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  • Oxford University Press  (56)
  • American Geophysical Union  (12)
  • Geological Society of America (GSA)
  • Nature Publishing Group (NPG)
  • Seismological Society of America (SSA)
  • 2010-2014  (85)
Collection
Year
  • 1
    Publication Date: 2013-02-13
    Description: Motivation: Reliable estimation of the mean fragment length for next-generation short-read sequencing data is an important step in next-generation sequencing analysis pipelines, most notably because of its impact on the accuracy of the enriched regions identified by peak-calling algorithms. Although many peak-calling algorithms include a fragment-length estimation subroutine, the problem has not been adequately solved, as demonstrated by the variability of the estimates returned by different algorithms. Results: In this article, we investigate the use of strand cross-correlation to estimate mean fragment length of single-end data and show that traditional estimation approaches have mixed reliability. We observe that the mappability of different parts of the genome can introduce an artificial bias into cross-correlation computations, resulting in incorrect fragment-length estimates. We propose a new approach, called mappability-sensitive cross-correlation (MaSC), which removes this bias and allows for accurate and reliable fragment-length estimation. We analyze the computational complexity of this approach, and evaluate its performance on a test suite of NGS datasets, demonstrating its superiority to traditional cross-correlation analysis. Availability: An open-source Perl implementation of our approach is available at http://www.perkinslab.ca/Software.html . Contact: tperkins@ohri.ca Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 2
    Publication Date: 2012-04-25
    Description: The stability of RNAs bearing AU-rich elements in their 3'-UTRs, and thus the level of expression of their protein products, is regulated by interactions with cytoplasmic RNA-binding proteins. Binding by HuR generally leads to mRNA stabilization and increased protein production, whereas binding by AUF1 isoforms generally lead to rapid degradation of the mRNA and reduced protein production. The exact nature of the interplay between these and other RNA-binding proteins remains unclear, although recent studies have shown close interactions between them and even suggested competition between the two for binding to their cognate recognition sequences. Other recent reports have suggested that the sequences recognized by the two proteins are different. We therefore performed a detailed in vitro analysis of the binding site(s) for HuR and AUF1 present in androgen receptor mRNA to define their exact target sequences, and show that the same sequence is contacted by both proteins. Furthermore, we analysed a proposed HuR target within the 3'-UTR of MTA1 mRNA, and show that the contacted bases lie outside of the postulated motif and are a better match to a classical ARE than the postulated motif. The defining features of these HuR binding sites are their U-richness and single strandedness.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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  • 3
    Publication Date: 2014-05-06
    Description: Uptake of nitrogen (N) by sequential root regions in six tree species was measured in roots of 16- to 26-month-old seedlings at 50 and 1500 µM NH 4 NO 3 concentration, at the cell level using oscillating microelectrodes and at the root region level using enriched 15 N application. Our objective was to determine the root regions making the greatest contribution to total N uptake in each species as measured by the two contrasting techniques. White and condensed tannin zones were the regions with the smallest surface area in all species, but these zones often had the highest net flux of NH 4 + and NO 3 – . For most species, little variation was found among root regions in N flux calculated using a 15 N mass balance approach, but where significant differences existed, high N flux was observed in white, cork or woody zones. When N fluxes measured by each of the two methods were multiplied by the estimated surface area or biomass of each root region, the effect of root region size had the greatest influence on regional N uptake. Root regions of greatest overall N uptake were the cork and woody zones, on average. Total N uptake may thus be greatest in older regions of tree seedling roots, despite low rates of uptake per unit area.
    Print ISSN: 0829-318X
    Electronic ISSN: 1758-4469
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
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  • 4
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    Geological Society of America (GSA)
    Publication Date: 2011-06-01
    Description: Despite their abundance, diversity, and importance today, organisms with mineralized skeletons are a relatively recent introduction. For the first three billion years of its history, life was soft-bodied, inducing mineralized structures passively, if at all. Beginning ca. 550 Ma, however, more than two dozen clades—primarily animal, but also protistan—independently evolved mineralized skeletons within a geologically short interval of time (Fig. 1; Bengtson, 1992). Now a new report by Cohen et al. (2011; p. 539 in this issue of Geology) describing beautifully intricate scale-like microfossils from the Fifteenmile Group, Yukon Territory, provides definitive evidence for mineralized skeletons some 150–250 m.y. earlier. These scale-like microfossils were first reported over two decades ago (Allison and Hilgert, 1986), but neither their age nor their mineralogy were well constrained. Work by Cohen and her colleagues has now shown that these scales (which perhaps enveloped a single-celled green alga) are between ca. 717 and ca. 812 Ma in age and composed of primary phosphate (Macdonald et al., 2010; Cohen et al., 2011). This adds to earlier suggestive evidence for mineralization at this time: the ca. 770–742 Ma vase-shaped microfossil (VSM) Melicerion poikilon, interpreted on the basis of taphonomic models to be a euglyphid amoeba whose organic-walled test was embedded with mineralized scales, possibly siliceous (Figs. 1B and 1C; Porter and Knoll, 2000; Porter et al., 2003); the mid-Neoproterozoic Tenuocharta cloudii, a multicellular, sheet-like fossil whose calcareous cell walls may reflect primary (Horodyski and Mankiewicz, 1990) or early diagenetic (Knoll, 2003) mineralization; and ca. 650 Ma millimeter- to centimeter-scale asymmetric bodies permeated with a network of canals and interpreted to be sponge-like organisms perhaps lightly mineralized with carbonate (Maloof et al., 2010b)...
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
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  • 5
    Publication Date: 2011-06-01
    Description: Understanding lower-crustal deformational processes and the related features that can be imaged by seismic waves is an important goal in active tectonics. We demonstrate that teleseismic receiver functions calculated for broadband seismic stations in Southern California reveal a signature of pervasive seismic anisotropy in the lower crust. The large amplitudes and small move-out of the diagnostic converted phases, as well as the broad similarity of data patterns from widely separated stations, support an origin primarily from a basal crustal layer of hexagonal anisotropy with a dipping symmetry axis. We conducted neighborhood algorithm searches for depth and thickness of the anisotropic layer and the trend and plunge of the anisotropy symmetry (slow) axis for 38 stations. The searches produced a wide range of results, but a dominant SW-NE trend of the symmetry axis emerged. When the results are divided into crustal blocks and restored to their pre–36 Ma locations, the regional-scale SW-NE trend becomes more consistent, although a small subset of the results can be attributed to NW-SE shearing related to San Andreas transform motion. We interpret this dominant trend as a fossilized fabric within schists, created from top-to-the-SW sense of shear that existed along the length of coastal California during pretransform, early Tertiary subduction or from shear that occurred during subsequent extrusion. Comparison of receiver-function common conversion point stacks to seismic models from the active Los Angeles Regional Seismic Experiment shows a strong correlation in the location of anisotropic layers with “bright” reflectors, further affirming these results.
    Print ISSN: 1941-8264
    Electronic ISSN: 1947-4253
    Topics: Geosciences
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  • 6
    Publication Date: 2014-10-26
    Description: Recent observations have probed the formation histories of nearby elliptical galaxies by tracking correlations between the stellar population parameters, age and metallicity, and the structural parameters that enter the Fundamental Plane, size R e , and velocity dispersion . These studies have found intriguing correlations between these four parameters. In this work, we make use of a semi-analytic model, based on halo merger trees extracted from the Bolshoi cosmological simulation, that predicts the structural properties of spheroid-dominated galaxies based on an analytic model that has been tested and calibrated against an extensive suite of hydrodynamic+ N -body binary merger simulations. We predict the R e , , luminosity, age, and metallicity of spheroid-dominated galaxies, enabling us to compare directly to observations. Our model predicts a strong correlation between age and for early-type galaxies, and no significant correlation between age and radius, in agreement with observations. In addition, we predict a strong correlation between metallicity and , and a weak correlation between metallicity and R e , in qualitative agreement with observations. We find that the correlations with arise as a result of the strong link between and the galaxy's assembly time. Minor mergers produce a large change in radius while leaving nearly the same, which explains the weaker trends with radius.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 7
    Publication Date: 2014-11-04
    Description: Before the onset of the Neoproterozoic Snowball Earth glaciations, eukaryotes had begun diversifying, and in their aftermath, macroscopic life, including both animals and macroalgae, became abundant and widespread. Although glacially driven mass extinctions have been hypothesized, little is known about the biosphere during and between these glaciations. Here we present new data from organic-walled microfossil assemblages from five successions in Australia and Svalbard that collectively span the first (Sturtian) glaciation and interglacial interval and integrate them with data derived from a critical evaluation of the literature to produce a new estimate of eukaryotic diversity from 850 to 650 Ma. These new glacial and interglacial assemblages consist of only smooth-walled spheroids (leiosphaerids), aggregates of cells, and filaments, in contrast to the much more diverse organic-walled microfossil assemblages found in early Neoproterozoic rocks. This contrast is not attributed to biases in deposition or preservation, but is instead interpreted as reflecting an interval of lowered eukaryotic diversity that spanned the glaciations and that may have begun millions of years prior to their onset.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
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  • 8
    Publication Date: 2014-09-20
    Description: Keratoconus, a common inherited ocular disorder resulting in progressive corneal thinning, is the leading indication for corneal transplantation in the developed world. Genome-wide association studies have identified common SNPs 100 kb upstream of ZNF469 strongly associated with corneal thickness. Homozygous mutations in ZNF469 and PR domain-containing protein 5 ( PRDM5 ) genes result in brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal recessive generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Some individuals with heterozygous PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly reduced corneal thickness, keratoconus and blue sclera. We hypothesized that heterozygous variants in PRDM5 and ZNF469 predispose to the development of isolated keratoconus. We found a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus ( P = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2014-08-29
    Description: We use a large suite of hydrodynamical simulations of binary galaxy mergers to construct and calibrate a physical prescription for computing the effective radii and velocity dispersions of spheroids. We implement this prescription within a semi-analytic model embedded in merger trees extracted from the Bolshoi cold dark matter N -body simulation, accounting for spheroid growth via major and minor mergers and disc instabilities. We find that without disc instabilities, our model does not predict sufficient numbers of intermediate-mass early-type galaxies in the local Universe. Spheroids also form earlier in models with spheroid growth via disc instabilities. Our model correctly predicts the normalization, slope, and scatter of the low-redshift size–mass and Fundamental Plane relations for early-type galaxies. It predicts a degree of curvature in the Faber–Jackson relation that is not seen in local observations, but this could be alleviated if higher mass spheroids have more bottom-heavy initial mass functions. The model also correctly predicts the observed strong evolution of the size–mass relation for spheroids out to higher redshifts, as well as the slower evolution in the normalization of the Faber–Jackson relation. We emphasize that these are genuine predictions of the model since it was tuned to match hydrodynamical simulations and not these observations.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 10
    Publication Date: 2014-10-22
    Description: Niemann–Pick C1 (NPC1) disease is a rare, neurodegenerative lysosomal cholesterol storage disorder, typified by progressive cognitive and motor function impairment. Affected individuals usually succumb to the disease in adolescence. 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) has emerged as a promising intervention that reduces lipid storage and prolongs survival in NPC1 disease animal models. A barrier to the development of HP-β-CD and other treatments for NPC disease has been the lack of validated biochemical measures to evaluate efficacy. Here we explored whether cholesterol homeostatic responses resulting from HP-β-CD-mediated redistribution of sequestered lysosomal cholesterol could provide biomarkers to monitor treatment. Upon direct CNS delivery of HP-β-CD, we found increases in plasma 24( S )-HC in two independent NPC1 disease animal models, findings that were confirmed in human NPC1 subjects receiving HP-β-CD. Since circulating 24( S )-HC is almost exclusively CNS-derived, the increase in plasma 24( S )-HC provides a peripheral, non-invasive measure of the CNS effect of HP-β-CD. Our findings suggest that plasma 24( S )-HC, along with the other cholesterol-derived markers examined in this study, can serve as biomarkers that will accelerate development of therapeutics for NPC1 disease.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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