Vascular Smooth Muscle Progenitor Cells: Building and Repairing Blood Vessels

Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair and remodeling, and progression of age-related disorders. Defects in these pathways will produce malformations of developing blood vessels, depletion of SMC progenitor pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular SMC precursors is essential if we are to utilize advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall

Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV(mac239)

BACKGROUND: The 5' untranslated region (UTR) or leader sequence of simian immunodeficiency virus (SIV(mac239)) is multifunctional and harbors the regulatory elements for viral replication, persistence, gene translation, expression, and the packaging and dimerization of viral genomic RNA (vRNA). We have constructed a series of deletions in the SIV(mac239 )leader sequence in order to determine the involvement of this region in both the packaging and dimerization of viral genomic RNA. We also assessed the impact of these deletions upon viral infectiousness, replication kinetics and gene expression in cell lines and monkey peripheral blood mononuclear cells (PBMC). RESULTS: Regions on both sides of the major splice donor (SD) were found to be necessary for the efficiency and specificity of viral genome packaging. However, stem-loop1 is critical for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the initiation site of SIV-Gag have additive effects on RNA packaging and contribute to a lesser degree to RNA dimerization. The targeted disruption of structures on both sides of the SD also severely impacts viral infectiousness, gene expression and replication in both CEMx174 cells and rhesus PBMC. CONCLUSION: In the leader region of SIV(mac239), stem-loop1 functions as the primary determinant for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the translational initiation site of SIV-Gag are classified as secondary determinants and play a role in dimerization. Collectively, these data signify a linkage between the primary encapsidation determinant of SIV(mac239 )and RNA dimerization

Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer

Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted pvalue 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74±0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51±0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk

Safety-oriented bicycling and traffic accident involvement

Many U.S. bicyclists are killed or injured in traffic accidents annually. Based on analysis of available research and published reports on traffic accidents, it was theorized that adherence to six safety-oriented on-road bicycling practices will reduce involvement in traffic accidents. This study investigated whether adherence to these safety-oriented bicycling practices is associated with reduced involvement in traffic accidents. U.S. adult bicycle riders responded to an anonymous on-line survey covering bicycling practices, recent traffic accident experiences, and potential confounding variables. Participants were recruited via on-line announcements to bicycling-related organizations. The results suggested that neither vigilance nor cautiousness will protect adult bicycle riders from traffic accident involvement, but predictability might reduce accident risk, particularly for younger adults. Results should be interpreted cautiously due to limitations in the study methodology. Further research of this type is warranted.This paper is a re-formulation of research originally presented as a conference paper and oral presentation at the International Cycling Safety Conference in Bologna, Italy, 3–4 November 2016. Keywords: Bicycling, Safety, Accidents, Crashes, Risk behavior