Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references (leaves 119-134). Also available in electronic version.

Agrin triggers the subsynaptic aggregation of acetylcholine receptor (AChR) via activation of the receptor tyrosine kinase MuSK (muscle-specific kinase). At present, the intracellular mechanisms utilized by MuSK to initiate such a complex process remain unknown. In the present study, I first tested if H-ras was involved in the process of synaptogenesis induced by agrin. The data presented suggest that ras could have a role in this process because a dominant inhibitory ras mutant (ras-N17) partially blocked the inductive effects of agrin while two activated ras mutants (ras-V12 and ras-V12-D38) induced agrin-independent AChR clusters. These effects were not due to major alterations in the levels of AChR, though more experiments are required to confirm these preliminary findings. / Second, I investigated whether the adaptor protein Shc was a downstream effector of activated MuSK. MuSK and Shc could be co-immunoprecipitated, but this association was not consistently observed nor was it modulated by agrin at all times. Generally, no alteration in Shc phosphotyrosine content was observed in response to agrin, and when an increase was detected, it was modest. Finally, agrin did not modulate the interaction between Shc and Grb2. Based on these results, I conclude that Shc interaction with MuSK is not regulated by agrin.

Access to abstract permanently restricted to Ball State community only. / Access to thesis permanently restricted to Ball State community only. / Department of Biology

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2005. / Includes bibliographical references (leaves 151-171). Also available in electronic version.

Thesis (Ph.D.)--York University, 2005. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 166-200). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNR11583

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The stretch reflex circuit is one of the most primitive circuits of mammalian system and serves mainly to control the length of the muscle. It consists of four elements: the stretch sensor (muscle spindle/ intrafusal fiber lie parallel between extrafusal, contractile musculature), extrafusal muscle fiber, sensory neuron and motoneuron. The basic principle of the stretch reflex arc circuit is as follows: whenever there is a sudden stretch in a muscle, it needs to compensate back to its original length so as to prevent any kind of injury. It performs this compensation process using a simple negative feed back circuit called the stretch reflex arc. Any form of stretch in a muscle activates the stretch sensors (muscle spindle/ intrafusal fiber) lying deep in each muscle. After the stretch sensors get activated, it sends a train of signals to the spinal cord through the sensory neurons. The sensory neurons relay this information to the motoneuron. The motoneuron performs the necessary information processing and sends the message to the extrafusal fibers so as to compensate for the sudden stretch action. The motoneuron conveys this message to the extrafusal fibers by communicating through the special synaptic junctions called neuromuscular junctions. Based on this information, the extrafusal fibers act accordingly so as to counter the effect of sudden stretch. This is also called the monosynaptic stretch reflex that involves a single synapse between a sensory neuron and a motoneuron. To date studying these stretch reflex circuits is only feasible in animal models. Almost no effort has been made to tissue engineer such circuits for a better understanding of the complex development and repair processes of the stretch reflex circuit formation. The long-term goal of this research is to tissue engineer a cellular prototype of the entire iii stretch reflex circuit. The specific theme of this dissertation research was to tissue engineer the motoneuron to muscle segment of the stretch reflex arc circuit utilizing micro-fabrication, interface design and defined medium formulations. In order to address this central theme, the following hypothesis has been proposed. The first part of the hypothesis is that microfabrication technology, interface design and defined medium formulations can be effectively combined to tissue engineer the motoneuron to muscle segment of the stretch reflex arc. The second part of the hypothesis is that different growth factors, hormones, nanoparticles, neurotransmitters and synthetic substrate can be optimally utilized to regenerate the adult mammalian spinal cord neurons so as to replace the embryonic motoneurons in the stretch reflex tissue engineered construct with adult motoneurons. In this body of work, the different tissue engineering strategies and technologies have been addressed to enable the recreation of a in vitro cellular prototype of the stretch reflex circuit with special emphasis on building the motoneuron to muscle segment of the circuit. In order to recreate the motoneuron to muscle segment of the stretch reflex arc, a successful methodology to tissue engineer skeletal muscle and motoneuron was essential. Hence the recreation of the motoneuron to muscle segment of the stretch reflex circuit was achieved in two parts. In the part 1 (Chapters 2-5), the challenges in skeletal muscle tissue engineering were examined. In part 2 (Chapters 6-7), apart from tissue engineering the motoneuron to muscle segment, the real time synaptic activity between motoneuron and muscle segment were studied using extensive video recordings. In part 3 (Chapters 8-10), an innovative attempt had been made to tissue engineer the adult mammalian spinal cord neurons so that in future this technology could utilized to replace the iv embryonic neurons used in the stretch reflex circuit with adult neurons. The advantage of using adult neurons is that it provides a powerful tool to study older neurons since these neurons are more prone to age related changes, neurodegenerative disorders and injuries. This study has successfully demonstrated the recreation of the motoneuron to muscle segment of the stretch reflex arc and further demonstrated the successful tissue engineering strategies to grow adult mammalian spinal cord neurons. The different cell culture technologies developed in these studies could be used as powerful tools in nerve-muscle tissue engineering, neuro-prosthetic devices and in regenerative medicine.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 147-163).

This thesis has investigated skeletal muscle fibers and neuromuscular junctions of the reptile Anolis carolinensis. The extensor digitorum communis and gastrocnemmius externus were used for observations and characterization. Cross sections were stained for oxidative and glycolytic activities and for contractile properties by the use of four histochemical stains. This revealed the extensor digitorum communis to be composed of predominately fast glycolytic fibers, with a central core of fast oxidative-glycolytic and slow oxidative fibers. The gastrocnemius externus exhibited a majority of fast oxidative-glycolytic fibers and random slow oxidative fibers.Ultra structural examination of the extensor digitorum communis revealed the nerve terminal of the neuromuscular junction to be smaller than that of the gastrocnemius externus, with junctional folds longer and straighter, and synaptic vesicles smaller and more closely packed. In both muscles, the nerve fibers terminated in a shallow groove of the muscle fiber. The characteristics and heterogeneity that exist are very similar to the homologous mammalian extensor digitorum longus and soleus skeletal muscle.Ball State UniversityMuncie, IN 47306

Thesis (Ph. D.)--University of Wisconsin, 1951. / Typescript (carbon copy). eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [82]-86).