More Than A Movement: Unpacking Contemporary Anti-Human Trafficking Efforts in Washington, D.C.

Trafficking in persons has attracted seemingly boundless attention over the last two decades and the work aimed at fighting it is best understood when this cause is contextualized against the backdrop of other social forces—economic, social, and cultural—shaping contemporary nonprofit activities. This project argues that the paid and volunteer labor that takes place in metro Washington, D.C., to combat trafficking in persons can be understood as both a movement and an industry. In addition to arguing that anti-trafficking work is part of a nonprofit industrial complex that situates activist and advocacy work firmly inside state and economic institutions, this project is concerned with the ways in which trafficking work and workers conduct their business collectively. As an organizational study, it identifies the key players in the D.C. region focused on this issue and traces their interactions, collaborations, and cooperation. Significantly, this project suggests that despite variations in objectives, methods, priorities, and characterizations of trafficking, thirty organizations in metro D.C. working on this issue “get along” because they are bound by the benign common goal of raising awareness. Awareness, in this context, is best understood as both a cultural anchor facilitating cohesion and as a social currency allowing groups to opt into joint efforts. The dissertation concludes that organizations centralize awareness in their collective activities over more drastic priorities around which consensus would need to be gained. This is a lost opportunity for making sense of the ways that individual bodies—men, women, and children—experience not just trafficking, but the world around them.

HIV Reverse Transcriptase Fidelity And Inhibition Are Modulated By Divalent Cations In A Concentration-Dependent Manner In Vitro

Human immunodeficiency virus (HIV) rapidly evolves through generation and selection of mutants that can escape drug therapy. This process is fueled, in part, by the presumably highly error prone polymerase reverse transcriptase (RT). Fidelity of polymerases can be influenced by cation co-factors. Physiologically, magnesium (Mg2+) is used as a co-factor by RT to perform catalysis, however, alternative cations including manganese (Mn2+), cobalt (Co2+), and zinc (Zn2+) can also be used. I demonstrate here that fidelity and inhibition of HIV RT can be influenced differently, in vitro, by divalent cations depending on their concentration. The reported mutation frequency for purified HIV RT in vitro is typically in the 10-4 range (per nucleotide addition), making the enzyme several-fold less accurate than most polymerases. Paradoxically, results examining HIV replication in cells indicate an error frequency that is ~10 times lower than the error rate obtained in the test tube. Here, I reconcile, at least in part, these discrepancies by showing that HIV RT fidelity in vitro is in the same range as cellular results, in physiological concentrations of free Mg2+ (~0.25 mM). At low Mg2+, mutation rates were 5-10 times lower compared to high Mg2+ conditions (5-10 mM). Alternative divalent cations also have a concentration-dependent effect on RT fidelity. Presumed promutagenic cations Mn2+ and Co2+ decreases the fidelity of RT only at elevated concentrations, and Zn2+, when present in low concentration, increases the fidelity of HIV-1 RT by ~2.5 fold compared to Mg2+. HIV-1 and HIV-2 RT inhibition by nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) in vitro is also affected by the Mg2+ concentration. NRTIs lacking 3'-OH group inhibited both enzymes less efficiently in low Mg2+ than in high Mg2+; whereas inhibition by the “translocation defective RT inhibitor”, which retains the 3ʹ-OH, was unaffected by Mg2+ concentration, suggesting that NRTIs with a 3ʹ-OH group may be more potent than other NRTIs. In contrast, NNRTIs were more effective in low vs. high Mg2+ conditions. Overall, the studies presented reveal strategies for designing novel RT inhibitors and strongly emphasize the need for studying HIV RT and RT inhibitors in physiologically relevant low Mg2+ conditions.

Experimentally Testing the Effect of Parent-Adolescent Conflict on HIV Risk, and Investigation of a Neurobiological Moderator of This Effect

Human immunodeficiency virus (HIV) is a condition in which immune cells become destroyed such that the body may become unable to fight off infections. Engaging in risk-taking behaviors (e.g., substance use) puts people at heightened risk for HIV infection, with mid-to-late adolescents at increasing risk (Leigh & Stall, 1993). Environmental and neurological reasons have been suggested for increased risk-taking among adolescents. First, family-level precursors such as parent-adolescent conflict have been significantly associated with and may pose risk for engaging in substance use and risk-taking (Duncan, Duncan, Biglan, & Ary, 1998). Thus, parent-adolescent conflict may be an important proximal influence on HIV risk behaviors (Lester et al., 2010; Rowe, Wang, Greenbaum, & Liddle, 2008). Yet, the temporal relation between parent-adolescent conflict and adolescent HIV risk-taking behaviors is still unknown. Second, at-risk adolescents may carry a neurobiological predisposition for engaging in trait-like expressions of disinhibited behavior and other risk-taking behaviors (Iacono, Malone, & McGue, 2008). When exposed to interpersonally stressful situations, their likelihood of engagement in HIV risk behaviors may increase. To investigate the role of parent-adolescent conflict in adolescent HIV risk-taking behaviors, 49 adolescents ages 14-17 and their parent were randomly assigned to complete a standardized discussion task to discuss a control topic or a conflict topic. Immediately after the discussion, adolescents completed a laboratory risk-taking measure. In a follow-up visit, eligible adolescents underwent electrophysiological (EEG) recording while completing a task designed to assess the presence of a neurobiological marker for behavioral disinhibition which I hypothesized would moderate the links between conflict and risk-taking. First, findings indicated that during the discussion task, adolescents in the conflict condition evidenced a significantly greater psychophysiological stress response relative to adolescents in the control condition. Second, a neurobiological marker of behavioral disinhibition moderated the relation between discussion condition and adolescent risk-taking, such that adolescents evidencing relatively high levels of a neurobiological marker related to sensation-seeking evidenced greater levels of risk-taking following the conflict condition, relative to the control condition. Lastly, I observed no significant relation between parent-adolescent conflict, the neurobiological marker of behavioral disinhibition and adolescent engagement in real-world risk-taking behavior.