Biology subjects

Kumar, P. S.

Publications and source records attributed to Kumar, P. S..

5 recordsLinked to original sources

bioRxiv2024

Telmisartan impedes JEV infection predominately via AT1/PPARγ axis

Japanese encephalitis, caused by Japanese encephalitis virus (JEV) is a vector born disease for which no specific therapeutics are available yet. Binding of angiotensin II (Ang II) to angiotensin II type 1 (AT1) receptor induces release of inflammatory cytokines associated with viral encephalitis. Accordingly, Ang II receptor blockers (ARBs) have been proposed to manage encephalitis. Since Telmisartan (TM, antagonist of AT1 and agonist of PPAR{gamma}) has relatively better brain access than other ARBs, this investigation aims to evaluate its anti-JEV efficacy in vitro and in vivo. TM reduced JEV titer, RNA and protein (NS3) significantly in the BHK-21 cells with IC50 of 24.68M and CC50 of >350 M (Selectivity Index >14.18) indicating its potential of repurposing against JEV. The anti-JEV efficacy of TM was further observed in macrophages (RAW264.7) and neuronal (SH-SY5Y) cells. Interestingly, the viral load was reduced significantly in pre, co and post-treatment conditions of TM, however most efficiently (80%) in post treatment. In presence of GW (PPAR{gamma} antagonist) and AG (AT1 agonist), viral infection was increased remarkably while AT1 was upregulated and PPAR{gamma} was downregulated. Whereas, TM treatment reversed the levels of AT1 and PPAR{gamma} during infection. Further, reduction of inflammatory markers like p-IRF-3, COX-2 and p-NF-{kappa}B was observed after TM treatment in RAW264.7 cells suggesting its immunomodulation through the AT1/PPAR{gamma} axis. Finally, the anti-JEV potential of TM was validated in mice model through the reduction of disease score, viral protein and histological changes. Thus, the preclinical efficacy of TM suggests its suitability for repurposing against JEV.

microbiology↗

bioRxiv2024

Evaluating Physiological Indicators in Detecting Deception using the Comparison Question Test (CQT)

Despite significant advancements in deception detection, traditional methods often fall short in real-world applications. This study addresses these limitations by evaluating the effectiveness of various physiological measures -- pupil response, electrodermal activity (EDA), heart rate (HR), and facial temperature changes -- in predicting deception using the Comparison Question Test (CQT). It also fills a critical research gap by validating these methods within an Asian context. Employing a between-subjects design, data was collected from a diverse sample of 118 participants from Singapore, including Chinese, Indian, and Malay individuals. The research aims to identify which physiological indicators, in combination, offer the most robust predictions of deceptive behavior. Key innovations include the adaptation of the CQT with a modified directed lie paradigm and an expanded sample size to assess the relative importance of each physiological measure. The studys findings reveal that pupil response is the most significant predictor of deception, with EDA enhancing the models explanatory power. HR, while relevant, adds limited value when combined with pupil response and EDA, and facial temperature changes were statistically non-significant. The study highlights the need for further research into the interactions among physiological measures and their application in varied contexts. This research contributes valuable insights into improving deception detection methodologies and sets the stage for future investigations that could incorporate additional physiological indicators and explore real-world applications.

bioengineering↗

bioRxiv2021

Elevation of TRPV1 expression on T cells during experimental immunosuppression

An intracellular rise in calcium (Ca2+) is an essential requisite underlying T cell activation and its associated pro-inflammatory cytokine production. Transient receptor potential vanilloid channel (TRPV1) is a thermo-sensitive, polymodal gated and permeable to cations such as Ca2+. It has been reported that TRPV1 expression increases during T cell activation. However, the possible involvement of TRPV1 during immunosuppression of T cells has not been studied yet. Here, we investigated the possible role of TRPV1 in FK506 or B16F10-culture supernatant (B16F10-CS) driven experimental immunosuppression in T cells. Intriguingly, it was found that TRPV1 expression is further elevated during immunosuppression compared to ConA or TCR activated T cells. Similarly, in B16F10 tumor-bearing mice, the TRPV1 expression was upregulated in T cells as compared to control mice, in vivo. Moreover, we observed an immediate rise in intracellular Ca2+ levels in FK506 and B16F10-CS treated T cells as compared to ConA or TCR treated T cells. Likewise, in B16F10 tumor-bearing mice, the basal intracellular calcium level was upregulated in T cells as compared to control mice, in vivo. To further investigate the possible mechanism of such rise in intracellular Ca2+ levels, TRPV1 specific functional inhibitor, 5 -iodoresiniferatoxin (5 -IRTX) was used in calcium influx studies. It was observed that the total intracellular Ca2+ levels decreased significantly in presence of 5 -IRTX for either the FK506 or B16F10-CS as well as with ConA or TCR stimulated T cells, indicating the functional role of TRPV1 channels in FK506 or B16F10-CS mediated increase in intracellular Ca2+ levels. The current findings highlight an essential role of the TRPV1 channel in upregulating intracellular calcium levels during both immune-activation and immunosuppression. This study might also have broad implications in the context of other immune-suppressive diseases as well.

immunology↗

bioRxiv2019

Transient Receptor Potential Ankyrin1 channel is endogenously expressed in T cells and regulates immune functions

Transient Receptor Potential channel subfamily A member 1 (TRPA1) is a non selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the role of TRPA1 towards T cell responses remains scanty. In this work, we explored the endogenous expression of TRPA1 in T cells. By RT-PCR we confirmed the expression of TRPA1 in T cell at RNA level. Using confocal microscopy as well as flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. The endogenous expression of TRPA1 is confirmed by using another antibody. TRPA1 was primarily located at the cell surface. TRPA1-specific activator namely AITC increases intracellular Ca2+-levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+-levels in T cells. Such Ca2+-influx can also be influenced by chelation of intracellular Ca2+ as well as extracellular Ca2+. TRPA1 expression was found to be increased during CD3/CD28 (TCR) or ConA driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of CD25, CD69 in ConA/TCR stimulated T cells and secretion of cytokines like TNF, IFN-{gamma} and IL-2 suggesting that endogenous activity of TRPA1 may be involved in T cell activation. Collectively these results may have implication in T cell-mediated responses and possible role of TRPA1 in immunological disorders.

immunology↗

bioRxiv2018

The Cuon Enigma: Genome survey and comparative genomics of the endangered Dhole (Cuon alpinus)

The Asiatic wild dog is an endangered monophyletic canid restricted to Asia; facing threats from habitat fragmentation and other anthropogenic factors. Dholes have unique adaptations as compared to other wolf-like canids for large litter size (larger number of mammae) and hypercarnivory making it evolutionarily notable. Over evolutionary time, dhole and the subsequent divergent wild canids have lost coat patterns found in African wild dog. Here we report the first high coverage genome survey of Asiatic wild dog and mapped it with African wild dog, dingo and domestic dog to assess the structural variants. We generated a total of 124.8 Gb data from 416140921 raw read pairs and retained 398659457 reads with 52X coverage and mapped 99.16% of the clean reads to the three reference genomes. We identified ~13553269 SNVs, ~2858184 InDels, ~41000 SVs, ~1854109 SSRs and about 1000 CNVs. We compared the annotated genome of dingo and domestic dog with dhole genome sequence to understand the role of genes responsible in pelage pattern, dentition and mammary glands. Positively selected genes for these phenotypes were looked for SNP variants and top ranked genes for coat pattern, dentition and mammary glands were found to play a role in signalling and developmental pathways. Mitochondrial genome assembly predicted 35 genes, 11 CDS and 24 tRNA. This genome information will help in understanding the divergence of two monophlyletic canids, Cuon and Lycaon, and the evolutionary adaptations of dholes with respect to other canids.

genomics↗