Transcriptional Regulation of Neurogenic Atrophy-Induced Gene Expression by Muscle Ring Finger-1 and Myogenic Regulatory Factors

Skeletal muscle wasting is a consequence of numerous physiological conditions, including denervation, corticosteroid treatment, immobilization, and aging. The E3 ubiquitin ligases, MuRF1 and MAFbx, are induced under nearly all atrophy conditions and are believed to play a key role in protein degradation in atrophying muscle. However, the preliminary data described in this study provides new evidence that MuRF1 may also act as a transcriptional modulator of atrophy-induced gene activity, including the regulation of MAFbx and MuRF1 expression. To characterize the transcriptional regulation of MuRF1 and MAFbx, reporter gene constructs containing fragments of the proximal promoter regions of these genes were developed, transfected into C2C12 cells with or without a MuRF1 expression plasmid and monitored for differences in reporter gene activity. The MuRF1 and MAFbx reporters each showed repressed activity in cells ectopically expressing MuRF1 compared to cells that did not overexpress MuRF1. Furthermore, ectopic expression of the myogenic regulatory factors (MRFs), MyoD1 and myogenin, caused significant activation of the MuRF1 and MAFbx reporter constructs. However, co-overexpression of MuRF1 with MyoD1 or myogenin resulted in reversal of MRF induction of reporter gene activity, and synergistic repression of a constructed E-box reporter system. To further characterize the role of the MuRF1 gene product in repression of MuRF1 expression, a MuRF1 RING domain mutant and a MuRF1 c-terminal mutant were created. The mutant constructs were then co-transfected along with MRF expression plasmids and the MuRF1 reporter construct into C2C12 cells and reporter gene activity was assessed. The MuRF1 RING mutant failed to reverse MRF activation of the reporter gene, while the c-terminal mutant successfully reversed activation of the reporter gene. These findings suggest that ubiquitin ligase activity is required for MuRF1 transcriptional regulatory effects. These data offer exciting evidence of a potential new function for MuRF1 as a transcriptional modulator of atrophy-induced changes in gene expression

The Evolution of an Image: An Analysis of Defining Depictions of Native Americans in Popular Cinema 1913-1970

Native Americans have been depicted in the movies since the birth of the medium. In this thesis, the depiction of Native Americans in seven exemplary films is analyzed. The films chosen illustrate the evolution of Native American depiction from the silent era through the classic studio era of the 1930s and 1940s, the post WWII era, and the 1960s Civil Rights period to 1970 when the Native American Civil Rights movement was at its most public. Classic tropes such as the Indian Princess/Squaw, the Screaming Savage, and the Noble Savage/Vanishing American that were defined in 19th Century literature and by Buffalo Bill Cody\u27s Wild West shows are shown to have evolved as audience attitudes about race and Manifest Destiny reflected a changing zeitgeist

Solicitors General Panel on the Legacy of the Rehnquist Court

All of us who are speaking probably share the same giddy feeling in front of a microphone with no red light. For years, my daughter told people that the greatest threat to Western civilization was her father at a podium without a red light. Before becoming Solicitor General, I spent my career as a trial lawyer, arguing only a few appeals. I found this red light tradition a little peculiar. More often than not, timers and lights in courts of appeals are viewed as advisory at best. I\u27ve had arguments where ten minutes were allocated per side, and yet argument extended until the afternoon. In another case that allocated ninety minutes per side and began at nine o\u27clock, we didn\u27t actually finish until four o\u27clock in the afternoon. So coming into the SG\u27s office, my view about the red light was, well, perhaps it shows your time has nominally expired, but undoubtedly the Justices will have other questions. And in any event, I might want to take a few extra minutes to address additional points. That was so wrong. The red light ended everything-absolutely everything-and not just for the advocates; it also ended the questioning of the Associate Justices. The Chief Justice was an equal opportunity cutter-offer. On many occasions, he cut off oral argument when a Justice was at the outset of a question he or she had been trying to get out in the open oral combat that was advocacy in the Supreme Court of Chief Justice Rehnquist