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  • Articles  (205)
  • Oxford University Press  (205)
  • Biology  (201)
  • Mathematics  (4)
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  • Articles  (205)
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  • 1
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    CVD: the intestinal crypt/villus in situ hybridization database (2004)
    Oxford University Press
    Details
    Publication Date: 2004-02-10
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 2
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    Diet of seals in the Baltic Sea region: a synthesis of published and new data from 1968 to 2013 (2018)
    Oxford University Press
    Details
    Publication Date: 2018-11-15
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press on behalf of International Council for the Exploration of the Sea.
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  • 3
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    TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data (2016)
    Oxford University Press
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    Publication Date: 2016-05-06
    Description: The Cancer Genome Atlas (TCGA) research network has made public a large collection of clinical and molecular phenotypes of more than 10 000 tumor patients across 33 different tumor types. Using this cohort, TCGA has published over 20 marker papers detailing the genomic and epigenomic alterations associated with these tumor types. Although many important discoveries have been made by TCGA's research network, opportunities still exist to implement novel methods, thereby elucidating new biological pathways and diagnostic markers. However, mining the TCGA data presents several bioinformatics challenges, such as data retrieval and integration with clinical data and other molecular data types (e.g. RNA and DNA methylation). We developed an R/Bioconductor package called TCGAbiolinks to address these challenges and offer bioinformatics solutions by using a guided workflow to allow users to query, download and perform integrative analyses of TCGA data. We combined methods from computer science and statistics into the pipeline and incorporated methodologies developed in previous TCGA marker studies and in our own group. Using four different TCGA tumor types (Kidney, Brain, Breast and Colon) as examples, we provide case studies to illustrate examples of reproducibility, integrative analysis and utilization of different Bioconductor packages to advance and accelerate novel discoveries.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Secondary coenzyme Q10 deficiency and oxidative stress in cultured fibroblasts from patients with riboflavin responsive multiple Acyl-CoA dehydrogenation deficiency (2013)
    Oxford University Press
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    Publication Date: 2013-09-08
    Description: Coenzyme Q10 (CoQ10) is essential for the energy production of the cells and as an electron transporter in the mitochondrial respiratory chain. CoQ10 links the mitochondrial fatty acid β-oxidation to the respiratory chain by accepting electrons from electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). Recently, it was shown that a group of patients with the riboflavin responsive form of multiple acyl-CoA dehydrogenation deficiency (RR-MADD) carrying inherited amino acid variations in ETF-QO also had secondary CoQ10 deficiency with beneficial effects of CoQ10 treatment, thus adding RR-MADD to an increasing number of diseases involving secondary CoQ10 deficiency. In this study, we show that moderately decreased CoQ10 levels in fibroblasts from six unrelated RR-MADD patients were associated with increased levels of mitochondrial reactive oxygen species (ROS). Treatment with CoQ10, but not with riboflavin, could normalize the CoQ10 level and decrease the level of ROS in the patient cells. Additionally, riboflavin-depleted control fibroblasts showed moderate CoQ10 deficiency, but not increased mitochondrial ROS, indicating that variant ETF-QO proteins and not CoQ10 deficiency are the causes of mitochondrial ROS production in the patient cells. Accordingly, the corresponding variant Rhodobacter sphaeroides ETF-QO proteins, when overexpressed in vitro , bind a CoQ10 pseudosubstrate, Q10Br, less tightly than the wild-type ETF-QO protein, suggesting that molecular oxygen can get access to the electrons in the misfolded ETF-QO protein, thereby generating superoxide and oxidative stress, which can be reversed by CoQ10 treatment.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 5
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    PharmacoGx: an R package for analysis of large pharmacogenomic datasets (2016)
    Oxford University Press
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    Publication Date: 2016-04-08
    Description: : Pharmacogenomics holds great promise for the development of biomarkers of drug response and the design of new therapeutic options, which are key challenges in precision medicine. However, such data are scattered and lack standards for efficient access and analysis, consequently preventing the realization of the full potential of pharmacogenomics. To address these issues, we implemented PharmacoGx , an easy-to-use, open source package for integrative analysis of multiple pharmacogenomic datasets. We demonstrate the utility of our package in comparing large drug sensitivity datasets, such as the Genomics of Drug Sensitivity in Cancer and the Cancer Cell Line Encyclopedia. Moreover, we show how to use our package to easily perform Connectivity Map analysis. With increasing availability of drug-related data, our package will open new avenues of research for meta-analysis of pharmacogenomic data. Availability and implementation : PharmacoGx is implemented in R and can be easily installed on any system. The package is available from CRAN and its source code is available from GitHub. Contact : bhaibeka@uhnresearch.ca or benjamin.haibe.kains@utoronto.ca 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
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  • 6
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    The repABC Plasmids with Quorum-Regulated Transfer Systems in Members of the Rhizobiales Divide into Two Structurally and Separately Evolving Groups (2015)
    Oxford University Press
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    Publication Date: 2015-12-28
    Description: The large repABC plasmids of the order Rhizobiales with Class I quorum-regulated conjugative transfer systems often define the nature of the bacterium that harbors them. These otherwise diverse plasmids contain a core of highly conserved genes for replication and conjugation raising the question of their evolutionary relationships. In an analysis of 18 such plasmids these elements fall into two organizational classes, Group I and Group II, based on the sites at which cargo DNA is located. Cladograms constructed from proteins of the transfer and quorum-sensing components indicated that those of the Group I plasmids, while coevolving, have diverged from those coevolving proteins of the Group II plasmids. Moreover, within these groups the phylogenies of the proteins usually occupy similar, if not identical, tree topologies. Remarkably, such relationships were not seen among proteins of the replication system; although RepA and RepB coevolve, RepC does not. Nor do the replication proteins coevolve with the proteins of the transfer and quorum-sensing systems. Functional analysis was mostly consistent with phylogenies. TraR activated promoters from plasmids within its group, but not between groups and dimerized with TraR proteins from within but not between groups. However, oriT sequences, which are highly conserved, were processed by the transfer system of plasmids regardless of group. We conclude that these plasmids diverged into two classes based on the locations at which cargo DNA is inserted, that the quorum-sensing and transfer functions are coevolving within but not between the two groups, and that this divergent evolution extends to function.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Function of the N-terminal segment of the RecA-dependent nuclease Ref (2015)
    Oxford University Press
    Details
    Publication Date: 2015-02-18
    Description: The bacteriophage P1 Ref (recombination enhancement function) protein is a RecA-dependent, HNH endonuclease. It can be directed to create targeted double-strand breaks within a displacement loop formed by RecA. The 76 amino acid N-terminal region of Ref is positively charged (25/76 amino acid residues) and inherently unstructured in solution. Our investigation of N-terminal truncation variants shows this region is required for DNA binding, contains a Cys involved in incidental dimerization and is necessary for efficient Ref-mediated DNA cleavage. Specifically, Ref N-terminal truncation variants lacking between 21 and 47 amino acids are more effective RecA-mediated targeting nucleases. We propose a more refined set of options for the Ref-mediated cleavage mechanism, featuring the N-terminal region as an anchor for at least one of the DNA strand cleavage events.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Genotoxic effects of two-generational selenium deficiency in mouse somatic and testicular cells (2015)
    Oxford University Press
    Details
    Publication Date: 2015-02-17
    Description: Many studies have investigated genotoxic effects of high Se diets but very few have addressed the genotoxicity of Se deprivation and its consequences in germ cells and none in somatic cells. To address these data gaps, C57BL/6 male mice were subjected to Se deprivation starting in the parental generation, i.e. before conception. Mice were given a diet of either low (0.01mg Se/kg diet) or normal (0.23mg Se/kg diet) Se content. Ogg1-deficient ( Ogg1 –/– ) mice were used as a sensitive model towards oxidative stress due to their reduced capacity to repair oxidised purines. Ogg1 –/– mice also mimic the repair characteristics of human post-meiotic male germ cells which have a reduced ability to repair such lesions. The genotoxicity of Se deficiency was addressed by measuring DNA lesions with the alkaline single cell gel electrophoresis (+ Fpg to detect oxidised DNA lesions) in somatic cells (nucleated blood cells and lung cells) and male germ cells (testicular cells). Total Se concentration in liver and GPx activity in plasma and testicular cells were measured. Gene mutation was evaluated by an erythrocyte-based Pig-a assay. We found that Se deprivation of F1 from their conception and until early adulthood led to the induction of DNA lesions in testicular and lung cells expressed as significantly increased levels of DNA lesions, irrespective of the mouse genotype. In blood cells, Se levels did not appear to affect DNA lesions or mutant cell frequencies. The results suggest that the testis was the most sensitive tissue. Thus, genotoxicity induced by the low Se diet in the spermatozoal genome has potential implications for the offspring.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 9
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    Evolutionary and ecological constraints of fish spawning habitats (2015)
    Oxford University Press
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    Publication Date: 2015-01-20
    Description: For marine fish, the choice of the spawning location may be the only means to fulfil the dual needs of surviving from the egg to juvenile stage and dispersing across different habitats while minimizing predation and maximizing food intake. In this article, we review the factors that affect the choice of fish spawning habitats and propose a framework to distinguish between ecological and evolutionary constraints. We define the former as the boundaries for phenotypically plastic responses to environmental change, in this case the ability of specific genotypes to change their spawning habitat. Processes such as predation, starvation, or aberrant dispersal typically limit the amount of variability in spawning habitat that fish may undergo from 1 year to the next, and thus regulate the intensity of ecological constraints. Evolutionary constraints, on the other hand, refer to aspects of the genetic make-up that limit the rate and direction of adaptive genetic changes in a population across generations; that is, the potential for micro-evolutionary change. Thus, their intensity is inversely related to the level of genetic diversity associated with traits that regulate spawning and developmental phases. We argue that fisheries oceanographers are well aware of, and more deeply focused on, the former set of constraints, while evolutionary biologists are more deeply focused on the latter set of constraints. Our proposed framework merges these two viewpoints and provides new insight to study fish habitat selection and adaptability to environmental changes.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press
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  • 10
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    Movements and site fidelity of harbour seals (Phoca vitulina) in Kattegat, Denmark, with implications for the epidemiology of the phocine distemper virus (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-12
    Description: Dietz, R., Teilmann, J., Andersen S. M. Rigét, F., and Olsen, M. T. 2013. Movements and site fidelity of harbour seals ( Phoca vitulina ) in Kattegat, Denmark, with implications for the epidemiology of the phocine distemper virus. – ICES Journal of Marine Science, 70:186–195. Twenty-seven harbour seals were caught and tagged at the island of Anholt in central Kattegat, Denmark, the epicentre of the phocine distemper virus (PDV) outbreaks in 1988 and 2002 that killed 50–60% of the populations. The satellite tagging shows that harbour seals from Anholt moved widely across Kattegat with a maximum distance of 249 km from the tagging haul-out site. Overall, females travelled over a wider area compared with males [90% kernel home range (KHR) females, 5189 km 2 ; males, 3293 km 2 ). KHR calculated for yearlings (6414 km 2 ) is larger than for subadults (2534 km 2 ), which again is larger than for adult seals (1713 km 2 ), showing a strong site fidelity, indicating limited gene flow between haul-out sites. Distances moved and home range sizes increased across autumn, peaked in February–March, and decreased through spring. During the breeding season in spring, all seals were very stationary around Anholt. The onset of the PDV epizootics in 1988 and 2002 took place when the Anholt harbour seals congregate on the Island during April. Anholt seal were also documented to have contact with infected seal locations at Hesselø, Læsø, and the Swedish west coast, although this contact takes place during winter prior to the documented summer outbreaks.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press
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