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/PRNewswire/ The global hot plate stirrer market size is estimated to grow by USD 437.42 million from 2024-2028, according to Technavio. The market is. ....
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Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2′3′-cyclic GMP-AMP (cGAMP)1–7. The indiscriminate activity of cGAS towards DNA demands tight regulatory mechanisms that are necessary to maintain cell and tissue homeostasis under normal conditions. Inside the cell nucleus, anchoring to nucleosomes and competition with chromatin architectural proteins jointly prohibit cGAS activation by genomic DNA8–15. However, the fate of nuclear cGAS and its role in cell physiology remains unclear. Here we show that the ubiquitin proteasomal system (UPS) degrades nuclear cGAS in cycling cells. We identify SPSB3 as the cGAS-targeting substrate receptor that associates with the cullin–RING ubiquitin ligase 5 (CRL5) complex to ligate ubiquitin onto nuclear cGAS. A cryo-electron microscopy structure of nucleosome-bound cGAS in a complex ....
Animals perform flexible goal-directed behaviours to satisfy their basic physiological needs1–12. However, little is known about how unitary behaviours are chosen under conflicting needs. Here we reveal principles by which the brain resolves such conflicts between needs across time. We developed an experimental paradigm in which a hungry and thirsty mouse is given free choices between equidistant food and water. We found that mice collect need-appropriate rewards by structuring their choices into persistent bouts with stochastic transitions. High-density electrophysiological recordings during this behaviour revealed distributed single neuron and neuronal population correlates of a persistent internal goal state guiding future choices of the mouse. We captured these phenomena with a mathematical model describing a global need state that noisily diffuses across a shifting energy landscape. Model simulations successfully predicted behavioural and neural data, including population ne ....