Thesis (Ph.D.)--McMaster University, 2004. / Advisor: James Dowling. Includes bibliographical references (p. 60-66). Also available via World Wide Web.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (M.Sc.)--York University, 2005. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 69-81). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss &rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR11868

Thesis (Ph. D.)--Lehigh University, 2000. / Includes vita. Includes bibliographical references (leaves 150-162).

Diss. (sammanfattning) Umeå : Univ., 2009. / Härtill 3 uppsatser.

Vibration stimulation has been used as a tool to relieve muscle pain and spasm in physical therapy for many years. However recently, vibration, mainly Whole Body Vibration (WBV), has been increasingly studied and used as an exercise intervention in sports and rehabilitation. Although the physiological mechanisms which guide the body's response to this exercise modality are relatively poorly understood, evidence indicates that vibration can enhance muscle strength, power, and flexibility as well as increase bone mineral density in the general population. Evidence also suggests that the neuromuscular response to vibration stimulation depends on muscle length, stretch level (contraction) along with the vibration characteristics. One way to alter muscle length and contraction levels while receiving vibration is to superimpose the stimulation on graded isometric contraction. However, current WBV device designs cannot facilitate the delivery of vibration stimulation superimposed on graded isometric voluntary contraction. The aim of this PhD project was twofold, firstly to develop and evaluate a prototype WBV device which enables the delivery of vibration stimulation that can be superimposed on graded isometric contraction and secondly, to assess the neuromuscular responses to vibration superimposed on graded isometric contractions in lower limbs using this device. Due to the novelty of the device design and the method of the delivery, this study initially investigated the effects of different vibration frequencies and amplitudes combined with various effort levels on neuromuscular responses in lower limbs. The results of this study confirm that isometric contraction superimposed on vibration stimulation induce enhanced neuromuscular activity in the lower limbs. The results also confirm that although the neuromuscular responses to vibration depend on multiple factors the main determinants seem to be the vibration frequency, amplitude and muscle contraction /forc The results also confirm that although the neuromuscular responses to vibration depend on multiple factors the main determinants seem to be the vibration frequency, amplitude and muscle contraction /force level. Another limitation of most existing vibration devices is that they are not capable of delivering frequency of the vibration independent of amplitude and vice versa. Further, the evidence suggests that vibration amplitude can play an important role in neuromuscular response to vibration, especially when superimposed with graded contraction/force levels. To address the above limitation, the second aim of this PhD project was to develop and evaluate a prototype miniature upper limb vibration device capable of delivering precise and independent vibration frequency and amplitude stimulation. The miniature upper limb vibration (ULV) device with piezo actuators developed for this thesis, enables precise vibration stimulation to be delivered in a seated position with graded voluntary contraction superimposed. The neuromuscular responses to vibration superimposed on graded isometric contractions in upper limbs were also assessed by investigating the fatiguing effects of superimposed vibration stimulation using this newly developed device. This study is the first to investigate and compare the fatiguing effects of superimposed vibration stimulation pre and postvibration exercise in upper limbs. The results of this study confirm that isometric contraction superimposed on vibration stimulation lead to increased fatigue levels and neuromuscular activity in upper limbs. The results also indicate that post-vibration treatment the muscles display enhanced force generation capability associated with lower fatigue levels. In summary, two (WBV and ULV) novel vibration exercise devices were successfully developed and evaluated for this thesis. The results of the studies on these devices confirm that vibration stimulation superimposed on graded isometric contraction can induce higher neuromuscular activity compared to isometric contraction alone in both upper and lower limbs. However the effects of vibration frequency, amplitude and contraction/force levels seem to differ between the upper and lower limbs.

The Hippo pathway is a master regulator of cell proliferation and organ size, namely through regulation of transcriptional co-activators Yap, Taz, Vgll family which bind Tead1-4 transcription factors. Recently the Hippo pathway has been shown to regulate muscle cell fate. Yap enhances the proliferation of myoblasts and inhibits their differentiation, Taz comparatively enhances both aspects. The mechanisms in which they regulate muscle cell fate and muscle development are poorly defined. In this thesis I determined the endogenous gene expression of Hippo transcription factors during myogenesis. Secondly their proteomic binding partners in myoblasts and myotubes. Thirdly, the gene sets targeted by YAP1 S127A, TAZ S89A and Vgll3 in myoblasts. Finally, I cloned chicken Yap1 to identify its role during embryonic muscle development, followed by retroviral YAP1 S127A overexpression during chicken embryonic limb development. The results demonstrated that the Hippo transcriptional regulators are mainly up-regulated during muscle regeneration in vivo. YAP1 and TAZ were mainly found to regulate the same gene sets and have the same binding partners. TAZ additionally had unique binding partners and gene sets that may promote muscle differentiation. Furthermore, Vgll3 also had many overlapping genes with YAP and TAZ, suggesting it is part of the Hippo pathway, but negatively regulates Hippo pathway gene expression. Yap expression during chicken embryonic development was observed in muscle related regions including the somites and limb buds. However, retroviral overexpression of YAP S127A did not lead to an overt phenotype but still up-regulated transcription musculoskeletal related genes. Collectively my data provides insight into how the Hippo transcriptional regulators control myogenesis, their binding partners and their transcription targets. Additionally, have characterised the expression of chicken Yap during embryonic muscle development.

Smooth muscles as a group exhibit great diversity of pharmacological and physiological properties. This makes it impossible to produce any but extremely generalised schemes for smooth muscle contractile mechanisms. However, knowledge of the detailed physiology and pharmacology of specific types of smooth muscle has been growing at an increasing rate, especially regarding vascular and visceral muscles. The rat anococcygeus muscle has, however, been investigated little. This work describes the excitation- contraction coupling mechanism in this preparation. The rat anococcygeus muscle was found to contract to all three of the agonists used (noradrenaline, acetylcholine and potassium chloride). In the first section of this work the properties of these contractions were investigated. It was found that the contractions induced by each agonist exhibited different pharmacological properties, (with regard to low calcium, sodium nitroprusside, verapamil, Stellazine and theophylline). This can be taken as an indication that the different agonists use different activation pathways. Electrophysiological studies showed that the membrane potential per se is not important in the regulation of contraction. (ie. the depolarisation produced by an agonist is not simply related to the tension produced ). KC1 produces the greatest change in membrane potential (from -55mV to -20mV for a maximal dose), but produces the least rise in tension of the three agonists. Evidence from other preparations and the results of the experiments with Stellazine suggest that the rise in tension produced by the agonists is not simply related to the rise in intracellular calcium concentration, but that some amplification of the response occurs. The way in which the agonists produce this amplification of the response is suggested as being related to changes in the levels of the cyclic nucleotides, cAMP and cGMP within the cells. It was found that the agonists did not substantially affect cAMP levels, but that all three reduced cGMP levels by varying amounts. The ratio of the levels of cAMP/cGMP produced by activation with each agonist correllates very well with the tension produced. This suggests that the ratio cAMP/cGMP is important in the regulation of contractility in this muscle. However, doubt is cast upon this theory by the results of experiments using sodium nitroprusside (NP). It was found that NP (2 X 10-7M) caused a pronounced change in the ratio cAMP/cGMP (by increasing cGMP levels ), but only a small change in tension (so that the tension in these experiments does not correllate well with the ratio cAMP/cGMP). In order to retain the hypothesis that cyclic nucleotides are important in the regulation of contractility in this preparation, it is proposed that some form of compartmentalisation of the cyclic nucleotide changes occurs within the cells.

It is in the best interests of sportsmen and sportswomen to try to avoid muscle stiffness and soreness. Apart from the discomfort experienced, muscle stiffness and soreness can cause unnecessary interruptions to training, may lead to injury and will reduce performance. Changes in muscle tone were quantified in terms of the Resonant Frequency (squared) (RF2) and the Amplitude of Movement (AM) in response to an applied torque. Muscle soreness was measured at twelve sites on the arm. Study One investigated the effects of a single bout of eccentric exercise on muscle stiffness and muscle soreness. RF2 increased and AM decreased following exercise and reached a maximum and minimum, respectively, 24-48 hours post exercise (p < 0.01). Muscle soreness also reached a peak 24-48 hours post-exercise (p < 0.01). Greatest soreness was in the biceps brachii and in the proximal ends of the brachioradialis and the flexor carpi radialis (p < 0.01). Voluntary extension was more painful than voluntary flexion following eccentric exercise. Study Two investigated the effect of performing two subsequent exercise bouts (EX1 and EX2), each separated by six days and an adaptation was observed. Each of the variables measured (RF2, AM, Soreness, Creatine Kinase, Limb Girth) showed a reduced response following EX2 when compared to the results of EX1 (p < 0.01). The resting angle of elbow flexion appeared to decrease following exercise. Study Three investigated the effect of muscle soreness on motor performance. The ability to perform a simple perception test was not affected while suffering from muscle soreness. The eccentric exercise is thought to cause damage to the connective tissue and muscle cell membrane leading to a build-up of fluid around the joint. This increased edema may explain the increase in muscle stiffness observed. Further research is required to determine whether changes in muscle tone are also observed following isometric and concentric exercise.

The primary objective of the present study was to examine the effects of three resistance training programs that varied in either inter-set rest interval length or volume of training on the development of strength and muscle fiber size. Male subjects with a minimum of 1- year of regular resistance training experience were randomly assigned to one of three, 8- week training groups. The first set of all three programs was similar in that 10 repetitions to failure were performed. In program A (n=5) the load (78% 1-RM) remained constant for all subsequent sets. Program B (n=7) also used a constant load (80% 1-RM), however the rest interval was reduced from 3 minutes (as in Program A) to 1 minute. Subjects in this group performed additional sets to equate training volume with Program A. The training load for Program C (n=7) was progressively reduced (80% to 70% 1-RM) before each subsequent set to ensure the completion of 10 repetitions. Therefore, the volume performed was greater than that of Programs A and B. Single arm elbow flexion 1-RM increased by 12.3 +/- 3.5% in Program A, 16.5 +/-3.5% in Program B, and 14.1 +/- 4.7% in Program C. Gains in 10-RM equaled 16.3 +/-4.1%, 18.0 +/- 5.0% and 13.9 +/- 3.1% for Programs A, B and C, respectively. Although these increases in strength were significant (p<.05), there were no differences in the magnitude of change between the three groups. Increases in the cross-sectional area of type I and type II muscle fibers were similar after all three training programs. The second objective of this investigation was to measure the acute neuromuscular fatigue produced during a single session of each of the training protocols incorporated in the longitudinal part of this study. Force and IEMG during maximal isometric voluntary contractions (MVIC) along with blood lactate were assessed prior to and upon the completion of each protocol. Subjects performed 3 sets of single-arm elbow flexion to failure using a training load of approximately 77.3% 1-RM in Protocol A. During Protocol B, subjects utilized the same constant resistance but the rest-intervals between each set were 1 minute. Protocol C was designed to maintain the repetitions completed per set at 10 while utilizing 3-minute rest interval. During Protocol C, the load used during the first set was equal to that used during Protocol A and was then reduced by about approximately 5% for each of the two subsequent sets. Protocol A and Protocol B resulted in similar reductions in MVIC, whereas Protocol C (24.8 +/- 7.2%) resulted in a significantly (p<.05) greater reduction in MVIC than Protocol A (20.2 +/- 7.7%). Protocols A and B elicited similar reductions in the force-time curve of the MVIC. A significantly greater reduction in the final 300ms of the force-time curve was observed following Protocol C (in comparison to Protocol A) (p<.05). There were no significant changes in IEMG after subjects performed protocols A and B. A significant time effect (with no interaction effect) in IEMG was observed following the comparison of Protocol A with Protocol C. Blood lactate increased significantly in response to all three protocols with no differences between the protocols. The third objective of this study was to compare the magnitude of resistance training-induced acute fatigue before and after the completion of 8 weeks of resistance training specific to the fatigue protocols used. The magnitude of resistance training-induced acute neuromuscular fatigue remained unchanged following the resistance training programs. The results appear to indicate that acute neuromuscular fatigue produced during resistance training may not be associated with the chronic increases in muscle strength and size. / Graduate