Pearce, A. | bioRxiv Science

bioRxiv2023

Differential effects of prolonged aerobic and resistance exercise on cognitive functioning in sedentary young adults

ObjectivesInconsistencies in the literature make it difficult to outline the relationship between exercise and cognition in young adults. Our aim is to better understand the relationship between prolonged aerobic and resistance exercise and cognitive abilities in sedentary young adults, and how this relationship is mediated by changes in cardiovascular fitness. MethodsTwenty-three volunteers were recruited and assigned to two groups to complete one hour of continuous daily workout sessions of aerobic (SPIN) and anaerobic (SCSW) exercises over a 30 day period. Each subject was provided with a Polar-10 wearable to record the heart rate (HR) activity during the workout sessions. The workout sessions were completed during five consecutive days over four consecutive weeks. Each week, HR data were collected from the last workout session. Volunteers also completed a neurocognitive test battery (Cambridge Brain Sciences, CBS) each exercise session, including an additional baseline measure before exercise regime began. ResultsWe found that memory, reasoning and verbal abilities improved throughout the aerobic, but not the resistance exercise program. We found a positive correlation between heart rate index (HRI) and memory and reasoning test scores. We also found a negative correlation between reasoning ability and HRM (heart rate mean), and heart rate skewness (SKW). The results of a regression model to predict memory and reasoning abiltiies revealed that memory was best predicted by HRI and HRM, while the reasoning ability was best predicted by only HRI. ConclusionRegular aerobic exercises improved specific cognitive performance and it was possible to predict the performance by employing the HR parameters HRI and HRM.

neuroscience↗

bioRxiv2022

Cancer-Associated Mutations Enhance The Sensitivity Of The Trupath GαQ/11 System

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and are a common drug target. They can be stabilised in different conformational states by ligands to activate multiple transducers and effectors leading to a variety of cellular responses. The potential of agonists to activate select pathways has important implications for drug discovery. Thus, there is a clear need to profile the initial GPCR signal transduction event, activation of G proteins, to enhance understanding of receptor coupling and guide drug design. The BRET-based biosensor suite, TRUPATH, was recently developed to enable quantification of the activation profiles of all non-visual G proteins (excluding Golf and G14) and has since been utilised in numerous studies. However, it fails to detect Gq/11 activation for a number of GPCRs previously reported to display promiscuous secondary coupling to Gq/11. Here we report modifications to the Gq and G11 biosensors in the switch I region that prevent intrinsic GTPase activity (R183C/Q). Except for the PAC1R, substitution with cancer-associated mutations, Cys or Gln, significantly increased sensitivity to allow detection of robust, reliable, and representative Gq/11 responses to Class B1 GPCRs. We also demonstrate the utility of these modified biosensors for promiscuously coupled class A GPCR that have primary Gs-coupling. Thus, we propose that modification to Gq/11 may also be necessary in other biosensor systems to enable detection of Gq/11 activation.

pharmacology and toxicology↗