Our data indicate that pharmacological activation of midbrain dopamine neurons using a ghrelin receptor agonist does not affect auditory fear extinction.  https://www.selleckchem.com/products/resatorvid.html  We also investigated the effect of non-pharmacological manipulation of the ghrelin system on auditory fear processing. However, we found that neither overnight food deprivation nor genetic ablation of the ghrelin receptor had a significant effect on auditory fear extinction. We conclude that the effects of manipulation of the ghrelin system on fear processing are subject to boundary conditions that remain poorly understood. This article is protected by copyright. All rights reserved.Previous results show that juvenile shortnose sturgeon are steady swimmers and, compared with salmonids, generally have low critical swimming (UCrit) and endurance swimming capacities. Most studies on swimming capacities of sturgeon, and other fishes, include those where fish have only been swum once and metrics of swimming performance are assessed (e.g., time swum, speed achieved). Under natural conditions, there are ample instances where fish would undergo multiple swimming cycles when traversing fish ways, culverts and other sources of fast water flow. While some evidence exists for salmonids, the effects of repeat swimming are not well known for sturgeon. The current study consisted of two experiments. The first examined the critical swimming (UCrit) of juvenile shortnose sturgeon following 3 consecutive swimming trials with a 30 minute recovery period between subsequent tests. The second examined the endurance swimming capacities of juvenile shortnose sturgeon following 3 consecutive swimming trials with a 60 minute recovery period between subsequent tests. Our findings indicate that (i) UCrit was consistent (~2 Body lengths/s) among swimming trials; (ii) significant individual variation exists between individuals in the endurance swimming trials; and (iii) consistent results exist for individuals across swimming trials in both the UCrit and the endurance swimming tests. These results suggest that juvenile shortnose sturgeon have a high recovery capacity, and their behaviour and morphology likely reflect aspects of their swimming capacities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.In Fisher's model of sexual selection, a female preference for a male trait spreads together with the trait because their genetic bases become correlated. This can be interpreted as a "greenbeard" system a preference gene, by inducing a female to mate with a trait-bearing male, favors itself because the male is disproportionately likely also to carry the preference gene. Here, we use this logic to argue that Fisherian sexual selection in diploids proceeds via two channels (i) trait-bearing males are disproportionately the product of matings between preference-bearing mothers and trait-bearing fathers, and thus trait and preference genes are correlated "in trans"; (ii) trait and preference genes come into gametic phase disequilibrium, and thus are correlated "in cis." Gametic phase disequilibrium is generated by three distinct mechanisms that we identify. The trans channel does not operate when sexual selection is restricted to the haploid phase, and therefore represents a fundamental difference between haploid and diploid models of sexual selection. We show that the cis and trans channels contribute equally to the spread of the preference when recombination between the preference and trait loci is free, but that the trans channel is substantially more important when linkage is tight. © 2020 The Authors. Evolution © 2020 The Society for the Study of Evolution.Bilirubin, the end product of heme redox metabolism, has cytoprotective properties and is an essential metabolite associated with cardiovascular disease, inflammatory bowel disease, type 2 diabetes, and neurodegenerative diseases including Parkinson's disease (PD). PD is characterized by progressive degeneration of nigral dopaminergic neurons and is associated with elevated oxidative stress due to mitochondrial dysfunction. In this study, using a ratiometric bilirubin probe, we revealed that the mitochondrial inhibitor, rotenone, which is widely used to create a PD model, significantly decreased intracellular bilirubin levels in HepG2 cells. Chemical screening showed that BRUP-1 was a top hit that restored cellular bilirubin levels that were lowered by rotenone. We found that BRUP-1 up-regulated the expression level of heme oxygenase-1 (HO-1), one of the rate-limiting enzyme of bilirubin production via nuclear factor erythroid 2-related factor 2 (Nrf2) activation. In addition, we demonstrated that this Nrf2 activation was due to a direct inhibition of the interaction between Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) by BRUP-1. Both HO-1 up-regulation and bilirubin restoration by BRUP-1 treatment were significantly abrogated by Nrf2 silencing. In neuronal PC12D cells, BRUP-1 also activated the Nrf2-HO-1 axis and increased bilirubin production, resulted in the suppression of neurotoxin-induced cell death, reactive oxygen species production, and protein aggregation, which are hallmarks of PD. Furthermore, BRUP-1 showed neuroprotective activity against rotenone-treated neurons derived from induced pluripotent stem cells. These findings provide a new member of Keap1-Nrf2 direct inhibitors and suggest that chemical modulation of heme metabolism using BRUP-1 may be beneficial for PD treatment. © 2020 International Society for Neurochemistry.PURPOSE Automatic segmentation offers many benefits for radiotherapy treatment planning; however, the lack of publicly available benchmark datasets limits the clinical use of automatic segmentation. In this work, we present a well-curated CT dataset of high-quality manually drawn contours from patients with thoracic cancer that can be used to evaluate the accuracy of thoracic normal tissue auto-segmentation systems. ACQUISITION AND VALIDATION METHODS CT scans of 60 patients undergoing treatment simulation for thoracic radiotherapy were acquired from three institutions MD Anderson Cancer Center, Memorial Sloan-Kettering Cancer Center, and the MAASTRO clinic. Each institution provided CT scans from 20 patients, including mean intensity projection (4D CT), exhale phase (4D CT), or free-breathing CT scans depending on their clinical practice. All CT scans covered the entire thoracic region with a 50-cm field of view and slice spacing of 1 mm, 2.5 mm, or 3 mm. Manual contours of left/right lungs, esophagus, heart, and spinal cord were retrieved from the clinical treatment plans.