Skeletal Muscle PGC-1β Signaling is Sufficient to Drive an Endurance Exercise Phenotype and to Counteract Components of Detraining in Mice

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy

The effect of time constraint on anticipation, decision making, and option generation in complex and dynamic environments

Researchers interested in performance in complex and dynamic situations have focused on how individuals predict their opponent(s) potential courses of action (i.e., during assessment) and generate potential options about how to respond (i.e., during intervention). When generating predictive options, previous research supports the use of cognitive mechanisms that are consistent with long-term working memory (LTWM) theory (Ericsson and Kintsch in Phychol Rev 102(2):211–245, 1995; Ward et al. in J Cogn Eng Decis Mak 7:231–254, 2013). However, when generating options about how to respond, the extant research supports the use of the take-the-first (TTF) heuristic (Johnson and Raab in Organ Behav Hum Decis Process 91:215–229, 2003). While these models provide possible explanations about how options are generated in situ, often under time pressure, few researchers have tested the claims of these models experimentally by explicitly manipulating time pressure. The current research investigates the effect of time constraint on option-generation behavior during the assessment and intervention phases of decision making by employing a modified version of an established option-generation task in soccer. The results provide additional support for the use of LTWM mechanisms during assessment across both time conditions. During the intervention phase, option-generation behavior appeared consistent with TTF, but only in the non-time-constrained condition. Counter to our expectations, the implementation of time constraint resulted in a shift toward the use of LTWM-type mechanisms during the intervention phase. Modifications to the cognitive-process level descriptions of decision making during intervention are proposed, and implications for training during both phases of decision making are discussed

Capturing and testing perceptual-cognitive expertise: A comparison of stationary and movement response methods

Numerous methods have been used to study expertise and performance. In the present article, we compare the cognitive thought processes of skilled soccer players when responding to film-based simulations of defensive situations involving two different experimental conditions. Participants either remained stationary in a seated position (n = 10) or were allowed to move (n = 10) in response to life-size film sequences of 11 versus 11 open-play soccer situations viewed from a player’s perspective. Response accuracy and retrospective verbal reports of thinking were collected across the two task conditions. In the movement-based response group, participants generated a greater number of verbal report statements, including a higher proportion of evaluation, prediction, and action planning statements, than did participants in the stationary group. Findings suggest that the processing strategies employed during performance differ depending on the nature of the response required of participants. Implications for behavioral methods and experimental design are discussed

Periodic density functional theory calculations of bulk and the (010) surface of goethite

<p>Abstract</p> <p>Background</p> <p>Goethite is a common and reactive mineral in the environment. The transport of contaminants and anaerobic respiration of microbes are significantly affected by adsorption and reduction reactions involving goethite. An understanding of the mineral-water interface of goethite is critical for determining the molecular-scale mechanisms of adsorption and reduction reactions. In this study, periodic density functional theory (DFT) calculations were performed on the mineral goethite and its (010) surface, using the Vienna <it>Ab Initio </it>Simulation Package (VASP).</p> <p>Results</p> <p>Calculations of the bulk mineral structure accurately reproduced the observed crystal structure and vibrational frequencies, suggesting that this computational methodology was suitable for modeling the goethite-water interface. Energy-minimized structures of bare, hydrated (one H₂O layer) and solvated (three H₂O layers) (010) surfaces were calculated for 1 × 1 and 3 × 3 unit cell slabs. A good correlation between the calculated and observed vibrational frequencies was found for the 1 × 1 solvated surface. However, differences between the 1 × 1 and 3 × 3 slab calculations indicated that larger models may be necessary to simulate the relaxation of water at the interface. Comparison of two hydrated surfaces with molecularly and dissociatively adsorbed H₂O showed a significantly lower potential energy for the former.</p> <p>Conclusion</p> <p>Surface Fe-O and (Fe)O-H bond lengths are reported that may be useful in surface complexation models (SCM) of the goethite (010) surface. These bond lengths were found to change significantly as a function of solvation (i.e., addition of two extra H₂O layers above the surface), indicating that this parameter should be carefully considered in future SCM studies of metal oxide-water interfaces.</p

Grasping Kinematics from the Perspective of the Individual Digits: A Modelling Study

Grasping is a prototype of human motor coordination. Nevertheless, it is not known what determines the typical movement patterns of grasping. One way to approach this issue is by building models. We developed a model based on the movements of the individual digits. In our model the following objectives were taken into account for each digit: move smoothly to the preselected goal position on the object without hitting other surfaces, arrive at about the same time as the other digit and never move too far from the other digit. These objectives were implemented by regarding the tips of the digits as point masses with a spring between them, each attracted to its goal position and repelled from objects' surfaces. Their movements were damped. Using a single set of parameters, our model can reproduce a wider variety of experimental findings than any previous model of grasping. Apart from reproducing known effects (even the angles under which digits approach trapezoidal objects' surfaces, which no other model can explain), our model predicted that the increase in maximum grip aperture with object size should be greater for blocks than for cylinders. A survey of the literature shows that this is indeed how humans behave. The model can also adequately predict how single digit pointing movements are made. This supports the idea that grasping kinematics follow from the movements of the individual digits

The influence of early aging on eye movements during motor simulation

Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging

Six-minute walking test in children with ESRD: discrimination validity and construct validity

The six-minute walking test (6MWT) may be a practical test for the evaluation functional exercise capacity in children with end-stage renal disease (ESRD). The aim of this study was to investigate the 6MWT performance in children with ESRD compared to reference values obtained in healthy children and, secondly, to study the relationship between 6MWT performance with anthropometric variables, clinical parameters, aerobic capacity and muscle strength. Twenty patients (13 boys and seven girls; mean age 14.1 ± 3.4 years) on dialysis participated in this study. Anthropometrics were taken in a standardized manner. The 6MWT was performed in a 20-m-long track in a straight hallway. Aerobic fitness was measured using a cycle ergometer test to determine peak oxygen uptake \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left( {\mathop {\text{V}}\limits^\cdot {{\text{O}}_{\text{2peak}}}} \right)$$\end{document}, peak rate (Wpeak) and ventilatory threshold (VT). Muscle strength was measured using hand-held myometry. Children with ESRD showed a reduced 6MWT performance (83% of predicted, p < 0.0001), irrespective of the reference values used. The strongest predictors of 6MWT performance were haematocrit and height. Regression models explained 59% (haematocrit and height) to 60% (haematocrit) of the variance in 6MWT performance. 6MWT performance was not associated with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathop {\text{V}}\limits^\cdot {{\text{O}}_{\text{2peak}}}}$$\end{document}, strength, or other anthropometric variables, but it was significantly associated with haematocrit and height. Children with ESRD scored lower on the 6MWT than healthy children. Based on these results, the 6MWT may be a useful instrument for monitoring clinical status in children with ESRD, however it cannot substitute for other fitness tests, such as a progressive exercise test to measure \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathop {\text{V}}\limits^\cdot {{\text{O}}_{\text{2peak}}}}$$\end{document} or muscle strength tests

Analysis of miRNA and mRNA Expression Profiles Highlights Alterations in Ionizing Radiation Response of Human Lymphocytes under Modeled Microgravity

BACKGROUND: Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of \u3b3-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. CONCLUSIONS/SIGNIFICANCE: On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL

Delayed Recovery of Skeletal Muscle Mass following Hindlimb Immobilization in mTOR Heterozygous Mice

The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/−) mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT) mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR+/− mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR+/− mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR+/− mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA) during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth