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Venugopal, N.

Publications and source records attributed to Venugopal, N..

4 recordsLinked to original sources

Short-term consumption of ultra-processed semi-synthetic diets impairs the sense of smell and brain metabolism in mice

The prevalence of highly-palatable, ultra-processed food in our modern diet has exacerbated obesity rates and contributed to a global health crisis. While accumulating evidence suggests that chronic consumption of ultra-processed semi-synthetic food is detrimental to sensory and neural physiology, it is unclear whether its short-term intake has adverse effects. Here, we assessed how short-term consumption (<2 months) of three ultra-processed diets (one grain-based diet, and two semi-synthetic) influence olfaction and brain metabolism in mice. Our results demonstrate that short-term consumption of semi-synthetic diets, regardless of macronutrient composition, adversely affect odor-guided behaviors, physiological responses to odorants, transcriptional profiles in the olfactory mucosa and brain regions, and brain glucose metabolism and mitochondrial respiration. These findings reveal that even short periods of ultra-processed semi-synthetic food consumption are sufficient to cause early olfactory and brain abnormalities, which has the potential to alter food choices and influence the risk of developing metabolic disease.

neuroscience↗

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. G0 cells extend a primary cilium, which functions as a signaling hub, but how it controls the quiescence program is not clear. Here, we report that primary cilia distinguish different states of cell cycle exit: quiescent myoblasts elaborate a primary cilium in vivo and in vitro, but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling, and elevated protein synthesis via inactivation of the translational repressor 4EBP1. Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program.\n\nSummary statementThe primary cilium contributes to reversible arrest (quiescence) in skeletal muscle myoblasts, by coordinating and dampening mitogenic signaling focused on a G2/M transcriptional program and protein synthesis.

cell biology↗

Comparative analyses of anther development in natural populations indicate premature degradation of sporogenous tissue as a cause of male sterility in Gaultheria fragrantissima

Gaultheria fragrantissima Wall. (Ericaceae) is a gynodioecious species having both hermaphrodite and male sterile plants. In this study, we present a comparative analysis of the different stages of anther development in naturally occuring hermaphrodite and male sterile populations of G. fragrantissima found in Meghalaya, India. While hermaphrodite flowers had well developed anther lobes, the male sterile flowers formed a white unorganized mass of tissues with a tuft of hairy outgrowth at the tip of the stamens. Histological analyses of progressive anther development in both the lines indicate an abnormal development of the sporogenous tissue in the developing anthers in the male steril line. While anther development in the hermaphrodite line was of the dicotyledonous type, the anthers of male sterile line showed progressive degradation of the sporogenous tissues and wall layers. Pollen development was also disrupted in male sterile line resulting in distorted pollen due to the irregular projection of exine wall. Our results suggest that premature degradation of the sporogenous tissues during anther development determines male sterility in G. fragrantissima.

plant biology↗

RNA polymerase II pausing regulates a quiescence-dependent transcriptional program, priming cells for cell cycle reentry

Adult stem cells persist in mammalian tissues by entering a state of reversible arrest or quiescence associated with low transcription. Using cultured myoblasts and primary muscle stem cells, we show that RNA synthesis is strongly repressed in G0, returning within minutes of activation. We investigate the underlying mechanism and reveal a role for promoter-proximal RNAPol II pausing: by mapping global Pol II occupancy using ChIP-seq, in conjunction with RNA-seq to identify repressed transcriptional networks unique to G0. Strikingly, Pol II pausing is enhanced in G0 on genes encoding regulators of RNA biogenesis (Ncl, Rps24, Ctdp1), and release of pausing is critical for cell cycle re-entry. Finally, we uncover a novel, unexpected repressive role of the super-elongation complex component Aff4 in G0-specific stalling. We propose a model wherein Pol II pausing restrains transcription to maintain G0, preconfigures gene networks required for the G0-G1 transition, and sets the timing of their transcriptional activation.

developmental biology↗