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Vang Melgaard posted an update 2 months ago
We investigated how differential payoffs affect the temporal discrimination of humans. In a temporal bisection task, participants learned to make one response after a short sample and another after a long sample. When presented with a range of intermediate samples, the proportion of responses fitted well a Gaussian-like distribution function characterized by a location (bias), a scale (sensitivity) parameter, and two asymptote (discrimination) parameters. In Experiment 1, when one response yielded more reinforcers than the other, parameters were unaltered, but overall responses increased for the response producing higher payoffs. In Experiment 2, we used a video game to track motion during the sample and participants learned to approach the “short” response location at sample onset and remain there before departing to the “long” location on long trials. Departure times were shorter when “long” choices produced higher payoffs than “short” and matched well the shifted psychometric functions. However, on some trials, subjects were biased for short, returning to the short side after having departed towards long. Evidence was found for effects of differential payoffs on response bias, but discrimination and sensitivity did not change consistently. These results favor a behavioral account of timing processes.The hypothalamic neuropeptide 26RFa is the most recently identified member of the RFamide peptide family, and this 26RFa signaling system has been shown to be implicated in regulating a variety of physiological processes. In zebrafish,26RFa and two putative receptors, DrGPR103A and DrGPR103B, have been in silico identified, and in vivo data derived from overexpression and loss of function mutation experiments suggest the 26RFa signaling system plays an important role in the hypothalamic regulation of sleep. However, the biochemical and pharmacological information on DrGPR103A/B receptors is still unknown. Here, after cloning of cDNAs of two putative 26RFa receptor genes, DrGPR103A and B, from the total RNA of zebrafish whole body, functional assays demonstrated that both receptors were activated by synthetic zebrafish 26RFa neuropeptide, leading to a significant increase in CRE-driven luciferase activity and intracellular Ca2+ mobilization in a Gαq inhibitor- and Gαi/o inhibitor-sensitive manner. Upon activation by 26RFa, DrGPR103A and B evoked ERK1/2 phosphorylation and underwent internalization. Further functional determination also revealed that zebrafish kisspeptin-1 exhibited a slight potency for activating both DrGPR103A and B, and vice versa, zebrafish 26RFa also showed some activity at zebrafish GPR54A and B. Our findings provided evidence that zebrafish GPR103A and B are two functional Gαq- and Gαi/o-dually coupled receptors for 26RFa, enabling the further elucidation of the endocrinological roles of zebrafish 26RFa signaling system in the regulation of physiological activities.Activation process of mature B cell is predominantly driven by specific BCR-mediated pathways, switched on and off all through late B cell differentiation stages. Mice deficient for APS, a member of the Lnk/SH2B family of adaptor proteins, showed that this adaptor plays a BCR-mediated regulatory role in mature B cells. However, the intermediates involved in this adaptor modulating functions in B cells are still unknown. In the present study, we investigated the role of APS in regulating BCR signalling notably through cytoskeleton remodeling in mature B cells. Herein, we showed that APS function is stage specific, as it exclusively intervenes in mature B cells. Upon activation, APS colocalizes with the BCR and associates with important regulators of BCR signalling, such as Syk and Cbl kinase. Importantly, APS interferes, as a scaffold protein, with the stability of Syk kinase by recruiting Cbl. This function is mainly mediated by APS SH2 domain, which regulates BCR-evoked cell dynamics. Our findings thus reveal that APS plays a regulatory role in BCR-induced responses by specifically modulating its interacting partners, which positions APS as a relevant modulator of BCR signalling in mature B cells.A gene encoding creatine kinase was identified in two cryptosporidia species, Cryptosporidium muris and C. andersonii. They were syntenic and shared 91% identity 94% identity at the amino acid level and nucleotide levels respectively. The C. muris creatine kinase was characterized biochemically and shown to phosphorylate both creatine and glycocyamine with a 20-fold greater preference for creatine. The observed catalytic turnover with creatine was kcat = 30 s-1 with a catalytic efficiency of 15.4 mM-1 s-1. Staurosporine datasheet These values were within the range observed for other creatine kinases. A search of all the apicomplexa genomes available on EuPathDB did not reveal any other phosphagen kinase genes raising the possibility of horizontal gene transfer. However, no definitive conclusion could be drawn regarding this hypothesis given the massive amount of gene loss in the apicomplexa species which are primarily parasitic species. The implications of a creatine kinase in the parasites’ infection cycle are discussed.Background While patients with cardiovascular disease face excess risks of severe illness with coronavirus disease-2019 (COVID-19), there may be indirect consequences of the pandemic on this high-risk patient segment. Objectives To examine longitudinal trends in hospitalizations for acute cardiovascular conditions across a tertiary care healthcare system. Methods We tracked acute cardiovascular hospitalizations between January 1st, 2019 and March 31st, 2020. We estimated daily hospitalization rates using negative binomial models. Temporal trends in hospitalization rates were compared across the first 3 months of 2020, with the first 3 months of 2019 as a reference. Results From January 1, 2019 to March 31, 2020, 6,083 patients experienced 7,187 hospitalizations for primary acute cardiovascular reasons. There was 43.4% (27.4% to 56.0%) fewer estimated daily hospitalizations in March 2020 as compared with March 2019 (P less then 0.001). The daily rate of hospitalizations did not change throughout 2019 (-0.01% per day [-0.