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  • 1
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    How Common Is Parallel Intron Gain? Rapid Evolution Versus Independent Creation in Recently Created Introns in Daphnia (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-19
    Description: The evolutionary history of the spliceosomal introns that interrupt nuclear genes in eukaryotes has been debated for four decades. Positions of introns show a high degree of coincidence between various eukaryotes, implying either than many modern introns are very old and/or that intron creation is highly biased toward certain sites, leading to rampant parallel intron gain. A series of articles in this and other journals reported evidence for a strikingly high degree of parallel insertion of introns in different alleles of the water flea Daphnia pulex . Here, I report several new analyses of these data. Among the 23 loci reported to be undergoing parallel intron gain, I find that in five cases introns reported to be unrelated show extended sequence similarity strongly suggesting that the introns are in fact homologous. Five additional cases show extended conserved motifs between allegedly unrelated introns. For nearly all loci including the 13 remaining loci, at least one intron shows hallmarks of rapid sequence evolution, thwarting confident inference about homology. In addition, I reanalyze gene trees reconstructed from flanking exonic sequences, claimed by the original authors as additional evidence for parallel gain. I show that these phylogenetic trees frequently fail to recover expected relationships, and in any case show relationships not consistent with parallel intron gains. In total, I conclude that the data do not support widespread parallel intron gain in D. pulex . These findings strengthen the notion that shared intron positions generally reflect ancestral introns, and thus the notion of complex genes in early eukaryotes.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane (2015)
    Oxford University Press
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    Publication Date: 2015-05-08
    Description: As part of the international Pig-a validation trials, we examined the induction of Pig-a mutant reticulocytes and red blood cells (RET CD59– and RBC CD59– , respectively) in peripheral blood of male Sprague Dawley ® rats treated with urethane (25, 100 and 250mg/kg/day) or saline by oral gavage for 29 days. Additional endpoints integrated into this study were: micronucleated reticulocytes (MN-RET) in peripheral blood; chromosome aberrations (CAb) and DNA damage (%tail intensity via the comet assay) in peripheral blood lymphocytes (PBL); micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow; and DNA damage (comet) in various organs at termination (the 29th dose was added for the comet endpoint at sacrifice). Ethyl methanesulfonate (EMS; 200mg/kg/day on Days 3, 4, 13, 14, 15, 27, 28 and 29) was evaluated as the concurrent positive control (PC). All animals survived to termination and none exhibited overt toxicity, but there were significant differences in body weight and body weight gain in the 250-mg/kg/day urethane group, as compared with the saline control animals. Statistically significant, dose-dependent increases were observed for urethane for: RET CD59– and RBC CD59– (on Days 15 and 29); MN-RET (on Days 4, 15 and 29); and MN-PCE (on Day 29). The comet assay yielded positive results in PBL (Day 15) and liver (Day 29), but negative results for PBL (Days 4 and 29) and brain, kidney and lung (Day 29). No significant increases in PBL CAb were observed at any sample time. Except for PBL CAb (likely due to excessive cytotoxicity), EMS-induced significant increases in all endpoints/tissues. These results compare favorably with earlier in vivo observations and demonstrate the utility and sensitivity of the Pig-a in vivo gene mutation assay, and its ability to be easily integrated, along with other standard genotoxicity endpoints, into 28-day rodent toxicity studies.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Topography of the western Pacific LLSVP constrained by S wave multipathing (2019)
    Oxford University Press
    Details
    Publication Date: 2019
    Description: 〈span〉〈div〉Summary〈/div〉We found that SH〈sub〉〈span〉diff〈/span〉〈/sub〉 phases generated by earthquakes in the Fiji-Tonga, recorded in India, are accompanied by secondary pulses. We interpreted them as a consequence of multipathing of S waves caused by the Pacific Large Low-Shear-Velocity Province (LLSVP). We analyzed the differential travel times between SH〈sub〉〈span〉diff〈/span〉〈/sub〉 and the secondary pulse, together with the absolute SH〈sub〉〈span〉diff〈/span〉〈/sub〉 arrival times, to constrain the thickness and velocity perturbations in the western end of the Pacific LLSVP. Our preferred model shows a lateral variation in the thickness of the LLSVP; the southern part reveals a thicker (300 km) low velocity region compared to the northern part (200 km). However, the velocity perturbations of the LLSVP appear to be comparable (-1.5%). The results are consistent with a scenario that the LLSVP is a chemically distinct pile with significant surface topography.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 4
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    A predictive modeling approach for cell line-specific long-range regulatory interactions (2015)
    Oxford University Press
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    Publication Date: 2015-10-15
    Description: Long range regulatory interactions among distal enhancers and target genes are important for tissue-specific gene expression. Genome-scale identification of these interactions in a cell line-specific manner, especially using the fewest possible datasets, is a significant challenge. We develop a novel computational approach, Regulatory Interaction Prediction for Promoters and Long-range Enhancers (RIPPLE), that integrates published Chromosome Conformation Capture (3C) data sets with a minimal set of regulatory genomic data sets to predict enhancer-promoter interactions in a cell line-specific manner. Our results suggest that CTCF, RAD21, a general transcription factor (TBP) and activating chromatin marks are important determinants of enhancer-promoter interactions. To predict interactions in a new cell line and to generate genome-wide interaction maps, we develop an ensemble version of RIPPLE and apply it to generate interactions in five human cell lines. Computational validation of these predictions using existing ChIA-PET and Hi-C data sets showed that RIPPLE accurately predicts interactions among enhancers and promoters. Enhancer-promoter interactions tend to be organized into subnetworks representing coordinately regulated sets of genes that are enriched for specific biological processes and cis -regulatory elements. Overall, our work provides a systematic approach to predict and interpret enhancer-promoter interactions in a genome-wide cell-type specific manner using a few experimentally tractable measurements.
    Keywords: Computational Methods, Genomics, Transcriptome Mapping - Monitoring Gene Expression
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Synchrotron spectral index and interstellar medium densities of star-forming galaxies (2015)
    Oxford University Press
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    Publication Date: 2015-04-12
    Description: The spectral index of synchrotron emission is an important parameter in understanding the properties of cosmic ray electrons (CREs) and the interstellar medium (ISM). We determine the synchrotron spectral index (α nt ) of four nearby star-forming galaxies, namely NGC 4736, NGC 5055, NGC 5236 and NGC 6946 at sub-kpc linear scales. The α nt was determined between 0.33 and 1.4 GHz for all the galaxies. We find the spectral index to be flatter ( –0.7) in regions with total neutral (atomic + molecular) gas surface density, gas 50 M pc – 2 , typically in the arms and inner parts of the galaxies. In regions with gas 50 M pc – 2 , especially in the interarm and outer regions of the galaxies, the spectral index steepens sharply to 〈–1.0. The flattening of α nt is unlikely to be caused due to thermal free–free absorption at 0.33 GHz. Our result is consistent with the scenario where the CREs emitting at frequencies below ~0.3 GHz are dominated by bremsstrahlung and/or ionization losses. For denser medium ( gas 200 M pc – 2 ), having strong magnetic fields ( ~ 30 μG), α nt is seen to be flatter than –0.5, perhaps caused due to ionization losses. We find that, due to the clumpy nature of the ISM, such dense regions cover only a small fraction of the galaxy (5 per cent). Thus, the galaxy-integrated spectrum may not show indication of such loss mechanisms and remain a power law over a wide range of radio frequencies (between ~0.1 to 10 GHz).
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    Role of PKC-{alpha} in NF-{kappa}B-MT1-MMP-mediated activation of proMMP-2 by TNF-{alpha} in pulmonary artery smooth muscle cells (2013)
    Oxford University Press
    Details
    Publication Date: 2013-02-13
    Description: We sought to evaluate the mechanism(s) associated with pro matrix metalloprotease 2 (proMMP-2) activation in bovine pulmonary artery smooth muscle cells. Preincubation of cells with anti-TNFR1 antibody prevented tumour necrosis factor-α (TNF-α)-induced proMMP-2 activation and increase in membrane type 1 matrix metalloprotease (MT1-MMP) expression as well as inhibition of tissue inhibitor of metalloproteinase 2 (TIMP-2) expression, indicating the role of TNFR1 receptor during TNF-α stimulation. Anti-MT1-MMP antibody abrogated proMMP-2 activation by TNF-α-stimulated cell membrane, suggesting the involvement of MT1-MMP in proMMP-2 activation. Induction of MT1-MMP expression in response to TNF-α occurs via activation of nuclear factor (NF)-B on inhibitory B kinase (IKK) activation and subsequently phosphorylation/degradation of IB-α. Inhibition of protein kinase C (PKC)-α activity by Go6976 and PKC-α siRNA prevented TNF-α-induced IKK activity, IB-α phosphorylation/degradation and NF-B activation. Inhibition of PKC-α activity also prevented TNF-α-induced MT1-MMP expression and proMMP-2 activation as well as down regulation of TIMP-2 expression. Inhibition of IB-α phosphorylation by PS-1145, an IKK selective inhibitor, prevented TNF-α-induced increase in MT1-MMP expression and proMMP-2 activation, which although did not alter inhibition of TIMP-2 expression. Overall, we unravelled a hitherto unknown mechanism of the involvement of PKC-α in proMMP-2 activation and inhibition of TIMP-2 expression by NF-B–MT1-MMP–dependent and –independent pathway, respectively, during TNF-α stimulation in pulmonary artery smooth muscle cells.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
    Published by Oxford University Press on behalf of The Japanese Biochemical Society (JBS).
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  • 7
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    A predictive modeling approach for cell line-specific long-range regulatory interactions (2016)
    Oxford University Press
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    Publication Date: 2016-03-01
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Mapping networks of light-dark transition in LOV photoreceptors (2015)
    Oxford University Press
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    Publication Date: 2015-11-05
    Description: Motivation: In optogenetics, designing modules of long or short signaling state lifetime is necessary for control over precise cellular events. A critical parameter for designing artificial or synthetic photoreceptors is the signaling state lifetime of photosensor modules. Design and engineering of biologically relevant artificial photoreceptors is based on signaling mechanisms characteristic of naturally occurring photoreceptors. Therefore identifying residues important for light–dark transition is a definite first step towards rational design of synthetic photoreceptors. A thorough grasp of detailed mechanisms of photo induced signaling process would be immensely helpful in understanding the behaviour of organisms. Results: Herein, we introduce the technique of differential networks. We identify key biological interactions, using light-oxygen-voltage domains of all organisms whose dark and light state crystal structures are simultaneously available. Even though structural differences between dark and light states are subtle (other than the covalent bond formation between flavin chromophore and active site Cysteine), our results successfully capture functionally relevant residues and are in complete agreement with experimental findings from literature. Additionally, using sequence-structure alignments, we predict functional significance of interactions found to be important from network perspective yet awaiting experimental validation. Our approach would not only help in minimizing extensive photo-cycle kinetics procedure but is also helpful in providing first-hand information on the fundamentals of photo-adaptation and rational design of synthetic photoreceptors in optogenetics. Contact: devrani.dbs@presiuniv.ac.in or soumen@jcbose.ac.in 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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  • 9
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    XRCC4's interaction with XLF is required for coding (but not signal) end joining (2012)
    Oxford University Press
    Details
    Publication Date: 2012-02-28
    Description: XRCC4 and XLF are structurally related proteins important for DNA Ligase IV function. XRCC4 forms a tight complex with DNA Ligase IV while XLF interacts directly with XRCC4. Both XRCC4 and XLF form homodimers that can polymerize as heterotypic filaments independently of DNA Ligase IV. Emerging structural and in vitro biochemical data suggest that XRCC4 and XLF together generate a filamentous structure that promotes bridging between DNA molecules. Here, we show that ablating XRCC4's affinity for XLF results in DNA repair deficits including a surprising deficit in VDJ coding, but not signal end joining. These data are consistent with a model whereby XRCC4/XLF complexes hold DNA ends together—stringently required for coding end joining, but dispensable for signal end joining. Finally, DNA-PK phosphorylation of XRCC4/XLF complexes disrupt DNA bridging in vitro , suggesting a regulatory role for DNA-PK's phosphorylation of XRCC4/XLF complexes.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Topography of the western Pacific LLSVP constrained by S-wave multipathing (2019)
    Oxford University Press
    Details
    Publication Date: 2019
    Description: 〈span〉〈div〉SUMMARY〈/div〉We found that 〈span〉SH〈/span〉〈sub〉diff〈/sub〉 phases generated by earthquakes in the Fiji–Tonga, recorded in India, are accompanied by secondary pulses. We interpreted them as a consequence of multipathing of 〈span〉S〈/span〉 waves caused by the Pacific large low-shear-velocity province (LLSVP). We analysed the differential traveltimes between 〈span〉SH〈/span〉〈sub〉diff〈/sub〉 and the secondary pulse, together with the absolute 〈span〉SH〈/span〉〈sub〉diff〈/sub〉 arrival times, to constrain the thickness and velocity perturbations in the western end of the Pacific LLSVP. Our preferred model shows a lateral variation in the thickness of the LLSVP; the southern part reveals a thicker (300 km) low-velocity region compared to the northern part (200 km). However, the velocity perturbations of the LLSVP appear to be comparable ($-1.5\hbox{ per cent}$). The results are consistent with a scenario that the LLSVP is a chemically distinct pile with significant surface topography.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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