The speed-gene study: methods, study design and preliminary results.

The Speed-Gene study aims to identify genetic variants influencing athletic performance and human locomotion using motion capture technology. Currently, 60 female participants have completed the testing protocol, and the overall aim is to recruit 283 moderately trained, healthy Southeast Asian individuals (18-45 y, BMI < 30). Participants will undergo biomechanical analysis and genetic testing. Several analyses will be performed, including (but not limited to) linear and angular kinematic analysis using motion capture technology, force plate dynamometry and genetic analyses to define novel power/torque related outcomes that would be more sensitive to allele-specific differences in athletic performance. Pretesting beverages will be provided, and activity history and current activity levels will be assessed by a questionnaire. The kinematic data will be obtained using a Qualisys Track Manager (QTM) system, and DNA will be extracted from white blood cells. The participants serve as their own controls. Although the Speed-Gene study is tightly controlled, our preliminary findings still indicate considerable individual variability. More participants and further genetic analysis are required to allow the investigation of potential underlying genetic mechanisms responsible for this individual variability.

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. METHODS: Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10-5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. RESULTS: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10-5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10-7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10-4) and the validation study (P < × 10-6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. CONCLUSIONS: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

Reinforcing adherence to lipid-lowering therapy after an acute coronary syndrome: A pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Achieving the low-density lipoprotein cholesterol (LDL-C) goal following an acute coronary syndrome (ACS) is a milestone often missed due to suboptimal adherence to secondary prevention treatments. Whether improved adherence could result in reduced LDL-C levels is unclear. We aimed to evaluate whether an educational-motivational intervention increases long-term lipid-lowering therapy (LLT) adherence and LDL-C goal attainment rate among post-ACS patients. METHODS: IDEAL-LDL was a parallel, two-arm, single-center, pragmatic, investigator-initiated randomized controlled trial. Hospitalized patients for ACS were randomized to a physician-led integrated intervention consisting of an educational session at baseline, followed by regular motivational interviewing phone sessions or usual care. Co-primary outcomes were the LLT adherence (measured by Proportion of Days Covered (PDC); good adherence defined as PDC>80%), and LDL-C goal (<70 mg/dl or 50% reduction from baseline) achievement rate at one year. RESULTS: In total, 360 patients (mean age 62 years, 81% male) were randomized. Overall, good adherence was positively associated with LDL-C goal achievement rate at one year. Median PDC was higher in the intervention group than the control group [0.92 (IQR, 0.82-1.00) vs. 0.86 (0.62-0.98); p = 0.03] while the intervention group had increased odds of good adherence (odds ratio: 1.76 (95% confidence interval 1.02 to 2.62; p = 0.04). However, neither the LDL-C goal achievement rate (49.6% in the intervention vs. 44.9% in the control group; p = 0.49) nor clinical outcomes differed significantly between the two groups. CONCLUSIONS: Α multifaceted intervention improved LLT adherence in post-ACS patients without a significant difference in LDL-C goal attainment.

Risk for Recurrent Cardiovascular Events and Expected Risk Reduction With Optimal Treatment 1 Year After an Acute Coronary Syndrome.

According to the latest European Society of Cardiology Guidelines for the diagnosis and management of chronic coronary syndromes, patients who suffered an acute coronary syndrome fall into a chronic stable phase after 1 year. In these patients, the estimated 10-year risk for recurrent cardiovascular events varies considerably. We applied the SMART (Second Manifestations of Arterial Disease) risk score in 281 patients 1 year after an acute coronary syndrome to estimate the 10-year risk for recurrent cardiovascular events (subsequent nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We assessed the distribution of the estimated risk and the potential risk reduction that might be achieved with optimal guideline-directed management of modifiable risk factors (systolic blood pressure, low-density lipoprotein cholesterol, smoking, and body mass index). In our cohort, the median SMART score was 16.1% (interquartile range [IQR] 9.7 to 27.3), particularly increased in patients with older age, diabetes, polyvascular disease or chronic kidney disease (median 28.6%, IQR 20.8 to 52.9; 23.8%, 4.8 to 41.6; 29.4%, 18.8 to 49.7; 53.8%, 26.5 to 71.6, respectively). If all modifiable risk factors met guideline-recommended targets, the median SMART risk score would be 9.6% (IQR 6.3 to 20.9), with 51% of the patients at a 10-year risk <10%, while 11% and 15% at 20% to 30% and >30% risk, respectively. In conclusion, the SMART score had a wide distribution in patients with chronic coronary syndromes. A quarter of patients remained at a >20% 10-year risk, even with optimal risk factor management, clearly underlining that residual risk is an unmet clinical challenge.

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 < .001) for all complexes, but the TEM was large (7.9-27 pmol s-1  mg-1 ; complex dependent), and the CV was >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.

Treatment practices and lipid profile of patients with acute coronary syndrome: results from a tertiary care hospital.

Background: Considering the increasing burden of cardiovascular risk factors and recent advances on the management of acute coronary syndromes (ACS), we studied the epidemiological characteristics and treatment strategies of patients presenting with ACS. We also evaluated the lipid profile and attainment of lipid goals in a 'real world' clinical setting.Methods: This was a substudy of IDEAL-LDL (Motivational interviewing to support low-density lipoprotein cholesterol (LDL-C) therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes), a single-centre, prospective, randomised controlled trial. Baseline data from a total of 357 ACS patients were gathered using standardised methods.Results: Median age of patients was 60 years and 81.2% were males. Arterial hypertension and smoking were the most prevalent risk factors for coronary artery disease (CAD). Patients with ST-elevation myocardial infarction (STEMI) were heavier smokers, but were younger and exercised more compared to those with non-ST-elevation acute coronary syndrome (NSTE-ACS). Conversely, more NSTE-ACS patients had arterial hypertension, dyslipidaemia and diabetes mellitus. One-fifth of ACS patients was treated conservatively without a percutaneous coronary intervention (PCI). A combination of statin, dual antiplatelet therapy and beta-blockers were prescribed to 79.6% of patients upon discharge. A renin-angiotensin-aldosterone system inhibitor and a beta-blocker were prescribed to 67.3 and 91.8% of patients with LVEF ≤40%, respectively. Of patients with prior history of CAD, 63.1%, 71.4% and 58.3% received regularly statins, antiplatelets and beta-blocker treatment, respectively. Only 22.3% of these CAD patients had an optimal LDL-C of <70 mg/dl at admission.Conclusions: In hospitalised patients with ACS, management practices differed by ACS type and discharge medication was, mostly, in line with the latest guidelines. However, medication adherence and lipid lowering goals of secondary CAD prevention were largely unachieved.

Ab Initio Study of Ternary W5Si3 Type TM5Sn2X Compounds (TM = Nb, Ti and X = Al, Si).

The adhesion of the scale formed on Nb-silicide based alloys at 1473 K improves when Al and Sn are in synergy with Si and Ti. This improvement is observed when there is segregation of Sn in the microstructure below the alloy/scale interface and a layer rich in intermetallics that include TM5Sn2X compounds is formed at the interface. Data for the ternary compounds is scarce. In this paper elastic and thermodynamic properties of the Nb5Sn2Al, Ti5Sn2Si, Ti5Sn2Al and Nb5Sn2Si compounds were studied using the first-principles, pseudopotential plane-wave method based on density functional theory. The enthalpy of formation of the ternary intermetallics was calculated using the quasi-harmonic approximation. The calculations suggest that the Nb5Sn2Si is the stiffest; that the Nb5Sn2Al and Ti5Sn2Si are the most and less ductile phases respectively; and that Nb significantly increases the bulk, shear and elastic moduli of the ternary compound compared with Ti.

Phase Equilibria in the Nb-Rich Region of Al-Nb-Sn at 900 and 1200 °C.

The Al-Nb-Sn phase diagram was studied experimentally in the Nb-rich region to provide important phase equilibria information for alloy design of Nb-silicide based materials for aero engine applications. Three alloys were produced: Nb-17Al-17Sn, Nb-33Al-13Sn and Nb-16Al-20Sn (at.%). As-cast and heat-treated alloys (900 and 1200 °C) were analysed using XRD (X-ray diffraction) and SEM/EDS (scanning electron microscopy/ electron dispersive x-ray spectroscopy). Tin showed a high solubility in Nb2Al, reaching up to 21 at.% in the Sn-rich areas, substituting for Al atoms. Tin and Al also substituted for each other in the A15 phases (Nb3Al and Nb3Sn). Tin showed limited solubility in NbAl3, not exceeding 3.6 at.% as it substituted Al atoms. The solubility of Al in NbSn2 varied from 4.8 to 6.8 at.%. A ternary phase, Nb5Sn2Al with the tI32 W5Si3 crystal structure, was found to be stable. This phase was observed in the 900 °C heat-treated samples, but not in the 1200 °C heated samples.

Anomalous Supersymmetry.

We show that supersymmetry is anomalous in N=1 superconformal quantum field theories (SCFTs) with an anomalous R symmetry. This anomaly was originally found in holographic SCFTs at strong coupling. Here we show that this anomaly is present, in general, and demonstrate it for the massless superconformal Wess-Zumino model via a one-loop computation. The anomaly appears first in four-point functions of two supercurrents either with two R currents or with an R current and an energy-momentum tensor. In fact, the Wess-Zumino consistency conditions together with the standard R-symmetry anomaly imply the existence of the anomaly. We outline the implications of this anomaly.

Mechanical Behavior of InP Twinning Superlattice Nanowires.

Taper-free InP twinning superlattice (TSL) nanowires with an average twin spacing of ∼13 nm were grown along the zinc-blende close-packed [111] direction using metalorganic vapor phase epitaxy. The mechanical properties and fracture mechanisms of individual InP TSL nanowires in tension were ascertained by means of in situ uniaxial tensile tests in a transmission electron microscope. The elastic modulus, failure strain, and tensile strength along the [111] direction were determined. No evidence of inelastic deformation mechanisms was found before fracture, which took place in a brittle manner along the twin boundary. The experimental results were supported by molecular dynamics simulations of the tensile deformation of the nanowires that also showed that the fracture of twinned nanowires occurred in the absence of inelastic deformation mechanisms by the propagation of a crack from the nanowire surface along the twin boundary.

The association between bone mineral density gene variants and osteocalcin at baseline, and in response to exercise: The Gene SMART study.

INTRODUCTION: Osteocalcin (OC) is used as a surrogate marker for bone turnover in clinical settings. As bone mineral density (BMD) is largely heritable, we tested the hypothesis that a) bone-associated genetic variants previously identified in Genome-Wide Association Studies (GWAS) and combined into a genetic risk score (GRS) are associated with a) circulating levels of OC and b) the changes in OC following acute exercise. METHODS: Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 73 healthy Caucasian males at baseline and after a single bout of high-intensity interval exercise. In addition, genotyping was conducted targeting GWAS variants previously reported to be associated with BMD and then combined into a GRS. Potential associations between the GRS and tOC, ucOC and cOC were tested with linear regressions adjusted for age. RESULTS: At baseline none of the individual SNPs associated with tOC, ucOC and cOC. However, when combined, a higher GRS was associated with higher tOC (ß = 0.193 ng/mL; p = 0.037; 95% CI = 0.012, 0.361) and cOC (ß = 0.188 ng/mL; p = 0.04; 95% CI = 0.004, 0.433). Following exercise, GRS was associated with ucOC levels, (ß = 3.864 ng/mL; p-value = 0.008; 95% CI = 1.063, 6.664) but not with tOC or cOC. CONCLUSION: Screening for genetic variations may assist in identifying people at risk for abnormal circulating levels of OC at baseline/rest. Genetic variations in BMD predicted the ucOC response to acute exercise indicating that physiological functional response to exercise may be influenced by bone-related gene variants.

A Multi-Center Comparison of O2peak Trainability Between Interval Training and Moderate Intensity Continuous Training.

There is heterogeneity in the observed O2peak response to similar exercise training, and different exercise approaches produce variable degrees of exercise response (trainability). The aim of this study was to combine data from different laboratories to compare O2peak trainability between various volumes of interval training and Moderate Intensity Continuous Training (MICT). For interval training, volumes were classified by the duration of total interval time. High-volume High Intensity Interval Training (HIIT) included studies that had participants complete more than 15 min of high intensity efforts per session. Low-volume HIIT/Sprint Interval Training (SIT) included studies using less than 15 min of high intensity efforts per session. In total, 677 participants across 18 aerobic exercise training interventions from eight different universities in five countries were included in the analysis. Participants had completed 3 weeks or more of either high-volume HIIT (n = 299), low-volume HIIT/SIT (n = 116), or MICT (n = 262) and were predominately men (n = 495) with a mix of healthy, elderly and clinical populations. Each training intervention improved mean O2peak at the group level (P < 0.001). After adjusting for covariates, high-volume HIIT had a significantly greater (P < 0.05) absolute O2peak increase (0.29 L/min) compared to MICT (0.20 L/min) and low-volume HIIT/SIT (0.18 L/min). Adjusted relative O2peak increase was also significantly greater (P < 0.01) in high-volume HIIT (3.3 ml/kg/min) than MICT (2.4 ml/kg/min) and insignificantly greater (P = 0.09) than low-volume HIIT/SIT (2.5 mL/kg/min). Based on a high threshold for a likely response (technical error of measurement plus the minimal clinically important difference), high-volume HIIT had significantly more (P < 0.01) likely responders (31%) compared to low-volume HIIT/SIT (16%) and MICT (21%). Covariates such as age, sex, the individual study, population group, sessions per week, study duration and the average between pre and post O2peak explained only 17.3% of the variance in O2peak trainability. In conclusion, high-volume HIIT had more likely responders to improvements in O2peak compared to low-volume HIIT/SIT and MICT.

Motivational interviewing to support LDL-C therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes (IDEAL-LDL) study: rationale and design.

BACKGROUND: Achieving low-density lipoprotein cholesterol (LDL-C) target levels after an acute coronary syndrome (ACS) is of paramount importance, and is often burdened by undertreatment and medication or lifestyle non-adherence issues. OBJECTIVE: We examined the effect of a patient-centered, physician-led motivational intervention following ACS on relevant secondary prevention aspects. METHODS-DESIGN: The IDEAL-LDL is a single-center, randomized controlled clinical trial, conducted among patients hospitalized due to an ACS. Following discharge, all patients undergo a baseline assessment of lipid profile. Patients in the intervention group receive an in-person educational session and an informative leaflet, and also undergo two phone-based, motivational interviewing sessions at 1 and 6 months. These interventions emphasize on LDL-C goals, adherence to lipid-lowering medication, and healthy dietary-lifestyle habits, and are not provided to patients in the control group, who receive usual care. At 12 months after each patient's discharge, an in-person interview and lipid profile reassessment are performed. The primary outcomes are the assessment of LDL-C goal achievement (<70 mg/dL or >50% reduction from baseline levels) from baseline to 1 year and changes in medication adherence. Secondary outcomes relate to the incidence of the composite outcome of cardiovascular death, nonfatal myocardial infarction/stroke, need for myocardial revascularization, and recurrent hospitalization during the follow-up period. DISCUSSION: This paper describes the protocol, design, and rationale for key methodology for an ongoing clinical trial featuring a simple and feasible intervention. Similar adherence efficacy trials have not led to sufficient improvements, and there remains a gap regarding how adherence interventions should be implemented into clinical care.

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease.

A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α-actinin-3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species-rich Eurasian climates suggesting that the absence of α-actinin-3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α-actinin-3. While the absence of α-actinin-3 influences skeletal muscle function and metabolism this does not result in overt muscle disease. α-Actinin-3 deficiency (ACTN3 XX genotype) is constantly underrepresented in sprint/power performance athletes. However, recent findings from our group and others suggest that the ACTN3 R577X genotype plays a role beyond athletic performance with effects observed in ageing, bone health, and inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy. In this review, we provide an update on the current knowledge regarding the influence of ACTN3 R577X on skeletal muscle function and its potential biological and clinical implications. We also outline future research directions to explore the role of α-actinin-3 in healthy and diseased populations.

ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study.

Angiotensin-converting enzyme (ACE) is expressed in human skeletal muscle. The ACE I/D polymorphism has been associated with athletic performance in some studies. Studies have suggested that the ACE I/D gene variant is associated with ACE enzyme content in serum, and there is an interaction between ACE and uncoupling proteins 2 and 3 (UCP2 and UCP3). However, no studies have explored the effect of ACE I/D on ACE, UCP2, and UCP3 protein content in human skeletal muscle. Utilizing the Gene SMART cohort ( n = 81), we investigated whether the ACE I/D gene variant is associated with ACE enzyme content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and following a session of high-intensity interval exercise (HIIE). Using a stringent and robust statistical analyses, we found that the ACE I/D gene variant was associated with ACE enzyme content in blood ( P < 0.005) at baseline but not the ACE, UCP2, and UCP3 protein content in muscle at baseline. A single session of HIIE tended (0.005 < P < 0.05) to increase blood ACE content immediately postexercise, whereas muscle ACE protein content was lower 3 h after a single session of HIIE ( P < 0.005). Muscle UCP3 protein content decreased immediately after a single session of HIIE ( P < 0.005) and remained low 3 h postexercise. However, those changes in the muscle were not genotype dependent. In conclusion, The ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content of human skeletal muscle. NEW & NOTEWORTHY This paper describes the association between ACE I/D gene variant and ACE protein content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and after exercise in a large cohort of healthy males. Our data suggest that ACE I/D is a strong predictor of blood ACE content but not muscle ACE content.

No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes.

BACKGROUND: Studies investigating associations between ACTN3 R577X and ACE I/D genotypes and endurance athletic status have been limited by small sample sizes from mixed sport disciplines and lack quantitative measures of performance. AIM: To examine the association between ACTN3 R577X and ACE I/D genotypes and best personal running times in a large homogeneous cohort of endurance runners. METHODS: We collected a total of 1064 personal best 1500, 3000, 5000 m and marathon running times of 698 male and female Caucasian endurance athletes from six countries (Australia, Greece, Italy, Poland, Russia and UK). Athletes were genotyped for ACTN3 R577X and ACE ID variants. RESULTS: There was no association between ACTN3 R577X or ACE I/D genotype and running performance at any distance in men or women. Mean (SD) marathon times (in s) were for men: ACTN3 RR 9149 (593), RX 9221 (582), XX 9129 (582) p = 0.94; ACE DD 9182 (665), ID 9214 (549), II 9155 (492) p = 0.85; for women: ACTN3 RR 10796 (818), RX 10667 (695), XX 10675 (553) p = 0.36; ACE DD 10604 (561), ID 10766 (740), II 10771 (708) p = 0.21. Furthermore, there were no associations between these variants and running time for any distance in a sub-analysis of athletes with personal records within 20% of world records. CONCLUSIONS: Thus, consistent with most case-control studies, this multi-cohort quantitative analysis demonstrates it is unlikely that ACTN3 XX genotype provides an advantage in competitive endurance running performance. For ACE II genotype, some prior studies show an association but others do not. Our data indicate it is also unlikely that ACE II genotype provides an advantage in endurance running.

The gene SMART study: method, study design, and preliminary findings.

The gene SMART (genes and the Skeletal Muscle Adaptive Response to Training) Study aims to identify genetic variants that predict the response to both a single session of High-Intensity Interval Exercise (HIIE) and to four weeks of High-Intensity Interval Training (HIIT). While the training and testing centre is located at Victoria University, Melbourne, three other centres have been launched at Bond University, Queensland University of Technology, Australia, and the University of Brighton, UK. Currently 39 participants have already completed the study and the overall aim is to recruit 200 moderately-trained, healthy Caucasians participants (all males 18-45 y, BMI < 30). Participants will undergo exercise testing and exercise training by an identical exercise program. Dietary habits will be assessed by questionnaire and dietitian consultation. Activity history is assessed by questionnaire and current activity level is assessed by an activity monitor. Skeletal muscle biopsies and blood samples will be collected before, immediately after and 3 h post HIIE, with the fourth resting biopsy and blood sample taken after four weeks of supervised HIIT (3 training sessions per week). Each session consists of eight to fourteen 2-min intervals performed at the pre-training lactate threshold (LT) power plus 40 to 70% of the difference between pre-training lactate threshold (LT) and peak aerobic power (Wpeak). A number of muscle and blood analyses will be performed, including (but not limited to) genotyping, mitochondrial respiration, transcriptomics, protein expression analyses, and enzyme activity. The participants serve as their own controls. Even though the gene SMART study is tightly controlled, our preliminary findings still indicate considerable individual variability in both performance (in-vivo) and muscle (in-situ) adaptations to similar training. More participants are required to allow us to better investigate potential underlying genetic and molecular mechanisms responsible for this individual variability.

The impact of Ti and temperature on the stability of Nb5Si3 phases: a first-principles study.

Nb-silicide based alloys could be used at T > 1423 K in future aero-engines. Titanium is an important additive to these new alloys where it improves oxidation, fracture toughness and reduces density. The microstructures of the new alloys consist of an Nb solid solution, and silicides and other intermetallics can be present. Three Nb5Si3 polymorphs are known, namely αNb5Si3 (tI32 Cr5B3-type, D8l), ßNb5Si3 (tI32 W5Si3-type, D8m) and γNb5Si3 (hP16 Mn5Si3-type, D88). In these 5-3 silicides Nb atoms can be substituted by Ti atoms. The type of stable Nb5Si3 depends on temperature and concentration of Ti addition and is important for the stability and properties of the alloys. The effect of increasing concentration of Ti on the transition temperature between the polymorphs has not been studied. In this work first-principles calculations were used to predict the stability and physical properties of the various Nb5Si3 silicides alloyed with Ti. Temperature-dependent enthalpies of formation were computed, and the transition temperature between the low (α) and high (ß) temperature polymorphs of Nb5Si3 was found to decrease significantly with increasing Ti content. The γNb5Si3 was found to be stable only at high Ti concentrations, above approximately 50 at. % Ti. Calculation of physical properties and the Cauchy pressures, Pugh's index of ductility and Poisson ratio showed that as the Ti content increased, the bulk moduli of all silicides decreased, while the shear and elastic moduli and the Debye temperature increased for the αNb5Si3 and γNb5Si3 and decreased for ßNb5Si3. With the addition of Ti the αNb5Si3 and γNb5Si3 became less ductile, whereas the ßNb5Si3 became more ductile. When Ti was added in the αNb5Si3 and ßNb5Si3 the linear thermal expansion coefficients of the silicides decreased, but the anisotropy of coefficient of thermal expansion did not change significantly.

The influence of α-actinin-3 deficiency on bone remodelling markers in young men.

There is a large individual variation in the bone remodelling markers (BRMs) osteocalcin (OC), procollagen 1 N-terminal propeptide (P1NP) and ß-isomerized C-terminal telopeptide (ß-CTx), as well as undercarboxylated osteocalcin (ucOC), at rest and in response to exercise. α-actinin-3 (ACTN3), a sarcomeric protein, is expressed in skeletal muscle and osteoblasts and may influence BRM levels and the cross-talk between muscle and bone. We tested the levels of serum BRMs in α-actinin-3 deficient humans (ACTN3 XX) at baseline, and following a single bout of exercise. Forty-three healthy Caucasian individuals were divided into three groups (ACTN3 XX, n=13; ACTN3 RX, n=16; ACTN3 RR, n=14). Participants completed a single session of High Intensity Interval Exercise (HIIE) on a cycle ergometer (8×2-min intervals at 85% of maximal power). Blood samples were taken before, immediately after, and three hours post exercise to identify the peak changes in serum BRMs. There was a stepwise increase in resting serum BRMs across the ACTN3 genotypes (XX>RX>RR) with significantly higher levels of tOC ~26%, P1NP ~34%, and ß-CTX (~33%) in those with ACTN3 XX compared to ACTN3 RR. Following exercise BRMs and ucOC were higher in all three ACTN3 genotypes, with no significant differences between groups. Serum levels of tOC, P1NP and ß-CTX are higher in men with ACTN3 XX genotype (α-actinin-3 deficiency) compared to RR and RX. It appears that the response of BRMs and ucOC to exercise is not explained by the ACTN3 genotype.