Effect of high-fat diet on isometric, concentric and eccentric contractile performance of skeletal muscle isolated from female CD-1 mice.

Despite evidence inferring muscle and contractile mode-specific effects of high-fat diet (HFD), no study has yet considered the impact of HFD directly on eccentric muscle function. The present work uniquely examined the effect of 20-week HFD on the isometric, concentric and eccentric muscle function of isolated mouse soleus (SOL) and extensor digitorum longus (EDL) muscles. CD-1 female mice were randomly split into a control (n = 16) or HFD (n = 17) group and for 20 weeks consumed standard lab chow or HFD. Following this period, SOL and EDL muscles were isolated and assessments of maximal isometric force and concentric work loop (WL) power were performed. Each muscle was then subjected to either multiple concentric or eccentric WL activations. Post-fatigue recovery, as an indicator of incurred damage, was measured via assessment of concentric WL power. In the EDL, absolute concentric power and concentric power normalised to muscle mass were reduced in the HFD group (P < 0.038). HFD resulted in faster concentric fatigue and reduced eccentric activity-induced muscle damage (P < 0.05). For the SOL, maximal isometric force was increased, and maximal eccentric power normalised to muscle mass and concentric fatigue were reduced in the HFD group (P < 0.05). HFD effects on eccentric muscle function are muscle-specific and have little relationship with changes in isometric or concentric function. HFD has the potential to negatively affect the intrinsic concentric and eccentric power-producing capacity of skeletal muscle, but a lack of a within-muscle uniform response indicates disparate mechanisms of action which require further investigation.

The effects of muscle starting length on work loop power output of isolated mouse soleus and extensor digitorum longus muscle.

Force-length relationships derived from isometric activations may not directly apply to muscle force production during dynamic contractions. As such, different muscle starting lengths between isometric and dynamic conditions could be required to achieve maximal force and power. Therefore, this study examined the effects of starting length [±5-10% of length corresponding to maximal twitch force (L0)] on work loop (WL) power output (PO), across a range of cycle frequencies, of the soleus (SOL) and extensor digitorum longus muscle (EDL; N=8-10) isolated from ∼8 week old C57 mice. Furthermore, passive work was examined at a fixed cycle frequency to determine the association of passive work and active net work. Starting length affected maximal WL PO of the SOL and EDL across evaluated cycle frequencies (P<0.030, ηp2>0.494). For the SOL, PO produced at -5% L0 was greater than that at most starting lengths (P<0.015, Cohen's d>0.6), except -10% L0 (P=0.135, d<0.4). However, PO produced at -10% L0 versus L0 did not differ (P=0.138, d=0.35-0.49), indicating -5% L0 is optimal for maximal SOL WL PO. For the EDL, WL PO produced at -10% L0 was lower than that at most starting lengths (P<0.032, d>1.08), except versus -5% L0 (P=0.124, d<0.97). PO produced at other starting lengths did not differ (P>0.163, d<1.04). For the SOL, higher passive work was associated with reduced PO (Spearman's r=0.709, P<0.001), but no relationship was observed between passive work and PO of the EDL (Pearson's r=0.191, r2=0.04, P=0.184). This study suggests that starting length should be optimised for both static and dynamic contractions and confirms that the force-length curve during dynamic contractions is muscle specific.

High-fat diet effects on contractile performance of isolated mouse soleus and extensor digitorum longus when supplemented with high dose vitamin D.

Evidence suggests vitamin D3 (VD) supplementation can reduce accumulation of adipose tissue and inflammation and promote myogenesis in obese individuals, and thus could mitigate obesity-induced reductions in skeletal muscle (SkM) contractility. However, this is yet to be directly investigated. This study, using the work-loop technique, examined effects of VD (cholecalciferol) supplementation on isolated SkM contractility. Female mice (n = 37) consumed standard low-fat diet (SLD) or high-fat diet (HFD), with or without VD (20,000 IU/kg-1 ) for 12 weeks. Soleus and EDL (n = 8-10 per muscle per group) were isolated and absolute and normalized (to muscle size and body mass) isometric force and power output (PO) were measured, and fatigue resistance determined. Absolute and normalized isometric force and PO of soleus were unaffected by diet (P > 0.087). However, PO normalized to body mass was reduced in HFD groups (P < 0.001). Isometric force of extensor digitorum longus (EDL) was unaffected by diet (P > 0.588). HFD reduced EDL isometric stress (P = 0.048) and absolute and normalized PO (P < 0.031), but there was no effect of VD (P > 0.493). Cumulative work during fatiguing contractions was lower in HFD groups (P < 0.043), but rate of fatigue was unaffected (P > 0.060). This study uniquely demonstrated that high-dose VD had limited effects on SkM contractility and did not offset demonstrated adverse effects of HFD. However, small and moderate effect sizes suggest improvement in EDL muscle performance and animal morphology in HFD VD groups. Given effect sizes observed, coupled with proposed inverted U-shaped dose-effect curve, future investigations are needed to determine dose/duration specific responses to VD, which may culminate in improved function of HFD SkM.

Can animals tune tissue mechanics in response to changing environments caused by anthropogenic impacts?

Anthropogenic climate change and pollution are impacting environments across the globe. This Review summarises the potential impact of such anthropogenic effects on animal tissue mechanics, given the consequences for animal locomotor performance and behaviour. More specifically, in light of current literature, this Review focuses on evaluating the acute and chronic effects of temperature on the mechanical function of muscle tissues. For ectotherms, maximal muscle performance typically occurs at temperatures approximating the natural environment of the species. However, species vary in their ability to acclimate to chronic changes in temperature, which is likely to have longer-term effects on species range. Some species undergo periods of dormancy to avoid extreme temperature or drought. Whilst the skeletal muscle of such species generally appears to be adapted to minimise muscle atrophy and maintain performance for emergence from dormancy, the increased occurrence of extreme climatic conditions may reduce the survival of individuals in such environments. This Review also considers the likely impact of anthropogenic pollutants, such as hormones and heavy metals, on animal tissue mechanics, noting the relative paucity of literature directly investigating this key area. Future work needs to determine the direct effects of anthropogenic environmental changes on animal tissues and related changes in locomotor performance and behaviour, including accounting for currently unknown interactions between environmental factors, e.g. temperature and pollutants.

High-fat diet affects measures of skeletal muscle contractile performance in a temperature-specific manner but does not influence regional thermal sensitivity.

The present study examined whether high-fat diet (HFD) consumption for 20 weeks had a temperature-specific effect on the contractile performance and regional thermal sensitivity of isolated mouse soleus and diaphragm muscle. Four-week-old female CD-1 mice were randomly selected to consume either a standard laboratory diet or a standard laboratory diet in conjunction with a HFD for 20 weeks. Peripheral soleus and core diaphragm were isolated from each animal and maximal isometric force and work loop power were assessed at 20, 28, 35 and 40°C. Increasing temperature to 35°C resulted in greater isometric stress, lower activation and relaxation time, and higher work loop power in both muscles. A further increase in temperature to 40°C did not affect isometric force but increased work loop power output of the soleus. Conversely, isometric force of the diaphragm was reduced and work loop power maintained when temperature was increased to 40°C. HFD consumption resulted in greater isometric force and absolute work loop power of the soleus and reduced isometric stress of the diaphragm, effects that were less apparent at lower temperatures. When the relationship between temperature and each measure of contractile function was examined by linear regression, there was no difference in slope between the control or HFD groups for either the soleus or diaphragm. These results indicate that whilst contractile function initially increases with temperature, the temperature to elicit maximal performance is muscle and contractile mode specific. Furthermore, HFD effects on contractile function are temperature specific, but HFD does not influence the relationship between temperature and performance.

Effect of stimulation frequency on force, power and fatigue of isolated mouse extensor digitorum longus muscle.

This study examined the effect of stimulation frequency (140, 200, 230 and 260 Hz) on isometric force, work loop (WL) power and the fatigue resistance of extensor digitorum longus (EDL) muscle (n=32), isolated from 8- to 10-week-old CD-1 female mice. Stimulation frequency had significant effects on isometric properties of isolated mouse EDL, whereby increasing stimulation frequency evoked increased isometric force, quicker activation and prolonged relaxation (P<0.047) up to 230 Hz and above; thereafter, force and activation did not differ (P>0.137). Increasing stimulation frequency increased maximal WL power output (P<0.001; 140 Hz, 71.3±3.5; 200 Hz, 105.4±4.1; 230 Hz, 115.5±4.1; 260 Hz, 121.1±4.1 W kg-1), but resulted in significantly quicker rates of fatigue during consecutive WLs (P<0.004). WL shapes indicate impaired muscle relaxation at the end of shortening and subsequent increased negative work appeared to contribute to fatigue at 230 and 260 Hz, but not at lower stimulation frequencies. Cumulative work was unaffected by stimulation frequency, except at the start of the fatigue protocol, where 230 and 260 Hz produced more work than 140 Hz (P<0.039). We demonstrate that stimulation frequency affects force, power and fatigue, but these effects are not uniform between different assessments of contractile performance. Therefore, future work examining the contractile properties of isolated skeletal muscle should consider increasing the stimulation frequency beyond that needed for maximal force when examining maximal power but should utilise a sub-maximal stimulation frequency for fatigue assessments to avoid a high degree of negative work atypical of in vivo function.

Intra and Inter-Rater Reliability of a Novel Isometric Test of Neck Strength.

There is no single, universally accepted method of measuring isometric neck strength to inform exercise prescription and injury risk prediction. This study aimed to establish the inter- and intra-rater reliability of a commercially available fixed frame dynamometer in measuring peak isometric neck strength. A convenience sample of male (n = 16) and female (n = 20) university students performed maximal isometric contractions for flexion (Flex), extension (Ext), left- (LSF) and right-side flexion (RSF) in a quadruped position over three sessions. The intra-rater reliability results were good-to-excellent for both males (ICC = 0.83−0.90) and females (ICC = 0.86−0.94) and acceptable (CV < 15%) across all directions for both males and females. The inter-rater reliability results were excellent (ICC = 0.96−0.97) and acceptable (CV < 11.1%) across all directions. Findings demonstrated a significant effect for sex (p ≤ 0.05): males were stronger in all four directions, and a significant effect for direction (p ≤ 0.05): Ext tested stronger (193 N) than Flex (176 N), LSF (130 N) and RSF (125 N). The findings show that the VALD fixed frame dynamometer can reliably assess isometric neck strength and can provides reference values for healthy males and females.

Pre-schoolers fundamental movement skills predict BMI, physical activity, and sedentary behavior: A longitudinal study.

AIMS: This study aimed to predict the variation in future fundamental movement skills (FMS), physical activity (PA) and body mass index (BMI) from prior FMS, PA, and BMI in British pre-schoolers. METHODS: British pre-schoolers (n = 177) underwent assessment of FMS, via the Test of Gross Motor Development 2 (TGMD-2), BMI, and PA, via accelerometer at two time points one year apart. Regression analysis was used to predict the change in PA and BMI in Year 2 from FMS variables in Year 1 and Year 2. RESULTS: Variation in FMS performance between individuals predicted a significant amount of change in BMI, with 12.3 and 9.8% of the change in Year 2 BMI data explained by change in Year 1 and Year 2 FMS data, respectively. Change in FMS performance between individuals predicted a significant amount of change in PA, but was better at predicting change in sedentary activity rather than light or moderate-vigorous activities. A combination of run, throw, dribble, and kick performance predicted 46.1% of the change in sedentary activity between individuals in the 2nd year of testing. CONCLUSIONS: FMS mastery at four years of age predicts children's BMI and time spent sedentary at five years of age.

Hero Turned Villain: Identification of Components of the Sex Pheromone of the Tomato Bug, Nesidiocoris tenuis.

Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae) is a tropical mirid bug used as a biocontrol agent in protected crops, including tomatoes. Although N. tenuis predates important insect pests, especially whitefly, it also causes damage by feeding on tomato plants when prey populations decline, resulting in significant economic losses for growers. The pest is now established in some all-year-round tomato crops in Europe and control measures involve the application of pesticides which are incompatible with current IPM programs. As part of future IPM strategies, the pheromone of N. tenuis was investigated. Volatile collections were made from groups and individuals of mated and unmated, females and males. In analyses of these collections by gas chromatography coupled with electroantennographic (EAG) recording from antennae of male bugs, two EAG-active components were detected and identified as 1-octanol and octyl hexanoate. Unlike other mirids, both male and female N. tenuis produced the two compounds, before and after mating, and both sexes gave EAG responses to both compounds. Furthermore, only octyl hexanoate was detected in whole body solvent washes from both sexes. These compounds are not related to the derivatives of 3-hydroxybutyrate esters found as pheromone components in other members of the Bryocrinae sub-family, and the latter could not be detected in volatiles from N. tenuis and did not elicit EAG responses. Nevertheless, experiments carried out in commercial glasshouses showed that traps baited with a blend of the synthetic pheromone components caught essentially only male N. tenuis, and significantly more than traps baited with octyl hexanoate alone. The latter caught significantly more N. tenuis than unbaited traps which generally caught very few bugs. Traps at plant height caught more N. tenuis males than traps 1 m above or at the base of the plants. The trap catches provided an indication of population levels of N. tenuis and were greatly reduced following an application of insecticide.

The effects of high adiposity on concentric and eccentric muscle performance of upper and lower limb musculature in young and older adults.

The present study uniquely examined the influence of old age and adiposity on maximal concentric and eccentric torque and fatigue of the elbow and knee (KF, KE) flexors and extensors. Forty males were recruited and categorised into young (n = 21, 23.7 ± 3.4) and old (n = 19, 68.3 ± 6.1) and then further into normal (young = 16.9 ± 2.5%, old = 20.6 ± 3.1%) and high adiposity (young = 28.9 ± 5.0%, old = 31.3 ± 4.2%) groups. Handgrip strength, sit-to-stand performance, and isokinetic assessments of peak torque at 60°, 120° and 180°·s-1 were measured. Older men produced significantly less concentric and eccentric peak torque (P < 0.016) but this was not influenced by adiposity (P > 0.055). For KE and KF, high adiposity groups demonstrated reduced peak torque normalised to body mass (P < 0.021), and muscle and contractile mode specific reduction in torque normalised to segmental lean mass. Eccentric fatigue resistance was unaffected by both age and adiposity (P > 0.30) and perceived muscle soreness, measured up to 72 hours after, was only enhanced in the upper body of the young group following eccentric fatigue (P = 0.009). Despite the impact of adiposity on skeletal muscle function being comparable between ages, these results suggest high adiposity will have greater impact on functional performance of older adults. Novelty: Irrespective of age, high adiposity may negatively impact force to body mass ratio and muscle quality in a muscle and contractile mode specific manner. Whilst the magnitude of adiposity effects is similar across ages, the impact for older adults will be more substantial given the age-related decline in muscle function.

Do muscle contractile properties drive differences in locomotor performance in invasive populations of Xenopus laevis in France?

Jumping and swimming are key locomotor traits in frogs intimately linked to survival and dispersal. French populations of the frog Xenopus laevis from the invasion front are known to possess greater terrestrial locomotor endurance. Here, we tested whether individuals from the invasion front show differences in their muscle physiology that may underlie the observed whole-organism performance differences. We measured muscle contractile properties of the isolated gastrocnemius muscle in vitro, including isometric stress, activation and relaxation time, and work loop power output, both before and during a period of fatiguing contractions. We found that frogs from the centre of the range can produce tetanus force in their gastrocnemius muscle faster than animals from the periphery of the range, which could contribute to higher performance in one-off jumps. Yet, populations did not differ in muscle endurance. These results, coupled with previous work on this invasive population of Xenopus laevis, suggest that the greater stamina observed in individuals from the periphery may be more due to anatomical differences such as longer hind limbs and larger hearts along with potentially other as of yet untested physiological differences rather than differences in the mechanical properties of skeletal muscle.

Age-related changes in isolated mouse skeletal muscle function are dependent on sex, muscle, and contractility mode.

The present study aimed to simultaneously examine the age-related, muscle-specific, sex-specific, and contractile mode-specific changes in isolated mouse skeletal muscle function and morphology across multiple ages. Measurements of mammalian muscle morphology, isometric force and stress (force/cross-sectional area), absolute and normalized (power/muscle mass) work-loop power across a range of contractile velocities, fatigue resistance, and myosin heavy chain (MHC) isoform concentration were measured in 232 isolated mouse (CD-1) soleus, extensor digitorum longus (EDL), and diaphragm from male and female animals aged 3, 10, 30, 52, and 78 wk. Aging resulted in increased body mass and increased soleus and EDL muscle mass, with atrophy only present for female EDL by 78 wk despite no change in MHC isoform concentration. Absolute force and power output increased up to 52 wk and to a higher level for males. A 23-36% loss of isometric stress exceeded the 14-27% loss of power normalized to muscle mass between 10 wk and 52 wk, although the loss of normalized power between 52 and 78 wk continued without further changes in stress (P > 0.23). Males had lower power normalized to muscle mass than females by 78 wk, with the greatest decline observed for male soleus. Aging did not cause a shift toward slower contractile characteristics, with reduced fatigue resistance observed in male EDL and female diaphragm. Our findings show that the loss of muscle quality precedes the loss of absolute performance as CD-1 mice age, with the greatest effect seen in male soleus, and in most instances without muscle atrophy or an alteration in MHC isoforms.

The cardiac work-loop technique: An in vitro model for identifying and profiling drug-induced changes in inotropy using rat papillary muscles.

The cardiac work-loop technique closely mimics the intrinsic in vivo movement and characteristics of cardiac muscle function. In this study, six known inotropes were profiled using the work-loop technique to evaluate the potential of this method to predict inotropy. Papillary muscles from male Sprague-Dawley rats were mounted onto an organ bath perfused with Krebs-Henseleit buffer. Following optimisation, work-loop contractions were performed that included an initial stabilisation period followed by vehicle control or drug administration. Six known inotropes were tested: digoxin, dobutamine, isoprenaline, flecainide, verapamil and atenolol. Muscle performance was evaluated by calculating power output during work-loop contraction. Digoxin, dobutamine and isoprenaline caused a significant increase in power output of muscles when compared to vehicle control. Flecainide, verapamil and atenolol significantly reduced power output of muscles. These changes in power output were reflected in alterations in work loop shapes. This is the first study in which changes in work-loop shape detailing for example the activation, shortening or passive re-lengthening have been linked to the mechanism of action of a compound. This study has demonstrated that the work-loop technique can provide an important novel method with which to assess detailed mechanisms of drug-induced effects on cardiac muscle contractility.

The likely effects of thermal climate change on vertebrate skeletal muscle mechanics with possible consequences for animal movement and behaviour.

Climate change can involve alteration in the local temperature that an animal is exposed to, which in turn may affect skeletal muscle temperature. The underlying effects of temperature on the mechanical performance of skeletal muscle can affect organismal performance in key activities, such as locomotion and fitness-related behaviours, including prey capture and predator avoidance. The contractile performance of skeletal muscle is optimized within a specific thermal range. An increased muscle temperature can initially cause substantial improvements in force production, faster rates of force generation, relaxation, shortening, and production of power output. However, if muscle temperature becomes too high, then maximal force production and power output can decrease. Any deleterious effects of temperature change on muscle mechanics could be exacerbated by other climatic changes, such as drought, altered water, or airflow regimes that affect the environment the animal needs to move through. Many species will change their location on a daily, or even seasonal basis, to modulate the temperature that they are exposed to, thereby improving the mechanical performance of their muscle. Some species undergo seasonal acclimation to optimize muscle mechanics to longer-term changes in temperature or undergo dormancy to avoid extreme climatic conditions. As local climate alters, species either cope with the change, adapt, avoid extreme climate, move, or undergo localized extinction events. Given that such outcomes will be determined by organismal performance within the thermal environment, the effects of climate change on muscle mechanics could have a major impact on the ability of a population to survive in a particular location.

Increased physical activity does not improve obesity-induced decreases in muscle quality in zebrafish (Danio rerio).

Obesity has a negative effect on muscle contractile function, and the effects of obesity are not reversed by weight loss. It is therefore important to determine how muscle function can be restored, and exercise is the most promising approach. We tested the hypothesis (in zebrafish, Danio rerio) that moderate aerobic exercise (forced swimming for 30 min/day, raising metabolic rates to at least twice resting levels) will alleviate the negative effects of obesity on muscle function. We allocated zebrafish randomly to experimental treatments in a fully factorial design with diet treatment [three levels: lean control, diet-induced obese, obese followed by weight loss (obese-lean)], and exercise (exercise and sedentary control) as independent factors. Treatments were conducted for 10 wk, and we measured locomotor performance, isolated muscle mechanics, and myosin heavy chain composition. Obesity led to decreased muscle force production per unit area (P = 0.01), and slowed muscle contraction (P = 0.004) and relaxation rates (P = 0.02). These effects were not reversible by weight loss or exercise. However, at the level implemented in our experimental animals, neither diet nor exercise affected swimming performance or myosin heavy chain concentrations. The moderate levels of exercise we implemented therefore are not sufficient to reverse the effects of obesity on muscle function, and higher intensity or a combination of modes of exercise may be necessary to improve muscle quality during obesity and following weight loss.NEW & NOTEWORTHY Obesity can have a negative effect on muscle function and thereby compromise mobility. Even though aerobic exercise has many physiological benefits in obese and normal-weight individuals, we show that in zebrafish aerobic exercise does not improve obesity-induced reductions in muscle contractile function. A combination between different modes of exercise may be more effective than aerobic exercise alone.

Assessment of Accuracy of an Artificial Intelligence Algorithm to Detect Melanoma in Images of Skin Lesions.

Importance: A high proportion of suspicious pigmented skin lesions referred for investigation are benign. Techniques to improve the accuracy of melanoma diagnoses throughout the patient pathway are needed to reduce the pressure on secondary care and pathology services. Objective: To determine the accuracy of an artificial intelligence algorithm in identifying melanoma in dermoscopic images of lesions taken with smartphone and digital single-lens reflex (DSLR) cameras. Design, Setting, and Participants: This prospective, multicenter, single-arm, masked diagnostic trial took place in dermatology and plastic surgery clinics in 7 UK hospitals. Dermoscopic images of suspicious and control skin lesions from 514 patients with at least 1 suspicious pigmented skin lesion scheduled for biopsy were captured on 3 different cameras. Data were collected from January 2017 to July 2018. Clinicians and the Deep Ensemble for Recognition of Malignancy, a deterministic artificial intelligence algorithm trained to identify melanoma in dermoscopic images of pigmented skin lesions using deep learning techniques, assessed the likelihood of melanoma. Initial data analysis was conducted in September 2018; further analysis was conducted from February 2019 to August 2019. Interventions: Clinician and algorithmic assessment of melanoma. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of the algorithmic and specialist assessment, determined using histopathology diagnosis as the criterion standard. Results: The study population of 514 patients included 279 women (55.7%) and 484 white patients (96.8%), with a mean (SD) age of 52.1 (18.6) years. A total of 1550 images of skin lesions were included in the analysis (551 [35.6%] biopsied lesions; 999 [64.4%] control lesions); 286 images (18.6%) were used to train the algorithm, and a further 849 (54.8%) images were missing or unsuitable for analysis. Of the biopsied lesions that were assessed by the algorithm and specialists, 125 (22.7%) were diagnosed as melanoma. Of these, 77 (16.7%) were used for the primary analysis. The algorithm achieved an AUROC of 90.1% (95% CI, 86.3%-94.0%) for biopsied lesions and 95.8% (95% CI, 94.1%-97.6%) for all lesions using iPhone 6s images; an AUROC of 85.8% (95% CI, 81.0%-90.7%) for biopsied lesions and 93.8% (95% CI, 91.4%-96.2%) for all lesions using Galaxy S6 images; and an AUROC of 86.9% (95% CI, 80.8%-93.0%) for biopsied lesions and 91.8% (95% CI, 87.5%-96.1%) for all lesions using DSLR camera images. At 100% sensitivity, the algorithm achieved a specificity of 64.8% with iPhone 6s images. Specialists achieved an AUROC of 77.8% (95% CI, 72.5%-81.9%) and a specificity of 69.9%. Conclusions and Relevance: In this study, the algorithm demonstrated an ability to identify melanoma from dermoscopic images of selected lesions with an accuracy similar to that of specialists.

Accelerometer-based physical activity levels, fundamental movement skills and weight status in British preschool children from a deprived area.

Preschool children are recommended to participate in a minimum of 180-min physical activity (PA) per day to enhance their development and overall health. Low PA and increased obesity are thought to be linked to low mastery of fundamental movement skills (FMS) in preschool children. This study sought to investigate whether FMS influences PA levels and weight status in preschool children, in an area of low socioeconomic status. Secondary aims of this study were to determine whether gender or day of the week affected the primary outcomes. One hundred eighty-five preschool children aged 3-4 years old, participated in the study. FMS proficiency was determined using the Test of Gross Motor Development-2. PA was determined using triaxial accelerometry over a 4-day period. None of the samples met the recommended 180 min of PA. There were no significant differences in PA or weight status between preschool children with high, medium or low FMS mastery (P < 0.05). There were also no significant correlations between overall FMS and moderate to vigorous PA during the week or weekend days.Conclusion: Girls scored significantly greater at the hop, leap, and skip (locomotor skills) and the boys significantly higher at the kick (object control) (P < 0.05). There were no significant differences in PA or weight status between preschool children with high, medium, or low FMS mastery, possibly because FMS mastery had not developed to a high enough level to affect PA and FMS are considered independent of physical fitness and physical features, such as weight and height. What is Known: •FMS are commonly developed in early childhood, providing the building blocks for future motor skills, good health and lifelong PA. •No study to date has measured FMS, PA levels and weight status in preschool children, to determine whether FMS competency influences PA levels and weight status in preschool children, in an area of low SES. What is New: •FMS competency did not appear to influence the level of PA or weight status in this sample of UK preschool children from a low SES area. •PA and FMS may not be fully established and consequently not strongly linked at the ages of 3-4 years, therefore, the preschool years could be influential in providing a window to maximise input of good/optimal development of motor competence before the proficiency barrier sets in and we need remedial intervention.

mRNA levels are buffered upon knockdown of RNA decay and translation factors via adjustment of transcription rates in human HepG2 cells.

Evidence from yeast and mammals argues the existence of cross-talk between transcription and mRNA decay. Stabilization of transcripts upon depletion of mRNA decay factors generally leads to no changes in mRNA abundance, attributing this to decreased transcription rates. We show that knockdown of human XRN1, CNOT6 and ETF1 genes in HepG2 cells led to significant alteration in stability of specific mRNAs, alterations in half-life were inversely associated with transcription rates, mostly not resulting in changes in abundance. We demonstrate the existence of the gene expression buffering mechanism in human cells that responds to both transcript stabilization and destabilization to maintain mRNA abundance via altered transcription rates and may involve translation. We propose that this buffering may hold novel cancer therapeutic targets.

Does Dietary-Induced Obesity in Old Age Impair the Contractile Performance of Isolated Mouse Soleus, Extensor Digitorum Longus and Diaphragm Skeletal Muscles?

Ageing and obesity independently have been shown to significantly impair isolated muscle contractile properties, though their synergistic effects are poorly understood. We uniquely examined the effects of 9 weeks of a high-fat diet (HFD) on isometric force, work loop power output (PO) across a range of contractile velocities, and fatigability of 79-week-old soleus, extensor digitorum longus (EDL) and diaphragm compared with age-matched lean controls. The dietary intervention resulted in a significant increase in body mass and gonadal fat pad mass compared to the control group. Despite increased muscle mass for HFD soleus and EDL, absolute isometric force, isometric stress (force/CSA), PO normalised to muscle mass and fatigability was unchanged, although absolute PO was significantly greater. Obesity did not cause an alteration in the contractile velocity that elicited maximal PO. In the obese group, normalised diaphragm PO was significantly reduced, with a tendency for reduced isometric stress and fatigability was unchanged. HFD soleus isolated from larger animals produced lower maximal PO which may relate to impaired balance in older, larger adults. The increase in absolute PO is smaller than the magnitude of weight gain, meaning in vivo locomotor function is likely to be impaired in old obese adults, with an association between greater body mass and poorer normalised power output for the soleus. An obesity-induced reduction in diaphragm contractility will likely impair in vivo respiratory function and consequently contribute further to the negative cycle of obesity.

Accelerometer-Based Physical Activity Levels Differ between Week and Weekend Days in British Preschool Children.

Participation in physical activity (PA) is fundamental to children's future health. Studies examining the temporal pattern of PA between weekdays and weekends in British preschool children are lacking. Therefore, the aim of this study was to compare PA levels between week and weekend days for UK preschool children, using objective measurements. One hundred and eighty-five preschool children (99 boys, 86 girls, aged 4-5 years), from central England wore a triaxial accelerometer (GENEActiv) for 4 days to determine PA. The time (min) and percentage (%) of time spent in light, moderate and vigorous PA (MVPA) was determined using specific cut-points for counts per minute related to 3-5 year olds. Of the sample, none of the children met the UK recommended 180 min or more of PA per day. A significant difference (P < 0.05) was observed between the amount of time that preschool children spent in sedentary behaviours on weekdays (91.9%) compared to weekend days (96.9%). During weekdays and weekend days, 6.3% and 2.0% of time was spent in MVPA, respectively. Therefore, a substantial proportion of British preschool children's day is spent in sedentary behaviours, with less MVPA accrued during the weekend. Regular engagement during the weekdays provides opportunities to accrue PA, which may not be present on weekend days.