ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Set7 mediated interactions regulate transcriptional networks in embryonic stem cells (2016)
    Oxford University Press
    Details
    Publication Date: 2016-11-01
    Description: Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell differentiation remains poorly understood. We show Set7 expression is increased during mouse embryonic stem cell (mESC) differentiation and is regulated by the pluripotency factors, Oct4 and Sox2. Transcriptional network analyses reveal smooth muscle (SM) associated genes are subject to Set7-mediated regulation. Furthermore, pharmacological inhibition of Set7 activity confirms this regulation. We observe Set7-mediated modification of serum response factor (SRF) and mono-methylation of histone H4 lysine 4 (H3K4me1) regulate gene expression. We conclude the broad substrate specificity of Set7 serves to control key transcriptional networks in embryonic stem cells.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Translocation and deletion breakpoints in cancer genomes are associated with potential non-B DNA-forming sequences (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-09
    Description: Gross chromosomal rearrangements (including translocations, deletions, insertions and duplications) are a hallmark of cancer genomes and often create oncogenic fusion genes. An obligate step in the generation of such gross rearrangements is the formation of DNA double-strand breaks (DSBs). Since the genomic distribution of rearrangement breakpoints is non-random, intrinsic cellular factors may predispose certain genomic regions to breakage. Notably, certain DNA sequences with the potential to fold into secondary structures [potential non-B DNA structures (PONDS); e.g. triplexes, quadruplexes, hairpin/cruciforms, Z-DNA and single-stranded looped-out structures with implications in DNA replication and transcription] can stimulate the formation of DNA DSBs. Here, we tested the postulate that these DNA sequences might be found at, or in close proximity to, rearrangement breakpoints. By analyzing the distribution of PONDS-forming sequences within ±500 bases of 19 947 translocation and 46 365 sequence-characterized deletion breakpoints in cancer genomes, we find significant association between PONDS-forming repeats and cancer breakpoints. Specifically, (AT) n , (GAA) n and (GAAA) n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints. Translocation breakpoints near PONDS-forming repeats also recur in different individuals and patient tumor samples. Hence, PONDS-forming sequences represent an intrinsic risk factor for genomic rearrangements in cancer genomes.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    An integrative approach to predicting the functional effects of non-coding and coding sequence variation (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-12
    Description: Motivation: Technological advances have enabled the identification of an increasingly large spectrum of single nucleotide variants within the human genome, many of which may be associated with monogenic disease or complex traits. Here, we propose an integrative approach, named FATHMM-MKL, to predict the functional consequences of both coding and non-coding sequence variants. Our method utilizes various genomic annotations, which have recently become available, and learns to weight the significance of each component annotation source. Results: We show that our method outperforms current state-of-the-art algorithms, CADD and GWAVA, when predicting the functional consequences of non-coding variants. In addition, FATHMM-MKL is comparable to the best of these algorithms when predicting the impact of coding variants. The method includes a confidence measure to rank order predictions. Availability and implementation: The FATHMM-MKL webserver is available at: http://fathmm.biocompute.org.uk Contact: H.Shihab@bristol.ac.uk or Mark.Rogers@bristol.ac.uk or C.Campbell@bristol.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    DDIG-in: detecting disease-causing genetic variations due to frameshifting indels and nonsense mutations employing sequence and structural properties at nucleotide and protein levels (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-12
    Description: Motivation : Frameshifting (FS) indels and nonsense (NS) variants disrupt the protein-coding sequence downstream of the mutation site by changing the reading frame or introducing a premature termination codon, respectively. Despite such drastic changes to the protein sequence, FS indels and NS variants have been discovered in healthy individuals. How to discriminate disease-causing from neutral FS indels and NS variants is an understudied problem. Results: We have built a machine learning method called DDIG-in (FS) based on real human genetic variations from the Human Gene Mutation Database (inherited disease-causing) and the 1000 Genomes Project (GP) (putatively neutral). The method incorporates both sequence and predicted structural features and yields a robust performance by 10-fold cross-validation and independent tests on both FS indels and NS variants. We showed that human-derived NS variants and FS indels derived from animal orthologs can be effectively employed for independent testing of our method trained on human-derived FS indels. DDIG-in (FS) achieves a Matthews correlation coefficient (MCC) of 0.59, a sensitivity of 86%, and a specificity of 72% for FS indels. Application of DDIG-in (FS) to NS variants yields essentially the same performance (MCC of 0.43) as a method that was specifically trained for NS variants. DDIG-in (FS) was shown to make a significant improvement over existing techniques. Availability and implementation : The DDIG-in web-server for predicting NS variants, FS indels, and non-frameshifting (NFS) indels is available at http://sparks-lab.org/ddig . Contact : yaoqi.zhou@griffith.edu.au Supplementary information : Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    GEneSTATION 1.0: a synthetic resource of diverse evolutionary and functional genomic data for studying the evolution of pregnancy-associated tissues and phenotypes (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-07
    Description: Mammalian gestation and pregnancy are fast evolving processes that involve the interaction of the fetal, maternal and paternal genomes. Version 1.0 of the GEneSTATION database ( http://genestation.org ) integrates diverse types of omics data across mammals to advance understanding of the genetic basis of gestation and pregnancy-associated phenotypes and to accelerate the translation of discoveries from model organisms to humans. GEneSTATION is built using tools from the Generic Model Organism Database project, including the biology-aware database CHADO, new tools for rapid data integration, and algorithms that streamline synthesis and user access. GEneSTATION contains curated life history information on pregnancy and reproduction from 23 high-quality mammalian genomes. For every human gene, GEneSTATION contains diverse evolutionary (e.g. gene age, population genetic and molecular evolutionary statistics), organismal (e.g. tissue-specific gene and protein expression, differential gene expression, disease phenotype), and molecular data types (e.g. Gene Ontology Annotation, protein interactions), as well as links to many general (e.g. Entrez, PubMed) and pregnancy disease-specific (e.g. PTBgene, dbPTB) databases. By facilitating the synthesis of diverse functional and evolutionary data in pregnancy-associated tissues and phenotypes and enabling their quick, intuitive, accurate and customized meta-analysis, GEneSTATION provides a novel platform for comprehensive investigation of the function and evolution of mammalian pregnancy.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres (2015)
    Oxford University Press
    Details
    Publication Date: 2015-10-23
    Description: Dominant mutations in TPM3 , encoding α-tropomyosin slow , cause a congenital myopathy characterized by generalized muscle weakness. Here, we used a multidisciplinary approach to investigate the mechanism of muscle dysfunction in 12 TPM3 -myopathy patients. We confirm that slow myofibre hypotrophy is a diagnostic hallmark of TPM3 -myopathy, and is commonly accompanied by skewing of fibre-type ratios (either slow or fast fibre predominance). Patient muscle contained normal ratios of the three tropomyosin isoforms and normal fibre-type expression of myosins and troponins. Using 2D-PAGE, we demonstrate that mutant α-tropomyosin slow was expressed, suggesting muscle dysfunction is due to a dominant-negative effect of mutant protein on muscle contraction. Molecular modelling suggested mutant α-tropomyosin slow likely impacts actin–tropomyosin interactions and, indeed, co-sedimentation assays showed reduced binding of mutant α-tropomyosin slow (R168C) to filamentous actin. Single fibre contractility studies of patient myofibres revealed marked slow myofibre specific abnormalities. At saturating [Ca 2+ ] (pCa 4.5), patient slow fibres produced only 63% of the contractile force produced in control slow fibres and had reduced acto-myosin cross-bridge cycling kinetics. Importantly, due to reduced Ca 2+ -sensitivity, at sub-saturating [Ca 2+ ] (pCa 6, levels typically released during in vivo contraction) patient slow fibres produced only 26% of the force generated by control slow fibres. Thus, weakness in TPM3 -myopathy patients can be directly attributed to reduced slow fibre force at physiological [Ca 2+ ], and impaired acto-myosin cross-bridge cycling kinetics. Fast myofibres are spared; however, they appear to be unable to compensate for slow fibre dysfunction. Abnormal Ca 2+ -sensitivity in TPM3 -myopathy patients suggests Ca 2+ -sensitizing drugs may represent a useful treatment for this condition.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    On the relevance of chaos for halo stars in the solar neighbourhood (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-27
    Description: We show that diffusion due to chaotic mixing in the neighbourhood of the Sun may not be as relevant as previously suggested in erasing phase space signatures of past Galactic accretion events. For this purpose, we analyse solar neighbourhood-like volumes extracted from cosmological simulations that naturally account for chaotic orbital behaviour induced by the strongly triaxial and cuspy shape of the resulting dark matter haloes, among other factors. In the approximation of an analytical static triaxial model, our results show that a large fraction of stellar halo particles in such local volumes have chaos onset times (i.e. the time-scale at which stars commonly associated with chaotic orbits will exhibit their chaotic behaviour) significantly larger than a Hubble time. Furthermore, particles that do present a chaotic behaviour within a Hubble time do not exhibit significant diffusion in phase space.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Making Sustainability Tangible: Land O'Lakes and the Dairy Supply Chain (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-31
    Description: This case study examines the challenges of implementing a vaguely defined concept called sustainability in a large organization that also has a cooperative structure. Stakeholder theory is described and applied to a multinational dairy firm. The case firm, Land O'Lakes, must balance the needs of multiple constituencies: the general public, employees, cooperative members, external funding organizations, and the management team. One challenge is to define sustainability for the entire dairy industry. The case discusses the strategies used by firms in developing a sustainability response where the tradeoffs between different strategies are between credibility and autonomy and using an industry rather than a firm-level response.
    Keywords: L15 - Information and Product Quality ; Standardization and Compatibility, L66 - Food ; Beverages ; Cosmetics ; Tobacco ; Wine and Spirits, M14 - Corporate Culture ; Social Responsibility, Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    On the relevance of chaos for halo stars in the solar neighbourhood (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-05
    Description: We show that diffusion due to chaotic mixing in the neighbourhood of the Sun may not be as relevant as previously suggested in erasing phase space signatures of past Galactic accretion events. For this purpose, we analyse solar neighbourhood-like volumes extracted from cosmological simulations that naturally account for chaotic orbital behaviour induced by the strongly triaxial and cuspy shape of the resulting dark matter haloes, among other factors. In the approximation of an analytical static triaxial model, our results show that a large fraction of stellar halo particles in such local volumes have chaos onset times (i.e. the time-scale at which stars commonly associated with chaotic orbits will exhibit their chaotic behaviour) significantly larger than a Hubble time. Furthermore, particles that do present a chaotic behaviour within a Hubble time do not exhibit significant diffusion in phase space.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Genome-Wide Biases in the Rate and Molecular Spectrum of Spontaneous Mutations in Vibrio cholerae and Vibrio fischeri (2017)
    Oxford University Press
    Details
    Publication Date: 2017-01-05
    Description: The vast diversity in nucleotide composition and architecture among bacterial genomes may be partly explained by inherent biases in the rates and spectra of spontaneous mutations. Bacterial genomes with multiple chromosomes are relatively unusual but some are relevant to human health, none more so than the causative agent of cholera, Vibrio cholerae . Here, we present the genome-wide mutation spectra in wild-type and mismatch repair (MMR) defective backgrounds of two Vibrio species, the low-%GC squid symbiont V. fischeri and the pathogen V. cholerae , collected under conditions that greatly minimize the efficiency of natural selection. In apparent contrast to their high diversity in nature, both wild-type V. fischeri and V. cholerae have among the lowest rates for base-substitution mutations (bpsms) and insertion–deletion mutations (indels) that have been measured, below 10 – 3 /genome/generation. Vibrio fischeri and V. cholerae have distinct mutation spectra, but both are AT-biased and produce a surprising number of multi-nucleotide indels. Furthermore, the loss of a functional MMR system caused the mutation spectra of these species to converge, implying that the MMR system itself contributes to species-specific mutation patterns. Bpsm and indel rates varied among genome regions, but do not explain the more rapid evolutionary rates of genes on chromosome 2, which likely result from weaker purifying selection. More generally, the very low mutation rates of Vibrio species correlate inversely with their immense population sizes and suggest that selection may not only have maximized replication fidelity but also optimized other polygenic traits relative to the constraints of genetic drift.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...