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Repeated blood feedings are required for adult female mosquitoes to maintain their gonadotrophic cycles, enabling them to be important pathogen carriers of human diseases. Elucidating the molecular mechanism underlying developmental switches between these mosquito gonadotrophic cycles will provide valuable insight into mosquito reproduction and could aid in the identification of targets to disrupt these cycles, thereby reducing disease transmission. We report here that the transcription factor ecdysone-induced protein 93 (E93), previously implicated in insect metamorphic transitions, plays a key role in determining the gonadotrophic cyclicity in adult females of the major arboviral vector Aedes aegypti Expression of the E93 gene in mosquitoes is down-regulated by juvenile hormone (JH) and up-regulated by 20-hydroxyecdysone (20E). We find that E93 controls Hormone Receptor 3 (HR3), the transcription factor linked to the termination of reproductive cycles. Moreover, knockdown of E93 expression via RNAi impaired fat body autophagy, suggesting that E93 governs autophagy-induced termination of vitellogenesis. E93 RNAi silencing prior to the first gonadotrophic cycle affected normal progression of the second cycle. Finally, transcriptomic analysis showed a considerable E93-dependent decline in the expression of genes involved in translation and metabolism at the end of a reproductive cycle. In conclusion, our data demonstrate that E93 acts as a crucial factor in regulating reproductive cycle switches in adult female mosquitoes.The TGFβ cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor α-like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated Gfral Cre and conditional Gfral CreERT mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating Gfral Cre -expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated pathophysiologic signals to suppress nutrient uptake and absorption.Complex systems can convert energy imparted by nonequilibrium forces to regulate how quickly they transition between long-lived states. While such behavior is ubiquitous in natural and synthetic systems, currently there is no general framework to relate the enhancement of a transition rate to the energy dissipated or to bound the enhancement achievable for a given energy expenditure. We employ recent advances in stochastic thermodynamics to build such a framework, which can be used to gain mechanistic insight into transitions far from equilibrium. We show that under general conditions, there is a basic speed limit relating the typical excess heat dissipated throughout a transition and the rate amplification achievable. We illustrate this tradeoff in canonical examples of diffusive barrier crossings in systems driven with autonomous and deterministic external forcing protocols. In both cases, we find that our speed limit tightly constrains the rate enhancement.The earliest dinosaurs (theropods and sauropodomorphs) are found in fossiliferous early Late Triassic strata dated to about 230 million years ago (Ma), mainly in northwestern Argentina and southern Brazil in the Southern Hemisphere temperate belt of what was Gondwana in Pangea. Sauropodomorphs, which are not known for the entire Triassic in then tropical North America, eventually appear 15 million years later in the Northern Hemisphere temperate belt of Laurasia. The Pangea supercontinent was traversable in principle by terrestrial vertebrates, so the main barrier to be surmounted for dispersal between hemispheres was likely to be climatic; in particular, the intense aridity of tropical desert belts and unstable climate in the equatorial humid belt accompanying high atmospheric pCO2 that characterized the Late Triassic. We revisited the chronostratigraphy of the dinosaur-bearing Fleming Fjord Group of central East Greenland and, with additional data, produced a correlation of a detailed magnetostratigraphy from more than 325 m of composite section from two field areas to the age-calibrated astrochronostratigraphic polarity time scale. This age model places the earliest occurrence of sauropodomorphs (Plateosaurus) in their northernmost range to ∼214 Ma. The timing is within the 215 to 212 Ma (mid-Norian) window of a major, robust dip in atmospheric pCO2 of uncertain origin but which may have resulted in sufficiently lowered climate barriers that facilitated the initial major dispersal of the herbivorous sauropodomorphs to the temperate belt of the Northern Hemisphere. Indications are that carnivorous theropods may have had dispersals that were less subject to the same climate constraints.Experiencing some early life adversity can have an “inoculating” effect that promotes resilience in adulthood. selleck chemicals llc However, the mechanisms underlying stress inoculation are unknown, and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal days 2 to 9 and their dams were exposed to a low-resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but in males, LBN reduced impulsive choice compared to controls. LBN males also self-administered less morphine and had a lower breakpoint on a progressive ratio reinforcement schedule than controls. These effects of LBN on addiction-related behaviors were not found in females. Because the nucleus accumbens (NAc) mediates these behaviors, we tested whether LBN altered NAc physiology in drug-naïve and morphine-exposed rats.