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<i>Trichinella spiralis</i> is a parasitic nematode of mammalian skeletal muscle.  Its life cycle includes two stages where developmental progression appears to be inhibited until a specific host niche is encountered.  The newborn larva, released within the host intestine depends upon entry to skeletal muscle for continued development.  The muscle larva encapsulates within skeletal muscle and further reproductive development is dependent upon ingestion by a new host.  Developmental arrest has been extensively characterised in <i>Caenorhabditis</i> <i>elegans</i>, where an alternative L3 larva, the dauer larva, is formed in response to environmental conditions refractive to continued reproductive development.  Using the wealth of genetic information regarding <i>C. elegans</i> dauer formation, putative periods of arrest were examined in <i>T. spiralis.</i> TGF-<span lang=EN-GB style='font-family:Symbol'>b-like and insulin-like signalling pathways are critical mediators of <i>C. elegans </i>dauer formation.  A <i>T. spiralis</i> TGF-<span lang=EN-GB style='font-family: Symbol'>b-ligand was identified and designated <i>ts-tll-1</i>.  Sequencing and analysis revealed <i>ts-tll-1</i> to be similar to vertebrate bone morphogenetic proteins and <i>C. elegans </i>DBL-1, is involved in body size regulation.  EST mining identified putative type I and II TGF-<span lang=EN-GB style='font-family:Symbol'>b receptors and a subtilsin-like proprotein convertase, suggesting conservation of TGF-<span lang=EN-GB style='font-family:Symbol'>b-like signalling in <i>T. spiralis.  </i>A partial <i>Trichinella </i>gene encoding an orthologue of the <i>C. elegans</i> insulin-like, tyrosine kinase receptor, DAF-2, was identified by degenerate PCR and designated <i>ts-tkr.  ts-tkr</i> is most similar to <i>C. elegans daf-2</i> within the highly conserved tyrosine kinase domain.  Two alternative transcripts of <i>ts-tkr</i> were identified by 3’ RACE, which differed in their 3’ UTRs.  Semi-quantitative RT-PCR analysis suggested <i>ts-tkr </i>expression was greatest in adult worms, implying a role in promoting reproductive development. Semi-quantitative RT-PCR was also to assess the expression of selected housekeeping and ES protein encoding genes during the <i>T. spiralis </i>life cycle.  While transcription in the <i>C. elegans</i> dauer is depressed, there was no obvious transcriptional repression in <i>Trichinella</i> newborn or muscle larva.

Although much work has been carried out to identify the mechanisms by which muscle is formed, many of the regulatory pathways involved have yet to be fully elucidated. In creating perturbations during the embryonic period, either nutritionally (with a marginal vitamin A deficiency model) or pharmacologically (with the b₂-adrenerguic agonist clenbuterol), a comparison with 'normal' muscle development may be attained. Differences in the temporal expression of specific regulatory proteins may then enhance the existing knowledge of their function in regulating muscle development. Prior to studying changes in muscle regulatory proteins due to perturbations, it was first necessary to illustrate their temporal pattern in "normal" muscle development. The results indicated that a complex regulatory system operates in myogenesis with a number of proteins appearing to be involved in the process of muscle development. A marginal vitamin A deficiency model was established in which maternal retinol levels were clearly reduced in treatment animals in comparison with controls. This resulted in offspring that showed clearly symptoms of marginal vitamin A deficiency. Changes in the abundance of five proteins were observed in response to marginal vitamin A deficiency. Overall, these changes suggested a potential reduction in secondary myogenesis, based on reduced levels of MHCfast, associated with secondary fibres, following birth. Analysis of RNA, DNA and protein values suggested that neonates from clenbuterol fed dams may have reduced hyperplasia and/or increased hypertrophy. Biochemical analysis revealed that proteins such as GATA-2, PKC and Shh, which have previously been associated with hypertrophy, were altered in response to clenbuterol. Further evidence in support of hypertrophy was indicated in an apparent increase in fibre size of neonates detected by MHC immunolocalisation. In conclusion, it has been demonstrated that both nutritional and pharmacological manipulations throughout are gestation capable of altering myogeneiss <i>in utero</i> by two different mechanisms.

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Background: Semitendinosus-gracilis (STG) autograft continues to increase in ACL reconstruction and a comprehensive study of the impact of what is essentially ‘surgically induced tenotomy’ of STG has not been undertaken. Purpose: To examine longitudinal changes in muscle morphometry and physical activity (PA) in relation to strength, functional tests, and subjective outcomes. Methods: Assessments at pre-, 2-weeks, 6- and 12-months post-surgery were performed on twenty moderately active adults undergoing ACL reconstruction. Participants were randomized to the Standard group (using STG tendon from the ACL deficient limb) or the Contra group (using STG from the opposite limb). Bilateral lower extremity MRI, Tegner, Lysholm, and IKDC scores, hop tests, and isovelocity strength testing in a seated and hipneutral supine position were completed. PA was assessed using a tri-axial accelerometer (GTX3, Actigraph, Pensacola, FL). Results: Subjective scores significantly improved from pre- to 12-months post-surgery, although Tegner score was significantly less (-1.25 levels) than pre-injury scores at 12- months. ST and G CSA significantly declined in donor limbs to 41.5% and 65.5% of presurgery,respectively and there was a 5.7 (2.9) cm proximal shift in ST and a 4.2 (2.3) cm shift in G donor muscles. In the donor limb, nine of 17 participants for ST and one for G had more than an 80% reduction in volume. There was significant difference between donor and non-donor limbs in peak knee flexor torque, but only in the hip-neutral testing position. There were no differences in hop tests between legs regardless of reconstruction or STG tendon harvest. PA did not significantly improve from pre-surgery, but was comparable an age-matched normative population. This level was less than that necessary for a healthy lifestyle (10,000 steps). Morphological parameters were moderately or highly predictive of outcomes in subjective findings, single hop test, PA, and strength. Conclusion: Changes in muscle morphology following tendon harvest of ST and G were found to be related to measured decreases in knee flexor strength, and post-operative deficiencies in objectively measured PA, hop tests, and subjective findings at 12-months post-surgery. PA did not increase in a statistically or clinically relevant degree consistent with a diminished self-report of function.

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Understanding the regulatory mechanisms controlling utrophin A expression at the sarcolemma of dystrophic muscles will facilitate the development of therapeutic strategies to ameliorate the pathophysiological features of Duchenne Muscular Dystrophy (DMD). The main goal of this study was to characterize the regulation of utrophin A IRES activity using a transgenic mouse model expressing the utrophin A 5’UTR bicistronic reporter and to identify trans-acting factors that could mediate IRES activity and endogenous expression of utrophin A. We found that utrophin A IRES activity is specifically expressed in skeletal muscles. Moreover, we identified eEF1A2 as a muscle-specific trans-acting factor that can interact with utrophin A and mediate IRES-dependent translation of utrophin A. Finally, we showed that eEF1A2 mediates endogenous utrophin A expression and localization in skeletal muscle. Identifying pharmacological compounds that would specifically target eEF1A2 and increase endogenous levels of utrophin A expression could serve as a drug-based therapy to treat DMD.

Since a significantly greater percentage of body weight is supported by the non-paretic limb following stroke, a greater amount of fatigue may be present during daily activities. This may affect the ability of these individuals to maintain a stable upright posture. The presence of falls following a stroke has been attributed in part to this asymmetrical stance post-stroke. Therefore the purpose of this study was to assess the effect of quadriceps muscle fatigue on bi-pedal posture in individuals who had a stroke and an age-matched control group. Although individuals after stroke displayed greater postural sway under the paretic limb than the non-paretic limb or control subjects, results of this study show that sustaining an isometric knee extension of the non-paretic limb induces changes in postural control for individuals after stroke, but that these changes do not markedly differ from those of healthy age-matched controls.

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