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Chattopadhyay, N.

Publications and source records attributed to Chattopadhyay, N..

4 recordsLinked to original sources

Integrative transcriptome analysis reveals distinct and common stress-responsive regulatory networks driving drought and heat responses in sorghum

Drought and heat are key abiotic stresses that severely affect crop production. Sorghum (Sorghum bicolor L. Moench), a drought-resilient cereal, serves as a model for studying abiotic stress responses in cereals. To elucidate the molecular responses to individual drought and heat stress, we conducted a transcriptome analysis of sorghum seedlings subjected to individual drought and heat treatment for 1h and 6h. Our analysis revealed distinct as well as overlapping patterns of gene expression between the two stresses at two time points, with a larger transcriptional shift observed at 6h of drought and heat treatment. We identified 410 and 4,136 differentially expressed genes (DEGs) in response to 1 and 6 h of drought treatments, respectively, whereas 1,807 and 2,776 DEGs were identified under 1 and 6 h of heat treatments. Among all four stress conditions, 32 common DEGs were identified. Genes encoding ion transporters were enriched among DEGs common in both 1h stress treatments. Genes involved in ribosome biogenesis were enriched among the common DEGs in both 6 h stress treatments. Specifically, drought-regulated genes were involved in ribosome biogenesis, whereas heat-induced genes were involved in protein folding and histone modifications. Enrichment of ribosome biogenesis in different sets of DEGs suggests that maintaining a balance between growth and survival by regulating protein synthesis may play a role in defining early stress response in sorghum. 6h of drought resulted in strong upregulation of abscisic acid and jasmonate-associated genes. Genes encoding bZIP, MYB, and HSF transcription factors displayed both stress-specific and common temporal regulation, suggesting vital regulatory roles of these transcription factors in mediating responses to drought and heat treatments. Extensive downregulation of genes encoding core histone proteins, in response to both 6h of drought and heat stress, was detected, indicating possible roles of chromatin structure and accessibility in mediating early responses to drought and heat treatments in sorghum.

plant biology↗

Mitigating inflammatory bone loss in post-menopausal osteoporosis via targeting the IL-9 producing osteoclastogenic Th9 cells

Recent discoveries have established the pivotal role of IL-9-secreting Th9 cells in a wide spectrum of inflammatory and autoimmune diseases. However, little is known about how Th9 cells contribute to the etiology of inflammatory bone loss in post-menopausal osteoporosis (PMO). We observed that IL-9 has a pathological impact on inflammatory bone loss in ovariectomized (Ovx) mice. Our in vivo temporal kinetics analysis further revealed that estrogen deprivation increased the release of IL-9 from Th which in turn enhances the IL-17-producing Th17 cells. Both ex vivo and in vivo studies corroborated these findings in Ovx mice, as estrogen diminishes IL-9s effect on the differentiation of Th17 cells as well as the potential of Th9 cells to produce IL-9. Mechanistically, Th9 cells in an IL-9-dependent manner enhance osteoclastogenesis and thereby establish themselves as a novel and independent osteoclastogenic Th subset. Blocking IL-9 improves bone health in Ovx mice by inhibiting the differentiation and function of both osteoclasts and Th9/Th17 cells. Our clinical findings further attested to the osteoporotic role of Th9 cells in post-menopausal osteoporotic human subjects. Collectively, our study establishes IL-9-secreting Th cells as the critical regulator of bone loss observed in PMO and highlights the fundamental implications of IL-9/Th9 targeted immunotherapies as an innovative approach for the treatment of inflammatory bone loss observed in osteoporosis.

immunology↗

Bifidobacterium longum attenuates ovariectomy-induced bone loss via modulating the Immunoporotic Breg-Treg-Th17 cell axis

Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between osteo-immune system. These discoveries fuel novel approaches for the treatment of several bone-pathologies including osteoporosis, an inflammatory bone anomaly affecting more than 500 million people globally. Bifidobacterium longum (BL) is preferred probiotic of choice due to its varied immunomodulatory potential in alleviating various inflammatory diseases. Here, we evaluate the effect of BL in ovariectomy (ovx)-induced post-menopausal osteoporotic mice model. Our in vitro findings reveal that BL suppresses the differentiation and functional activity of RANKL-induced osteoclastogenesis in both mouse bone marrow cells and human PBMCs. Our in vivo data clearly establish that BL exhibits osteoprotective potential via modulating the "immunoporotic" Breg-Treg-Th17 cell-axis. Furthermore, {micro}CT and bone mechanical strength data support that BL supplementation significantly enhanced bone mass and strength, and improved microarchitecture in ovx mice. Remarkably, alteration in frequencies of CD19+CD1dhiCD5+ Bregs, CD4+Foxp3+IL-10+ Tregs, and CD4+Ror{gamma}t+IL-17+ Th17 immune cells in distinct lymphoid organs along with serum-cytokine data (enhanced anti-osteoclastogenic cytokines IFN-{gamma} and IL-10 and reduced osteoclastogenic-cytokines IL-6, IL-17, and TNF-) strongly support the immunomodulatory potential of BL. Altogether our findings establish a novel osteo-protective and immunoporotic potential of BL in augmenting bone health under osteoporotic conditions.

immunology↗

Development of noninvasive biomarkers of response to proteasome inhibitor therapy (ixazomib) by imaging disrupted protein homeostasis in mouse models of solid tumors

With clinically-approved proteasome inhibitors now a standard of care for multiple myeloma, and increasing interest in their use in solid tumors, methods for monitoring therapeutic response in vivo are critically required. Here, we show that tumor protein homeostasis can be noninvasively monitored, using chemical exchange (CEST) magnetic resonance imaging (MRI) as a surrogate marker for proteasome inhibition, alongside diffusion MRI and relaxometry. We show that the in vivo CEST signal associated with amides and amines increases in proportion to proteasome inhibitor dose (ixazomib) and the magnitude of therapeutic effect in colorectal cancer xenografts. Moreover, we show that SW1222 and LS174T human colorectal cancer cell lines demonstrate differing sensitivities to ixazomib, which was reflected in our MRI measurements. We also found evidence of a mild stimulation in tumor growth at low ixazomib doses. Our results therefore identify CEST MRI as a promising method for safely and noninvasively monitoring changes in tumor protein homeostasis.

biophysics↗