Mutation accumulation in H. sapiens F508del CFTR countermands dN/dS type genomic analysis.

Understanding the mechanisms that underlie de novo mutations (DNMs) can be essential for interpreting human evolution, including aspects such as rapidly diverging genes, conservation of non-coding regulatory elements, and somatic DNA adaptation, among others. DNM accumulation in Homo sapiens is often limited to evaluation of human trios or quads across a single generation. Moreover, human SNPs in exons, pseudogenes, or other non-coding elements can be ancient and difficult to date, including polymorphisms attributable to founder effects and identity by descent.

Relationships between genomic dissipation and de novo SNP evolution.

Patterns of single nucleotide polymorphisms (SNPs) in eukaryotic DNA are traditionally attributed to selective pressure, drift, identity descent, or related factors-without accounting for ways in which bias during de novo SNP formation, itself, might contribute. A functional and phenotypic analysis based on evolutionary resilience of DNA points to decreased numbers of non-synonymous SNPs in human and other genomes, with a predominant component of SNP depletion in the human gene pool caused by robust preferences during de novo SNP formation (rather than selective constraint). Ramifications of these findings are broad, belie a number of concepts regarding human evolution, and point to a novel interpretation of evolving DNA across diverse species.

Doppler Echocardiographic Phenotypes in Suspected 'Severe' Aortic Stenosis: Matrix-Based Approach to Diagnosis and Management.

Background: Among patients with suspected severe aortic stenosis (AS), Doppler echocardiographic (DE) data are often discordant, and further analysis is required for accurate diagnosis and optimal management. In this study, an automated matrix-based approach was applied to an echocardiographic database of patients with AS that identified 5 discrete echocardiographic data patterns, 1 concordant and 4 discordant, each reflecting a particular pathophysiology/measurement error that guides further workup and management.

Methods: A primary/discovery cohort of consecutive echocardiographic studies with at least 1 DE parameter of severe AS and analogous data from an independent secondary/validation cohort were retrospectively analyzed.

Barriers to Healthy Family Dinners and Preventing Child Obesity: Focus Group Discussions with Parents of 5-to-8-Year-Old Children.

Background: Although numerous physical and mental health benefits for children have been linked to family dinners, many families still do not have regular family meals together. This study sought to identify the barriers that keep families from having dinners together.

Methods: We interviewed 42 parents of 5-to-8-year-old children in small focus groups to identify barriers and challenges that keep families from having healthy and consistent dinners together.

Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1.

Malaria parasites break down host haemoglobin into peptides and amino acids in the digestive vacuole for export to the parasite cytoplasm for growth: interrupting this process is central to the mode of action of several antimalarial drugs. Mutations in the chloroquine (CQ) resistance transporter, pfcrt, located in the digestive vacuole membrane, confer CQ resistance in Plasmodium falciparum, and typically also affect parasite fitness. However, the role of other parasite loci in the evolution of CQ resistance is unclear.