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Biology subjects

Gowda, R.

Publications and source records attributed to Gowda, R..

2 recordsLinked to original sources

Density-dependent plasticity of female reproductive output mediates Allee effects in Drosophila melanogaster

Allee effects are positive relationships between components of individual fitness and the number or density of individuals in a population. Negative density effects are well documented in Drosophila melanogaster across life stages, while Allee effects are rare and largely confined to the larval stages. However, despite the costs of high density, adult flies are found to exhibit attraction to same-sex conspecifics, suggesting some fitness value to the presence of conspecifics. We measured fitness related traits of singly mated-females housed at same-sex densities of 1, 2, or 10 and found clear reductions in lifetime reproductive output at low densities. Additionally, these females concentrated reproductive effort within early adulthood, albeit without improving estimates of fitness. When housed at variable densities, females altered their reproductive output in response to immediate densities, but were unable to improve it unless remating was possible, indicating an interaction between mating and density. Overall, our findings suggest that reproductive plasticity in response to the presence of conspecifics mediates positive effects of density on fitness in female Drosophila melanogaster. Understanding the physiological and ecological bases of such plasticity may help explain the evolution of social tendency in the fly.

evolutionary biology↗

Suppression of p16 increases nucleotide synthesis via mTORC1

Reprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogene-induced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis. Whether p16 loss affects pro-tumorigenic metabolism is unclear. We report that suppression of p16 plays a central role in reprogramming metabolism by increasing nucleotide synthesis. This occurred via activation of mTORC1 signaling, which directly mediated increased translation of the mRNA encoding ribose-5-phosphate isomerase A (RPIA), a pentose phosphate pathway enzyme. p16 loss correlated with activation of the mTORC1-RPIA axis in multiple cancer types. Suppression of RPIA inhibited proliferation only in p16-low cells by inducing senescence both in vitro and in vivo. These data reveal the molecular basis whereby p16 loss modulates pro-tumorigenic metabolism through mTORC1-mediated upregulation of nucleotide synthesis and reveals a metabolic vulnerability of p16-null cancer cells.\n\nHighlightsO_LImTORC1 is activated by p16 knockdown to increase nucleotide synthesis and bypass senescence\nC_LIO_LImTORC1 directly increases translation RPIA to increase ribose-5-phosphate\nC_LIO_LIActivation of mTORC1 pathway downstream of p16 suppression is independent of RB\nC_LIO_LIRPIA suppression induces senescence only in cells and tumors with low p16\nC_LI

cancer biology↗