Med15 is a general transcriptional regulator and tail module subunit within the RNA Pol II mediator complex. The Med15 protein has a well-structured N-terminal KIX domain, three activator binding domains (ABDs) and several naturally variable polyglutamine (poly-Q) tracts (Q1, Q2, Q3) embedded in an intrinsically disordered central region, and a C-terminal mediator association domain (MAD). We investigated how the presence of ABDs and changes in length and composition of poly-Q tracts influences Med15 activity using phenotypic, gene expression, transcription factor interaction and phase separation assays of truncation, deletion, and synthetic alleles.
View Article and Find Full Text PDFThe objective of this study was to identify utilization of housing support provided by the U.S. Department of Housing and Urban Development (HUD) among autistic people in the U.
View Article and Find Full Text PDFThis study examined whether exposure to different patterns of poverty-related adversity (i.e., risk profiles) was associated with longitudinal child outcomes and children's response to Head Start.
View Article and Find Full Text PDFBrain disorders, in particular mental disorders, might be effectively treated by direct electrical brain stimulation, but clinical progress requires understanding of therapeutic mechanisms. Animal models have not helped, because there are no direct animal models of mental illness. Here, we propose a potential path past this roadblock, by leveraging a common ingredient of most mental disorders: impaired cognitive control.
View Article and Find Full Text PDFIt has been challenging to determine how a ligand that binds to a receptor activates downstream signaling pathways and to predict the strength of signaling. The challenge is compounded by functional selectivity, in which a single ligand binding to a single receptor can activate multiple signaling pathways at different levels. Spectroscopic studies show that in the largest class of cell surface receptors, 7 transmembrane receptors (7TMRs), activation is associated with ligand-induced shifts in the equilibria of intracellular pocket conformations in the absence of transducer proteins.
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