Transfer RNA-mediated restoration of potassium current and electrical correction in premature termination long-QT syndrome hERG mutants.

Disease-causing premature termination codons (PTCs) individually disrupt the functional expression of hundreds of genes and represent a pernicious clinical challenge. In the heart, loss-of-function mutations in the hERG potassium channel account for approximately 30% of long-QT syndrome arrhythmia, a lethal cardiac disorder with limited treatment options. Premature termination of ribosomal translation produces a truncated and, for potassium channels, a potentially dominant-negative protein that impairs the functional assembly of the wild-type homotetrameric hERG channel complex. We used high-throughput flow cytometry and patch-clamp electrophysiology to assess the trafficking and voltage-dependent activity of hERG channels carrying patient PTC variants that have been corrected by anticodon engineered tRNA. Adenoviral-mediated expression of mutant hERG channels in cultured adult guinea pig cardiomyocytes prolonged action potential durations, and this deleterious effect was corrected upon adenoviral delivery of a human ArgUGA tRNA to restore full-length hERG protein. The results demonstrate mutation-specific, context-agnostic PTC correction and elevate the therapeutic potential of this approach for rare genetic diseases caused by stop codons.

The role of perceived social support on depression and sleep during the COVID-19 pandemic.

The aim of the present study was to examine the role of perceived social support pertaining to a range of psychological health outcomes amongst individuals undergoing social isolation and social distancing during COVID-19. A total of 2,020 participants provided responses to an online cross-sectional survey comprised of validated instruments including the Multidimensional Scale of Perceived Social Support (MSPSS), the Generalized Anxiety Disorder Scale (GAD-7), the Patient Health Questionnaire (PHQ-9), the Brief Irritability Test (BITe) and the UCLA Loneliness Scale (UCLA-LS). Individuals experiencing self-isolation had significantly higher rates of depression, irritability and loneliness compared to those who were not. The risk for elevated levels of depression symptoms was 63% lower in individuals who reported higher levels of social support compared to those with low perceived social support. Similarly, those with high social support had a 52% lower risk of poor sleep quality compared to those with low social support. Social support was found to be significantly associated with elevated risk for depression and poorer sleep quality. The results contribute to our understanding of differential psychological outcomes for individuals experiencing anti-pandemic measures.