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  • Oxford University Press  (50)
  • American Meteorological Society (AMS)
  • 2015-2019  (50)
  • 1965-1969
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  • 2015  (50)
  • 1
    Publication Date: 2015-08-25
    Description: : Current methods for motif discovery from chromatin immunoprecipitation followed by sequencing (ChIP-seq) data often identify non-targeted transcription factor (TF) motifs, and are even further limited when peak sequences are similar due to common ancestry rather than common binding factors. The latter aspect particularly affects a large number of proteins from the Cys 2 His 2 zinc finger (C2H2-ZF) class of TFs, as their binding sites are often dominated by endogenous retroelements that have highly similar sequences. Here, we present recognition code-assisted discovery of regulatory elements (RCADE) for motif discovery from C2H2-ZF ChIP-seq data. RCADE combines predictions from a DNA recognition code of C2H2-ZFs with ChIP-seq data to identify models that represent the genuine DNA binding preferences of C2H2-ZF proteins. We show that RCADE is able to identify generalizable binding models even from peaks that are exclusively located within the repeat regions of the genome, where state-of-the-art motif finding approaches largely fail. Availability and implementation: RCADE is available as a webserver and also for download at http://rcade.ccbr.utoronto.ca/ . Supplementary information: Supplementary data are available at Bioinformatics online. Contact: t.hughes@utoronto.ca
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 2
    Publication Date: 2015-09-22
    Description: The genomic G+C content of ocean bacteria varies from below 30% to over 60%. This broad range of base composition is likely shaped by distinct mutational processes, recombination, effective population size, and selection driven by environmental factors. A number of studies have hypothesized that depletion of G/C in genomes of marine bacterioplankton cells is an adaptation to the nitrogen-poor pelagic oceans, but they failed to disentangle environmental factors from mutational biases and population history. Here, we reconstructed the evolutionary changes of bases at synonymous sites in genomes of two marine SAR11 populations and a freshwater counterpart with its evolutionary origin rooted in the marine lineage. Although they all have similar genome sizes, DNA repair gene repertoire, and base compositions, there is a stronger bias toward A/T changes, a reduced frequency of nitrogenous amino acids, and an exclusive occurrence of polyamine, opine, and taurine transport systems in the ocean populations, consistent with a greater nitrogen stress in surface oceans compared with freshwater lakes. Furthermore, the ratio of nonsynoymous to synonymous nucleotide diversity is not statistically distinguishable among these populations, suggesting that population history has a limited effect. Taken together, the ecological transition of SAR11 from ocean to freshwater habitats makes nitrogen more available to these organisms, and thus relaxation of purifying selection drove a genome-wide reduction in the frequency of G/C to A/T changes in the freshwater population.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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  • 3
    Publication Date: 2015-11-22
    Description: We report periods and JHKL observations for 643 oxygen-rich Mira variables found in two outer bulge fields at b = –7° and l = ±8° and combine these with data on 8057 inner bulge Miras from the Optical Gravitational Lensing Experiment, MACHO and Two Micron All Sky Survey surveys, which are concentrated closer to the Galactic Centre. Distance moduli are estimated for all these stars. Evidence is given showing that the bulge structure is a function of age. The longer period Miras (log P 〉 2.6, age ~5 Gyr and younger) show clear evidence of a bar structure inclined to the line of sight in both the inner and outer regions. The distribution of the shorter period (metal-rich globular cluster age) Miras appears spheroidal in the outer bulge. In the inner region these old stars are also distributed differently from the younger ones and possibly suggest a more complex structure. These data suggest a distance to the Galactic Centre, R 0 , of 8.9 kpc with an estimated uncertainty of ~0.4 kpc. The possible effect of helium enrichment on our conclusions is discussed.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 4
    Publication Date: 2015-03-27
    Description: The ability of an organism to detect threats is fundamental to mounting a successful defense and this is particularly important when resisting parasites. Early detection of parasites allows for initiation of defense mechanisms, which are vital in mitigating the cost of infection and are likely to be especially important in social species, particularly those whose life history makes parasite pressure more significant. However, understanding the relative strength of behavioral responses in different species and situations is still limited. Here, we test the response of individual ants to fungal parasites in 3 different contexts, for 4 ant species with differing life histories. We found that ants from all 4 species were able to detect fungi on their food, environment, and nest mates and initiate avoidance or upregulate grooming behaviors accordingly to minimize the threat to themselves and the colony. Individuals avoided fungal-contaminated surfaces and increased grooming levels in response to fungal-contaminated nest mates. Ants from all species responded qualitatively in a similar way although the species differed quantitatively in some respects that may relate to life-history differences. The results show that ants of multiple species are capable of recognizing fungal threats in various contexts. The recognition of parasite threats may play an important role in enabling ant colonies to deal with the ever-present threat from disease.
    Print ISSN: 1045-2249
    Electronic ISSN: 1465-7279
    Topics: Biology
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  • 5
    Publication Date: 2015-04-12
    Description: We present Southern African Large Telescope follow-up observations of seven massive clusters detected by the Atacama Cosmology Telescope (ACT) on the celestial equator using the Sunyaev–Zel'dovich (SZ) effect. We conducted multi-object spectroscopic observations with the Robert Stobie Spectrograph in order to measure galaxy redshifts in each cluster field, determine the cluster line-of-sight velocity dispersions, and infer the cluster dynamical masses. We find that the clusters, which span the redshift range 0.3 〈  z  〈 0.55, range in mass from (5–20) 10 14  M ( M 200 c ). Their masses, given their SZ signals, are similar to those of Southern hemisphere ACT clusters previously observed using Gemini and the VLT. We note that the brightest cluster galaxy in one of the systems studied, ACT-CL J0320.4+0032 at z  = 0.38, hosts a type II quasar. Only a handful of such systems are currently known, and therefore ACT-CL J0320.4+0032 may be a rare example of a very massive halo in which quasar-mode feedback is actively taking place.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 6
    Publication Date: 2015-12-26
    Description: We combine Spitzer and Herschel data of the star-forming region N11 in the Large Magellanic Cloud (LMC) to produce detailed maps of the dust properties in the complex and study their variations with the interstellar-medium conditions. We also compare Atacama Pathfinder EXperiment/Large APEX Bolometer Camera (APEX/LABOCA) 870 μm observations with our model predictions in order to decompose the 870 μm emission into dust and non-dust [free–free emission and CO(3–2) line] contributions. We find that in N11, the 870 μm can be fully accounted for by these three components. The dust surface density map of N11 is combined with H  i and CO observations to study local variations in the gas-to-dust mass ratios. Our analysis leads to values lower than those expected from the LMC low-metallicity as well as to a decrease of the gas-to-dust mass ratio with the dust surface density. We explore potential hypotheses that could explain the low ‘observed’ gas-to-dust mass ratios (variations in the X CO factor, presence of CO-dark gas or of optically thick H  i or variations in the dust abundance in the dense regions). We finally decompose the local spectral energy distributions (SEDs) using a principal component analysis (i.e. with no a priori assumption on the dust composition in the complex). Our results lead to a promising decomposition of the local SEDs in various dust components (hot, warm, cold) coherent with that expected for the region. Further analysis on a larger sample of galaxies will follow in order to understand how unique this decomposition is or how it evolves from one environment to another.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 7
    Publication Date: 2015-08-27
    Description: Merging galaxy clusters with radio relics provide rare insights to the merger dynamics as the relics are created by the violent merger process. We demonstrate one of the first uses of the properties of the radio relic to reduce the uncertainties of the dynamical variables and determine the three-dimensional (3D) configuration of a cluster merger, ACT-CL J0102-4915, nicknamed El Gordo. From the double radio relic observation and the X-ray observation of a comet-like gas morphology induced by motion of the cool core, it is widely believed that El Gordo is observed shortly after the first core passage of the subclusters. We employ a Monte Carlo simulation to investigate the 3D configuration and dynamics of El Gordo. Using the polarization fraction of the radio relic, we constrain the estimate of the angle between the plane of the sky and the merger axis to be $\alpha = 21\mathrm{^{\circ }}\pm ^9_{11}$ . We find the relative 3D merger speed of El Gordo to be $2400\pm ^{400}_{200}\,\mathrm{km\,s}^{-1}$ at pericentre. The two possible estimates of the time since pericentre (TSP) are $0.46\pm ^{0.09}_{0.16}$ and $0.91\pm ^{0.22}_{0.39}$ Gyr for the outgoing and returning scenario, respectively. We put our estimates of the TSP into context by showing that if the time-averaged shock velocity is approximately equal to or smaller than the pericentre velocity of the corresponding subcluster in the centre-of-mass frame, the two subclusters are more likely to be moving towards, rather than away, from each other, post apocentre. We compare and contrast the merger scenario of El Gordo with that of the Bullet Cluster, and show that this late-stage merging scenario explains why the south-east (SE) dark matter lensing peak of El Gordo is closer to the merger centre than the SE cool core.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 8
    Publication Date: 2015-10-15
    Description: With many safety and technical limitations partly mitigated through chemical modifications, antisense oligonucleotides (ASOs) are gaining recognition as therapeutic entities. The increase in potency realized by ‘third generation chemistries’ may, however, simultaneously increase affinity to unintended targets with partial sequence complementarity. However, putative hybridization-dependent off-target effects (OTEs), a risk historically regarded as low, are not being adequately investigated. Here we show an unexpectedly high OTEs confirmation rate during screening of fully phosphorothioated (PS)-LNA gapmer ASOs designed against the BACH1 transcript. We demonstrate in vitro mRNA and protein knockdown of off-targets with a wide range of mismatch (MM) and gap patterns. Furthermore, with RNase H1 activity residing within the nucleus, hybridization predicted against intronic regions of pre-mRNAs was tested and confirmed. This dramatically increased ASO-binding landscape together with relatively high potency of such interactions translates into a considerable safety concern. We show here that with base pairing-driven target recognition it is possible to predict the putative off-targets and address the liability during lead design and optimization phases. Moreover, in silico analysis performed against both primary as well as spliced transcripts will be invaluable in elucidating the mechanism behind the hepatoxicity observed with some LNA-modified gapmers.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 9
    Publication Date: 2015-07-08
    Description: We report the discovery of a gravitationally lensed hyperluminous infrared galaxy (intrinsic L IR   10 13 L ) with strong radio emission (intrinsic L 1.4 GHz   10 25  W Hz –1 ) at z  = 2.553. The source was identified in the citizen science project Space Warps  through the visual inspection of tens of thousands of iJK s colour composite images of luminous red galaxies (LRGs), groups and clusters of galaxies and quasars. Appearing as a partial Einstein ring ( r e   3 arcsec) around an LRG at z  = 0.2, the galaxy is extremely bright in the sub-millimetre for a cosmological source, with the thermal dust emission approaching 1 Jy at peak. The redshift of the lensed galaxy is determined through the detection of the CO(3-〉2) molecular emission line with the Large Millimetre Telescope's Redshift Search Receiver and through [O iii ] and Hα line detections in the near-infrared from Subaru/Infrared Camera and Spectrograph. We have resolved the radio emission with high-resolution (300–400 mas) eMERLIN L -band and Very Large Array C -band imaging. These observations are used in combination with the near-infrared imaging to construct a lens model, which indicates a lensing magnification of μ  10. The source reconstruction appears to support a radio morphology comprised of a compact (〈250 pc) core and more extended component, perhaps indicative of an active nucleus and jet or lobe.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 10
    Publication Date: 2015-10-15
    Description: We present a generalization of the giant molecular cloud identification problem based on cluster analysis. The method we designed, SCIMES (Spectral Clustering for Interstellar Molecular Emission Segmentation) considers the dendrogram of emission in the broader framework of graph theory and utilizes spectral clustering to find discrete regions with similar emission properties. For Galactic molecular cloud structures, we show that the characteristic volume and/or integrated CO luminosity are useful criteria to define the clustering, yielding emission structures that closely reproduce ‘by-eye’ identification results. SCIMES performs best on well-resolved, high-resolution data, making it complementary to other available algorithms. Using 12 CO(1-0) data for the Orion–Monoceros complex, we demonstrate that SCIMES provides robust results against changes of the dendrogram-construction parameters, noise realizations and degraded resolution. By comparing SCIMES with other cloud decomposition approaches, we show that our method is able to identify all canonical clouds of the Orion–Monoceros region, avoiding the overdivision within high-resolution survey data that represents a common limitation of several decomposition algorithms. The Orion–Monoceros objects exhibit hierarchies and size–line width relationships typical to the turbulent gas in molecular clouds, although ‘the Scissors’ region deviates from this common description. SCIMES represents a significant step forward in moving away from pixel-based cloud segmentation towards a more physical-oriented approach, where virtually all properties of the ISM can be used for the segmentation of discrete objects.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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