Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.

Without women: Masculinities, gay male sexual culture and sexual behaviors in Miami, Florida

Recent studies have reported alarmingly high rates of HIV infection and risky sexual behaviors among gay men in Miami, Florida. Previous research has suggested that the risky sexual behaviors of many gay men reflect the pursuit of intimacy and love, and that barriers to intimate relationships among gay men may stem from traditional masculinity norms. This dissertation examines the meanings which gay men ascribe to their sexual behaviors, as well as the intersections of those meanings with both traditional masculinity constructions and Miami's gay male sexual culture. ^ The study is based upon participant observation, print media content analysis, surveys and ethnographic interviews of a purposive snowball sample of 30 Cuban American, Puerto Rican, African American and Anglo gay men who reside in Miami-Dade County, Florida. Analysis of research questions was accomplished through grounded theory methods and descriptive and non-parametric statistics, including Pearson chi-square, Fisher's Exact and Mann-Whitney U tests. ^ The study shows that culturally-specified masculinity norms vary in the relative importance ascribed to heterosexual prowess, economic providership and competitiveness. These cultural differences appear important not only to the timing of sexual awareness and to the strength of homosexual stereotyping as effeminacy, but also to men's strategies in coming out as gay. The meanings men attributed to their sexual behaviors were, however, constructed in response to both inherited masculinity norms and the hypermasculine structure of Miami's gay male sexual culture. In addition to providing an ethnographic account of this subculture, the study elaborates men's issues relative to casual sex and committed relationships. Unprotected anal intercourse with casual partners during the previous twelve months was associated with growing up without one's father in the home, having been teased for effeminacy during childhood, being defensive about one's masculinity, not trusting men, having been cheated on by boyfriends, and believing that long-term gay male relationships are problematic. ^ It is concluded that the continuing epidemic of HIV infections among local gay men, as well as the hypermasculine form of the gay sexual subculture itself, are nihilistic symptoms embedded in the masculinist gender structure of the larger society. ^

Gender differences in the influence of protective factors, risk factors, and health risk behaviors on HIV risk behaviors among youth in South Florida

Adolescents engage in a range of risk behaviors during their transition from childhood to adulthood. Identifying and understanding interpersonal and socio-environmental factors that may influence risk-taking is imperative in order to meet the Healthy People 2020 goals of reducing the incidence of unintended pregnancies, HIV, and other sexually transmitted infections among youth. The purpose of this study was to investigate gender differences in the predictors of HIV risk behaviors among South Florida youth. More specifically, this study examined how protective factors, risk factors, and health risk behaviors, derived from a guiding framework using the Theory of Problem Behavior and Theory of Gender and Power, were associated with HIV risk behavior. A secondary analysis of 2009 Youth Risk Behavior Survey data sets from Miami-Dade, Broward, and Palm Beach school districts tested hypotheses for factors associated with HIV risk behaviors. The sample consisted of 5,869 high school students (mean age 16.1 years), with 69% identifying as Black or Hispanic. Logistic regression analyses revealed gender differences in the predictors of HIV risk behavior. An increase in the health risk behaviors was related to an increase in the odds that a student would engage in HIV risk behavior. An increase in risk factors was also found to significantly predict an increase in the odds of HIV risk behavior, but only in females. Also, the probability of participation in HIV risk behavior increased with grade level. Post-hoc analyses identified recent sexual activity (past 3 months) as the strongest predictor of condom nonuse and having four or more sexual partners for both genders. The strongest predictors of having sex under the influence of drugs/alcohol were alcohol use in both genders, marijuana use in females, and physical fighting in males. Gender differences in the predictors of unprotected sex, multiple sexual partners, and having sex under the influence were also found. Additional studies are warranted to understand the gender differences in predictors of HIV risk behavior among youth in order to better inform prevention programming and policy, as well as meet the national Healthy People 2020 goals.

Gender Differences in the Influence of Protective Factors, Risk Factors, and Health Risk Behaviors on HIV Risk Behaviors Among Youth in South Florida

Adolescents engage in a range of risk behaviors during their transition from childhood to adulthood. Identifying and understanding interpersonal and socio-environmental factors that may influence risk-taking is imperative in order to meet the Healthy People 2020 goals of reducing the incidence of unintended pregnancies, HIV, and other sexually transmitted infections among youth. The purpose of this study was to investigate gender differences in the predictors of HIV risk behaviors among South Florida youth. More specifically, this study examined how protective factors, risk factors, and health risk behaviors, derived from a guiding framework using the Theory of Problem Behavior and Theory of Gender and Power, were associated with HIV risk behavior. A secondary analysis of 2009 Youth Risk Behavior Survey data sets from Miami-Dade, Broward, and Palm Beach school districts tested hypotheses for factors associated with HIV risk behaviors. The sample consisted of 5,869 high school students (mean age 16.1 years), with 69% identifying as Black or Hispanic. Logistic regression analyses revealed gender differences in the predictors of HIV risk behavior. An increase in the health risk behaviors was related to an increase in the odds that a student would engage in HIV risk behavior. An increase in risk factors was also found to significantly predict an increase in the odds of HIV risk behavior, but only in females. Also, the probability of participation in HIV risk behavior increased with grade level. Post-hoc analyses identified recent sexual activity (past 3 months) as the strongest predictor of condom nonuse and having four or more sexual partners for both genders. The strongest predictors of having sex under the influence of drugs/alcohol were alcohol use in both genders, marijuana use in females, and physical fighting in males. Gender differences in the predictors of unprotected sex, multiple sexual partners, and having sex under the influence were also found. Additional studies are warranted to understand the gender differences in predictors of HIV risk behavior among youth in order to better inform prevention programming and policy, as well as meet the national Healthy People 2020 goals.