Transcriptional adaptations following exercise in Thoroughbred horse skeletal muscle highlights molecular mechanisms that lead to muscle hypertrophy

<p>Abstract</p> <p>Background</p> <p>Selection for exercise-adapted phenotypes in the Thoroughbred racehorse has provided a valuable model system to understand molecular responses to exercise in skeletal muscle. Exercise stimulates immediate early molecular responses as well as delayed responses during recovery, resulting in a return to homeostasis and enabling long term adaptation. Global mRNA expression during the immediate-response period has not previously been reported in skeletal muscle following exercise in any species. Also, global gene expression changes in equine skeletal muscle following exercise have not been reported. Therefore, to identify novel genes and key regulatory pathways responsible for exercise adaptation we have used equine-specific cDNA microarrays to examine global mRNA expression in skeletal muscle from a cohort of Thoroughbred horses (<it>n = </it>8) at three time points (before exercise, immediately post-exercise, and four hours post-exercise) following a single bout of treadmill exercise.</p> <p>Results</p> <p>Skeletal muscle biopsies were taken from the <it>gluteus medius </it>before (T₀), immediately after (T₁) and four hours after (T₂) exercise. Statistically significant differences in mRNA abundance between time points (T₀<it>vs </it>T₁and T₀<it>vs </it>T₂) were determined using the empirical Bayes moderated <it>t</it>-test in the Bioconductor package Linear Models for Microarray Data (LIMMA) and the expression of a select panel of genes was validated using real time quantitative reverse transcription PCR (qRT-PCR). While only two genes had increased expression at T₁(<it>P </it>< 0.05), by T₂932 genes had increased (<it>P </it>< 0.05) and 562 genes had decreased expression (<it>P </it>< 0.05). Functional analysis of genes differentially expressed during the recovery phase (T₂) revealed an over-representation of genes localized to the actin cytoskeleton and with functions in the MAPK signalling, focal adhesion, insulin signalling, mTOR signaling, p53 signaling and Type II diabetes mellitus pathways. At T₁, using a less stringent statistical approach, we observed an over-representation of genes involved in the stress response, metabolism and intracellular signaling. These findings suggest that protein synthesis, mechanosensation and muscle remodeling contribute to skeletal muscle adaptation towards improved integrity and hypertrophy.</p> <p>Conclusions</p> <p>This is the first study to characterize global mRNA expression profiles in equine skeletal muscle using an equine-specific microarray platform. Here we reveal novel genes and mechanisms that are temporally expressed following exercise providing new knowledge about the early and late molecular responses to exercise in the equine skeletal muscle transcriptome.</p

A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses

<p>Abstract</p> <p>Background</p> <p>Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important.</p> <p>Results</p> <p>A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of <it>n </it>= 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (<it>MSTN</it>) [<it>P</it>_unadj.= 6.96 × 10^-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (<it>P</it>_unadj.= 1.61 × 10^-9; <it>P</it>_Bonf.= 6.58 × 10^-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in <it>MSTN </it>associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the <it>MSTN </it>gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (<it>r</it>²= 0.86).</p> <p>Conclusions</p> <p>Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, <it>P </it>= 1.02 × 10^-10; BIEC2-417495, <it>P</it>_unadj.= 1.61 × 10^-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.</p

Nature, prevalence and factors associated with depression among the elderly in a rural south Indian community

Background: Depression in old age is an important public health problem causing considerable morbidity and disability worldwide. There is a dearth of community studies from India investigating geriatric depression and its associated risk factors. This study aimed to establish the nature, prevalence and factors associated with geriatric depression in a rural south Indian community

Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training

<p>Abstract</p> <p>Background</p> <p>Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from the <it>gluteus medius </it>at two time points: T₁- untrained, (9 ± 0.5 months old) and T₂- trained (20 ± 0.7 months old).</p> <p>Results</p> <p>The most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genes <it>ACADVL</it>, <it>MRPS21 </it>and <it>SLC25A29 </it>encoded by the nuclear genome. Among the 58 genes with decreased expression, <it>MSTN</it>, a negative regulator of muscle growth, had the greatest decrease.</p> <p>Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (<it>P </it>< 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton.</p> <p>Conclusion</p> <p>Exercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.</p

Fellowships in Community Pharmacy Research: Experiences of Five Schools and Colleges of Pharmacy

Objective To describe common facilitators, challenges, and lessons learned in 5 schools and colleges of pharmacy in establishing community pharmacy research fellowships. Setting: Five schools and colleges of pharmacy in the United States. Practice description: Schools and colleges of pharmacy with existing community partnerships identified a need and ability to develop opportunities for pharmacists to engage in advanced research training. Practice innovation: Community pharmacy fellowships, each structured as 2 years long and in combination with graduate coursework, have been established at the University of Pittsburgh, Purdue University, East Tennessee State University, University of North Carolina at Chapel Hill, and The Ohio State University. Evaluation: Program directors from each of the 5 community pharmacy research fellowships identified common themes pertaining to program structure, outcomes, and lessons learned to assist others planning similar programs. Results: Common characteristics across the programs include length of training, prerequisites, graduate coursework, mentoring structure, and immersion into a pharmacist patient care practice. Common facilitators have been the existence of strong community pharmacy partnerships, creating a fellowship advisory team, and networking. A common challenge has been recruitment, with many programs experiencing at least one year without filling the fellowship position. All program graduates (n = 4) have been successful in securing pharmacy faculty positions. Conclusion: Five schools and colleges of pharmacy share similar experiences in implementing community pharmacy research fellowships. Early outcomes show promise for this training pathway in growing future pharmacist-scientists focused on community pharmacy practice

Effects of resistance and all-round, functional training on quality of life, vitality and depression of older adults living in long-term care facilities: a 'randomized' controlled trial [ISRCTN87177281]

BACKGROUND: Regular physical activity may improve different aspects of wellbeing in older people, such as quality of life, vitality and depression. However, there is little experimental evidence to support this assumption. Therefore, we examined the effect of different training protocols on quality of life, vitality and depression of older adults living in long-term care facilities. METHODS: Subjects (n = 173, aged 64 to 94 years, living in long-term care facilities), were randomized to six months of three different moderate-intensity group exercise training protocols, or to an 'educational' control condition. Exercise consisted of two 45–60-minute training sessions per week of 1) resistance training; 2) all-round, functional training; or 3) a combination of both. Perceived health, the Geriatric Depression Scale (GDS), the Vitality Plus Scale (VPS) and the Dementia Quality of Life questionnaire (DQoL) were administered at baseline and after six months. RESULTS: In the combined training group a small but significant decline was seen in perceived health, DQoL and VPS score compared to the control group. CONCLUSIONS: We conclude that neither strength training nor all-round, functional training of moderate intensity is effective in improving quality of life, vitality or depression of older people living in long-term care facilities

Less time to study, less well prepared for work, yet satisfied with higher education: A UK perspective on links between higher education and the labour market

This paper explores graduates’ views on the relationship between higher education and employment. It draws on a major European study involving graduates five years after graduation and highlights similarities and differences between UK graduates’ experiences and their European counterparts. Specifically we address questions raised in the study about subjects studied and their relevance to entry into the labour market, if the academic level obtained was appropriate, whether graduates, with hindsight of five years, would choose the same subjects or the same institution again, and if they were satisfied with their current job. Such specific questions relate to broader perspectives such as the perceived value of higher education study in relation to initial employment and future life histories. These have to be seen in the context of cultural differences in higher education systems at the time of the research and, perhaps increasing convergences in light of the Bologna agreement

Good for your soul? Adult learning and mental well-being

Although there is a widely held view that adult learning has a positive impact on well-being, only recently has this proposition been systematically tested. The paper reviews recent research findings on the influence of adult learning on earnings and employability, both of which may influence well-being indirectly. These are more important for some groups than others: in economically advanced societies, additional earnings produce limited gains in well-being for most groups except the poorest, while employability is most significant for groups that are most vulnerable in the labour market. The author then reviews recent research findings showing that participating in learning in adult life has some positive direct influence on well-being; analyses of cohort studies suggest that the influence is comparatively small, but nevertheless significant. There has been less study of learning’s negative consequences for well-being, and the paper draws on history data to illustrate some of these less desirable influences. It concludes by identifying areas for further research, and outlining a number of implications for policy and practice. These are particularly important in the current context, where environmental movements appear to be challenging the primacy of economic growth as the overarching goal of policy

The potential of a mobile group blog to support cultural learning among overseas students

We explored the use of mobile social software, in the form of a mobile group blog, to assist cultural learning. The potential of using this technology for cultural adaptation among overseas students was examined as those students adapted to the everyday life of studying abroad. Two pilot studies and a successful field study of a mobile group blog as used by UK overseas students are reported. A further study with prospective overseas students witnessing this ‘moblogging’ in China revealed the advantages of communicating through this technology as a form of peer-supported preparation for cultural adaptation. Potential advantages for learning a second language via this system, were highlighted as communication was interweaved with cultural adaptation and exercised in the blog entries. Given mobile internet, the language experience together with cultural observation impressively supported these students' growing confidence with time, space and imagination