Biology subjects

Ghosh, P.

Publications and source records attributed to Ghosh, P..

134 records · Page 8Linked to original sources

bioRxiv2018

EcRBPome: a comprehensive database of all known E. coli RNA-binding proteins

BackgroundThe repertoire of RNA-binding proteins (RBPs) in bacteria play crucial role for their survival, and interactions with the host machinery, but there is little information, record or characterisation in bacterial genomes. As a first step towards this, we have chosen the bacterial model system Escherichia coli, and organised all RBPs in this organism into a comprehensive database named EcRBPome.\n\nResultsEcRBPome contains RBPs recorded from 166 complete E. coli proteomes available in the RefSeq database (as of May 2016). The database provides various features related to the E. coli RBPs, like their domain architectures, PDB structures, GO and EC annotations etc. It provides the assembly, bioproject and biosample details of each strain, as well as cross-strain comparison of occurrences of various RNA-binding domains (RBDs). The percentage of RBPs, the abundance of the various RBDs harboured by each strain have been graphically represented in this database and available alongside other files for user download.\n\nConclusionTo the best of our knowledge, this is the first database of its kind and we hope that it will be of great use to the biological community. Database URL: http://caps.ncbs.res.in/ecrbpome

bioinformatics↗

bioRxiv2018

hRBPome: a central repository of all known human RNA-binding proteins

BackgroundRNA-binding proteins (RBPs) have been extensively studied in humans over the past few years. Multiple reports have been made in the literature for genome-wide survey for this class of proteins in the human genome using different tools and techniques. Due to the inherent difference in the nature of the methods used in identifying human RBPs, as well as the diverse sources for data collection in each of these studies, there exists immense heterogeneity (including diversity in data formats) and poor intersection among the datasets available from the different studies.\n\nDescriptionhRBPome is a comprehensive database of human RBPs known from six different studies. We have introduced considerable uniformity in the data, by mapping the various data formats reported by the different studies to gene names. This makes comparison across studies (datasets) easier than was possible before. We also provide confidence scores to each of these known RBPs, on the basis of their presence across studies.\n\nConclusionThis database presents a set of 837 high confidence RBP genes, identified in three or more resources, out of the six studies considered. Hence, it forms a \"gold standard\" for RBPs in the human genome. It also provides information for all the human RBPs from multiple resources, known to the best of our knowledge, on a common platform. The database can be accessed from the following URL: http://caps.ncbs.res.in/hrbpome

bioinformatics↗

bioRxiv2018

Development and worldwide use of a non-lethal and minimal population-level impact protocols for the isolation of chytrids from amphibians

Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into sterile culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to interested researchers worldwide as part of the BiodivERsA project RACE - here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been widely applied across at least 5 continents, 23 countries and in 62 amphibian species, and have been successfully used to isolate chytrids in remote field locations. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in a significant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this important group of emerging fungal pathogens.

ecology↗

bioRxiv2017

Systemic Inflammation Mediates the Relationship between Obesity and Health Related Quality of Life

BackgroundAt the population level, obesity has been reported to be positively associated with low-level chronic inflammation, and negatively associated with several indices of health-related quality of life (HRQOL). It is however not clear if obesity-associated inflammation is partly responsible for the observed negative associations between obesity and HRQOL. The present study investigates this question by testing the hypothesis that systemic inflammation is a mediator of the observed association between obesity and a specific HRQOL index called \"healthy days\", as measured via a subset of the CDC HRQOL-4 questionnaire.\n\nMethodsDemographic, body mass index (BMI), C-reactive protein (CRP), inflammatory disease status, medication use, smoking, and HRQOL data were obtained from NHANES (2005-2008) and analyzed using sampling-weighted generalized linear models. Both main effects and interaction effects were analyzed to evaluate possible mediator-outcome confounding. Model robustness was tested via sensitivity analysis. Prior to model development, data was subjected to multiple imputation in order to mitigate information loss from survey non-response. Averaged results from the imputed datasets were reported in the form of odds ratios (OR) and confidence intervals (CI).\n\nResultsObesity (BMI >30kg/m2) was positively associated with poor physical healthy days (OR: 1.59, 95% CI: 1.15-2.21) in unadjusted models. Elevated and clinically raised levels of the inflammation marker CRP were also positively associated with poor physical healthy days (OR= 1.61, 95% CI: 1.23-2.12, and OR= 2.45, 95% CI: 1.84-3.26, respectively); additionally clinically raised CRP was positively associated with mental unhealthy days (OR= 1.66, 95% CI: 1.26-2.19). The association between obesity and physical HRQOL was rendered non-significant in models including CRP. Association between elevated and clinically raised CRP and physical unhealthy days remained significant even after adjustment for obesity or inflammation-modulating covariates (OR= 1.36, 95% CI :1.02-1.82, and OR= 1.75, 95% CI: 1.21-2.54, respectively).\n\nConclusionsSystemic inflammation is a significant mediator of the association between obesity and physical unhealthy days. and is also an independent determinant of physical and mental unhealthy days. Importantly, elevated inflammation below the clinical threshold is also negatively associated with physical healthy days and may warrant more attention from a population health perspective than currently appreciated.

epidemiology↗

bioRxiv2017

Allosteric Activation of p300 Autoacetylation by the Tumor Suppressor p53

The transcriptional coactivator p300 is essential for p53 transactivation, although its precise mechanism remains unclear. We report that, p53 allosterically activates the acetyltransferase activity of p300 through the enhancement of p300 autoacetylation. Cryo-electron microscopy revealed that the domain organization of p300 is substantially altered upon binding of p53, suggesting that a structural switch may underpin the activation. Acetylated p300 accumulates near the transcription start sites accompanied by a similar enrichment of activating histone marks near those sites. Disruption of p53-p300 interaction by a site-directed peptide inhibitor abolished autoacetylated p300-mediated enhanced histone acetylation, suggesting a crucial role played by the allosteric activation in p53-mediated gene regulation. Gain-of-function mutant p53, known to impart aggressive proliferative properties in tumor cells, also activate p300 autoacetylation. The same peptide abolished many of the gain-of-functions of mutant p53 as well. We conclude that allosteric activation of p300 by p53 underpins gene regulation by p53. Reversal of gain-of-function properties of mutant p53 suggests that molecules targeting the p53-p300 interface may be good candidates for anti-tumor drugs.

molecular biology↗

bioRxiv2017

Akt/PKB enhances non-canonical Wnt signals by compartmentalizing β-Catenin

Cellular proliferation is antagonistically regulated by canonical and non-canonical Wnt signals; their dysbalance triggers cancers. It is widely believed that the PI3-K[->] Akt pathway enhances canonical Wnt signals by affecting transcriptional activity and stability of {beta}-catenin. Here we demonstrate that the PI3-K[->]Akt pathway also enhances non-canonical Wnt signals by compartmentalizing {beta}-catenin. By phosphorylating the phosphoinositide(PI)-binding domain of a multimodular signal transducer, Daple, Akt abolishes Daples ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of {beta}-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs). Phosphorylation compartmentalizes Daple/{beta}-catenin/E-cadherin complexes to cell-cell contact sites, enhances non-canonical Wnt signals, and thereby, suppresses colony growth. Dephosphorylation compartmentalizes {beta}-catenin on PCREs, a specialized compartment for prolonged unopposed canonical Wnt signaling, and enhances colony growth. Cancer-associated Daple mutants that are insensitive to Akt mimic a constitutively dephosphorylated state. This work not only identifies Daple as a platform for crosstalk between Akt and the non-canonical Wnt pathway, but also reveals the impact of such crosstalk during cancer initiation and progression.

cell biology↗

bioRxiv2017

Guanine-nucleotide Exchange Modulator, GIV/Girdin, Serves as a Tunable Valve for Growth Factor-Stimulated Cyclic AMP Signals

Cellular levels of the versatile second messenger, cyclic-(c)AMP are regulated by the antagonistic actions of the canonical G protein[->]adenylyl cyclase pathway that is initiated by G-protein-coupled receptors (GPCRs) and by phosphodiesterases (PDEs); dysregulated cAMP signaling drives many diseases, including cancers. Recently, an alternative paradigm for cAMP signaling has emerged, in which growth factor-receptor tyrosine kinases (RTKs; e.g., EGFR) access and modulate G proteins via cytosolic guanine-nucleotide exchange modulator (GEM), GIV/Girdin; dysregulation of this pathway is frequently encountered in cancers. Here we present a comprehensive network-based compartmental model for the paradigm of GEM-dependent signaling that reveals unforeseen crosstalk and network dynamics between upstream events and the various feedback-loops that fine-tune the GEM action of GIV, and captures the experimentally determined dynamics of cAMP. The model also reveals that GIV acts a tunable control-valve within the RTK[->]cAMP pathway; hence, it modulates cAMP via mechanisms distinct from the two most-often targeted classes of cAMP modulators, GPCRs and PDEs.

systems biology↗

bioRxiv2017

Convergence of Wnt, Growth Factor and Trimeric G protein signals on Daple

Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades; their concurrent dysregulation plays an integral role in cancer progression and is a common feature of many malignancies. Three such cascades that contribute to the oncogenic potential are the Wnt/Frizzled(FZD), growth factor-receptor tyrosine kinases (RTKs), and G-proteins/GPCRs. Here we identify Daple, a modulator of trimeric G-proteins and a Dishevelled (Dvl)-binding protein as an unexpected point of convergence for all three cascades. Daple-dependent activation of Gi and enhancement of non-canonical Wnt signals is not just triggered by Wnt5a/FZD to suppress tumorigenesis, but also hijacked by growth factor-RTKs to stoke tumor progression. Phosphorylation of Daple by both RTKs and non-RTKs triggers Gi activation and potentiates non-canonical Wnt signals that trigger epithelial-mesenchymal transition. In patients with colorectal cancers, concurrent upregulation of Daple and the prototype RTK, EGFR, carried poor prognosis. Thus, this work defines a novel growth factor{leftrightarrow}G-protein{leftrightarrow}Wnt crosstalk paradigm in cancer biology.

cancer biology↗