Mental Attention: Improving Motor Imagery by Adding Focus

Research has delineated the values of motor imagery for physical tasks; subjects consistently outperform control groups when mentally rehearsing a task and transferring it to a physical medium. Additionally, an external focus of attention has been shown to increase accuracy and performance while performing a physical task as compared to an internal focus. There had been no previous research addressing a focus of attention while mentally rehearsing a task. Therefore, the objective of this study was to see if varying foci of attention during practice of a dart-throwing task could enhance mental rehearsal. Consistency was significantly depressed for mental internal and control conditions I the first test block

Mental Attention: Improving Motor Imagery by Adding Focus

Research has delineated the values of motor imagery for physical tasks; subjects consistently outperform control groups when mentally rehearsing a task and transferring it to a physical medium. Additionally, an external focus of attention has been shown to increase accuracy and performance while performing a physical task as compared to an internal focus. There had been no previous research addressing a focus of attention while mentally rehearsing a task. Therefore, the objective of this study was to see if varying foci of attention during practice of a dart-throwing task could enhance mental rehearsal. Consistency was significantly depressed for mental internal and control conditions in the first test block

Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening

International audiencetrans-Sialidase from Trypanosoma cruzi (TcTS) has emerged as a potential drug target for treatment of Chagas disease. Here, we report the results of virtual screening for the discovery of novel TcTS inhibitors, which targeted both the sialic acid and sialic acid acceptor sites of this enzyme. A library prepared from the Evotec database of commercially available compounds was screened using the molecular docking program GOLD, following the application of drug-likeness filters. Twenty-three compounds selected from the top-scoring ligands were purchased and assayed using a fluorimetric assay. Novel inhibitor scaffolds, with IC 50 values in the submillimolar range were discovered. The 3-benzothiazol-2-yl-4-phenyl-but-3-enoic acid scaffold was studied in more detail, and TcTS inhibition was confirmed by an alternative sialic acid transfer assay. Attempts to obtain crystal structures of these compounds with TcTS proved unsuccessful but provided evidence of ligand binding at the active site

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97

Abstract The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP’s potential as a novel therapeutic target