Neutron Star Physics in the Square Kilometre Array Era: An Indian Perspective

It is an exceptionally opportune time for astrophysics when a number of next-generation mega-instruments are poised to observe the Universe across the entire electromagnetic spectrum with unprecedented data quality. The Square Kilometre Array (SKA) is undoubtedly one of the major components of this scenario. In particular, the SKA is expected to discover tens of thousands of new neutron stars giving a major fillip to a wide range of scientific investigations. India has a sizeable community of scientists working on different aspects of neutron star physics with immediate access to both the uGMRT (an SKA pathfinder) and the recently launched X-ray observatory Astrosat. The current interests of the community largely centre around studies of (a) the generation of neutron stars and the SNe connection, (b) the neutron star population and evolutionary pathways, (c) the evolution of neutron stars in binaries and the magnetic fields, (d) the neutron star equation of state, (e) the radio pulsar emission mechanism, and (f) the radio pulsars as probes of gravitational physics. Most of these studies are the main goals of the SKA first phase, which is likely to be operational in the next four years. This article summarizes the science goals of the Indian neutron star community in the SKA era, with significant focus on coordinated efforts among the SKA and other existing/upcoming instruments

Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor-mediated disease.

Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that are sites of SUMOylation. We determined that replacement of these residues by arginine enhances polyQ AR activity as a hormone-dependent transcriptional regulator. In a murine model, disruption of polyQ AR SUMOylation rescued exercise endurance and type I muscle fiber atrophy; it also prolonged survival. These changes occurred without overt alterations in polyQ AR expression or aggregation, revealing the favorable trophic support exerted by the ligand-activated receptor. Our findings demonstrate beneficial effects of enhancing the transcriptional function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may be a potential target for therapeutic intervention in SBMA

Dynamic recruitment of microRNAs to their mRNA targets in the regenerating liver.

BACKGROUND: Validation of physiologic miRNA targets has been met with significant challenges. We employed HITS-CLIP to identify which miRNAs participate in liver regeneration, and to identify their target mRNAs. RESULTS: miRNA recruitment to the RISC is highly dynamic, changing more than five-fold for several miRNAs. miRNA recruitment to the RISC did not correlate with changes in overall miRNA expression for these dynamically recruited miRNAs, emphasizing the necessity to determine miRNA recruitment to the RISC in order to fully assess the impact of miRNA regulation. We incorporated RNA-seq quantification of total mRNA to identify expression-weighted Ago footprints, and developed a microRNA regulatory element (MRE) prediction algorithm that represents a greater than 20-fold refinement over computational methods alone. These high confidence MREs were used to generate candidate \u27competing endogenous RNA\u27 (ceRNA) networks. CONCLUSION: HITS-CLIP analysis provide novel insights into global miRNA:mRNA relationships in the regenerating liver

The 2021 FASEB science research conference on NAD metabolism and signaling

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Black tea polyphenols restrict benzopyrene-induced mouse lung cancer progression through inhibition of Cox-2 and induction of caspase-3 expression

Lung cancer is one of the leading causes of cancer related death in most developed and many developing countries of the world. Due to lack of validated screening methods and poor prognosis, treatment of lung cancer has not improved significantly over the last two decades. Therefore the risk of the disease needs to be minimized by preventive measures. One approach for lung cancer prevention envisages reversal or restriction of precancerous lesions by chemopreventive intervention. It demands a deeper understanding of the pathogenesis of the disease and identification of the ideal point of intervention. In the present investigation, tea components, epigallocatechin gallate (EGCG) and theaflavins (TF) were assessed for their chemopreventive potential when administered in the post initiation phase of lung carcinogenesis in an experimental mouse model. Histopathological changes in lungs of mice administered benzo(a)pyrene (BP) were followed serially and correlated with the expression of Cox-2, caspase-3 and caspase-7, which play key roles in histopathogenesis of neoplasia. The observations strongly indicate that both EGCG and TF can influence the expression of these genes to modulate the process of carcinogenesis, resulting in delayed onset and lowered incidence of pre-invasive lung lesions