THE 2011 CGS/PROQUEST DISSERTATIONS PUBLISHING DISTINGUISHED DISSERTATIONS AWARD WINNER IN BIOLOGICAL & LIFE SCIENCES:
Nathaniel Adam Sowa, University of North Carolina at Chapel Hill, 2010
Characterization of ectonucleotidases in nociceptive circuits
Pain is one of the most common medical complaints in the United States, affecting almost a quarter of American adults. There are numerous treatments for acute and chronic pain, but none of them are completely effective and many have intolerable side effects. New treatments are needed that are safer, more efficacious, and more cost-effective. We have focused on trying to understand better the mechanisms involved in the regulation of pain (nociceptive) signaling in order to develop novel therapies. Two important compounds involved in pain signaling are adenosine triphosphate (ATP) and adenosine. ATP has pronociceptive properties, while adenosine is antinociceptive. ATP can be converted to adenosine through a step-wise process catalyzed by enzymes on the surface of cells called ectonucleotidases. These enzymes could play a pivotal role in regulation of nociception by degrading pro-nociceptive ATP while simultaneously producing antinociceptive adenosine. Prior to this work, the exact ectonucleotidases present in nociceptive circuits were unknown.
Here, we identify and characterize the first two known AMP-degrading ectonucleotidases involved in nociception, prostatic acid phosphatase (PAP) and Ecto-5'-nucleotidase (NT5E). Genetic deletion of these enzymes does not affect acute nociception, but leads to enhanced pain sensitivity in chronic inflammatory and neuropathic pain models. Conversely, intraspinal injection of PAP or NT5E protein has antinociceptive, antihyperalgesic, and antiallodynic effects that last longer than the opioid analgesic morphine. Both PAP and NT5E suppress pain by the production of adenosine from endogenous AMP and subsequent activation of the A 1 -adenosine receptor (A 1 R). Further, chronic activation of A 1 R by PAP leads to depletion of cellular levels of the signaling molecule PIP 2. Depletion of PIP 2 before or after chemical or physical injury (through injection of PAP) reduces pain hypersensitivity, highlighting an important role for PIP 2 levels in the modulation of nociceptive signaling. We are the first to show this important role for PIP 2 in setting the dynamic pain threshold in nociceptors. These studies not only identify two potentially new targets for the development of chronic pain therapy, but also highlight a new model for the dynamic modulation of pain sensitivity through the regulation of neuronal PIP 2 levels.
THE 2011 CGS/PROQUEST DISSERTATIONS PUBLISHING DISTINGUISHED DISSERTATIONS AWARD WINNER IN THE HUMANITIES AND FINE ARTS:
Kristin A. Weld, Yale University, 2010
Reading the politics of history in Guatemala's National Police archives
This work uses the 2005 unearthing of Guatemala's National Police archives -- at 75 million pages, the largest secret state document discovery in Latin American history -- as an entry point into studying the politics of history. It explores how Guatemala, a post-conflict society deeply scarred after 36 years of brutal civil war (1960-1996), struggles to manage this unprecedented amount of evidence of past state-sponsored crimes. It investigates how dominant narratives of the war years are contested and rewritten by human rights activists based on what the records do, and do not, reveal.
Scholarly investigations of the war have left its urban theatre and the police's surgical, political repression understudied. Using historical and anthropological methods, this study makes two main interventions. It writes the National Police, the capital city, and left-wing social movements back into the conflict's history. It also tracks how Guatemalans themselves, both insurgency veterans and young members of the postwar generation, experience the complex process of trying to reconfigure terror archives into implements of social change. The study is rooted in historical research on the urban counterinsurgency and the police, focusing particularly on the police's use of archives as a tool -- honed by USAID technical assistance -- of social control. However, the research is equally rooted in participant observation and ethnographic analysis of the Project for the Recovery of the National Police Historical Archives, the effort to transform the decayed and disordered piles of records into a powerful body of evidence for human rights prosecutions against wartime military and police officials. It treats archives as shifting sites of political struggle, and it reads the National Police archives for their form, politics, and silences as much as for their content.
Based on extensive archival and ethnographic research in Guatemala and the U.S., Reading the Politics of History dialogues with historians, political scientists, archivists, and anthropologists across geographic specialties about the uses of history and archives; transitional justice; the Cold War in Latin America; human rights; non-governmental organizations and international cooperation; state formation; state terror; political violence; police and military structures; post-conflict security reform; and social movements.
