Single-molecule analysis of transcription activation: dynamics of SAGA coactivator recruitment.

Transcription activators are said to stimulate gene expression by 'recruiting' coactivators, yet this vague term fits multiple kinetic models. To directly analyze the dynamics of activator-coactivator interactions, single-molecule microscopy was used to image promoter DNA, a transcription activator and the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex within yeast nuclear extract. SAGA readily but transiently binds nucleosome-free DNA without an activator, while chromatin association occurs primarily when an activator is present.

The utility of multiple assessments in infancy and toddlerhood to predict middle childhood ADHD symptoms: Temperamental, behavioral, and genetic contributions.

Background: Early intervention is effective for reducing ADHD symptoms and related impairments, yet methods of identifying young children in need of services are lacking. Most early predictors of ADHD previously identified are of limited clinical utility. This study examines several theoretically relevant predictors of ADHD in infancy and toddlerhood and whether assessment at multiple time points improves prediction.

Mechanisms of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.

Transcription activators trigger transcript production by RNA Polymerase II (RNApII) via the Mediator coactivator complex. Here the dynamics of activator, Mediator, and RNApII binding at promoter DNA were analyzed using multi-wavelength single-molecule microscopy of fluorescently labeled proteins in budding yeast nuclear extract. Binding of Mediator and RNApII to the template required activator and an upstream activator sequence (UAS), but not a core promoter.

Drillers and bulldozer operators have experienced exceptionally high exposures to respirable crystalline silica in US surface coal mines.

Introduction: Previous studies suggest respirable crystalline silica (RCS) is an important driver of resurgent pneumoconiosis among US coal miners. Although greater attention has been focused on dust exposures in underground coal miners, surface miners are also at risk of severe disease. This study explores RCS exposure in this population.