A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair.

DHX9 is a multifunctional DExH-box RNA helicase with important roles in the regulation of transcription, translation, and maintenance of genome stability. Elevated expression of DHX9 is evident in multiple cancer types, including colorectal cancer (CRC). Microsatellite instable-high (MSI-H) tumors with deficient mismatch repair (dMMR) display a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery.

Video-Based Remote Administration of Cognitive Assessments and Interventions: a Comparison with In-Lab Administration.

While remote data collection is not a new concept, the quality and psychometric properties of data collected remotely often remain unclear. Most remote data collection is done via online survey tools or web-conferencing applications (i.e.

Multisensory Facilitation of Working Memory Training.

Research suggests that memorization of multisensory stimuli benefits performance compared to memorization of unisensory stimuli; however, little is known about multisensory facilitation in the context of working memory (WM) training and transfer. To investigate this, 240 adults were randomly assigned to an N-back training task that consisted of visual-only stimuli, alternating visual and auditory blocks, or audio-visual (multisensory) stimuli, or to a passive control group. Participants in the active groups completed 13 sessions of N-back training (6.

c-Myc activates BRCA1 gene expression through distal promoter elements in breast cancer cells.

Background: The BRCA1 gene plays an important role in the maintenance of genomic stability. BRCA1 inactivation contributes to breast cancer tumorigenesis. An increasing number of transcription factors have been shown to regulate BRCA1 expression.

dsRNA activation of endothelin-1 and markers of vascular activation in endothelial cells and fibroblasts.

Background: In patients with systemic sclerosis (SSc), the relationship between innate immune activation, represented by increased expression of interferon (IFN)-regulated genes, and vascular injury/activation, manifest by increased endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE1) and intercellular adhesion molecule-1, is uncertain.

Objective: To investigate the potential roles of innate immune ligands in both these pathogenic pathways.

Methods: The effect of known Toll-like receptor (TLR) ligands was tested in vitro on dermal microvascular and pulmonary arterial endothelial cells, and on dermal fibroblasts cultured from healthy controls and patients with SSc.

Poly(I:C) drives type I IFN- and TGFβ-mediated inflammation and dermal fibrosis simulating altered gene expression in systemic sclerosis.

Immune activation of fibrosis likely has a crucial role in the pathogenesis of systemic sclerosis (SSc). The aim of this study was to better understand the innate immune regulation and associated IFN- and transforming growth factor-β (TGFβ)-responsive gene expression in SSc skin and dermal fibroblasts, in particular the effect of different Toll-like receptor (TLR) ligands. To better understand the relationship between inflammation and fibrosis in vivo, we developed a murine model for chronic innate immune stimulation.

CpG island methylation affects accessibility of the proximal BRCA1 promoter to transcription factors.

To understand the mechanism of transcriptional down-regulation of BRCA1 by promoter methylation, we screened 51 breast cancer cell lines and identified HCC38 as another BRCA1 promoter-methylated cell line in addition to UACC3199. There was low expression of BRCA1 mRNA and BRCA1 protein in both cell lines as measured by quantitative RT-PCR and western blot analysis. After transient treatment with 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A (TSA), re-expression of BRCA1 mRNA and BRCA1 protein was detected in UACC3199 cells, but not in HCC38 cells.