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Nayak, S. P.

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

3 recordsLinked to original sources

Unraveling the regulatory role of miRNAs responsible for proanthocyanidin biosynthesis in the underutilized legume Psophocarpus tetragonolobus (L.) DC.

The underutilized legume winged bean (Psophocarpus tetragonolobus (L.) DC.) is deposited with various degrees of proanathocyanidin (PA) or condensed tannin (CT) on its seed-coat. PA content of two different lines of P. tetragonolobus was estimated and accordingly they were denoted as high-proanthocyanidin containing winged bean (HPW) and low-proanthocyanidin containing winged bean (LPW). The level of PA-content varied as 59.23 mg/g in HPW and 8.68 mg/g in LPW when estimated through vanillin-HCl assay. The identification and quantification of catechin and epigallocatechin gallate were estimated in a range of 63.8 mg/g and 2.3mg/g respectively in HPW whereas only epigallocatechin gallate was reported in LPW line with a value of 3 mg/g. A comparative miRNA profiling of the leaf-tissues of these contrasting lines of P. tetragonolobus revealed a total of 139 mature miRNAs. Isoforms of known novel miRNAs were also identified in this study. Differentially expressed miRNAs e.g., miR156, miR396, miR4414b, miR4416c, miR894, miR2111 and miR5139 were validated through qRT-PCR analysis. Target prediction of the identified miRNAs especially miR156, miR396, miR4416b shows that they have a potential role in the proanthocyanidin biosynthesis of P. tetragonolobus. The study will provide the basis for understanding the role of miRNAs in regulating the biosynthesis of proanthocyanidin.

genomics

Immunosuppressive traits of the hybrid epithelial/mesenchymal phenotype

Recent preclinical and clinical data suggests enhanced metastatic fitness of hybrid epithelial/ mesenchymal (E/M) phenotypes, but mechanistic details regarding their survival strategies during metastasis remain unclear. Here, we investigate immune-evasive strategies of hybrid E/M states. We construct and simulate the dynamics of a minimalistic regulatory network encompassing the known associations among regulators of EMT (epithelial-mesenchymal transition) and PD-L1, an established immune-suppressor. Our model simulations, integrated with single-cell and bulk RNA-seq data analysis, elucidate that hybrid E/M cells can have high levels of PD-L1, similar to those seen in cells with a full EMT phenotype, thus obviating the need for cancer cells to undergo a full EMT to be immune-evasive. Specifically, in breast cancer, we show the co-existence of hybrid E/M phenotypes, enhanced resistance to anti-estrogen therapy and increased PD-L1 levels. Our results underscore how the emergent dynamics of interconnected regulatory networks can coordinate different axes of cellular fitness during metastasis.

cancer biology

Immune phase transition under steroid treatment

The steroid hormone, Glucocorticoid (GC) is a well-known immunosuppressant that controls T cell-mediated adaptive immune response. In this work, we have developed a minimal kinetic network model of T-cell regulation connecting relevant experimental and clinical studies to quantitatively understand the long-term effects of GC on pro-inflammatory T-cell (Tpro) and anti-inflammatory T-cell (Tanti) dynamics. Due to the antagonistic relation between these two types of T-cells, their long-term steady-state population ratio helps us to characterize three classified immune-regulations: (i) weak ([Tpro]>[Tanti]); (ii) strong ([Tpro]<[Tanti]), and (iii) moderate ([Tpro] [~] [Tanti]); holding the characteristic bistability). In addition to the differences in their long-term steady-state outcome, each immune-regulation shows distinct dynamical phases. In the pre-steady, a characteristic intermediate stationary phase is observed to develop only in the moderate regulation regime. In the medicinal field, the resting time in this stationary phase is distinguished as a clinical latent period. GC dose-dependent steady-state analysis shows an optimal level of GC to drive a phase-transition from the weak/auto-immune prone to the moderate regulation regime. Subsequently, the pre-steady state clinical latent period tends to diverge near that optimal GC level where [Tpro]: [Tanti] is highly balanced. The GC-optimized elongated stationary phase explains the rationale behind the requirement of long-term immune diagnostics, especially when long-term GC-based chemotherapeutics and other immunosuppressive drugs are administrated. Moreover, our study reveals GC sensitivity of clinical latent period which might serve as an early warning signal in the diagnosis of different immune phases and determining immune phase-wise steroid treatment.

systems biology