Differences in risk behaviours and HIV status between primary amphetamines and opioid injectors in Estonia and Russia

Background and objective People who inject drugs (PWID) account for over half of new HIV infections in Eastern Europe and central Asia, where opioids continue to be the dominant illicit drugs injected. Stimulants including amphetamines (ATS) have been associated with HIV infection risk in several settings. We sought to examine whether primary ATS injection was associated with greater HIV risk, compared to opioid injection in two European locales with significant HIV epidemics. Methods PWID in Kohtla-Järve and St. Petersburg were recruited using respondent-driven sampling in 2012–2013. Survey data on demographic characteristics, service use, injecting and sexual risk behaviours and HIV-status (and HCV in Kohtla-Järve) were compared between primary opioid and ATS injectors using logistic regression models. Results Of 591 injectors recruited in Kohtla-Järve and 811 in St. Petersburg, 195 (33%) and 27 (4%) primarily injected ATS in each city. In both cities, ATS injectors were younger than opioid injectors, initiated injection later, injected less frequently and were more likely to have been paid for sex. In both cities, PWID had high levels of multiple sex partners. In Kohtla-Järve, ATS-injectors had lower odds of back-loading and greater odds of polydrug use than opioid-injectors. In St. Petersburg, where over half of PWID reported unsafe sharing practices, ATS-injectors were less likely to report these practices. ATS-injection was negatively associated with being HIV positive in Kohtla-Järve (aOR = 0.6; 95%CI: 0.5–0.8) and St. Petersburg (aOR = 0.3; 95%CI: 0.1–0.7). ATS-injection was negatively associated with HCV-reactivity in Kohtla-Järve (aOR = 0.5; 95%CI: 0.3–0.6). Conclusions In both locations, primary ATS injection was associated with lower injecting risk behaviours, lower odds of HIV and being paid for sex compared to opioid injection. Interventions targeting the characteristics and needs of ATS injectors are needed to increase contact with services and reduce sexual and injecting risk. Harm reduction services, including sexual risk reduction, need to be expanded for all PWID in St. Petersburg

Interaction of Rio1 Kinase with Toyocamycin Reveals a Conformational Switch That Controls Oligomeric State and Catalytic Activity

Rio1 kinase is an essential ribosome-processing factor required for proper maturation of 40 S ribosomal subunit. Although its structure is known, several questions regarding its functional remain to be addressed. We report that both Archaeoglobus fulgidus and human Rio1 bind more tightly to an adenosine analog, toyocamycin, than to ATP. Toyocamycin has antibiotic, antiviral and cytotoxic properties, and is known to inhibit ribosome biogenesis, specifically the maturation of 40 S. We determined the X-ray crystal structure of toyocamycin bound to Rio1 at 2.0 Å and demonstrated that toyocamycin binds in the ATP binding pocket of the protein. Despite this, measured steady state kinetics were inconsistent with strict competitive inhibition by toyocamycin. In analyzing this interaction, we discovered that Rio1 is capable of accessing multiple distinct oligomeric states and that toyocamycin may inhibit Rio1 by stabilizing a less catalytically active oligomer. We also present evidence of substrate inhibition by high concentrations of ATP for both archaeal and human Rio1. Oligomeric state studies show both proteins access a higher order oligomeric state in the presence of ATP. The study revealed that autophosphorylation by Rio1 reduces oligomer formation and promotes monomerization, resulting in the most active species. Taken together, these results suggest the activity of Rio1 may be modulated by regulating its oligomerization properties in a conserved mechanism, identifies the first ribosome processing target of toyocamycin and presents the first small molecule inhibitor of Rio1 kinase activity

Non-Invasive In Vivo Imaging of Calcium Signaling in Mice

Rapid and transient elevations of Ca2+ within cellular microdomains play a critical role in the regulation of many signal transduction pathways. Described here is a genetic approach for non-invasive detection of localized Ca2+ concentration ([Ca2+]) rises in live animals using bioluminescence imaging (BLI). Transgenic mice conditionally expressing the Ca2+-sensitive bioluminescent reporter GFP-aequorin targeted to the mitochondrial matrix were studied in several experimental paradigms. Rapid [Ca2+] rises inside the mitochondrial matrix could be readily detected during single-twitch muscle contractions. Whole body patterns of [Ca2+] were monitored in freely moving mice and during epileptic seizures. Furthermore, variations in mitochondrial [Ca2+] correlated to behavioral components of the sleep/wake cycle were observed during prolonged whole body recordings of newborn mice. This non-invasive imaging technique opens new avenues for the analysis of Ca2+ signaling whenever whole body information in freely moving animals is desired, in particular during behavioral and developmental studies

Gendered self-views across 62 countries: a test of competing models

Social role theory posits that binary gender gaps in agency and communion should be larger in less egalitarian countries, reflecting these countries’ more pronounced sex-based power divisions. Conversely, evolutionary and self-construal theorists suggest that gender gaps in agency and communion should be larger in more egalitarian countries, reflecting the greater autonomy support and flexible self-construction processes present in these countries. Using data from 62 countries (N = 28,640), we examine binary gender gaps in agentic and communal self-views as a function of country-level objective gender equality (the Global Gender Gap Index) and subjective distributions of social power (the Power Distance Index). Findings show that in more egalitarian countries, gender gaps in agency are smaller and gender gaps in communality are larger. These patterns are driven primarily by cross-country differences in men’s self-views and by the Power Distance Index (PDI) more robustly than the Global Gender Gap Index (GGGI). We consider possible causes and implications of these findings

Psychometric Properties and Correlates of Precarious Manhood Beliefs in 62 Nations

Precarious manhood beliefs portray manhood, relative to womanhood, as a social status that is hard to earn, easy to lose, and proven via public action. Here, we present cross-cultural data on a brief measure of precarious manhood beliefs (the Precarious Manhood Beliefs scale [PMB]) that covaries meaningfully with other cross-culturally validated gender ideologies and with country-level indices of gender equality and human development. Using data from university samples in 62 countries across 13 world regions (N = 33,417), we demonstrate: (1) the psychometric isomorphism of the PMB (i.e., its comparability in meaning and statistical properties across the individual and country levels); (2) the PMB’s distinctness from, and associations with, ambivalent sexism and ambivalence toward men; and (3) associations of the PMB with nation-level gender equality and human development. Findings are discussed in terms of their statistical and theoretical implications for understanding widely-held beliefs about the precariousness of the male gender role

Effect of toyocamycin on the synthesis of the 70S RNA of a murine retrovirus.

The murine Eveline cell line chronically infected by Friend virus was treated with Toyocamycin (TMC), an adenosin analog and the virions released in the presence of the drug were examined for their RNA. It was found that 70S RNA which was synthesized incorporated Toyocamycin. However, its subunit structure and its poly (A) content were apparently preserved. This incorporation may explain loss of endogenous reverse transcriptase activity