Increased ACTL6A occupancy within mSWI/SNF chromatin remodelers drives human squamous cell carcinoma.

Mammalian SWI/SNF (BAF) chromatin remodelers play dosage-sensitive roles in many human malignancies and neurologic disorders. The gene encoding the BAF subunit actin-like 6a (ACTL6A) is amplified early in the development of many squamous cell carcinomas (SCCs), but its oncogenic role remains unclear. Here we demonstrate that ACTL6A overexpression leads to its stoichiometric assembly into BAF complexes and drives their interaction and engagement with specific regulatory regions in the genome.

Distress among cancer patients attending rehabilitation in the community.

Purpose: The aim of this study is to identify sources of distress among cancer patients attending rehabilitation in the community.

Methods: Participants were 430 patients recruited from a cancer rehabilitation center in Singapore between 2017 and 2018, who had rated their distress using the distress thermometer (DT) and indicated associated problems on the problem list. Chi-square tests were used to detect differences in the reported symptoms among three age groups.

Psychometric properties of reverse-scored items on the CES-D in a sample of ethnically diverse older adults.

Reverse-scored items on assessment scales increase cognitive processing demands and may therefore lead to measurement problems for older adult respondents. In this study, the objective was to examine possible psychometric inadequacies of reverse-scored items on the Center for Epidemiologic Studies Depression Scale (CES-D) when used to assess ethnically diverse older adults. Using baseline data from a gerontologic clinical trial (n = 460), we tested the hypotheses that the reversed items on the CES-D (a) are less reliable than nonreversed items, (b) disproportionately lead to intraindividually atypical responses that are psychometrically problematic, and (c) evidence improved measurement properties when an imputation procedure based on the scale mean is used to replace atypical responses.

An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency.

Mammalian SWI/SNF [also called BAF (Brg/Brahma-associated factors)] ATP-dependent chromatin remodeling complexes are essential for formation of the totipotent and pluripotent cells of the early embryo. In addition, subunits of this complex have been recovered in screens for genes required for nuclear reprogramming in Xenopus and mouse embryonic stem cell (ES) morphology. However, the mechanism underlying the roles of these complexes is unclear.

Enhanced NFATc1 nuclear occupancy causes T cell activation independent of CD28 costimulation.

TCR signals induce the nuclear localization of NFATc proteins, which are removed from the nucleus after rephosphorylation by glycogen synthase kinase 3 and other kinases. Rapid nuclear export might allow continuous monitoring of receptor occupancy, making the transcriptional response proportional to the duration of TCR/CD28 signaling. To investigate this possibility, we analyzed mice in which T cells express a NFATc1 variant (NFATc1(nuc)) with serine-to-alanine changes at the glycogen synthase kinase 3 phosphorylation sites.

A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis.

The delicate leaflets that make up vertebrate heart valves are essential for our moment-to-moment existence. Abnormalities of valve formation are the most common serious human congenital defect. Despite their importance, relatively little is known about valve development.

Identification of a polymorphic, neuron-specific chromatin remodeling complex.

A variety of chromatin remodeling complexes are thought to assist sequence-specific transcription factors. The complexes described to date are expressed ubiquitously, suggesting that they have general transcriptional functions. We show that vertebrate neurons have a specialized chromatin remodeling complex, bBAF, specifically containing the actin-related protein, BAF53b, which is first expressed in postmitotic neurons at about murine embryonic day 12.