A major QTL on mouse chromosome 17 resulting in lifespan variability in SOD1-G93A transgenic mouse models of amyotrophic lateral sclerosis.

Abstract Amyotrophic lateral sclerosis is a late-onset degenerative disease affecting motor neurons in the spinal cord, brainstem, and motor cortex. There is great variation in the expression of ALS symptoms even between siblings who both carry the same Cu/Zn superoxide dismutase (SOD1) mutations. One important use of transgenic mouse models of SOD1-ALS is the study of genetic influences on ALS severity. We utilized multiple inbred mouse strains containing the SOD1-G93A transgene to demonstrate a major quantitative trait locus (QTL) on mouse chromosome 17 resulting in a significant shift in lifespan. Reciprocal crosses between long- and short-lived strains identified critical regions, and we have narrowed the area for potential genetic modifier(s) to \u3c 2Mb of the genome. Results showed that resequencing of this region resulted in 28 candidate genes with potentially functional differences between strains. In conclusion, these studies provide the first major modifier locus affecting lifespan in this model of FALS and, once identified, these candidate modifier genes may provide insight into modifiers of human disease and, most importantly, define new targets for the development of therapies. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15:588-600

Physical Activity, Confidence, and Social Norms Associated With Teachers\u27 Classroom Physical Activity Break Implementation

Despite the benefits of classroom physical activity breaks on student health and academic outcomes, more research is needed to understand what factors may be associated with classroom physical activity break implementation, to bolster buy-in from school stakeholders and increase implementation. This quantitative study examined frequency of classroom physical activity break implementation in relation to (1) objectively measured teachers\u27 physical activity and sedentary behaviors, (2) confidence for leading classroom physical activity breaks, (3) social norms (perceptions of other teachers\u27 classroom physical activity break implementation), and (4) teacher- and school-level demographics. In total, 153 classroom teachers in 20 elementary and middle schools completed a survey including classroom physical activity break frequency, confidence, and social norms, one item each, dichotomized (1 = most/all the time OR agree/strongly agree ). Accelerometry assessed total activity and daytime sedentary behavior. Analyses included multilevel binary logistic regression. Teachers were 90% female, 68% White, and 55% in elementary schools. Odds of implementing classroom physical activity breaks were lower among middle school teachers, 14 times greater among those with greater confidence, and over 17 times greater when teachers perceived others frequently implementing classroom physical activity breaks. Teacher activity was not associated with classroom physical activity break implementation. Future interventions to increase classroom physical activity break implementation should focus on increasing teachers\u27 confidence to lead classroom physical activity breaks and creating more buy-in from classroom teachers to enhance each school\u27s culture of health. By enhancing teacher confidence and social norms for implementing classroom physical activity breaks, we may increase school-based physical activity opportunities

Photoregulation of PRMT-1 Using a Photolabile Non-Canonical Amino Acid

Protein methyltransferases are vital to the epigenetic modification of gene expression. Thus, obtaining a better understanding of and control over the regulation of these crucial proteins has significant implications for the study and treatment of numerous diseases. One ideal mechanism of protein regulation is the specific installation of a photolabile-protecting group through the use of photocaged non-canonical amino acids. Consequently, PRMT1 was caged at a key tyrosine residue with a nitrobenzyl-protected Schultz amino acid to modulate protein function. Subsequent irradiation with UV light removes the caging group and restores normal methyltransferase activity, facilitating the spatial and temporal control of PRMT1 activity. Ultimately, this caged PRMT1 affords the ability to better understand the protein’s mechanism of action and potentially regulate the epigenetic impacts of this vital protein