排序方式: 共有509条查询结果,搜索用时 46 毫秒
61.
Gaurav Dwivedi Margaret A. Gran Pritha Bagchi Melissa L. Kemp 《PLoS computational biology》2015,11(11)
Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. 相似文献
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Mapping DNA damage‐dependent genetic interactions in yeast via party mating and barcode fusion genetics 下载免费PDF全文
J Javier Díaz‐Mejía Albi Celaj Joseph C Mellor Atina Coté Attila Balint Brandon Ho Pritpal Bansal Fatemeh Shaeri Marinella Gebbia Jochen Weile Marta Verby Anna Karkhanina YiFan Zhang Cassandra Wong Justin Rich D'Arcy Prendergast Gaurav Gupta Sedide Öztürk Daniel Durocher Grant W Brown Frederick P Roth 《Molecular systems biology》2018,14(5)
Condition‐dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State‐of‐the‐art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double‐mutant strains, does not scale readily to multi‐condition studies. Here, we describe barcode fusion genetics to map genetic interactions (BFG‐GI), by which double‐mutant strains generated via en masse “party” mating can also be monitored en masse for growth to detect genetic interactions. By using site‐specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG‐GI enables multiplexed quantitative tracking of double mutants via next‐generation sequencing. We applied BFG‐GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4‐nitroquinoline 1‐oxide (4NQO), bleomycin, zeocin, and three other DNA‐damaging environments. BFG‐GI recapitulated known genetic interactions and yielded new condition‐dependent genetic interactions. We validated and further explored a subnetwork of condition‐dependent genetic interactions involving MAG1, SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to an increase in the activation of the checkpoint protein kinase Rad53. 相似文献
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A twinfilin‐like protein coordinates karyokinesis by influencing mitotic spindle elongation and DNA replication in Leishmania 下载免费PDF全文
Gaurav Kumar Lova P. Kajuluri Chhitar M. Gupta Amogh A. Sahasrabuddhe 《Molecular microbiology》2016,100(1):173-187
Twinfilin is an evolutionarily conserved actin‐binding protein, which regulates actin‐dynamics in eukaryotic cells. Homologs of this protein have been detected in the genome of various protozoan parasites causing diseases in human. However, very little is known about their core functions in these organisms. We show here that a twinfilin homolog in a human pathogen Leishmania, primarily localizes to the nucleolus and, to some extent, also in the basal body region. In the dividing cells, nucleolar twinfilin redistributes to the mitotic spindle and remains there partly associated with the spindle microtubules. We further show that approximately 50% depletion of this protein significantly retards the cell growth due to sluggish progression of S phase of the cell division cycle, owing to the delayed nuclear DNA synthesis. Interestingly, overexpression of this protein results in significantly increased length of the mitotic spindle in the dividing Leishmania cells, whereas, its depletion adversely affects spindle elongation and architecture. Our results indicate that twinfilin controls on one hand, the DNA synthesis and on the other, the mitotic spindle elongation, thus contributing to karyokinesis in Leishmania. 相似文献
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Sterol glycosyltransferases required for adaptation of Withania somnifera at high temperature 下载免费PDF全文
Gaurav Singh Manish Tiwari Surendra P. Singh Ruchi Singh Surendra Singh Pramod A. Shirke Prabodh K. Trivedi Pratibha Misra 《Physiologia plantarum》2017,160(3):297-311
Heat is a major environmental stress factor that confines growth, productivity, and metabolism of plants. Plants respond to such unfavorable conditions through changes in their physiological, biochemical and developmental processes. Withania somnifera, an important medicinal plant, grows in hot and dry conditions, however, molecular mechanisms related to such adaptive properties are not known. Here, we elucidated that members of the sterol glycosyltransferases (SGT) gene family play important roles in the survival of W. somnifera under adverse conditions through maintaining the integrity of the membrane. SGTs are enzymes involved in sterol modifications and participate in metabolic flexibility during stress. Silencing of WsSGT members, for instance WsSGTL1, WsSGTL2 and WsSGTL4, was inimical for important physiological parameters, such as electron transport rate, photochemical quantum yield, acceptor side limitation, non‐photochemical quenching (NPQ), Fv/Fm and net photosynthetic rate, whereas stomatal conductance, transpiration rate and dark respiration rates (Rds) were increased. Decreased NPQ and increased Rds helped to generate significant amount of ROS in the Wsamisgt lines. After heat stress, H2O2, lipid peroxidation and nitric oxide production increased in the Wsamisgt lines due to high ROS generation. The expression of HSPs in Wsamisgt lines might be involved in regulation of physiological processes during stress. We have also observed increased proline accumulation which might be involved in restricting water loss in the Wsamisgt lines. Taken together, our observations revealed that SGTL enzyme activity is required to maintain the internal damages of the cell against high temperature by maintaining the sterol vs sterol glycosides ratio in the membranes of W. somnifera. 相似文献
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Gaurav Krishnamurthy Akinobu Itoh Julia C. Swanson Wolfgang Bothe Matts Karlsson Ellen Kuhl D. Craig Miller Neil B. Ingels 《Journal of biomechanics》2009,42(16):2697-2701
Left atrial muscle extends into the proximal third of the mitral valve (MV) anterior leaflet and transient tensing of this muscle has been proposed as a mechanism aiding valve closure. If such tensing occurs, regional stiffness in the proximal anterior mitral leaflet will be greater during isovolumic contraction (IVC) than isovolumic relaxation (IVR) and this regional stiffness difference will be selectively abolished by β-receptor blockade. We tested this hypothesis in the beating ovine heart. Radiopaque markers were sewn around the MV annulus and on the anterior MV leaflet in 10 sheep hearts. Four-dimensional marker coordinates were obtained from biplane videofluoroscopy before (CRTL) and after administration of esmolol (ESML). Heterogeneous finite element models of each anterior leaflet were developed using marker coordinates over matched pressures during IVC and IVR for CRTL and ESML. Leaflet displacements were simulated using measured left ventricular and atrial pressures and a response function was computed as the difference between simulated and measured displacements. Circumferential and radial elastic moduli for ANNULAR, BELLY and EDGE leaflet regions were iteratively varied until the response function reached a minimum. The stiffness values at this minimum were interpreted as the in vivo regional material properties of the anterior leaflet. For all regions and all CTRL beats IVC stiffness was 40–58% greater than IVR stiffness. ESML reduced ANNULAR IVC stiffness to ANNULAR IVR stiffness values. These results strongly implicate transient tensing of leaflet atrial muscle during IVC as the basis of the ANNULAR IVC–IVR stiffness difference. 相似文献
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Himanshu Gupta M. Aqil R. K. Khar Asgar Ali Aseem Bhatnagar Gaurav Mittal Sanyog Jain 《AAPS PharmSciTech》2009,10(2):540-546
In situ gel-forming systems have drawn much attention of current researchers to overcome the poor bioavailability from the conventional
eye drops. The present work described formulation and pharmacoscintigraphic evaluation of timolol-maleate-loaded chitosan/hydroxy
propyl methyl cellulose (HPMC)-based polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was optimized and
formulation was characterized for various in vitro parameters. The ocular retention was studied on New Zealand rabbits by gamma scintigraphy, which is a very simple and noninvasive
technique. For scintigraphy study, the drug timolol maleate was radiolabeled 99mTc by direct labeling method using SnCl2·2H2O as reducing agent. The labeling procedure was optimized to get maximum labeling efficiency (>98%). In vitro stability of the radiolabeled drug (99mTc-timolol maleate complex) was checked and it was found to be stable for up to 24 h. Plain drug eliminates rapidly as significant
activity was recorded in kidney and bladder after 2 h of ocular administration. It was evident from the scintigraphic images
and the time–activity curve plotted from the data that the plain drug solution cleared very rapidly from the corneal region
and reached into systemic circulation via nasolachrymal drainage system, as significant activity was recorded in kidney and
bladder after 2 h of ocular administration. Developed formulation cleared at a slow rate and remained at corneal surface for
longer time duration. No radioactivity was observed in systemic circulation after 2 h. Ocular irritation of the developed
formulation was also checked by hen’s egg chorioallantoic membrane test and formulation was found to be practically nonirritant.
The study signified the potential of gamma scintigraphy in evaluation of novel drug delivery systems in a noninvasive manner. 相似文献
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Therese Eriksson Gaurav Varshney Pontus Aspenström Ruth H Palmer 《BMC developmental biology》2010,10(1):86