Workplace incivility experienced by Health Administration faculty

Workplace incivility is low-intensity, nonspecific, discourteous behavior towards others and may negatively affect employee and organizational outcomes. This exploratory study sought to examine the prevalence of and factors related to experiencing several different types of workplace incivility using a national sample of Health Administration full-time faculty members in the United States. We found that 27–36% of respondents have experienced at least one type of uncivil behavior from students, coworkers, or supervisors. Further, 4–9% of faculty respondents experience such incidents frequently. Faculty respondents who experienced workplace incivility were significantly more likely to report lower job satisfaction and indicated an intention to leave their position within the next three years. Academic leaders should work to foster an environment where incivility towards others is actively discouraged, as it may contribute to dissatisfaction and turnover

Mitochondrial respiration variability and simulations in human skeletal muscle: The Gene SMART study

Mitochondrial respiration using the oxygraph‐2k respirometer (Oroboros) is widely used to estimate mitochondrial capacity in human skeletal muscle. Here, we measured mitochondrial respiration variability, in a relatively large sample, and for the first time, using statistical simulations, we provide the sample size required to detect meaningful respiration changes following lifestyle intervention. Muscle biopsies were taken from healthy, young men from the Gene SMART cohort, at multiple time points. We utilized samples for each measurement with two technical repeats using two respirometer chambers (n = 160 pairs of same muscle after removal of low‐quality samples). We measured the Technical Error of measurement (TEM) and the coefficient of variation (CV) for each mitochondrial complex. There was a high correlation between measurements from the two chambers (R > 0.7 P 15% for all complexes. We performed statistical simulations of a range of effect sizes at 80% power and found that 75 participants (with duplicate measurements) are required to detect a 6% change in mitochondrial respiration after an intervention, while for interventions with 11% effect size, ~24 participants are sufficient. The high variability in respiration suggests that the typical sample sizes in exercise studies may not be sufficient to capture exercise‐induced changes

Muscle miRNAs are influenced by sex at baseline and in response to exercise

Background: Sex differences in microRNA (miRNA) expression profiles have been found across multiple tissues. Skeletal muscle is one of the most sex-biased tissues of the body. MiRNAs are necessary for development and have regulatory roles in determining skeletal muscle phenotype and have important roles in the response to exercise in muscle. Yet there is limited research into the role and regulation of miRNAs in the skeletal muscle at baseline and in response to exercise, a well-known modulator of miRNA expression. The aim of this study was to investigate the effect of sex on miRNA expression in the skeletal muscle at baseline and after an acute bout of high-intensity interval exercise. A total of 758 miRNAs were measured using Taqman®miRNA arrays in the skeletal muscle of 42 healthy participants from the Gene SMART study (23 males and 19 females of comparable fitness levels and aged 18–45 years), of which 308 were detected. MiRNAs that differed by sex at baseline and whose change in expression following high-intensity interval exercise differed between the sexes were identified using mixed linear models adjusted for BMI and Wpeak. We performed in silico analyses to identify the putative gene targets of the exercise-induced, sex-specific miRNAs and overrepresentation analyses to identify enriched biological pathways. We performed functional assays by overexpressing two sex-biased miRNAs in human primary muscle cells derived from male and female donors to understand their downstream effects on the transcriptome. Results: At baseline, 148 miRNAs were differentially expressed in the skeletal muscle between the sexes. Interaction analysis identified 111 miRNAs whose response to an acute bout of high-intensity interval exercise differed between the sexes. Sex-biased miRNA gene targets were enriched for muscle-related processes including proliferation and differentiation of muscle cells and numerous metabolic pathways, suggesting that miRNAs participate in programming sex differences in skeletal muscle function. Overexpression of sex-biased miRNA-30a and miRNA-30c resulted in profound changes in gene expression profiles that were specific to the sex of the cell donor in human primary skeletal muscle cells. Conclusions: We uncovered sex differences in the expression levels of muscle miRNAs at baseline and in response to acute high-intensity interval exercise. These miRNAs target regulatory pathways essential to skeletal muscle development and metabolism. Our findings highlight that miRNAs play an important role in programming sex differences in the skeletal muscle phenotype

EPAS1 gene variants are associated with sprint/power athletic performance in two cohorts of European athletes

BACKGROUND: The endothelial PAS domain protein 1 (EPAS1) activates genes that are involved in erythropoiesis and angiogenesis, thus favoring a better delivery of oxygen to the tissues and is a plausible candidate to influence athletic performance. Using innovative statistical methods we compared genotype distributions and interactions of EPAS1 SNPs rs1867785, rs11689011, rs895436, rs4035887 and rs1867782 between sprint/power athletes (n = 338), endurance athletes (n = 254), and controls (603) in Polish and Russian samples. We also examined the association between these SNPs and the athletes’ competition level (‘elite’ and ‘sub-elite’ level). Genotyping was performed by either Real-Time PCR or by Single-Base Extension (SBE) method. RESULTS: In the pooled cohort of Polish and Russian athletes, 1) rs1867785 was associated with sprint/power athletic status; the AA genotype in rs1867785 was underrepresented in the sprint/power athletes, 2) rs11689011 was also associated with sprint/power athletic status; the TT genotype in rs11689011 was underrepresented sprint/power athletes, and 3) the interaction between rs1867785, rs11689011, and rs4035887 was associated with sprint/power athletic performance; the combinations of the AA genotype in rs4035887 with either the AG or GG genotypes in rs1867785, or with the CT or CC genotypes in rs11689011, were underrepresented in two cohorts of sprint/power athletes. CONCLUSIONS: Based on the unique statistical model rs1867785/rs11689011 are strong predictors of sprint/power athletic status, and the interaction between rs1867785, rs11689011, and rs4035887 might contribute to success in sprint/power athletic performance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-382) contains supplementary material, which is available to authorized users

Aerobic capacity and telomere length in human skeletal muscle and leukocytes across the lifespan

A reduction in aerobic capacity and the shortening of telomeres are hallmarks of the ageing process. We examined whether a lower aerobic capacity is associated with shorter TL in skeletal muscle and/or leukocytes, across a wide age range of individuals. We also tested whether TL in human skeletal muscle (MTL) correlates with TL in leukocytes (LTL). Eighty-two recreationally active, healthy men from the Gene SMART cohort (31.4±8.2 years; body mass index (BMI)=25.3±3.3kg/m2), and 11 community dwelling older men (74.2±7.5years-old; BMI=28.7±2.8kg/m2) participated in the study. Leukocytes and skeletal muscle samples were collected at rest. Relative telomere length (T/S ratio) was measured by RT-PCR. Associations between TL, aerobic capacity (VO2 peak and peak power) and age were assessed with robust linear models. Older age was associated with shorter LTL (45% variance explained, P<0.001), but not MTL (P= 0.7). Aerobic capacity was not associated with MTL (P=0.5), nor LTL (P=0.3). MTL and LTL were correlated across the lifespan (rs=0.26, P=0.03). In healthy individuals, age explain most of the variability of LTL and this appears to be independent of individual aerobic capacity. Individuals with longer LTL also have a longer MTL, suggesting that there might be a shared molecular mechanism regulating telomere length

A “human knockout” model to investigate the influence of the α-actinin-3 protein on exercise-induced mitochondrial adaptations

Research in α-actinin-3 knockout mice suggests a novel role for α-actinin-3 as a mediator of cell signalling. We took advantage of naturally-occurring human knockouts (lacking α-actinin-3 protein) to investigate the consequences of α-actinin-3 deficiency on exercise-induced changes in mitochondrial-related genes and proteins, as well as endurance training adaptations. At baseline, we observed a compensatory increase of α-actinin-2 protein in ACTN3 XX (α-actinin-3 deficient; n = 18) vs ACTN3 RR (expressing α-actinin-3; n = 19) participants but no differences between genotypes for markers of aerobic fitness or mitochondrial content and function. There was a main effect of genotype, without an interaction, for RCAN1-4 protein content (a marker of calcineurin activity). However, there was no effect of genotype on exercise-induced expression of genes associated with mitochondrial biogenesis, nor post-training physiological changes. In contrast to results in mice, loss of α-actinin-3 is not associated with higher baseline endurance-related phenotypes, or greater adaptations to endurance exercise training in humans

PL - 030 The effects of ACE gene polymorphisms on ACE content before and after High-Intensity Interval Exercise

Objective Angiotensin Converting Enzyme (ACE) is expressed in human skeletal muscle.&nbsp; The ACE I/D polymorphism (rs4341) has been associated with athletic performance in some studies. Studies suggested that the ACE I/D gene polymorphism is associated with ACE enzyme content in serum, however, the effect of ACE I/D on ACE protein content in human skeletal muscle in unclear. Angiotensin-converting enzyme 2 (ACE2) is a new component of the renin-angiotensin system (RAS), which is counter-regulatory to the ACE enzyme. The polymorphisms in the ACE2 gene (rs1978124 and rs2285666) have been reported to be associated with hypertension, however, their effects on ACE content in the blood and in skeletal muscle have yet to be explored. Utilising the Gene SMART cohort (n=81), we investigated whether the ACE I/D gene polymorphism (rs4341) and two ACE2 gene polymorphisms (rs1978124 and rs2285666) were associated with ACE enzyme content in the blood and skeletal muscle at baseline, and following a single session of High-Intensity Interval Exercise (HIIE). Methods ACE and ACE2 gene polymorphisms were determined using the TaqMan SNP assay (Applied Biosystems, Foster City, California, United States) by Mastercycler® ep realplex2 (Eppendorf, Hamburg, Germany), and QuantStudio™ 7 Flex Real-Time PCR System (Applied Biosystems, Foster City, California, United States). For quantitation of ACE content in the plasma, Abcam Human ELISA Kit (ab119577 –ACE (CD143)) was used (Abcam, Cambridge, United Kingdom). Western blots were used to measure ACE content in skeletal muscle. We used robust linear models adjusted for age to test the effect of the ACE I/D polymorphism on outcomes at baseline, using the MASS package in the R statistical software. p-values were adjusted for multiple comparisons using the Benjamini and Hochberg method, and all reported p-values are adjusted p-values. An adjusted p value &lt; 0.005 was considered significant. Results We found that the ACE I/D gene polymorphism was associated with ACE content in the blood (p&lt;0.005) at baseline, but not the ACE protein content in skeletal muscle at baseline. The ACE2 polymorphisms (rs1978124 and rs2285666) were not associated with ACE enzyme content in the blood or in skeletal muscle at baseline. A single session of HIIE tended (0.005 &lt; p &lt; 0.05) to increase blood ACE content immediately post exercise, while skeletal muscle ACE protein content was lower 3 hours post&nbsp; a single session of HIIE (p&lt;0.005). However, those changes were not related to ACE I/D or ACE2 polymorphisms. Conclusions The ACE I/D gene polymorphism influences ACE enzyme content in the blood but not the ACE protein content of human skeletal muscle. ACE I/D gene polymorphism does not influence the changes of ACE content after a single session of HIIE. ACE2 gene polymorphisms seem to have no effect on ACE content in the blood and skeletal muscle, before or after a session of HIIE

Methylome and proteome integration in human skeletal muscle uncover group and individual responses to high-intensity interval training.

Exercise is a major beneficial contributor to muscle metabolism, and health benefits acquired by exercise are a result of molecular shifts occurring across multiple molecular layers (i.e., epigenome, transcriptome, and proteome). Identifying robust, across-molecular level targets associated with exercise response, at both group and individual levels, is paramount to develop health guidelines and targeted health interventions. Sixteen, apparently healthy, moderately trained (VO2 max = 51.0 ± 10.6 mL min-1  kg-1 ) males (age range = 18-45 years) from the Gene SMART (Skeletal Muscle Adaptive Responses to Training) study completed a longitudinal study composed of 12-week high-intensity interval training (HIIT) intervention. Vastus lateralis muscle biopsies were collected at baseline and after 4, 8, and 12 weeks of HIIT. DNA methylation (~850 CpG sites) and proteomic (~3000 proteins) analyses were conducted at all time points. Mixed models were applied to estimate group and individual changes, and methylome and proteome integration was conducted using a holistic multilevel approach with the mixOmics package. A total of 461 proteins significantly changed over time (at 4, 8, and 12 weeks), whilst methylome overall shifted with training only one differentially methylated position (DMP) was significant (adj.p-value 0.5, among them are two novel exercise-related proteins, LYRM7 and EPN1. Integration analysis showed bidirectional relationships between the methylome and proteome. We showed a significant influence of HIIT on the epigenome and more so on the proteome in human muscle, and uncovered groups of proteins clustering according to similar patterns across the exercise intervention. Individual responses to exercise were observed in the proteome with novel mitochondrial and metabolic proteins consistently changed across individuals. Future work is required to elucidate the role of these proteins in response to exercise

Investigating the influence of mtDNA and nuclear encoded mitochondrial variants on high intensity interval training outcomes

Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n = 62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but eight nuclear encoded variants in seven separate genes were found to be associated with exercise responses (FDR < 0.05) (rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2). Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities.</p