Sequence-Dependent Repolarization Is Modulated by Endogenous Action Potential Duration Gradients Rather Than Electrical Coupling in Ventricular Myocardium.

Background: Previous studies suggest the relationship between activation time (AT) and action potential duration (APD) in the heart is dependent on electrotonic coupling, but this has not been directly tested. This study assessed whether acute changes in electrical coupling, or other determinants of conduction or repolarization, modulate APD heterogeneity.

Methods And Results: Langendorff-perfused guinea pig hearts were epicardially paced and optically mapped after treatment with the gap junction uncoupler carbenoxolone, ephaptic uncoupler mannitol, ephaptic enhancer dextran 2MDa, sodium channel inhibitor flecainide, or rapid component of the delayed rectifier potassium channel inhibitor E4031.

Multi-ancestry Genome Wide Association Study Meta-analysis of Non-syndromic Orofacial Clefts.

Non-syndromic orofacial clefts (NSOC) are common craniofacial birth defects, and result from both genetic and environmental factors. NSOC include three major sub-phenotypes: non-syndromic cleft lip with palate (NSCLP), non-syndromic cleft lip only (NSCLO) and non-syndromic cleft palate only (NSCPO), NSCLP and NSCLO are also sometimes grouped as non-syndromic cleft lip with or without cleft palate (NSCL/P) based on epidemiology. Currently known loci only explain a limited proportion of the heritability of NSOC.

Syndrome-informed phenotyping identifies a polygenic background for achondroplasia-like facial variation in the general population.

Human craniofacial shape is highly variable yet highly heritable with numerous genetic variants interacting through multiple layers of development. Here, we hypothesize that Mendelian phenotypes represent the extremes of a phenotypic spectrum and, using achondroplasia as an example, we introduce a syndrome-informed phenotyping approach to identify genomic loci associated with achondroplasia-like facial variation in the general population. We compare three-dimensional facial scans from 43 individuals with achondroplasia and 8246 controls to calculate achondroplasia-like facial scores.

Mapping genes for human face shape: Exploration of univariate phenotyping strategies.

Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g.

Sex, cells, and metabolism: Androgens temper Th17-mediated immunity.

Sex-based differences in autoimmune disease susceptibility have long been recognized, prompting investigations into how sex hormones influence immunity. Recent advances suggest that hormones may shape immune responses by altering cellular metabolism. In this issue of the JCI, Chowdhury et al.