Skeletal muscle (SM) atrophy complicates many illnesses, diminishing quality of life and increasing disease morbidity, health resource utilization and health care costs. In animal models of muscle atrophy, loss of SM mass results predominantly from ubiquitin-mediated proteolysis and ubiquitin ligases are the key enzymes that catalyze protein ubiquitination. We have previously shown that ubiquitin ligase Nedd4-1 is up-regulated in a rodent model of denervation-induced SM atrophy and the constitutive expression of Nedd4-1 is sufficient to induce myotube atrophy in vitro, suggesting an important role for Nedd4-1 in the regulation of muscle mass. In this study we generate a Nedd4-1 SM specific-knockout mouse and demonstrate that the loss of Nedd4-1 partially protects SM from denervation-induced atrophy confirming a regulatory role for Nedd4-1 in the maintenance of muscle mass in vivo. Nedd4-1 did not signal downstream through its known substrates Notch-1, MTMR4 or FGFR1, suggesting a novel substrate mediates Nedd4-1’s induction of SM atrophy.

Brain atrophy has been used as a marker for disease progression in Multiple Sclerosis (MS). SIENA, an automated tool for measuring brain volume change, was tested to see whether MRI slice thickness and gap presence affect longitudinal atrophy measures. Isotropic global scan-rescan images were used to simulate 3 mm and 5 mm axial slice thicknesses with 1 and 2mm gaps, respectively. SIENA remained accurate and precise with increasing slice thickness and gap presence. Furthermore, symmetric pre-registration was crucial for scans with larger slice-thickness and gaps. / SIENA was used to observe atrophy in children who have experienced a Clinically Isolated Syndrome (CIS) of the type leading to MS (CIS-MS). Brain atrophy was present within the first three months after a CIS event, and then subsided over the rest of the year. If the first acute episode was excluded, there was no significant difference in atrophy rates between the CIS-MS group and the CIS group, and no significant difference between those with T2-weighted brain lesions versus those who had none.

Diss. (sammanfattning) Göteborg : Univ. , 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 6 uppsatser.

Thesis (Ph.D.). / Written for the Dept. of Human Genetics. Title from title page of PDF (viewed 2008/02/12). Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2008" Includes bibliographical references.

Thesis--Copenhagen. / Summary in Danish. Includes bibliographical references (p. 127-130).

Thesis (Ph. D.)--Case Western Reserve University, 2005. / [School of Medicine] Department of Genetics. Includes bibliographical references. Available online via OhioLINK's ETD Center.