To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.
View Article and Find Full Text PDFBackground: Tuberous sclerosis complex (TSC) is a multisystemic genetic disorder with clinical variability. As the needs of children with TSC may differ, parenting demands may similarly differ. Characterizing parenting stress, or emotional maladaptation from parenting duties, can enable health care providers to assist parents of children with TSC.
View Article and Find Full Text PDFJ Exp Psychol Learn Mem Cogn
December 2024
Previous research has demonstrated that attentional prioritization is shaped by prior experience of reward uncertainty: Attention is more likely to be captured by a stimulus associated with a variable (uncertain) reward than a stimulus that provides diagnostic information about available reward. This finding is noteworthy, because it runs counter to the principle that cognition is motivated to reduce uncertainty and hence surprise. Here we investigated whether this pattern of uncertainty-modulated attentional capture (UMAC) reflects a process of attention for learning, wherein uncertainty-related stimuli are prioritized in an attempt to learn about their true predictive status.
View Article and Find Full Text PDFOsteoarthritis (OA) is a chronic and degenerative joint disease affecting more than 500 million patients worldwide with no disease-modifying treatment approved to date. Several publications report on the transforming growth factor β-activated kinase 1 (TAK1) as a potential molecular target for OA, with complementary anti-catabolic and anti-inflammatory effects. We report herein on the development of TAK1 inhibitors with physicochemical properties suitable for intra-articular injection, with the aim to achieve high drug concentration at the affected joint, while avoiding severe toxicity associated with systemic inhibition.
View Article and Find Full Text PDFJudge, LW, Marsh, JP, Petersen, JC, Pearson, D, and Bellar, D. Unveiling gaps in high school strength and conditioning: CSCS certification, coaching leadership and facilities. J Strength Cond Res 38(12): 2088-2098, 2024-The aim of this study was to examine the prevalence of Certified Strength and Conditioning Specialist (CSCS) and/or dedicated strength coaches overseeing strength and conditioning facilities (SCFs) at the high school level in a Southwestern state.
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