The Effect of Heavy Metal Stress on Avian Proximal Tubule Urate Secretion

In both humans and birds, urate is an important antioxidant when maintained at normal plasma concentrations. Though human kidneys primarily reabsorb filtered urate, while those of birds perform mostly secretion, both maintain urate levels at ~300microM. The importance of maintaining urate levels within the homeostatic range was observed when the study of several prominent diseases revealed an association with hyperuricemia. This study examined the effect of elevated zinc concentration on avian urate secretion. Here, acute exposure of chicken proximal tubule epithelial cells (cPTCs) to zinc stress had no effect on urate secretion, but prolonged zinc-induced cellular stress inhibited active transepithelial urate secretion with no change in Mrp4 expression, glucose transport, or transepithelial resistance. Moreover, zinc had no effect on urate transport by isolated brush border membrane vesicles, suggesting involvement of a more complex cellular stress adaptation. Previous work has demonstrated that AMP-activated protein kinase (AMPK), a critical metabolic regulator, conserves energy during cellular stress by shutting down ATP-utilizing processes and activating ATP-generating processes. Pharmacological activation of AMPK by AICAR produced decreased urate secretion by cPTCs similar to the effect seen with prolonged exposure to zinc, while the AMPK inhibitor Compound C prevented both AICAR and zinc inhibition of urate secretion, suggesting a stress induced mechanism of regulation. Supported by NSF. IACUC #A08-046.

Beyond Racial Precedents: Loving v. Virginia as an Appropriate Legal Model and Strategy for Same-Sex Marriage Litigation

This thesis explores how LGBT marriage activists and lawyers have employed a racial interpretation of due process and equal protection in recent same-sex marriage litigation. Special attention is paid to the Supreme Court's opinion in Loving v. Virginia, the landmark case that declared anti-miscegenation laws unconstitutional. By exploring the use of racial precedent in same-sex marriage litigation and its treatment in state court cases, this thesis critiques the racial interpretation of due process and equal protection that became the basis for LGBT marriage briefs and litigation, and attempts to answer the question of whether a racial interpretation of due process and equal protection is an appropriate model for same-sex marriage litigation both constitutionally and strategically. The existing scholarly literature fails to explore how this issue has been treated in case briefs, which are very important elements in any legal proceeding. I will argue that through an analysis of recent state court briefs in Massachusetts and Connecticut, Loving acts as logical precedent for the legalization of same-sex marriage. I also find, more significantly, that although this racial interpretation of due process and equal protection represented by Loving can be seen as an appropriate model for same-sex marriage litigation constitutionally, questions remain about its strategic effectiveness, as LGBT lawyers have moved away from race in some arguments in these briefs. Indeed, a racial interpretation of Due Process and Equal Protection doctrine imposes certain limits on same-sex marriage litigation, of which we are warned by some Critical Race theorists, Latino Critical Legal theorists, and other scholars. In order to fully incorporate a discussion of race into the argument for legalizing same-sex marriage, the dangers posed by the black/white binary of race relations must first be overcome.