Thesis (Ph. D.)--University of Wisconsin--Madison, 1980. / Typescript. Vita. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1982. / Typescript. Vita. Includes bibliographical references (leaves 61-67).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 94-101).

Thesis (Ph. D. in Cell and Developmental Biology)--Vanderbilt University, May 2007. / Title from title screen. Includes bibliographical references.

No description available.

The goals of this research were to a) characterize the protein-function relationships of skeletal muscle single fibers from the mouse hindlimb b) examine mouse-strain related differences in myosin heavy chain composition (MHC) and single fiber contractile function, and c) quantify changes in fiber size and contractile function in response to 7 days of non-weight bearing. This research is significant because mechanistic approaches to understanding relationships between muscle protein expression, contractile function, and mechanical loading will likely benefit from a transition from the traditional laboratory rat to genetically modified mouse models. The methods used in this research feature an in vitro skinned-fiber preparation and single-fiber gel electrophoresis. Hindlimb muscles of mice were excised, and dissected into smaller bundles from which single muscle fibers were isolated. Single fibers were placed in skinning solution that permeabilized the fiber's membrane. The ends of skinned single muscle segments were attached to stainless steel troughs, which were connected to an isometric force transducer and a direct-current position motor. This system allowed the measurement of the fiber's cross-sectional area (CSA), peak isometric force (P���), and unloaded maximal shortening velocity (V���) during maximal Ca�����-activating. The identification of the fiber's MHC content was subsequently achieved by electrophoresis of a sample of each fiber segment. The results showed that the C57BL/6 mouse soleus muscle contains a MHC composition (20% type I) that is dramatically different than the ICR and CBA/J mouse strains (50% type I, respectively). Type I fibers from the C57BL/6 mouse had V��� that was 25% lower than type I fibers from ICR and CBA/J mice. Following 7 days of hindlimb suspension (HS) all strains experienced significant soleus muscle and single-fiber atrophy and decreases in the absolute and specific (force/fiber CSA) of type I and II fibers. However, type I fibers from C57BL/6 mice showed no change in V��� whereas type I fibers from ICR and CBA/J showed increased V���. In conclusion, this research demonstrates that unlike the rat and human models of non-weight bearing, mouse soleus type I and II fibers are equally affected by HS with respect to decreases in fiber CSA and force. However, type I fiber V��� was elevated only in mouse strains with solei containing at least 50% type I MHC. These findings challenge the current view that non-weight bearing affects slow fibers more than fast fibers, and suggests that changes in single fiber contractile function with HS may be influenced in part by the MHC distribution of the muscle. / Graduation date: 2003

The first goal of this study was to understand the role of calpains in skeletal muscle protein degradation in cultured cells. We have developed a genetic approach to inhibit endogenous calpain activity through over-expressing dominant negative m-calpain (DN), antisense m-calpain (AS) and calpastatin inhibitory domain (CID). We observed that, under conditions of accelerated degradation (serum withdrawal), inhibition of m-calpain through DN-m-calpain over-expression caused a 30% inhibition of total protein degradation whereas CID over-expression reduced degradation by 63%. These constructs did not significantly affect degradation in the presence of serum. These data indicate that calpains participate in the accelerated degradation associated with serum withdrawal. Inhibition of calpain also stabilized nebulin, a major structural protein of the sarcomere. These observations indicate that calpains play significant roles in muscle protein turnover. Finally, over-expression of antisense m-calpain caused a transient reduction in m-calpain concentration after which normal m-calpain concentration was quickly re-established. These observations indicate that m-calpain is a short half-life protein in muscle cells. The second goal of this study is to investigate the role of calpain in the mediation of PARP protein level in differentiating myoblasts. Poly(ADP-ribosyl)ation, catalyzed by PARP, is involved in various physiological events, such as DNA excision repair, DNA recombination, DNA replication, cell differentiation, cell growth and transformation, and apoptosis. A protease participating in PARP turnover could be a significant regulator to the events which PARP is involved. A relationship between apoptosis and myofibrillar protein degradation via a common protease might suggest the basis for muscle wasting and atrophy which characterize in many muscle diseases. We established a genetic approach to inhibit endogenous calpain activity through over-expressing calpastatin inhibitory domain (CID). We observed that (1) inhibition of calpain activity increased PARP concentration when post-confluent myoblasts were cultured with 2% HS medium, an inducer of differentiation and (2) inhibition of calpain activity prevented PARP degradation induced by A23187 and etoposide in differentiating myoblasts. These data demonstrate that calpain is involved in regulation of PARP in cultured cells. / Graduation date: 1998

Thesis (Ph. D.)--University of North Texas, Aug., 2007. / Title from title page display. Includes bibliographical references.

Thesis (M.Sc. Biological Sciences)--University of Waikato, 2006. / Title from PDF cover (viewed March 18, 2008) Includes bibliographical references (p. 98-112)

Thesis (Ph. D.)--Lehigh University, 1998. / Includes vita. Bibliography: leaves 111-118.