Dissertations / Theses on the topic 'Muscle'

Thesis (Ph. D.)--West Virginia University, 2007.
Title from document title page. Document formatted into pages; contains xii, 270 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

The present study was undertaken to determine the relationship between perinatal complications and subsequent development of Attention Deficit Hyperactivity Disorder (ADHD) and other behavioral characteristics. The biological mothers of 74 children diagnosed with ADHD and 77 children displaying no characteristics of the disorder completed the Maternal Perinatal Scale (MPS), the Behavior Assessment System for Children-Parent Rating Scales (BASC-PRS), and a demographic survey. In addition, the biological mothers of 120 children with no characteristics of ADHD or any other behavior disorders completed only the MPS so that exploratory factor analysis of the MPS could be completed.Following factor analysis, stepwise discriminant analysis of the resulting five factors was utilized to explore the nature of the relationship between such perinatal factors and ADHD. Results of this analysis indicated that emotional factors, or the amount of stress encountered during pregnancy and the degree to Relationship Between Perinatal Complications 3 was planned, were the items that maximized the separation between the ADHD and Non-ADHD groups. Additional discrimination between the groups was attributed to the extent of insult or trauma to the developing fetus and the outcome of prior pregnancies. ADHD children were also found to have experienced twice as many behavioral, social, or medical problems, and were more likely to reach developmental milestones with delays.Stepwise discriminant analysis also revealed the Attention Problems and Hyperactivity scales of the BASC-PRS were most significant in differentiating between the ADHD and Non-ADHD subjects. Using the BASC-PRS resulted in approximately 90% of the total sample being correctly classified as ADHD or Non-ADHD. Canonical correlation analysis indicated that emotional factors and the general health of both the mother and the developing fetus were the best predictors of later behavioral patterns reported on the BASC-PRS.
Human Performance Laboratory

Thesis (Ph.D.)--University of Florida, 2005.
Typescript. Title from title page of source document. Document formatted into pages; contains 171 pages. Includes Vita. Includes bibliographical references.

Thesis (M.S.)--West Virginia University, 1999.
Title from document title page. Document formatted into pages; contains viii, 81 p. : ill. Vita. Includes abstract. Includes bibliographical references.

The purpose of the present study was to examine the relationship between exercise induced muscle damage and growth factors during two different modes of exercise. Nine healthy untrained male subjects participated in this study and performed two separate single bouts of isokinetic concentric (Con) and eccentric (Ecc) leg extension exercise on the CYBEX NORMT°". The workload was maintained at 75% of 1 RM for each trial, respectively. The maximum sets of 10 repetitions were performed during the Con trial, and the number was also duplicated during the Ecc trial, with 40 seconds of rest between sets. Serum levels of hGH, creatine kinase (CK), and lactic acid were measured, and the CK level was used to determine the degree of muscle tissue damage. A muscle soreness questionnaire was provided to the subjects to assess the degree of quadriceps muscle soreness following each trial. The EMG activity of the rectus femoris and vastus medialis muscles was recorded during each trial. The results of the present study demonstrated no significant differences in hGH output and CK activity between the exercise trials, although there was a significant different lactic acid response (P < 0.05). However, the Con trial produced significant increases (P < 0.05) in hGH and CK levels above the resting value at the post-exercise times. In fact, the 75% Con trial conducted in this study induced an increase in hGH release (peak: 8.23 ± 3.21 ng/ml) that was 2 X higher than a 120% Ecc trial (peak: 3.8 ± 1.2 ng/mI) of the prior study. The results of the present study demonstrate that a single bout of Con resistance exercise at the same intensity (75% of 1 RM), angular velocity, and ROM as a single bout of Ecc exercise can produce greater increases in hGH output and CK response than its Ecc counterpart. This finding does not support the previous results from this laboratory, showing that Ecc exercise is a stronger promoter of hGH output. However, it suggests that the amount of work performed is an important factor for hGH release because the exercise volume applied in the present study was greater than that of the prior study. The CK response of the subjects in this study, as well as the previous work indicate that hGH output is also dependent on exercise that elicits muscle damage. Therefore, the results of the present study suggest that the mode of exercise, Con vs. Ecc, is not as important as the stress placed on the exercising muscle in order to induce optimal muscle hypertrophy.
School of Physical Education

Thèse de doctorat : Sciences de la vie et de la santé : Paris 12 : 2006.
Version électronique uniquement consultable au sein de l'Université Paris 12 (Intranet). Titre provenant de l'écran-titre. Bibliogr. : 410 réf.

This thesis investigated the effect of knee angle position on the electrical signal of two hamstring muscles using a traditional technique (bipolar electromyography) and a modern technique (high-density electromyography). The results suggest that changes in knee position affect the electrical activity on bipolar electromyography and these changes are associated with the rotation of muscle fibers under the pair of electrodes. However, using high-density electromyography, there was no difference between different knee positions. These findings suggest that high-density electromyography has different responses compared to bipolar electromyography. Hence, studies using bipolar montages need to be interpreted with caution to avoid wrong conclusions.

Muscle function after exercise-induced muscle damage has traditionally been evaluated by measures of isometric strength at a single joint angle or muscle length. The thesis investigates the effect of muscle damage on other muscle function parameters such as, isometric strength as a function of muscle length, concentric strength as a function of angular velocity, strength across muscle actions, the stretch-shortening cycle, power output, and fatigability. Study 1 The first part of this study aimed to determine how the muscle length at which strength is measured affects reductions in isometric strength following eccentric exercise-induced muscle damage. The damaging exercise protocol consisted of 100 maximal voluntary eccentric actions of the knee extensors, performed in the prone position through a range of motion from 40° to 140° (0° = full extension) at an angular velocity of 90 deg's-1. Isometric strength of the knee extensors was measured at short muscle length (10° knee flexion) and optimal length (80°). A significantly greater relative loss of strength was observed at short versus optimal muscle length (76.3 ± 2.5% vs. 82.1 ± 2.7% of pre-exercise values, P<0.05) over the seven day testing period following eccentric exercise. The second part of the study investigated isometric strength at optimal length and concentric strength at slow (30 deg's 1) and fast (180 deg's 1) angular velocities of movement. No differences were apparent in the magnitude and rate of recovery of strength across isometric (82.1 ± 2.7%) and slow (86.6 ± 2.0%) and fast (84.3 ± 1.5%) concentric muscle actions. Both the popping sarcomere hypothesis of 2 muscle damage and a failure in excitation-contraction coupling are possible explanations for the reduction in strength being affected by the muscle length at which it is measured. Both would be expected to affect strength to a greater extent at short versus optimal muscle lengths. Study 2 The second study investigated knee extensor muscle strength during isometric, concentric and eccentric muscle actions and vertical jump performance under conditions of squat jump (SJ), countermovement jump (CMJ) and drop jump (DJ). These measures were taken before, 1 hour after, and on days 1,2,3,4 and 7 following a damaging exercise protocol consisting of 100 barbell squats (10 sets x 10 reps @ 70% body mass load). Strength was significantly reduced for four days, however, no differences were observed in the magnitude or rate of recovery of isometric strength at 80° knee flexion and concentric and eccentric strength at 90 deg's'. Vertical jump performance was significantly reduced for three days and was dependent on the type of jump being performed. The relative decline in SJ performance was significantly greater than that in CMJ performance (91.6 ± 1.1% vs. 95.2 ± 1.3% of pre-exercise values, P<0.05) and the relative decline in SJ was significantly greater than that in DJ performance (91.6 ± 1.1% vs. 95.2 ± 1.4%, P<0.05). No differences were observed in the relative decline in CMJ and DJ performance (95.2 ± 1.3% vs. 95.2 ± 1.4%, P> 0.05). The stretch-shortening cycle (SSC) of muscle function is utilised in CMJ and DJ but not in SJ. The SSC has a clear purpose: to allow the final phase (concentric action) to take place with greater force or power output, as compared to the condition where the movement is initiated by a concentric action alone. 3 Utilisation of the SSC in performance seems to attenuate the detrimental performance effects of exercise-induced muscle damage. Study 3 The third and final study investigated the effects of exercise-induced muscle damage on maximal power output and knee extensor fatigability under isometric and dynamic conditions. Under isometric conditions, strength was assessed at 40° and 80° knee flexion and fatigability was assessed by a sustained 60s maximum voluntary contraction (MVC) at each joint angle. For dynamic conditions, maximum power output and fatigue were assessed during a maximal 30s cycle ergometer test. These measures were taken before, 1 hour after, and on days 1,2,3, and 7 following a damaging exercise protocol consisting of 100 eccentric squats (10 sets x 10 reps @ 80% concentric 1 RM). Isometric strength was significantly reduced (P < 0.05) for seven days but no significant differences were observed in the magnitude of strength loss and the pattern of recovery between the two joint angles. Fatigability was quantified as the slope (b) of a linear regression line fitted to the torque and power decay during the 60s MVC and the 30s cycle test, respectively. Prior to muscle damage, subjects were significantly less fatigable (P < 0.05) at 40° (b = -2.39 ± 0.26) versus 80° (b = -5.50 ± 0.72). After muscle damage, subjects became significantly less fatigable at both 40° and 80° with recovery taking three days at 401 and seven days at 80°. Before damaging exercise, a greater rate of fatigue was observed under dynamic (b = -12.75 ± 2.3) versus isometric (80°) conditions (b = -5.50 ± 0.72). Isometric and dynamic fatigue 4 followed a similar temporal pattern after damaging exercise. When the effects of muscle damage on strength at 801 and maximal power output were compared, differences in the extent of performance loss and the time course of recovery were observed. At 1 hour post-exercise, strength was affected to a greater extent (30% reduction) than power (13% reduction) and whereas strength followed a linear recovery pattern, power suffered further decrements at day 1 (18%) and day 2 (16%) before starting to recover. The results indicate that under conditions of voluntary activation muscle becomes weaker but less fatigable under isometric and dynamic conditions following exercise-induced muscle damage. The lower starting torque / power output and the slower rate of decline in torque / power output observed in post-damage fatigue curves may be a phenomenon of selective type II fibre damage. Evidence suggests that type II fibres are selectively damaged during eccentric exercise and therefore post-damage fatigue curves may be missing their contribution to performance. The different recovery patterns observed for isometric and dynamic performance may indicate an inability to maintain central motor drive during complex dynamic tasks when damage is present.

Le système musculaire joue un rôle primordial dans l’homéostasie de l’organisme. Il est impliqué dans différentes fonctions indispensables aux activités de la vie quotidienne telles que la production de mouvement, la locomotion, le maintien postural et l’équilibre. La qualité du tissu musculaire est donc primordiale dans le maintien de la qualité de vie et, à long terme, à la longévité. L'hypoactivité et le vieillissement sont deux situations qui entraînent le déconditionnement musculaire, et qui partagent une caractéristique commune: une perte de force musculaire, une atrophie et la modification du typage musculaire, ainsi que l'accumulation de tissu adipeux intramusculaire. Aujourd'hui, il existe de nombreuses données dans la littérature indiquant un lien entre le stress oxydant et le déconditionnement musculaire. Le but de cette thèse était d'évaluer l'impact de la modulation des défenses antioxydantes sur la prévention du déconditionnement musculaire. Cela a été étudié sous deux angles, l'un dans le contexte du vieillissement, et le second dans un contexte d'hypoactivité. La première étude avait pour but d'évaluer la fragilité chez un modèle souris âgées, utilisant un groupe de souris WT et un groupe de souris transgéniques sur-exprimant l'enzyme G6PD. Nous avons évalué des paramètres de qualité musculaire et de stress oxydant et avons réalisé une analyse transcriptomique à partir d'échantillons musculaires des souris de chacun des deux groupes. La seconde étude a été conduite dans le but d'évaluer les effets d'un cocktail enrichi en composés anti-oxydants et anti-inflammatoires, durant deux mois d'hypoactivité (modèle Bedrest). Nos résultats ont démontré l’inefficacité de cette supplémentation sur la prévention de la perte de masse et de force musculaire. De plus, les données concernant les mécanismes moléculaires ont démontré une altération des processus de récupération chez les sujets supplémentés.Les conclusions de nos études donnent des pistes sur les stratégies anti-oxydantes les plus appropriées contre le déconditionnement musculaire. Il semble préférable de intéresser à la stimulation des systèmes de défenses endogènes, plutôt que de se centrer sur une supplémentation nutritionnelle exogène. Néanmoins, la complexité des voies de signalisation redox requièrent une meilleure compréhension pour optimiser les mesures de prévention afin de limiter la perte de fonction musculaire
Musculoskeletal system plays a key role in organism’s well-functioning and is responsible for a large variety of functions such as posture, locomotion, balance, and activities of daily life. The quality of the skeletal muscle is therefore capital to maintain quality of life and, in the long term, survival. Hypoactivity and aging are two situations that cause skeletal muscle deconditioning, therefore sharing common characteristics: loss of muscle strength, muscular atrophy and MyHC redistribution, as well as IMAT accumulation. To date, there is plenty of evidence supporting a causative link between oxidative stress phenomenon and muscle deconditioning.The general aim of this PhD thesis was to evaluate the impact of the modulation of the antioxidant defenses on the prevention of muscle deconditioning. It has been studied from two perspectives, the first one in the context of aging and the second in the context of hypoactivity.The first study aimed to evaluate frailty in old female animals, using WT and G6PD-overexpressing mice. We evaluated muscle quality parameters and oxidative stress markers. Finally, we performed a transcriptomic analysis of muscle samples and highlighted differentially expressed genes in both groups of mice.The second study was conducted to evaluate the effects of a cocktail enriched in antioxidant/anti-inflammatory molecules in a 2-month hypoactivity experiment (Bedrest model). Our results clearly demonstrate the ineffectiveness of this type of supplementation in the prevention of muscle mass and strength loss. Moreover, data regarding muscle molecular mechanisms highlight an alteration of recovery processes in the supplemented subjects.Finally, the conclusions of our two studies gave clues on the suitable antioxidant modulation strategy for the prevention of skeletal muscle deconditioning. It seems preferable to focus on the stimulation of endogenous defense system whether than towards exogenous supply of nutritional antioxidants. Nevertheless, the complexity of redox signaling requires better understanding to optimize countermeasures in muscle wasting situations

Thesis (M.S.)--California Polytechnic State University, 2008.
"July 2008." "In partial fulfillment of the requirements for the degree [of] Master of Science in Engineering with a specialization in Biomedical Engineering." "Presented to the faculty of California Polytechnic State University, San Luis Obispo." Major professor: Trevor Cardinal, Ph.D. Includes bibliographical references (leaves 96-101). Also available on microfiche and online.

There is a dearth of knowledge on the functional organization of the anatomically complex human masseter muscle. Limited physiological studies suggest a functional organization which may differ significantly from human limb muscles. The present studies aimed to examine the putative relationship between structure and function in the human masseter muscle as a basis for understanding function and dysfunction in human jaw muscles. In the first experiment single motor unit (SMU) activity was recorded from pairs of recording sites distributed throughout the masseter muscle. In each case SMU activity at a chosen location was used as a reference to search for synchronized SMU activity at another selected site. The locations of the needle tips were estimated in 3-dimensions (3-D) by means of an optical system, then transferred to 3-D reconstructions derived from Magnetic Resonance images. This approach permitted calculation of the linear distances between verified muscle recording sites. The mean separation of the sites from which synchronous SMU activity could be recorded was 8.8±3.4mm. The putative territories had a preferred orientation in the antero-posterior axis. Motor unit territories were larger than described previously, and appeared to be related to anatomical compartments. The second experiment involved recording activity from stereotactically mapped masseter SMUs. In each case, the lowest sustainable firing frequency (LSFF) was reached by slow increases and decreases in voluntary firing rate, followed by sustained firing at the lowest possible rate. Pulse-discrimination and digital sampling of consecutive inter-spike intervals (ISIs) were then used to measure LSFF for 2-6 separate occlusal and postural tasks to which each unit contributed. There were significant differences between mean ISIs for the tasks performed by most units, which suggests descending drive to masseter units is highly task-dependent. There were also regional differences in unit task specificities. In the third paradigm, reflex SMU activity was recorded from units in the masseter muscle and the inferior head of the lateral pterygoid muscle. Bipolar electrodes fixed to the gingiva near the maxillary canine delivered single pulses of 1ms duration at sub-noxious levels of intensity. At constrained firing frequencies (10, 15Hz), pulses were injected sequentially, with increasing delays, after preselected spikes. More profound inhibition occurred in units firing at 10 than 15Hz. There were significant differences in masseter inhibitory responses when the unit task varied. Reflex inhibition in masseter and lateral pterygoid SMUs is highly frequency-dependent, and also task-dependent in masseter units. The fourth study involved recording activity from SMUs in the masseter muscle. A midline load cell was fixed to the incisor teeth and aligned either perpendicular (P) or 30 degrees anterior (A) to the occlusal plane, without altering jaw position. A rigid spike-triggered averaging (STA) paradigm was used to extract the contribution of individual SMUs to the overall force at load cell orientations P and A. Spikes preceded or followed by an interval of less than 100ms were rejected prior to averaging. At background bite forces from 0.06-8N, the isometric forces apparently developed by individual units varied randomly with load cell orientations, (P range 36.2±19.6mN; A range 38.2±28.4mN). All units could be fired slowly with varying degrees of muscle coactivation, in some instances without contact on the load cell. The use of STA as a method for determining SMU tension in the masseter muscle appears to be task-dependent and in the presence of coactivation may be inappropriate. The findings collectively indicate the heterogeneous nature of SMU behaviour in the human masseter muscle which is consistent with internal muscle compartments based on anatomical features and functional behaviour. There thus appear to be both physiological and anatomical substrates for differential motor control of selected regions of the human masseter muscle.
Dentistry, Faculty of
Graduate

The investigation of motor-unit fatigability in reduced-animal models has been dominated by a single fatigue test, one fatigue index, and an emphasis on changes in the magnitude of (usually peak) force. Although the standard fatigue test has been reported to elicit changes in the dynamic phases of an isometric tetanus, this has not been systematically studied in single motor units. Furthermore, changes in the profile of individual tetani during the fatigue test have led some investigators to suggest that other force parameters (i.e., integrated force) or fatigue indices may provide additional information about motor-unit performance during the test. The purposes of this project were to: (1) evaluate the time courses of a variety of force parameters characterizing both the magnitude of force and the dynamic aspects of force during a 4-min fatigue test of functionally isolated cat, tibialis posterior motor units; and (2) determine if motor units could be classified into the conventional motor-unit types based on these new parameters. There was considerable variability in the average time course of the magnitude of force during the fatigue test. The variability within the type FR and F(int) motor-unit groups resulted in several units whose characteristics bordered those which, by definition, separate unit types. The classification of these units depended on the force parameter and fatigue index used to quantify their fatigability. The time course of the magnitude of force also revealed differences in the behavior of potentiating and non-potentiating groups. There were many differences between motor-unit types in terms of dynamic-force parameters before, during and after the fatigue test. Comparison of initial and 2-min values revealed a preferential effect of stimulation on force development in type S and FR units (i.e., increased rate) and on force decay in type F(int) and FF units (i.e., prolonged duration and decreased rate). The time courses of these effects further revealed qualitative differences between different combinations of motor-unit types. Groups of units (or lack thereof) revealed by dynamic-force parameters were compared to conventional motor-unit types by discriminant analysis. The results were not always consistent with conventional types.

Low frequency mechanical vibrations (<100 Hz) are naturally generated by skeletal muscles during voluntary contractions. Recording of these vibrations at the muscle surface are called surface mechanomyograms (S-MMGs). In this study, S-MMGs were recorded over a 3 x 5 grid of skin mounted accelerometers on the biceps brachii muscle during submaximal voluntary isometric contractions with the arm in a pronated position for ten healthy and young male subjects with no overt sign of neuromuscular diseases. For a given pair of accelerometers, the spatial coherence of S-MMG is a measure of the similarity of the S-MMG signals propagating between those two sensors. Two common techniques to estimate the spatial coherence for narrowband S-MMG signals, namely the magnitude squared coherence function and the maximum of the time-domain cross-correlation function, were found to yield similar results. In particular, high spatial coherence values were measured for sensor pairs aligned along the proximal to distal ends of the biceps, i.e. the longitudinal direction. On the other hand, the spatial coherence values for sensor pairs oriented perpendicular to the muscle fiber, i.e. along the transverse direction, were found to be significantly lower. This finding indicates that coherent S-MMGs were mainly propagating along the muscle fibers direction (longitudinal) of the biceps brachii within a frequency band varying between 10Hz to 50Hz. Additionally, the spatial coherence of S-MMGs along the longitudinal direction was found to decrease with increasing frequency and increasing sensor separation distance and to increase with contraction level varying between 20% to 60% of the maximum contraction level.

L’expérience du laboratoire en matière de muscles artificiels pneumatiques pour la robotique est appliquée au développement de mini-actionneurs à muscles artificiels destinés à des systèmes robotiques miniatures. Le domaine de la robotique médicale est tout particulièrement visé. Le but de ce travail est de mettre au point et développer des actionneurs dont les caractéristiques et les performances correspondent à ceux présentés par les muscles naturels. Ces actionneurs seront utilisés dans le domaine de la robotique et dans le domaine médical. Ainsi, dans un premier temps on s’est intéressé au développement et à l’étude du muscle artificiel pneumatique de McKibben. Il s’agit d’un type d’actionneur très performant, présentant des propriétés satisfaisantes, se rapprochant énormément de celles des muscles naturels. De ce fait, leur utilisation dans le domaine de la robotique est très avantageuse. Cependant, la source énergétique qu’ils utilisent - l’air comprimé – présente un sérieux frein vis-à-vis d’une utilisation flexible ou médicale. De ce fait, dans un deuxième temps, on a adapté ces muscles de McKibben au domaine biomédical en remplaçant l’air comprimé par des résines échangeuses d’ions ou des hydrogels. On a ainsi développé et étudié des muscles mécanochimiques basés sur des muscles de McKibben
The experience of the laboratory in the matter of pneumatic artificial muscle for the robotics is applied to the development of mini-actuators with artificial muscles intended for miniature robot-like systems. The field of medical robotics is particularly aimed. The goal of this work is to develop actuators whose characteristics and performances correspond to those presented by the natural muscles. These actuators will be used in the field of robotics and the medical field. Thus, initially we were interested in the development and the study of the pneumatic artificial muscle of McKibben. It is a type of very powerful actuator, presenting satisfactory properties, approaching those of the natural muscles enormously. So their use in the field of robotics is very advantageous. However, the energy source that they use - compressed air - presents a serious restraint with respect to a flexible or medical use. So in the second time, we adapted these muscles of McKibben to the biomedical field by replacing the compressed air by exchanging resins of ions or hydrogels. We thus developed and studied muscles mecanochimic based on McKibben’s muscles

Cells contain an elaborate cytoskeleton which plays a major role in a variety of cellular functions including: maintenance of cell shape and dimension, providing mechanical strength, cell motility, cytokinesis during mitosis and meiosis and intracellular transport. The cell cytoskeleton is made up of three types of protein filaments: the microtubules, the intermediate filaments and the actin cytoskeleton. These components interact with each other to allow the cell to function correctly. When functioning incorrectly, disruptions to many cellular pathway have been observed with mutations in various cytoskeletal proteins causing an assortment of human disease phenotypes. Characterization of these filament systems in different cell types is essential to the understanding of basic cellular processes and disease causation. The studies in this thesis are concerned with examining specific cytoskeletal tropomyosin-defined actin filament systems in skeletal muscle. The diversity of the actin filament system relies, in part, on the family of actin binding proteins, the tropomyosins (Tms). There are in excess of forty Tm isoforms found in mammals which are derived from four genes: α, β, γ and δTm. The role of the musclespecific Tms in striated muscle is well understood, with sarcomeric Tm isoforms functioning as part of the thin filament where it regulates actin-myosin interactions and hence muscle contraction. However, relatively little known about the roles of the many cytoskeletal Tm isoforms. Cytoskeletal Tms have been shown to compartmentalise to form functionally distinct filaments in a range of cell types including neurons (Bryce et al., 2003), fibroblasts (Percival et al., 2000) and epithelial cells (Dalby-Payne et al., 2003). Recently it has been shown that cytoskeletal Tm, Tm5NM1 defines a cytoskeletal structure in skeletal muscle called the Z-line associated cytoskeleton (Z-LAC) (Kee et al., 2004).The disruption of this structure by over-expression of an exogenous Tm in transgenic mice results in a muscular dystrophy phenotype, indicating that the Z-LAC plays an important role in maintenance of muscle structure (Kee et al., 2004). In this study, specific cytoskeletal Tms are further investigated in the context of skeletal muscle. Here, we examine the expression, localisation and potential function of cytoskeletal Tm isoforms, focussing on Tm4 (derived from the δ- gene) and Tm5NM1 (derived from the γ-gene). By western blotting and immuno-staining mouse skeletal muscle, we show that cytoskeletal Tms are expressed in a range of muscles and define separate populations of filaments. These filaments are found in association with a number of muscle structures including the myotendinous junction, neuromuscular junction, the sarcolemma, the t-tubules and the sarcoplasmic reticulum. Of particular interest, Tm4 and Tm5NM1 define cytoskeletal elements in association with the saroplasmic reticulum and T-tubules, respectively, with a separation of less than 90 nm between distinct filamentous populations. The segregation of Tm isoforms indicates a role for Tms in the specification of actin filament function at these cellular regions. Examination of muscle during development, regeneration and disease revealed that Tm4 defines a novel cytoskeletal filament system that is orientated perpendicular to the sarcomeric apparatus. Tm4 is up-regulated in both muscular dystrophy and nemaline myopathy and also during induced regeneration and focal repair in mouse muscle. Transition of the Tm4-defined filaments from a predominsnatly longitudinal to a predominantly Z-LAC orientation is observed during the course of muscle regeneration. This study shows that Tm4 is a marker of regeneration and repair, in response to disease, injury and stress in skeletal muscle. Analysis of Tm5NM1 over-expressing (Tm5/52) and null (9d89) mice revealed that compensation between Tm genes does not occur in skeletal muscle. We found that the levels of cytoskeletal Tms derived from the δ-gene are not altered to compensate for the loss or gain of Tm5NM1 and that the localisation of Tm4 is unchanged in skeletal muscle of these mice. Also, excess Tm5NM1 is sorted correctly, localising to the ZLAC. This data correlates with evidence from previous investigations which indicates that Tm isoforms are not redundant and are functionally distinct (Gunning et al., 2005). Transgenic and null mice have also allowed the further elucidation of cytoskeletal Tm function in skeletal muscle. Analyses of these mice suggest a role for Tm5NM1 in glucose regulation in both skeletal muscle and adipose tissue. Tm5NM1 is found to colocalise with members of the glucose transport p fibres and analysis of both transgenic and null mice has shown an alteration to glucose uptake in adipose tissue. Taken together these data indicate that Tm5NM1 may play a role in the translocation of the glucose transport molecule GLUT4. In addition to this Tm5NM1 may play a role in adipose tissue regulation, since over-expressing mice found to have increased white adipose tissue and an up-regulation of a transcriptional regulator of fat-cell formation, PPAR-γ.

It is well established that unilateral exercise can produce contralateral effects. However, it is unclear whether unilateral exercise that leads to muscle injury and inflammation also affects the homologous contralateral muscles. To test the hypothesis that unilateral muscle injury causes contralateral muscle changes, an experimental rabbit model with unilateral muscle overuse caused by a combination of electrical muscle stimulation and exercise (EMS/E) was used. The soleus and gastrocnemius muscles of both exercised and non-exercised legs were analyzed with enzyme-and immunohistochemical methods after 1, 3 and 6 weeks of repeated EMS/E. After 1 w of unilateral EMS/E there were structural muscle changes such as increased variability in fiber size, fiber splitting, internal myonuclei, necrotic fibers, expression of developmental MyHCs, fibrosis and inflammation in the exercised soleus muscle. Only limited changes were found in the exercised gastrocnemius muscle and in both non-exercised contralateral muscles. After 3 w of EMS/E, muscle fiber changes, presence of developmental MyHCs, inflammation, fibrosis and affections of nerve axons and AChE production were observed bilaterally in both the soleus and gastrocnemius muscles. At 6 w of EMS/E, the severity of these changes significantly increased in the soleus muscles and infiltration of fat was observed bilaterally in both the soleus and the gastrocnemius muscles. The affections of the muscles were in all three experimental groups restricted to focal regions of the muscle samples. We conclude that repetitive unilateral muscle overuse caused by EMS/E overtime leads to both degenerative and regenerative tissue changes and myositis not only in the exercised muscles, but also in the homologous non-exercised muscles of the contralateral leg. Although the mechanism behind the contralateral changes is unclear, we suggest that the nervous system is involved in the cross-transfer effects.

Fourteen college softball players were recruited to participate in this study to determine if a strength imbalance between the lower extremities, how significant this difference this may be and of any correlations existed among all the functional tests. Subjects took part in isokinetic flexion and extension at 60 and 240 deg/sec, parallel squats, 2-legged vertical jump, single leg vertical jump, and a five-hop test. Peak and average torque was recorded for isokinetic testing and revealed significant differences between the dominant and non-dominant limbs (13.00%- 16.00%). Peak and average force was analyzed for squats and all vertical jumps. Significance was found among all activities between dominant and non-dominant legs, other than average force for single leg vertical jump. A significant difference was also exhibited for the five-hop test between the lower extremities. Significant correlations were also found at the 0.05 and 0.01 levels amongst the various functional tests. Overall findings revealed a significant strength imbalance between the dominant and non-dominant limbs. Further research needs to be conducted in determining how detrimental these differences could be in daily performance for athletes.
School of Physical Education

PURPOSE: High-resistance inspiratory muscle work results in inspiratory muscle fatigue and sympathetically mediated increases in heart rate (HR) and mean arterial pressure (MAP). We hypothesized that 5 wks of inspiratory muscle training (IMT) would attenuate such a response. METHODS: An experimental group (EXP, n = 8) performed IMT 6 days/wk for 5-wks at 50% of maximal inspiratory pressure (MIP), while a mock training group (SHAM, n = 8) performed IMT at 10% MIP. Pre- and post- training, subjects underwent a eucapnic resistive breathing protocol (RBT) at a resistance of approx. 50% MIP (breathing frequency = 15 breaths/min, duty cycle = 0.70) while HR and MAP were continuously monitored. RBT duration was matched within each subject pre and post. MIP was assessed weekly. RESULTS: MIP increased significantly (p < 0.05) in the EXP group (-125.0 ± 28.4 to - 145.5 ± 33.3 cm H₂0, mean ± SD) but not in the SHAM group (-141.2 ± 31.8 to -147.5 ± 32.0 cm H₂0) . Mean RBT duration was significantly shorter in the SHAM group (392 ± 93.7 sec vs. 677 ± 197 sec). Prior to IMT, the RBT resulted in significant, rises in HR (SHAM: 58.7 ± 5.2 to 82.9 ± 11.6 beats/min; EXP : 61.7 ± 9.3 to 82.7 ± 12.1 beats/min) and MAP (SHAM: 88.1 ± 4.6 to 106.2 ± 7.3 mmHg; EXP : 84.5 ± 4.0 to 99.2 ± 8.1 mmHg) in both groups. The SHAM group responded similarly to the RBT post-training (HR: 56.9 ± 6.2 to 76.8 ± 8.5 beats/min; MAP : 89.3 ± 9.0 to 102.5 ± 8.0 mmHg). Following IMT in the EXP group, the RBT failed to increase HR and MAP to the same extent as before training (HR: 58.6 ± 8.7 to 73.8 ± 7.1 beats/min; MAP : 84.5 ± 3.3 to 88.7 ± 6.1 mmHg). MIP measured before and after the RBT did not change in either group pre or post training. CONCLUSIONS: IMT reduces the HR and MAP response to resistive inspiratory muscle work. This may indicate a reduction in sympatho-excitation due to either reduced accumulation of, or reduced responsiveness to, metabolites within the inspiratory muscles.
Education, Faculty of
Kinesiology, School of
Graduate

L’asthme est un désordre respiratoire obstructif qui affecte plus de 330 millions de personnes à travers le monde. Les symptômes de cette pathologie comprennent de l’essoufflement, de l’oppression thoracique, de la sibilance et de la toux, et surviennent suivant l’inhalation de facteurs déclencheurs (virus, allergène, pollution…). La pathologie de l’asthme est caractérisée par une inflammation chronique et variable au sein du système respiratoire, un remodelage des voies aériennes ainsi qu’une hyperréactivité bronchique. L’équipe de recherche du Dr Ynuk Bossé travaille sur la physiologie du muscle lisse des voies aériennes, et plus spécifiquement sur l’augmentation des capacités contractiles du muscle lisse en réponse à un tonus (i.e. contraction soutenue). Ce phénomène nommé le gain de force du muscle lisse a été observé avant mon arrivée dans ce laboratoire sur des trachées de moutons et de souris montées en bain d’organe, ainsi qu’in vivo chez la souris. Des travaux antérieurs ont démontré que la présence d’un tonus augmentait la réactivité bronchique de souris en réponse à l’inhalation d’une forte dose de métacholine. Le but de cette thèse était d’explorer dans une dynamique translationnelle, les rouages moléculaires de ce phénomène et d’en définir les impacts sur la fonction respiratoire in vivo. Dans une première étude réalisée au début de mon doctorat, nous avons étudié les conséquences du tonus sur la réactivité bronchique in vivo chez l’humain. Nous avons ainsi observé que l’augmentation du tonus, provoquée par l’inhalation répétée de faibles doses de métacholine durant une période de 30 minutes, augmentait la réactivité bronchique en réponse à l’inhalation d’une forte dose de métacholine. De plus, nous avons également observé grâce à l’utilisation de la technique des oscillations forcées que cette augmentation de la réactivité bronchique était liée à une augmentation de la résistance des voies périphériques. Nous avons donc confirmé dans cette étude que la présence d’un tonus augmente la réactivité bronchique chez de jeunes humains en santé. Dans une seconde étude, conduite tout au long de mon doctorat, nous avons étudié les mécanismes moléculaires responsables du gain de force du muscle lisse en réponse à un tonus. Nous avons ainsi observé que ce phénomène n’était pas lié à une potentialisation de la phosphorylation de la chaîne légère de myosine, mais plutôt provoqué par une augmentation de la filamentogénèse d’actine. Nous avons également déterminé que cette augmentation de la filamentogénèse d’actine était en partie provoquée par une inhibition de la dépolymérisation des filaments d’actine suite à l’inhibition de la protéine cofiline. Nous avons donc démontré que le tonus augmente la filamentogénèse d’actine au sein des cellules musculaires lisses, ce qui pourrait contribuer à une augmentation des capacités contractiles. Finalement, dans une troisième étude entreprise durant la dernière partie de mon doctorat, nous tentons de comprendre les liens entre le phénomène du gain de force du muscle lisse et l’inflammation présente dans l’asthme. Il semblerait que la présence d’une inflammation provoquée par de la poudre d’acariens chez la souris augmente la réactivité bronchique, mais empêche le développement du gain de force du muscle lisse. En revanche, les résultats obtenus sont encore préliminaires. Il est actuellement impossible de tirer des conclusions fermes. Ainsi, nous nous interrogeons toujours à l’égard du rôle de l’inflammation sur le gain de force du muscle lisse des voies aériennes. Dans sa globalité, cette thèse démontre que le gain de force du muscle lisse des voies aériennes est provoqué par un remodelage du cytosquelette d’actine, et que ce phénomène augmente la réactivité bronchique in vivo chez l’humain. De plus, cette thèse ouvre des voies de recherche afin de déterminer si ce phénomène pourrait être impliqué dans l’hyperréactivité bronchique dans l’asthme.
L’asthme est un désordre respiratoire obstructif qui affecte plus de 330 millions de personnes à travers le monde. Les symptômes de cette pathologie comprennent de l’essoufflement, de l’oppression thoracique, de la sibilance et de la toux, et surviennent suivant l’inhalation de facteurs déclencheurs (virus, allergène, pollution…). La pathologie de l’asthme est caractérisée par une inflammation chronique et variable au sein du système respiratoire, un remodelage des voies aériennes ainsi qu’une hyperréactivité bronchique. L’équipe de recherche du Dr Ynuk Bossé travaille sur la physiologie du muscle lisse des voies aériennes, et plus spécifiquement sur l’augmentation des capacités contractiles du muscle lisse en réponse à un tonus (i.e. contraction soutenue). Ce phénomène nommé le gain de force du muscle lisse a été observé avant mon arrivée dans ce laboratoire sur des trachées de moutons et de souris montées en bain d’organe, ainsi qu’in vivo chez la souris. Des travaux antérieurs ont démontré que la présence d’un tonus augmentait la réactivité bronchique de souris en réponse à l’inhalation d’une forte dose de métacholine. Le but de cette thèse était d’explorer dans une dynamique translationnelle, les rouages moléculaires de ce phénomène et d’en définir les impacts sur la fonction respiratoire in vivo. Dans une première étude réalisée au début de mon doctorat, nous avons étudié les conséquences du tonus sur la réactivité bronchique in vivo chez l’humain. Nous avons ainsi observé que l’augmentation du tonus, provoquée par l’inhalation répétée de faibles doses de métacholine durant une période de 30 minutes, augmentait la réactivité bronchique en réponse à l’inhalation d’une forte dose de métacholine. De plus, nous avons également observé grâce à l’utilisation de la technique des oscillations forcées que cette augmentation de la réactivité bronchique était liée à une augmentation de la résistance des voies périphériques. Nous avons donc confirmé dans cette étude que la présence d’un tonus augmente la réactivité bronchique chez de jeunes humains en santé. Dans une seconde étude, conduite tout au long de mon doctorat, nous avons étudié les mécanismes moléculaires responsables du gain de force du muscle lisse en réponse à un tonus. Nous avons ainsi observé que ce phénomène n’était pas lié à une potentialisation de la phosphorylation de la chaîne légère de myosine, mais plutôt provoqué par une augmentation de la filamentogénèse d’actine. Nous avons également déterminé que cette augmentation de la filamentogénèse d’actine était en partie provoquée par une inhibition de la dépolymérisation des filaments d’actine suite à l’inhibition de la protéine cofiline. Nous avons donc démontré que le tonus augmente la filamentogénèse d’actine au sein des cellules musculaires lisses, ce qui pourrait contribuer à une augmentation des capacités contractiles. Finalement, dans une troisième étude entreprise durant la dernière partie de mon doctorat, nous tentons de comprendre les liens entre le phénomène du gain de force du muscle lisse et l’inflammation présente dans l’asthme. Il semblerait que la présence d’une inflammation provoquée par de la poudre d’acariens chez la souris augmente la réactivité bronchique, mais empêche le développement du gain de force du muscle lisse. En revanche, les résultats obtenus sont encore préliminaires. Il est actuellement impossible de tirer des conclusions fermes. Ainsi, nous nous interrogeons toujours à l’égard du rôle de l’inflammation sur le gain de force du muscle lisse des voies aériennes. Dans sa globalité, cette thèse démontre que le gain de force du muscle lisse des voies aériennes est provoqué par un remodelage du cytosquelette d’actine, et que ce phénomène augmente la réactivité bronchique in vivo chez l’humain. De plus, cette thèse ouvre des voies de recherche afin de déterminer si ce phénomène pourrait être impliqué dans l’hyperréactivité bronchique dans l’asthme.
Asthma is an obstructive respiratory disorder affecting more than 330 million people worldwide. The symptoms include breathlessness, chest oppression, wheezing and cough. The symptoms are variable in nature and severity and generally coincide with the inhalation of environmental factors (viruses, allergens, pollution…). The pathology of asthma is characterized by several typical features, such as airway inflammation, airway remodeling and airway hyperresponsiveness. The research team of Dr Ynuk Bossé is specialized in the study of lung physiology and airway smooth muscle mechanics. Of particular interest is a phenomenon called ‘force adaptation’. Force adaptation is a time-dependent gain in the contractile capacity of airway smooth muscle in response to tone (i.e., a sustained contraction). This phenomenon was observed in vitro in isolated ovine and murine tissues, as well as in vivo in mice. Previous work has demonstrated that the presence of tone, provoked by repeated exposures to low doses of methacholine during 20 min, increases airway responsiveness to the inhalation of a high dose of methacholine. The aim of this thesis was to decipher the molecular mechanisms of force adaptation in vitro and to explore the impact of this phenomenon on respiratory function in vivo. In a first study, which was conducted at the beginning of my PhD, we assessed the effect of tone on airway responsiveness in young healthy adults. We demonstrated that tone, which was generated by repeated inhalations of low doses of methacholine during 30 min, enhances airway responsiveness to a high dose of methacholine. Moreover, with the use of the force oscillation technique, we demonstrated that this effect was predominant in the peripheral airways. Therefore, this study confirmed that airway smooth muscle tone increases airway responsiveness in young healthy adults. In a second study, conducted over the entire course of my PhD, we investigated the molecular mechanisms responsible for the gain in contractile capacity induced by tone. We observed that force adaptation does not rely on molecular mechanisms enhancing the phosphorylation of the myosin light chain but rather occurs in conjunction with an increase in actin filamentogenesis. We further demonstrated that this increase in actin filamentogenesis may stem not only from actin polymerization but also from the inhibition of actin filament depolymerization via the inhibition of the protein cofilin. Therefore, the results of this study suggested that tone increase the contractile capacity of airway smooth muscle by fostering actin filamentogenesis. Finally, in a third study started at the end of my PhD, we are trying to understand the links between the gain in contractile capacity induced by tone and airway inflammation in asthma. We are using a mouse model of allergic airway inflammation induced by repeated exposures to house dust mite. While allergic inflammation increases airway responsiveness, it seems to diminish the phenomenon of force adaptation. However, the results obtained so far will require further investigations. It is currently impossible to reach authoritative conclusions. We are still left wondering whether airway inflammation alters the gain in contractile capacity induced by tone. Overall, this thesis is demonstrated that force adaptation increases airway responsiveness in vivo in human and, at the molecular level, the phenomenon seems to rely on an active remodeling of the actin cytoskeleton. Moreover, this thesis opens new research areas, which will need to be further explored in order to determine whether the gain in contractile capacity induced by tone is implicated in airway hyperresponsiveness in asthma
Asthma is an obstructive respiratory disorder affecting more than 330 million people worldwide. The symptoms include breathlessness, chest oppression, wheezing and cough. The symptoms are variable in nature and severity and generally coincide with the inhalation of environmental factors (viruses, allergens, pollution…). The pathology of asthma is characterized by several typical features, such as airway inflammation, airway remodeling and airway hyperresponsiveness. The research team of Dr Ynuk Bossé is specialized in the study of lung physiology and airway smooth muscle mechanics. Of particular interest is a phenomenon called ‘force adaptation’. Force adaptation is a time-dependent gain in the contractile capacity of airway smooth muscle in response to tone (i.e., a sustained contraction). This phenomenon was observed in vitro in isolated ovine and murine tissues, as well as in vivo in mice. Previous work has demonstrated that the presence of tone, provoked by repeated exposures to low doses of methacholine during 20 min, increases airway responsiveness to the inhalation of a high dose of methacholine. The aim of this thesis was to decipher the molecular mechanisms of force adaptation in vitro and to explore the impact of this phenomenon on respiratory function in vivo. In a first study, which was conducted at the beginning of my PhD, we assessed the effect of tone on airway responsiveness in young healthy adults. We demonstrated that tone, which was generated by repeated inhalations of low doses of methacholine during 30 min, enhances airway responsiveness to a high dose of methacholine. Moreover, with the use of the force oscillation technique, we demonstrated that this effect was predominant in the peripheral airways. Therefore, this study confirmed that airway smooth muscle tone increases airway responsiveness in young healthy adults. In a second study, conducted over the entire course of my PhD, we investigated the molecular mechanisms responsible for the gain in contractile capacity induced by tone. We observed that force adaptation does not rely on molecular mechanisms enhancing the phosphorylation of the myosin light chain but rather occurs in conjunction with an increase in actin filamentogenesis. We further demonstrated that this increase in actin filamentogenesis may stem not only from actin polymerization but also from the inhibition of actin filament depolymerization via the inhibition of the protein cofilin. Therefore, the results of this study suggested that tone increase the contractile capacity of airway smooth muscle by fostering actin filamentogenesis. Finally, in a third study started at the end of my PhD, we are trying to understand the links between the gain in contractile capacity induced by tone and airway inflammation in asthma. We are using a mouse model of allergic airway inflammation induced by repeated exposures to house dust mite. While allergic inflammation increases airway responsiveness, it seems to diminish the phenomenon of force adaptation. However, the results obtained so far will require further investigations. It is currently impossible to reach authoritative conclusions. We are still left wondering whether airway inflammation alters the gain in contractile capacity induced by tone. Overall, this thesis is demonstrated that force adaptation increases airway responsiveness in vivo in human and, at the molecular level, the phenomenon seems to rely on an active remodeling of the actin cytoskeleton. Moreover, this thesis opens new research areas, which will need to be further explored in order to determine whether the gain in contractile capacity induced by tone is implicated in airway hyperresponsiveness in asthma

Thesis (Ph.D.)--University of Western Sydney, 2007.
A thesis presented to the University of Western Sydney, College of Health and Science, School of Natural Sciences, in fulfilment of the requirements for the degree of Doctor of Philosophy. Includes bibliographies.

In skeletal muscle, loss of neuronal nitric oxide synthase (nNOS) from the sarcolemma has been observed in a few muscular dystrophies and myopathies. However, the extent of this phenomenon, its mechanism, and its physiological impact are not well understood. Using immunofluorescent staining for nNOS, a survey of 161 patient biopsies found absent or reduced sarcolemmal nNOS in 43% of patients. Patient mobility and muscle functional status correlated with nNOS mislocalization from the sarcolemma. Mouse models of inherited and acquired myopathies showed similar loss of sarcolemmal nNOS and impaired mobility and muscle function. A proteomic approach, using mass spectrometry and differentially labeled control and steroid-induced myopathy (SIM) mouse samples, found novel nNOS binding proteins including alpha-actinin-3 (ACTN3), which exhibited decreased interaction with nNOS after steroid treatment. It revealed a potential explanation for impaired muscle function in SIM as nNOS interactions were lost at the sarcomere and gained at the sarcoplasmic reticulum impairing contractility. Treating nNOS-deficient mice with steroids demonstrated that loss of sarcolemmal nNOS reduces muscle contractility and strength in SIM through increased nitric oxide (NO) signaling. In SIM mice treated with a nitric oxide donor and steroids, nitric oxide partially protects the muscle from atrophy and improves muscle fatigability and recovery suggesting nNOS mislocalization also decreases NO availability. These findings show that loss of sarcolemmal nNOS is a common phenomenon that negatively impacts muscle function. Therapeutic strategies targeting nNOS or NO signaling need to allow for the complexity of local nitric oxide content and cellular context.

To determine whether muscle contractions can increase muscle blood flow independently from metabolic factors, we isolated the diaphragmatic vasculature of 16 anesthetized and mechanically ventilated dogs. Phrenic inflow (Qphr) was controlled with a constant pressure source and the pressure (Pa) was decreased in steps to obtain the pressure-flow relation (P-Q). The vasculture was maximally vasodilated and contractions occurred spontaneously (n = 6) or were induced by twitches (n = 12) or tetanic trains (n = 7). The P-Q relations with contractions were compared to those with vasodilatation alone. With spontaneous contractions, the pressure intercept decreased from 47.35 $ pm$ 17.44 to 33.77 $ pm$ 16.82 mmHg (p $<$ 0.05) and the slope remained unchanged so that at Pa = 100 mmHg, Qphr increased from 36.22 $ pm$ 34.85 to 43.91 $ pm$ 38.22 ml/min/100g (p $<$ 0.05). Flow increased slightly with twitches but not with trains. We also elicited twitches, 12/min and 60/min trains in vascularly isolated gastrocnemius muscles (n = 6) and found no change in flow. In conclusion, the muscle pump has only a small effect on muscle blood flow.

This project was aimed to elucidate the sub-cellular and molecular regulation of Lipopolysaccharide (LPS) induced muscle protein turnover (protein synthesis (PS) and protein degradation) in two in vitro models, C2C12 murine myotubes and avian primary skeletal muscle cell line. In addition, the effect of natural challenge of chicken with Salmonella serotypes gallinarium or Enteritidis on mRNA expression levels in skeletal muscle was assessed. LPS (1 μgml-1) transiently decreased PS rate by 50% compared with control cells. This effect was mediated via decreased phosphorylation of translation initiation mediators (p70S6K, 4E-BP1 and eIF-4E). This effect was preceded by decreased Akt and mTOR phosphorylation. Although, LPS significantly increased p38, Erk1/2 and their down stream target Mnk1, however, this effect was not sufficient to abolish LPS-induced decreased PS. The role of Akt and MAPKs (p38 or Erk1/2) was verified using specific pathway inhibitors. Inhibition of Akt by LY0294002 (PI3-K/Akt inhibitor) dramatically decreased PS by 80% compared with control cells. Incubation of C2C12 myotubes with SB203580 (p38 inhibitor) or with PD098059 (MEK/Erk inhibitor) alone significantly decreased the PS rate at the 3 h time point by -63 ± 12.48% and -64 ± 5.05% respectively compared with control cells (P < 0.01). In contrast, LPS (1 μgml-1) significantly increased the chymotrypsin-like enzyme at all the time points. This effect was preceded by a significant increase in the IkB-α phosphorylation and nuclear translocation of NF-kB, and significant increase in TNF-α, atrogin-1, MuRF1 and TLR4 mRNA expression. Of note, increased atrogin-1 mRNA is the prominent feature of our septic model. The data presented in chapter 4 and 5 showed that, there is no absolute correlation between the expression levels of atrogens (atrogin-1 and MuRF1) and the overall proteolytic activity in LPS-stimulated C2C12 myotubes. The beneficial roles of the curcumin were evaluated LPS-stimulated C2C12 myotubes for 3 h. Incubation of C2C12 myotubes with LPS (1 μgml-1) and curcumin (25 μM) significantly decreased the LPS-induced chymotrypsin-like enzyme activity. This effect was mediated via decreased p38 and IkB-α phosphorylation. Although, curcumin blocked LPS-induced decreased Akt and p70S6K phosphorylation and significantly increased Erk1/2 phosphorylation, however, curcumin still had no effect on LPS-induced decreased protein synthesis. The effect of the LPS on the muscle protein turnover in the avian primary skeletal muscle was summarised in chapter (7). Incubation of avian primary skeletal cells with LPS (1 μgml-1) for 3 h, significantly decreased the proteasomal activity and increased PS rate. The difference in response to LPS between C2C12 myotubes and avian primary skeletal muscle cells could be attributed to the different incubation parameters mainly the presence of insulin in case of avian primary cells. Finally, the effect of natural challenge of chicken with S. Gallinarum or S. Enteritidis on skeletal muscle mRNA expression was summarised in chapter 9. Natural challenge of chicken with S. Gallinarum or S. Enteritidis had no effect on the expression of many atrophic genes in chicken skeletal muscle (gastrocnemius and pectoral muscle). The data collected from this project showed that, LPS is a strong catabolic stimulus significantly decreased PS along with increased protein breakdown rates in skeletal muscle. This effect was mediated via two main pathways PI3-K/Akt and MAPKs (p38 or Erk1/2) and the cross talk between them is exists. The better understanding of these signalling cascades and their cross talk will be the starting point for developing the appropriate and safe therapeutic intervention in order to decrease the sepsis-induced muscle proteolysis.

Background and Aims: Temporomandibular disorders are clinical conditions that often involve pain in the masticatory muscles, the temporomandibular jaw joint and/or associated structures. The association between muscle pain and muscle activity is often explained by uniform increases or decreases in motor unit activity throughout a muscle but recent evidence suggests more complex changes within a painful muscle. The general aim of this study was to determine if experimentally induced masseter muscle pain modifies temporalis muscle activity. Methods: 20 healthy participants received experimental pain through hypertonic saline (5% NaCl) infusion into the right masseter; pain intensity was maintained at 40-60/100 mm on a visual analogue scale (VAS). Standardized biting tasks were performed with an intraoral force transducer while single motor unit (SMU) activity was recorded from 2 intramuscular electrodes (right masseter and right temporalis). The tasks were repeated in 4 blocks: baseline 1, hypertonic saline infusion, isotonic saline infusion, baseline 2. Each block had 3 isometric biting tasks: a slow and a fast ramp jaw closing task and a 2 step-levels jaw closing task (2 force levels: step 1 and step 2). Results: 83 SMUs were discriminated from the temporalis and 58 from the masseter muscle. This study demonstrated that induced muscle pain in the right masseter can be associated with the activation of new SMUs and the silencing of other single motor units in the painful masseter muscle as well as in the right temporalis muscle, which did not receive noxious stimulation with the hypertonic saline. No differences between pain and no pain trials were found in thresholds and firing rates of SMUs from the temporalis muscle. Discussion and conclusion: The present findings are consistent with previous findings from the limb (Hodges and Tucker 2011; Tucker et al. 2009) and rather than supporting uniform increases or decreases in motor unit activity throughout a muscle, suggest that there is a reorganization of motor unit activity across the entire jaw motor system in experimental pain.

Improving stem cell therapy is a major goal for the treatment of muscle diseases, where physiological muscle regeneration is progressively exhausted. Mesoangioblasts are vessel-associated stem cells that appear to be the most promising cell type for the cell therapy for muscular dystrophies because of their significant contribution to restoration of muscle structure and function in different muscular dystrophy model. Here we report that MAGE protein Necdin enhances muscle differentiation and regeneration by mesoangioblasts. Indeed, when Necdin is constitutively overexpressed, it accelerates their differentiation and fusion in vitro and it increases their efficacy to restore dystrophic phenotype of α-sarcoglycan mutant mouse. Moreover, Necdin confers a enhanced survival ability when mesoangioblasts are exposed to cytotoxic stimuli that mimic inflammatory dystrophic environment. Taken together, these data demonstrate the pivotal role of Necdin in muscle reconstitution from which we could take advantage to boost therapeutic applications of mesoangioblasts.

Thesis (Ph. D.)--State University of New York at Binghamton, Thomas J. Watson School of Engineering and Applied Science, Department of Bioengineering, Biomedical Engineering, 2009.
Includes bibliographical references.

Muscle pain is felt during exercise or daily activities for several days after performing unaccustomed exercise, which is referred to as delayed onset muscle soreness (DOMS). Many people experience DOMS, but its underlying mechanisms are not fully understood. One of the challenges in the investigation of DOMS is its subjective nature, which makes the assessment ambiguous, thus establishing a standardised protocol is necessary. The present thesis scrutinised muscle pain assessments (Study 1, Study 2), developed a new assessment of muscle pain focusing on muscle fascia (Study 3), and investigated why DOMS is reduced after the second than the first bout of eccentric exercise (Study 4). From these studies, DOMS was thought to be more associated with connective tissue than muscle fibre damage and inflammation. In Study 1, the relationship between pain level assessed by a visual analogue scale (VAS) and pain sensitivity assessed by pressure pain threshold (PPT) was examined. Thirty-one healthy young men performed 10 sets of 6 maximal isokinetic eccentric contractions with their non-dominant arm. Before and 1 - 4 days after the exercise, muscle pain perceived upon palpation of the biceps brachii at three sites (5, 9, and 13 cm above the elbow crease) was assessed by VAS with a 100 mm line (0 = no pain, 100 = extremely painful), and PPT of the same sites was determined by an algometer. The VAS increased after exercise and peaked two days post-exercise, while the PPT decreased most at 1 day post-exercise and did not return to baseline for 4 days following exercise (P Muscle pain induced by elbow flexor eccentric exercise was investigated using different assessments in Study 2. Ten untrained men performed 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors with one arm. Maximal voluntary isometric contraction torque (MVC), range of motion (ROM) and serum creatine kinase (CK) activity were measured before, immediately after, and 1 to 5 days after exercise as indirect markers of muscle damage. PPT of 50 sites over an exercised upper arm, VAS with a 100-mm line for pain level upon static pressure by a cuff and fingers, and palpation of the biceps brachii at three sites (3, 9, and 15 cm above the elbow crease) and different palpation methods (longitudinal, transverse and circular movements) on the mid-belly of biceps were assessed. Large decreases in MVC and ROM, and significant increases in serum CK activity indicated muscle damage. A significant difference (P In Study 3, changes in the electrical pain threshold (EPT) of the biceps brachii fascia, biceps brachii muscle and brachialis fascia following eccentric elbow flexor contractions, and the relationship between EPT and VAS or PPT were investigated. Ten healthy untrained men performed two eccentric exercise bouts (ECC1, ECC2) consisting of 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors with the same arm separated by 4 weeks. Changes in MVC, ROM, VAS and PPT were smaller (P The purpose of Study 4 was to investigate the magnitude of muscle lengthening during the first and second bout of eccentric exercise bouts and whether the muscle length changes are associated with the magnitude of DOMS and changes in other indirect markers of muscle damages between bouts. Ten healthy untrained men performed two eccentric exercise bouts (ECC1, ECC2) consisting of 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors using the same arm separated by 4 weeks. Changes in MVC, ROM, muscle thickness, ultrasound echo intensity, serum CK activity and muscle soreness (VAS) were smaller (P

Background: Acute hamstring strains are common injuries in different sports. They are often serious, causing long rehabilitation times and a proneness for re-injury. Preliminary observations indicate that the injuries can be of at least two types, one occurring during high-speed running and the other during motions where the hamstring muscles reach extreme lengths.

Aims: To investigate the possible existence of different types of acute hamstring strains in two specific athletic groups, namely sprinters and dancers, as well as the generality of these findings in other sports.

Methods: In the first project, 18 sprinters and 15 dancers with acute first time hamstring strains were prospectively included. All subjects were examined, clinically and with magnetic resonance imaging (MRI), on 4 occasions after injury: at day 2-4, 10, 21 and 42. The follow-up period was 2 years. In the second project, 30 subjects from 21 different sports were prospectively included. All subjects were examined clinically and with MRI. The follow-up period lasted until the subjects returned to sport or finished their sport activity due to the injury.

Results: All sprinters sustained their injuries during competitive high-speed running. In contrast, all dancers encountered their injuries during slow-speed stretching type of exercises. The initial loss of strength and flexibility was significantly greater in sprinters than in dancers. At 42 days after injury, both groups could perform more than 90% of the test values of the uninjured leg. All the sprinters’ injuries were primarily located in biceps femoris long head, whereas the dancers’ injuries were mainly (87%) involving the proximal free tendon of semimembranosus. For the sprinters, involvement of the proximal free tendon, as estimated by MRI, and proximity to the ischial tuberosity, as estimated both by palpation and MRI, were associated with significantly longer time to return to pre-injury level. In the dancers, there were no significant correlations between clinical or MRI parameters and time to return to per-injury level. The time to pre-injury level was significantly longer (median 50 weeks, range 30-76) for the dancers compared to the sprinters (16, 6-50). In the second project, all injuries occurred during movements reaching a position with combined extensive hip flexion and knee extension. They were all located close to the ischial tuberosity and 83% involved the proximal free tendon of semimembranosus. Fourteen subjects (47%) decided to end their sport activity and for the remaining 16 subjects the median time back to sport was 31 (range 9-104) weeks. There were no significant correlations between clinical and MRI parameters and time to return to sport.

Conclusions: There seems to be a link between the injury situation and the two types of acute hamstring strain in sprinters and dancers with respect to clinical findings, injury location, muscles and tissues involved, and time to return to pre-injury level. Proximity of the injury to the ischial tuberosity, as estimated both by palpation and MRI, is associated with longer recovery time. Also in other sports, an injury situation where the hamstrings reach extensive lengths caused a specific injury to the proximal posterior thigh similar to that described in dancers. Due to the prolonged recovery time associated with this type of injury, correct diagnosis based on history, clinical and MRI investigation, and adequate information to the athletes are essential.

För att beställa tryckta exemplar av avhandlingen kontakta Carl Askling, carl.askling@gih.se

Colin Lewis was Professor of Geography at Rhodes University, Grahamstown, South Africa from 1989 until his retirement at the end of 2007. In 1990, with the strong support of the incumbent Vice-Chancellor, Dr Derek Henderson, he instigated the Certificate in Change Ringing (Church Bell Ringing) in the Rhodes University Department of Music and Musicology - the first such course to be offered in Africa. Since that date he has lectured in the basic theory, and taught the practice of change ringing. He is the Ringing Master of the Cathedral of St Michael and St George, Grahamstown, South Africa.

La dystrophie FacioScapuloHumérale (FSHD), décrite pour la première fois en 1885 par Landouzy Dejerine, est la première dystrophie musculaire de l’adulte en France affectant entre 4000 et 5000 personnes. La destruction progressive des fibres musculaires entraîne une atrophie et une faiblesse musculaires s’aggravant progressivement, avec cependant une grande variabilité intra-familiale du degré des atteintes. Une caractéristique de l’atteinte musculaire est généralement son asymétrie. Les premières manifestations concernent souvent les muscles du visage, les muscles de l’omoplate et des muscles perihuméraux. En progressant la pathologie va toucher d’autres territoires musculaires. Dans environ 10 à 15 % des cas, à un stade évolué, les patients sont contraints d'utiliser un fauteuil roulant. En dépit d’avancées majeures dans la compréhension du locus morbide, les mécanismes exacts responsables des défauts musculaires de la FSHD ne sont toujours pas compris et il n’existe aucune thérapie. Toutefois, il existe de plus en plus de données qui permettent une implication probable du stress oxydant dans cette pathologie. L’hypothèse selon laquelle les réponses antioxydantes sont altérées dans la FSHD s’appuie sur des dérégulations d’enzymes impliqués dans le stress oxydant. Une étude prospective réalisée sur des patients FSHD et des volontaires sains nous a ainsi permis de mettre en évidence une corrélation entre le stress oxydant systémique et musculaire et leurs déficits fonctionnels musculaires. Ces données nous ont conduit à la mise en place d’un essai clinique randomisé, contrôlé, en double aveugle contre placébo, visant à évaluer les effets d’une supplémentation en antioxydants chez 54 patients atteints de FSHD pendant 17 semaines. Cet essai a ainsi permis de montrer une augmentation significative de la force et l’endurance des quadriceps corrélée à une diminution du stress oxydant et une augmentation des défenses antioxydantes chez les patients atteints de FSHD. De nombreuses caractéristiques de la FSHD pourraient être causées et/ou exacerbées par des perturbations de la production des espèces radicalaires ou une réponse non adaptée à cette production. Aussi le premier objectif de ma thèse est de mener une étude comparative des profils d’oxygénation par spectroscopie dans le proche infrarouge de patients atteints de FSHD et sains. Le second objectif est d’évaluer l’effet de la supplémentation en antioxydant sur le volume des quadriceps par IRM et leur qualité musculaire déterminée par le ratio Force/Volume musculaire du quadriceps et d’évaluer les corrélations entre ces variables, la force et le stress oxydant. Les données obtenues ont permis de montrer une réduction de la capacité oxydative lors d’une contraction isométrique volontaire des quadriceps et ont permis d’étudier l’effet de la supplémentation sur les volumes et la qualité musculaire des quadriceps. Ces augmentations sont associées non seulement à une augmentation de la force des quadriceps mais aussi à une diminution du stress oxydant et une augmentation des défenses antioxydantes. L’ensemble de ces données montrent que le stress oxydant pourrait jouer un rôle important dans la FSHD et qu’une approche antioxydante semble adaptée à cette pathologie. Des analyses plus fines sur l’action des espèces réactives de l’oxygène (ROS) et leurs sources pourraient contribuer à une meilleure compréhension des bases physiopathologiques de la FSHD
Facioscapulohumeral muscular dystrophy (FSHD), first described in 1885 by Landouzy Dejerine, is the most common inherited skeletal muscle disease of adult life affecting 4000 to 5000 persons in France. Progressive evolution of the disease leads to progressive weakness and atrophy of muscle fibers associated to a wide variability. The pattern of muscle weakness is often asymmetrical and the rate and extent of progression may vary considerably with sudden periods of unexplained rapid disease progression. This muscle disorder is characterized by progressive muscle weakness, beginning with facial muscles and the shoulder girdle, followed by the pelvic girdle and the muscles of the lower extremities. In 10 to 15% of cases, patients need to use a wheelchair. Despite major progress in the understanding of the genetic basis of FSHD, the exact mechanisms that lead to FSHD defects are not completely understood and no curative treatment is available. However, there is growing evidence that oxidative stress may contribute to FSHD pathology. The hypothesis that oxidative stress responses might be specifically altered in FSHD is supported by the deregulation of enzymes involved in oxidative stress.A prospective study realized with FSHD patients and healthy subjects unrevealed the correlation between systemic and muscular oxidative stress and functional muscle defects. Based on these data, we organized a randomized, double-blind, placebo-controlled pilot clinical trial in order to evaluate the effects of 17 weeks antioxidant supplementation in 54 FSHD patients. This clinical trial demonstrates a significant increase in muscle force and quadriceps endurance correlated to a decrease in oxidative stress and an increase in antioxidant defense in FSHD patientsFurthermore, many FSHD features may be caused or exacerbated by perturbations in the production of free radicals or inappropriate response to such stressors. Therefore the first objective was planned to investigate muscle oxygenation patterns during and after a MVCQ by near-infrared diffuse optical spectroscopy (NIRS). The second objective is to evaluate the effect of antioxidant supplementation on quadriceps volumes by IRM and determine the muscle quality using Strength/ Volume ratio of quadriceps muscles and correlate this variables with force and oxidative stress parameters.The major findings of this study show a significant decrease in oxidative capacity during voluntary isometric contraction in quadriceps and demonstrate the effect of supplementation on muscle volume and quality. Indeed, vitamin E, vitamin C, zinc and selenium supplementation improves muscle volume and quality of both quadriceps by enhancing the antioxidant defences and reducing oxidative stress.This increase are associated to increase in strength and decrease in oxidative stress and increase in antioxidant defences. Taken together, we show that oxidative stress plays an important role in FSHD and that an anti-oxidant strategy adapted to the FSHD-specific “oxidative stress” may be a relevant therapeutic approach for these patients. Further analyses of ROS production and sources could contribute to a better understanding of the pathophysiological mechanisms implicated in FSHD

Le but de cette dissertation doctorale était de mieux comprendre les mécanismes de contrôle tant centraux que périphériques qui sont à l’origine de la régulation neuromusculaire lors de mouvement impliquant des contractions de type excentrique. Lors d’une première étude réalisée sur le muscle jambier antérieur, nous avons montré qu’un exercice utilisant des contractions excentriques présentait une meilleure résistance à la fatigue que lorsque des contractions concentriques étaient impliquées puisque celui-ci conduit à une moindre diminution du couple de force et de l’activité électromyographique. L’absence de fatigue nerveuse centrale et l’observation d’un comportement spécifique du couple de force et de l’activité électromyographique lors de ces épreuves de fatigue semblait traduire la mise en jeu de processus périphériques différents. La plus grande fatigue observée lors de l’épreuve concentrique suggérait une activation plus importante que pour l’épreuve excentrique, dont les conséquences métaboliques renforcent les altérations du couplage excitation-contraction. Dans un second temps, nous avons étudié l’effet des modifications de longueur de fascicule du muscle jambier antérieur sur le comportement spécifique des unités motrices (ordre, fréquence et seuil de recrutement) lors de contractions isométriques. Nous avons ensuite analysé le comportement d’unités motrices selon les différentes modalités de contractions (concentrique vs. excentrique) sur ce même muscle. Pour y répondre, différentes techniques d’analyse ont été utilisées dont l’enregistrement électromyographique intramusculaire et l’ultrasonographie. Enfin, nous avons cherché à analyser l’évolution des différents mécanismes de régulation d’origine périphérique et /ou central susceptible de modifier l’excitabilité du pool de motoneurone lors de contractions concentriques et excentriques. Pour y répondre, les modulations d’une part, du réflexe de Hoffmann (réflexe H) par stimulation électrique et d’autre part, celles du potentiel moteur évoqué (MEP) par stimulation magnétique transcorticale, ont été investiguées. Ces réponses ont été enregistrées à différents angles de la plage articulaires étudiée lors des contractions concentriques et excentriques, ainsi qu’aux deux extrémités angulaires lors de contraction isométriques. Notre travail indique que l’ordre de recrutement des unités motrices entre les contractions concentriques et excentriques étant identique, le système nerveux n’utilise qu’une seule et même stratégie d’activation liée à la taille des motoneurones impliqués dans ces deux types de contractions. En outre, les contractions excentriques lorsqu’elles sont réalisées à vitesse constante, sont associées à une modulation spécifique de la fréquence de décharge des unités motrices. Ce comportement diffère de celui observé lors de contractions concentriques, malgré une modification linéaire et similaire de la longueur des fascicules et du couple de force au cours de ces deux tâches. Les modulations du recrutement des unités motrices semblent davantage dépendre de la longueur musculaire tandis que les modulations de fréquence prédominent pendant les contractions en raccourcissement. Ce comportement spécifique semble dépendant de mécanismes de régulation principalement localisés au niveau spinal. Ainsi, le degré d’inhibition des afférences fusoriales affectant le pool de motoneurones du muscle tibial antérieur lors de sollicitations actives du muscle, dépend davantage de l’angle articulaire et donc de la longueur du muscle plutôt que du mode de contraction. Lors de sollicitations isométriques, le retour sensoriel Ia est principalement contrôlé au niveau présynaptique en fonction de la longueur du muscle. Lors de sollicitations concentriques et excentriques, ces mécanismes présynaptiques réguleraient l'excitabilité spinale de manière similaire entre les deux modes. Néanmoins, bien que l'inhibition présynaptique soit probablement plus marquée lors des sollicitations excentriques, ce mode de contraction semble également régulé par des mécanismes d'inhibition intervenant au niveau postsynaptique tel que l'inhibition récurrente de Renshaw. Ce mécanisme localisé au niveau postsynaptique permettrait de réguler la fréquence de pulsation des unités motrices lors de sollicitations excentriques dans le but le faciliter l'exécution du mouvement. L'originalité de notre travail a été d’étudier le comportement d’une même unité dans les deux modes de contractions alors que la méthode d’analyse généralement adoptée consistait à comparer des populations d’unités motrices entre-elles. De plus, les changements de la longueur du muscle au cours du mouvement ainsi que les vitesses de raccourcissement ou d'allongement ont été estimés à partir de la mesure directe de la longueur des fascicules musculaires. Cette dernière présente l’avantage de fournir une information de longueur et de vitesse sur la portion de muscle à partir de laquelle les enregistrements d’unités motrices ont été obtenus. Enfin, étant donné les modulations possibles tant au niveau spinal que supraspinal des mécanismes nerveux mis en jeu, il semblait important d’analyser celles-ci pendant le mouvement et aux différents angles investigués. Cette précision méthodologique a permis d'élargir la discussion concernant les possibles modifications de la balance "excitation-inhibition" lors de sollicitations excentriques, qui, jusqu’à présent, n'avaient été analysées que pour un angle articulaire donné.
Doctorat en Sciences de la motricité
info:eu-repo/semantics/nonPublished

The human body is an over-actuated multibody system, as each joint degree of freedom can be controlled by more than one muscle. Usually, optimization techniques are used to solve the muscle force sharing problem, that is, finding out how the resultant joint torque is shared among the muscles spanning that joint. The reduction of muscle force redundancy can be achieved in several ways. Although the strategy followed by the central nervous system (CNS) to activate the muscles is not completely clear, one of the most used hypotheses to overcome this redundancy is to consider that the CNS minimizes a physiological variable. In the first study presented in this thesis, the solution to the muscle force sharing problem was approached by minimizing the sum of squared normalized muscle forces. For this purpose, a weighted cost function was designed to evaluate which muscles were more penalized in a subject with anterior cruciate ligament (ACL) deficiency during walking. The results showed that the cost function that best fitted normalized electromyography signals with muscle activations did not treat all muscles equally. Another way to reduce muscle redundancy is using the idea that muscles are activated synergistically when performing a task. In the second study, a muscle synergy analysis was carried out to compare the muscle activation information at two levels: onset-offset activation patterns and muscle synergy components of a sample of 18 ACL-deficient subjects and a sample of 10 healthy subjects. Some differences were found at both levels, what suggests that ACL-deficient subjects alter the muscle activations of their injured leg to stabilize the joint. Finally, in the third study, muscle synergies were used in a two-step optimization method to predict physiologically consistent muscle and knee contact forces, while calibrating muscle parameters. In the outer level, muscle parameters were calibrated; while, in the inner level, muscle activations were calculated using the current muscle parameters. The results showed that a set of muscle parameters were able to reproduce knee contact forces with high accuracy when knee contact forces were used during the calibration process. This study shows the main differences when these forces are available for calibrating muscle parameters and when they are not. The most important differences in the muscle parameter calibration affected lateral muscles. Therefore, this fact suggests that trials where lateral muscles play a more important role should be used to obtain a better calibration when no contact forces are available.
El cos humà és un sistema multisòlid sobreactuat, ja que cada grau de llibertat pot estar controlat per més d’un múscul. Per resoldre el problema d’indeterminació en el càlcul de les forces musculars, es sol utilitzar un mètode d’optimització. Consisteix en distribuir els moments articulars resultants entre els diferents músculs que actuen a l’articulació, i per tant, estimar la força que aquests realitzen. La reducció de la indeterminació en el càlcul de les forces musculars es pot aconseguir de diferents maneres. Malgrat que l’estratègia que fa servir el sistema nerviós central (SNC) per activar els músculs no es coneix amb exactitud, una de les hipòtesis més utilitzades per solucionar la indeterminació és el fet de considerar que el SNC minimitza una variable fisiològica. El primer estudi presentat en aquesta tesi tractava de resoldre el problema del repartiment muscular minimitzant la suma de les forces musculars normalitzades al quadrat. Per a tal fi, es va utilitzar una funció de cost ponderada per avaluar quins músculs es penalitzen més en la marxa d’un subjecte amb el lligament creuat anterior trencat. Els resultats mostren que la funció de cost que millor aproximava les activacions musculars amb el senyal d’EMG mesurat no tractava tots els músculs per igual. Una altra manera de reduir la indeterminació en el càlcul de les forces muscular és utilitzar la idea que els músculs s’activen sinèrgicament quan l’ésser humà realitza un moviment. En el segon estudi, es presenta una anàlisi de les sinergies musculars que compara la informació de les activacions a dos nivells: en els patrons d’activació-desactivació i en els components de les sinergies musculars d’una mostra de 18 subjectes amb ruptura del lligament creuat i una mostra de 10 subjectes sans. Es van observar diferències als dos nivells, el qual suggereix que els subjectes amb ruptura al lligament creuat alteren les activacions musculars de la seva cama lesionada per tal d’estabilitzar l’articulació lesionada, en aquest cas el genoll. Per últim, en el tercer estudi, es van utilitzar les sinergies musculars junt amb un problema d’optimització de dues etapes per tal de predir les forces musculars i de contacte al genoll de manera fisiològicament consistent, alhora que es calibren els paràmetres musculars. En el nivell exterior de l’optimització, es calibren els paràmetres musculars, mentre que en el nivell interior, es calculen les activacions musculars amb els corresponents paràmetres musculars. Els resultats indiquen que un conjunt de paràmetres musculars pot predir les forces de contacte al genoll amb alta precisió quan es disposa de les forces experimentals de contacte al genoll durant el procés de calibratge. Aquest estudi presenta les diferències entre el cas en què s’utilitzen les forces experimentals de contacte al genoll per calibrar els paràmetres i quan no s’utilitzen. A més, suggereix que si s’utilitzessin captures biomecàniques de moviments on els músculs laterals tinguessin un rol més important que en la marxa, el calibratge dels paràmetres seria més acurat. Per tant, es podrien predir les forces de contacte al genoll amb més precisió quan no es disposa d’aquestes.