Mismatch negativity affects muscle fatigue during repeated contraction trials of different durations

We examined the effect of involuntary attention switching (related to mismatch negativity generation in the oddball paradigm) on fatigue development during trials of different durations. The experiment consisted of two trials, long (40 minutes) and short (15 minutes), and two experimental conditions in each trial: the simple reaction task (deviants-only paradigm) and the stimuli recognition task (oddball paradigm). In each condition, a participant responded to each target acoustic stimulus by squeezing a handgrip dynamometer. We found the significantly lower rates of fatigue development in the short-trial deviants-only paradigm compared to the long trial. The short- and the long-trial oddball paradigms differed significantly from both the short- and the long-trial deviants-only paradigms. The results demonstrated that the fatigue developed differently depending on the expected trial duration. The involuntary activation of attention broke this subconscious regulative mechanism leading to increase of the compression force during the long trial and its decrease during the short

Structure-guided combination therapy to potently improve the function of mutant CFTRs

Available drugs are unable to effectively rescue the folding defects in vitro and ameliorate the clinical-phenotype of cystic fibrosis (CF), caused by deletion of F508 (ΔF508 or F508del) and some point mutations in the CF transmembrane conductance regulator (CFTR), a plasma membrane (PM) anion channel. To overcome the corrector efficacy ceiling, here we show that compounds targeting distinct structural defects of CFTR can synergistically rescue mutants expression and function at the PM. High throughput cell-based screens and mechanistic analysis identified three small-molecule series that target defects at the nucleotide binding domain (NBD1), NBD2 and their membrane spanning domains (MSDs) interfaces. While individually these compounds marginally improve ΔF508-CFTR folding efficiency, function, and stability, their combinations lead to ~50-100% of wild type-level correction in immortalized and primary human airway epithelia, and in mouse nasal epithelia. Likewise, corrector combinations were effective for rare missense mutations in various CFTR domains, probably acting via structural allostery, suggesting a mechanistic framework for their broad application

Abstracts of The Second Eurasian RISK-2020 Conference and Symposium

This abstract book contains abstracts of the various research ideas presented at The Second Eurasian RISK-2020 Conference and Symposium.The RISK-2020 Conference and Symposium served as a perfect venue for practitioners, engineers, researchers, scientists, managers and decision-makers from all over the world to exchange ideas and technology about the latest innovation developments dealing with risk minimization