HL066681/HL/NHLBI NIH HHS/ -- MC_U127561093/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1346-50. doi: 10.1126/science.1159974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772437" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Body Patterning/*genetics ; Conserved Sequence ; Embryonic Development ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Extremities/*embryology ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Humans ; Limb Buds/embryology/metabolism ; Macaca mulatta/genetics ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; PAX9 Transcription Factor/metabolism ; Pan troglodytes/genetics ; Selection, Genetic ; Transcription Factors/metabolism
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  • 86
    Publication Date: 2008-12-06
    Description: Female meiotic drive, in which paired chromosomes compete for access to the egg, is a potentially powerful but rarely documented evolutionary force. In interspecific monkeyflower (Mimulus) hybrids, a driving M. guttatus allele (D) exhibits a 98:2 transmission advantage via female meiosis. We show that extreme interspecific drive is most likely caused by divergence in centromere-associated repeat domains and document cytogenetic and functional polymorphism for drive within a population of M. guttatus. In conspecific crosses, D had a 58:42 transmission advantage over nondriving alternative alleles. However, individuals homozygous for the driving allele suffered reduced pollen viability. These fitness effects and molecular population genetic data suggest that balancing selection prevents the fixation or loss of D and that selfish chromosomal transmission may affect both individual fitness and population genetic load.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fishman, Lila -- Saunders, Arpiar -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1559-62. doi: 10.1126/science.1161406.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA. lila.fishman@mso.umt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056989" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Base Sequence ; Biological Evolution ; Centromere/*physiology ; Chromosome Segregation ; Chromosomes, Plant/*physiology ; Crosses, Genetic ; Genetic Markers ; Heterozygote ; Hybridization, Genetic ; Linkage Disequilibrium ; *Meiosis ; Mimulus/*genetics/physiology ; Molecular Sequence Data ; Polymorphism, Genetic ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic
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  • 87
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strasser, Bruno J -- New York, N.Y. -- Science. 2008 Oct 24;322(5901):537-8. doi: 10.1126/science.1163399.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of the History of Medicine, Yale University, New Haven, CT 06520, USA. bruno.strasser@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948528" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Databases, Nucleic Acid/*history/organization & administration ; Editorial Policies ; History, 20th Century ; History, 21st Century ; National Institutes of Health (U.S.)/*history ; National Library of Medicine (U.S.)/history ; Natural History/history ; Publishing ; United States
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  • 88
    Publication Date: 2008-07-19
    Description: Cyclic di-guanosine monophosphate (di-GMP) is a circular RNA dinucleotide that functions as a second messenger in diverse species of bacteria to trigger wide-ranging physiological changes, including cell differentiation, conversion between motile and biofilm lifestyles, and virulence gene expression. However, the mechanisms by which cyclic di-GMP regulates gene expression have remained a mystery. We found that cyclic di-GMP in many bacterial species is sensed by a riboswitch class in messenger RNA that controls the expression of genes involved in numerous fundamental cellular processes. A variety of cyclic di-GMP regulons are revealed, including some riboswitches associated with virulence gene expression, pilus formation, and flagellum biosynthesis. In addition, sequences matching the consensus for cyclic di-GMP riboswitches are present in the genome of a bacteriophage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sudarsan, N -- Lee, E R -- Weinberg, Z -- Moy, R H -- Kim, J N -- Link, K H -- Breaker, R R -- GM 068819/GM/NIGMS NIH HHS/ -- HV28186/HV/NHLBI NIH HHS/ -- R33 DK07027/DK/NIDDK NIH HHS/ -- RR19895-02/RR/NCRR NIH HHS/ -- T32GM007223/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Jul 18;321(5887):411-3. doi: 10.1126/science.1159519.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18635805" target="_blank"〉PubMed〈/a〉
    Keywords: Aptamers, Nucleotide/*metabolism ; Bacillus cereus/genetics/metabolism ; Bacteria/*genetics/metabolism ; Bacteriophages/genetics ; Base Sequence ; Clostridium difficile/genetics/metabolism ; Cyclic GMP/*analogs & derivatives/metabolism ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Ligands ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Bacterial/chemistry/*metabolism ; RNA, Messenger/chemistry/*metabolism ; Regulon ; *Second Messenger Systems ; Vibrio cholerae/genetics/metabolism
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  • 89
    Publication Date: 2008-11-22
    Description: We present single-molecule, real-time sequencing data obtained from a DNA polymerase performing uninterrupted template-directed synthesis using four distinguishable fluorescently labeled deoxyribonucleoside triphosphates (dNTPs). We detected the temporal order of their enzymatic incorporation into a growing DNA strand with zero-mode waveguide nanostructure arrays, which provide optical observation volume confinement and enable parallel, simultaneous detection of thousands of single-molecule sequencing reactions. Conjugation of fluorophores to the terminal phosphate moiety of the dNTPs allows continuous observation of DNA synthesis over thousands of bases without steric hindrance. The data report directly on polymerase dynamics, revealing distinct polymerization states and pause sites corresponding to DNA secondary structure. Sequence data were aligned with the known reference sequence to assay biophysical parameters of polymerization for each template position. Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eid, John -- Fehr, Adrian -- Gray, Jeremy -- Luong, Khai -- Lyle, John -- Otto, Geoff -- Peluso, Paul -- Rank, David -- Baybayan, Primo -- Bettman, Brad -- Bibillo, Arkadiusz -- Bjornson, Keith -- Chaudhuri, Bidhan -- Christians, Frederick -- Cicero, Ronald -- Clark, Sonya -- Dalal, Ravindra -- Dewinter, Alex -- Dixon, John -- Foquet, Mathieu -- Gaertner, Alfred -- Hardenbol, Paul -- Heiner, Cheryl -- Hester, Kevin -- Holden, David -- Kearns, Gregory -- Kong, Xiangxu -- Kuse, Ronald -- Lacroix, Yves -- Lin, Steven -- Lundquist, Paul -- Ma, Congcong -- Marks, Patrick -- Maxham, Mark -- Murphy, Devon -- Park, Insil -- Pham, Thang -- Phillips, Michael -- Roy, Joy -- Sebra, Robert -- Shen, Gene -- Sorenson, Jon -- Tomaney, Austin -- Travers, Kevin -- Trulson, Mark -- Vieceli, John -- Wegener, Jeffrey -- Wu, Dawn -- Yang, Alicia -- Zaccarin, Denis -- Zhao, Peter -- Zhong, Frank -- Korlach, Jonas -- Turner, Stephen -- R01HG003710/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):133-8. doi: 10.1126/science.1162986. Epub 2008 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pacific Biosciences, 1505 Adams Drive, Menlo Park, CA 94025, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19023044" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Consensus Sequence ; DNA/biosynthesis ; DNA, Circular/chemistry ; DNA, Single-Stranded/chemistry ; DNA-Directed DNA Polymerase/*metabolism ; Deoxyribonucleotides/metabolism ; Enzymes, Immobilized ; Fluorescent Dyes ; Kinetics ; Nanostructures ; Sequence Analysis, DNA/*methods ; Spectrometry, Fluorescence
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  • 90
    Publication Date: 2008-12-17
    Description: Might DNA sequence variation reflect germline genetic activity and underlying chromatin structure? We investigated this question using medaka (Japanese killifish, Oryzias latipes), by comparing the genomic sequences of two strains (Hd-rR and HNI) and by mapping approximately 37.3 million nucleosome cores from Hd-rR blastulae and 11,654 representative transcription start sites from six embryonic stages. We observed a distinctive approximately 200-base pair (bp) periodic pattern of genetic variation downstream of transcription start sites; the rate of insertions and deletions longer than 1 bp peaked at positions of approximately +200, +400, and +600 bp, whereas the point mutation rate showed corresponding valleys. This approximately 200-bp periodicity was correlated with the chromatin structure, with nucleosome occupancy minimized at positions 0, +200, +400, and +600 bp. These data exemplify the potential for genetic activity (transcription) and chromatin structure to contribute to molding the DNA sequence on an evolutionary time scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757552/" 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/PMC2757552/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sasaki, Shin -- Mello, Cecilia C -- Shimada, Atsuko -- Nakatani, Yoichiro -- Hashimoto, Shin-Ichi -- Ogawa, Masako -- Matsushima, Kouji -- Gu, Sam Guoping -- Kasahara, Masahiro -- Ahsan, Budrul -- Sasaki, Atsushi -- Saito, Taro -- Suzuki, Yutaka -- Sugano, Sumio -- Kohara, Yuji -- Takeda, Hiroyuki -- Fire, Andrew -- Morishita, Shinichi -- R01 GM037706/GM/NIGMS NIH HHS/ -- R01 GM037706-24/GM/NIGMS NIH HHS/ -- R01 GM37706/GM/NIGMS NIH HHS/ -- T32 CA009151/CA/NCI NIH HHS/ -- T32 CA09151/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):401-4. doi: 10.1126/science.1163183. Epub 2008 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, 277-0882, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19074313" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Base Sequence ; Chromatin/*physiology/ultrastructure ; DNA/chemistry/*genetics ; DNA Repair ; *Genetic Variation ; Genome ; INDEL Mutation ; Mutagenesis ; Mutation ; Nucleosomes/*physiology/ultrastructure ; Oryzias/embryology/*genetics ; Point Mutation ; Promoter Regions, Genetic ; *Transcription Initiation Site ; Transcription, Genetic
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  • 91
    Publication Date: 2008-04-05
    Description: The timing of the first human migration into the Americas and its relation to the appearance of the Clovis technological complex in North America at about 11,000 to 10,800 radiocarbon years before the present (14C years B.P.) remains contentious. We establish that humans were present at Paisley 5 Mile Point Caves, in south-central Oregon, by 12,300 14C years B.P., through the recovery of human mitochondrial DNA (mtDNA) from coprolites, directly dated by accelerator mass spectrometry. The mtDNA corresponds to Native American founding haplogroups A2 and B2. The dates of the coprolites are 〉1000 14C years earlier than currently accepted dates for the Clovis complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, M Thomas P -- Jenkins, Dennis L -- Gotherstrom, Anders -- Naveran, Nuria -- Sanchez, Juan J -- Hofreiter, Michael -- Thomsen, Philip Francis -- Binladen, Jonas -- Higham, Thomas F G -- Yohe, Robert M 2nd -- Parr, Robert -- Cummings, Linda Scott -- Willerslev, Eske -- New York, N.Y. -- Science. 2008 May 9;320(5877):786-9. doi: 10.1126/science.1154116. Epub 2008 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Ancient Genetics, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18388261" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Canidae/genetics ; *DNA, Mitochondrial ; *Emigration and Immigration ; *Feces ; *Fossils ; Humans ; Molecular Sequence Data ; North America ; Oregon ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Sciuridae/genetics ; Sigmodontinae/genetics ; Time
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  • 92
    Publication Date: 2008-10-11
    Description: The high photostability of DNA is commonly attributed to efficient radiationless electronic relaxation processes. We used femtosecond time-resolved fluorescence spectroscopy to reveal that the ensuing dynamics are strongly dependent on base sequence and are also affected by higher-order structure. Excited electronic state lifetimes in dG-doped d(A)20 single-stranded DNA and dG.dC-doped d(A)20.d(T)20 double-stranded DNA decrease sharply with the substitution of only a few bases. In duplexes containing d(AGA).d(TCT) or d(AG).d(TC) repeats, deactivation of the fluorescing states occurs on the subpicosecond time scale, but the excited-state lifetimes increase again in extended d(G) runs. The results point at more complex and molecule-specific photodynamics in native DNA than may be evident in simpler model systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwalb, Nina K -- Temps, Friedrich -- New York, N.Y. -- Science. 2008 Oct 10;322(5899):243-5. doi: 10.1126/science.1161651.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Physikalische Chemie, Christian-Albrechts-Universitat zu Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany. schwalb@phc.uni-kiel.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18845751" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Circular Dichroism ; DNA/*chemistry ; DNA, Single-Stranded/chemistry ; Hydrogen Bonding ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/*chemistry ; Photochemistry ; Purines/chemistry ; Pyrimidines/chemistry ; Spectrometry, Fluorescence
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  • 93
    Publication Date: 2008-08-16
    Description: Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brouns, Stan J J -- Jore, Matthijs M -- Lundgren, Magnus -- Westra, Edze R -- Slijkhuis, Rik J H -- Snijders, Ambrosius P L -- Dickman, Mark J -- Makarova, Kira S -- Koonin, Eugene V -- van der Oost, John -- New York, N.Y. -- Science. 2008 Aug 15;321(5891):960-4. doi: 10.1126/science.1159689.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18703739" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriophage lambda/*genetics/*growth & development ; Base Sequence ; DNA, Intergenic ; DNA, Viral/metabolism ; Escherichia coli/genetics/metabolism ; Escherichia coli K12/*genetics/metabolism/*virology ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Genes, Bacterial ; Molecular Sequence Data ; RNA Precursors/metabolism ; RNA, Bacterial/*genetics/metabolism ; RNA, Guide/genetics/metabolism ; *Repetitive Sequences, Nucleic Acid ; Transcription, Genetic ; Viral Plaque Assay
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  • 94
    Publication Date: 2008-08-30
    Description: Plants use many means to attract pollinators, including visual cues and odor. We investigated how nonpigment floral chemistry influences nectar removal, floral visitation, florivory, rates of outcrossing, and fitness through both male and female functions. We blocked expression of biosynthetic genes of the dominant floral attractant [benzyl acetone (Nachal1)] and nectar repellent [nicotine (Napmt1/2)] in all combinations in the native tobacco Nicotiana attenuata and measured their effects on plants in their native habitat. Both repellent and attractant were required to maximize capsule production and seed siring in emasculated flowers and flower visitation by native pollinators, whereas nicotine reduced florivory and nectar robbing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kessler, Danny -- Gase, Klaus -- Baldwin, Ian T -- New York, N.Y. -- Science. 2008 Aug 29;321(5893):1200-2. doi: 10.1126/science.1160072.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Ecology, Max-Planck-Institute for Chemical Ecology, Hans-Knoll-Strasse 8, DE-07745 Jena, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18755975" target="_blank"〉PubMed〈/a〉
    Keywords: Acetone/*analogs & derivatives/metabolism ; Acyltransferases/genetics ; Animals ; Base Sequence ; Birds/*physiology ; Cloning, Molecular ; Flowers/chemistry/*physiology ; Methyltransferases/genetics ; Molecular Sequence Data ; Nicotine/*metabolism ; *Odors ; Plants, Genetically Modified ; Pollen/physiology ; RNA Interference ; Reproduction ; Seeds ; Tobacco/genetics/*physiology ; Transformation, Genetic
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  • 95
    Publication Date: 2008-03-22
    Description: Hermaphroditic organisms avoid inbreeding by a system of self-incompatibility (SI). A primitive chordate (ascidian) Ciona intestinalis is an example of such an organism, but the molecular mechanism underlying its SI system is not known. Here, we show that the SI system is governed by two gene loci that act cooperatively. Each locus contains a tightly linked pair of polycystin 1-related receptor (s-Themis) and fibrinogen-like ligand (v-Themis) genes, the latter of which is located in the first intron of s-Themis but transcribed in the opposite direction. These genes may encode male- and female-side self-recognition molecules. The SI system of C. intestinalis has a similar framework to that of flowering plants but utilizing different molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harada, Yoshito -- Takagaki, Yuhei -- Sunagawa, Masahiko -- Saito, Takako -- Yamada, Lixy -- Taniguchi, Hisaaki -- Shoguchi, Eiichi -- Sawada, Hitoshi -- New York, N.Y. -- Science. 2008 Apr 25;320(5875):548-50. doi: 10.1126/science.1152488. Epub 2008 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sugashima Marine Biological Laboratory, Graduate School of Science, Nagoya University, Sugashima, Toba 517-0004, Japan. yharada@bio.nagoya-u.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18356489" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Ciona intestinalis/*genetics/*physiology ; Disorders of Sex Development ; Female ; Fertility ; Fertilization ; *Genes ; Male ; Molecular Sequence Data ; Ovum/metabolism/physiology ; Spermatozoa/physiology ; *TRPP Cation Channels/chemistry
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  • 96
    Publication Date: 2008-09-13
    Description: Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor-binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor-binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717767/" 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/PMC3717767/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Michael D -- Barbosa-Morais, Nuno L -- Schmidt, Dominic -- Conboy, Caitlin M -- Vanes, Lesley -- Tybulewicz, Victor L J -- Fisher, Elizabeth M C -- Tavare, Simon -- Odom, Duncan T -- 080174/Wellcome Trust/United Kingdom -- 15603/Cancer Research UK/United Kingdom -- 202218/European Research Council/International -- A15603/Cancer Research UK/United Kingdom -- G0601056/Medical Research Council/United Kingdom -- MC_U117527252/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):434-8. doi: 10.1126/science.1160930. Epub 2008 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18787134" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Nucleus/metabolism ; Chromatin Assembly and Disassembly ; Chromatin Immunoprecipitation ; Chromosomes, Human, Pair 21/*genetics/metabolism ; Disease Models, Animal ; Down Syndrome/genetics ; *Gene Expression Regulation ; Hepatocyte Nuclear Factors/*metabolism ; Hepatocytes/*metabolism ; Histones/metabolism ; Humans ; Methylation ; Mice ; Oligonucleotide Array Sequence Analysis ; *Regulatory Sequences, Nucleic Acid ; Species Specificity ; Transcription Initiation Site ; *Transcription, Genetic
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  • 97
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-03-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Endy, Drew -- New York, N.Y. -- Science. 2008 Feb 29;319(5867):1196-7. doi: 10.1126/science.1155749.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. endy@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18309068" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Cloning, Molecular ; Conserved Sequence ; DNA, Bacterial/*chemical synthesis ; *Genome, Bacterial ; Genomics/*methods ; Mycoplasma genitalium/*genetics ; Oligodeoxyribonucleotides/chemical synthesis ; Sequence Analysis, DNA
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  • 98
    Publication Date: 2008-04-26
    Description: We have assembled a proteome map for Arabidopsis thaliana from high-density, organ-specific proteome catalogs that we generated for different organs, developmental stages, and undifferentiated cultured cells. We matched 86,456 unique peptides to 13,029 proteins and provide expression evidence for 57 gene models that are not represented in the TAIR7 protein database. Analysis of the proteome identified organ-specific biomarkers and allowed us to compile an organ-specific set of proteotypic peptides for 4105 proteins to facilitate targeted quantitative proteomics surveys. Quantitative information for the identified proteins was used to establish correlations between transcript and protein accumulation in different plant organs. The Arabidopsis proteome map provides information about genome activity and proteome assembly and is available as a resource for plant systems biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baerenfaller, Katja -- Grossmann, Jonas -- Grobei, Monica A -- Hull, Roger -- Hirsch-Hoffmann, Matthias -- Yalovsky, Shaul -- Zimmermann, Philip -- Grossniklaus, Ueli -- Gruissem, Wilhelm -- Baginsky, Sacha -- New York, N.Y. -- Science. 2008 May 16;320(5878):938-41. doi: 10.1126/science.1157956. Epub 2008 Apr 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Sciences, ETH (Swiss Federal Institute of Technology) Zurich, Universitatstrasse 2, 8092 Zurich, Switzerland. kbaerenfaller@ethz.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18436743" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Sequence ; Arabidopsis/*chemistry/cytology/*genetics/physiology ; Arabidopsis Proteins/*analysis/chemistry/genetics ; Base Sequence ; Biomarkers/analysis ; Cells, Cultured ; Computational Biology ; Databases, Genetic ; Flowers/chemistry/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; *Genome, Plant ; Models, Genetic ; Molecular Sequence Data ; Peptides/analysis/chemistry ; Plant Roots/chemistry/genetics ; Proteome/*analysis ; *Proteomics ; Seeds/chemistry/genetics ; Transcription, Genetic
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  • 99
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-01-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rokas, Antonis -- New York, N.Y. -- Science. 2008 Jan 25;319(5862):416-7. doi: 10.1126/science.1153156.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Vanderbilt University, VU Station B 35-1634, Nashville, TN 37235, USA. antonis.rokas@vanderbilt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18218881" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Sequence ; Base Sequence ; Bias (Epidemiology) ; Computational Biology ; Evolution, Molecular ; *Genome, Fungal ; *Genomics ; Phylogeny ; Saccharomyces/*genetics ; Sequence Alignment/*methods/standards ; Software ; Uncertainty
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  • 100
    Publication Date: 2008-04-12
    Description: Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA (dsRNA) as a defense against viral infection. We identified endogenous siRNAs (endo-siRNAs), 21 nucleotides in length, that correspond to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. We also detected endo-siRNAs complementary to messenger RNAs (mRNAs); these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs requires the siRNA-generating ribonuclease Dicer-2 and the RNAi effector protein Argonaute2 (Ago2). We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953241/" 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/PMC2953241/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghildiyal, Megha -- Seitz, Herve -- Horwich, Michael D -- Li, Chengjian -- Du, Tingting -- Lee, Soohyun -- Xu, Jia -- Kittler, Ellen L W -- Zapp, Maria L -- Weng, Zhiping -- Zamore, Phillip D -- F30 AG030283-02/AG/NIA NIH HHS/ -- F30 AG030283-03/AG/NIA NIH HHS/ -- F30 AG030283-04/AG/NIA NIH HHS/ -- F30AG030283/AG/NIA NIH HHS/ -- GM080625/GM/NIGMS NIH HHS/ -- GM62862/GM/NIGMS NIH HHS/ -- GM65236/GM/NIGMS NIH HHS/ -- HG003367/HG/NHGRI NIH HHS/ -- P30 AI042845/AI/NIAID NIH HHS/ -- P30 AI042845-119008/AI/NIAID NIH HHS/ -- R01 AI043208/AI/NIAID NIH HHS/ -- R01 AI043208-08/AI/NIAID NIH HHS/ -- R01 GM062862/GM/NIGMS NIH HHS/ -- R01 GM062862-08/GM/NIGMS NIH HHS/ -- R01 GM062862-09/GM/NIGMS NIH HHS/ -- R01 GM065236/GM/NIGMS NIH HHS/ -- R01 GM065236-07/GM/NIGMS NIH HHS/ -- R01 GM065236-08/GM/NIGMS NIH HHS/ -- R01 GM080625/GM/NIGMS NIH HHS/ -- R01 GM080625-02/GM/NIGMS NIH HHS/ -- R01 GM080625-03/GM/NIGMS NIH HHS/ -- R01 HG003367/HG/NHGRI NIH HHS/ -- R01 HG003367-03/HG/NHGRI NIH HHS/ -- R37 GM062862/GM/NIGMS NIH HHS/ -- R37 GM062862-11/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 May 23;320(5879):1077-81. doi: 10.1126/science.1157396. Epub 2008 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18403677" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Base Sequence ; Cell Line ; *DNA Transposable Elements ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*genetics/metabolism ; Mutation ; RNA Helicases/genetics/metabolism ; *RNA Interference ; RNA, Double-Stranded/metabolism ; RNA, Messenger/*genetics ; RNA, Small Interfering/*genetics/*metabolism ; RNA-Induced Silencing Complex/genetics/metabolism ; Retroelements ; Ribonuclease III
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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