Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols.

The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. However, some receptors, including the mu opioid receptor, are non-functional, which may be due to the presence of the fungal sterol ergosterol instead of cholesterol. Here we engineer yeast to produce cholesterol and introduce diverse mu, delta, and kappa opioid receptors to create sensitive opioid biosensors that recapitulate agonist binding profiles and antagonist inhibition. Additionally, human mu opioid receptor variants, including those with clinical relevance, largely display expected phenotypes. By testing mu opioid receptor-based biosensors with systematically adjusted cholesterol biosynthetic intermediates, we relate sterol profiles to biosensor sensitivity. Finally, we apply sterol-modified backgrounds to other human receptors revealing sterol influence in SSTR5, 5-HTR4, FPR1, and NPY1R signaling. This work provides a platform for generating human G protein-coupled receptor-based biosensors, facilitating receptor deorphanization and high-throughput screening of receptors and effectors.

The effects of a mid-day nap on the neurocognitive performance of first-year medical residents: a controlled interventional pilot study.

PURPOSE: Despite shorter duty hours, fatigue remains a problem among medical residents. The authors tested the effect of a short, mid-day nap on the cognitive functioning and alertness of first-year internal medicine (IM) residents during normal duty hours. METHOD: This was a controlled, interventional study performed between July 2008 and April 2010. The authors recruited a nap group of 18 residents and a rest (control) group of 11 residents. Investigators connected all participants to an ambulatory sleep monitor before the beginning of their shifts in order to monitor rolling eye movements, a proxy for attention failures. At mid-day, both groups took Conner's Continuous Performance Test (CPT II) to evaluate their cognitive functioning and then were placed in a reclining chair designed for napping. The authors instructed nap group residents to nap for up to 20 minutes and chatted with control group residents to prevent them from napping. All residents took the CPT II again immediately after the intervention. Residents' attention failures were recorded until the end of the workday. The authors compared the mean outcome parameters of the two groups through analysis of variance, using effect-of-treatment and baseline covariates. RESULTS: Nap group participants slept a mean of 8.4±3.0 minutes. Compared with controls whose cognitive functioning and number of attention failures did not change from morning to afternoon, the nap group's cognitive functioning improved and their number of attention failures decreased. CONCLUSIONS: A short, mid-day nap can improve cognitive functioning and alertness among first-year IM residents.