DNA replication stress-induced loss of reproductive capacity in S. cerevisiae and its inhibition by caloric restriction

In many organisms, attenuation of growth signaling by caloric restriction or mutational inactivation of growth signaling pathways extends lifespan and protects against cancer and other age-related diseases. The focus of many efforts to understand these effects has been on the induction of oxidative stress defenses that inhibit cellular senescence and cell death. Here we show that in the model organism S. cerevisiae, growth signaling induces entry of cells in stationary phase into S phase in parallel with loss of reproductive capacity, which is enhanced by elevated concentrations of glucose. Overexpression of RNR1 encoding a ribonucleotide reductase subunit required for the synthesis of deoxynucleotide triphosphates and DNA replication suppresses the accelerated loss of reproductive capacity of cells cultured in high glucose. The reduced reproductive capacity of these cells is also suppressed by excess threonine, which buffers dNTP pools when ribonucleotide reductase activity is limiting. Caloric restriction or inactivation of the AKT homolog Sch9p inhibits senescence and death in stationary phase cells caused by the DNA replication inhibitor hydroxyurea or by inactivation of the DNA replication and repair proteins Sgs1p or Rad27p. Inhibition of DNA replication stress represents a novel mechanism by which caloric restriction promotes longevity in S. cerevisiae. A similar mechanism may promote longevity and inhibit cancer and other age-related diseases in humans.We wish to thank Molly Burhans for preparing plasmid DNA and Figure 5. This research was supported by a National Cancer Institute Support Grant (P30CA016056) to Roswell Park Cancer Institute and by FCT - Fundacao para a Ciencia e Tecnologia (PTDC/BIA-MIC/114116/2009), Portugal. B. S. M. received a fellowship from FCT (SRFH/BD/41674/2007)

Assessment of HIV Disclosure and Sexual Behavior Among Black Men Who Have Sex With Men Following a Randomized Controlled Intervention

Disclosure is important in human immunodeficiency virus (HIV) transmission risk reduction. This randomized controlled intervention assessed changes in and predictors of disclosure and risky sexual behavior among Black men who have sex with men (BMSM) living with HIV in the U.S. BMSM were randomly assigned to either the disclosure intervention or attention control case management group. Predictors of three disclosure types (behavior, beliefs, intentions) and condomless anal intercourse (CAI) included disclosure consequences (rewards and costs), disclosure readiness, and safer sex readiness. Mixed-effect results showed no differences between the groups in any of the outcomes; although disclosure behavior increased over time. Relationships were found between readiness to change and CAI; disclosure consequences and different disclosure types; and disclosure behavior and receptive CAI. When working with BMSM living with HIV, practitioners and prevention specialists should consider the importance of disclosure pertaining to receptive CAI and factors that support overall disclosure and safer sex

Mediator and Moderator Effects on the Relationship Between HIV-positive Status Disclosure Concerns and Health-related Quality of Life

HIV-related stigma and the effect on quality of life is an on-going public health concern despite decades of education, prevention, and intervention efforts. The main purposes of this study were to examine the mediating role of four coping styles and the moderating role of gender on the relationship between HIV-positive status disclosure concerns and eight health-related quality of life outcomes. Data were collected from 346 women and men living with HIV. Results indicated that two coping styles – acquiring social support and positive reframing – mediated the negative relationship between disclosure concerns and health-related quality of life outcomes. There was no support for a moderated mediation. Interventions aimed at helping people living with HIV should focus on identifying and acquiring coping styles that transform perceptions of HIV-related stigma to support disclosure and improve health-related quality of life

Age and Racial Disparities in Substance Use and Self-Reported Viral Suppression among Men who have Sex with Men with HIV

HIV disproportionately affects men who have sex with men (MSM). Substance use is common among people living with HIV and may affect antiretroviral therapy adherence. Nevertheless, research examining the association between substance use and viral suppression is lacking. The aims of this study were to determine the association between substance use and self-reported viral suppression, and by age and race among MSM living with HIV. Data were obtained from 309 HIV-positive MSM. Logistic regression was used to determine the association between substance use and self-reported viral suppression at baseline, and by age and race. Approximately 67% of participants reported they were virally suppressed. After adjusting for sociodemographics, every increase in substance use score was associated with a 7% decrease in the odds of reporting viral suppression (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.89–0.98; p = 0.003). The negative association between substance use and self-reported viral suppression remained statistically significant among MSM aged 25–34 years (OR = 0.89; 95% CI: 0.79–1.00; p = 0.041) and statistically significant for Black MSM (OR = 0.92; 95% CI: 0.86–0.98; p = 0.009). Intervention programs for MSM living with HIV aimed at improving viral suppression should address substance use and consider the differences by age and race

Assessment of HIV Disclosure and Sexual Behavior Among Black Men Who Have Sex With Men Following a Randomized Controlled Intervention

Disclosure is important in human immunodeficiency virus (HIV) transmission risk reduction. This randomized controlled intervention assessed changes in and predictors of disclosure and risky sexual behavior among Black men who have sex with men (BMSM) living with HIV in the U.S. BMSM were randomly assigned to either the disclosure intervention or attention control case management group. Predictors of three disclosure types (behavior, beliefs, intentions) and condomless anal intercourse (CAI) included disclosure consequences (rewards and costs), disclosure readiness, and safer sex readiness. Mixed-effect results showed no differences between the groups in any of the outcomes; although disclosure behavior increased over time. Relationships were found between readiness to change and CAI; disclosure consequences and different disclosure types; and disclosure behavior and receptive CAI. When working with BMSM living with HIV, practitioners and prevention specialists should consider the importance of disclosure pertaining to receptive CAI and factors that support overall disclosure and safer sex

Mediator and Moderator Effects on the Relationship Between HIV-positive Status Disclosure Concerns and Health-related Quality of Life

HIV-related stigma and the effect on quality of life is an on-going public health concern despite decades of education, prevention, and intervention efforts. The main purposes of this study were to examine the mediating role of four coping styles and the moderating role of gender on the relationship between HIV-positive status disclosure concerns and eight health-related quality of life outcomes. Data were collected from 346 women and men living with HIV. Results indicated that two coping styles – acquiring social support and positive reframing – mediated the negative relationship between disclosure concerns and health-related quality of life outcomes. There was no support for a moderated mediation. Interventions aimed at helping people living with HIV should focus on identifying and acquiring coping styles that transform perceptions of HIV-related stigma to support disclosure and improve health-related quality of life