The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors.

Centrosomes are organelles that nucleate microtubules via the activity of gamma-tubulin ring complexes (γ-TuRC). In the developing brain, centrosome integrity is central to the progression of the neural progenitor cell cycle, and its loss leads to microcephaly. We show that NPCs maintain centrosome integrity via the endocytic adaptor protein complex-2 (AP-2). NPCs lacking AP-2 exhibit defects in centrosome formation and mitotic progression, accompanied by DNA damage and accumulation of p53. This function of AP-2 in regulating the proliferative capacity of NPCs is independent of its role in clathrin-mediated endocytosis and is coupled to its association with the GCP2, GCP3, and GCP4 components of γ-TuRC. We find that AP-2 maintains γ-TuRC organization and regulates centrosome function at the level of MT nucleation. Taken together, our data reveal a novel, noncanonical function of AP-2 in regulating the proliferative capacity of NPCs and open new avenues for the identification of novel therapeutic strategies for the treatment of neurodevelopmental and neurodegenerative disorders with AP-2 complex dysfunction.

Lactate acidosis and simultaneous recruitment of TGF-ß leads to alter plasticity of hypoxic cancer cells in tumor microenvironment.

Lactate acidosis is often observed in the tumor microenvironment (TME) of solid tumors. This is because glucose breaks down quickly via glycolysis, causing lactate acidity. Lactate is harmful to healthy cells, but is a major oncometabolite for solid cancer cells that do not receive sufficient oxygen. As an oncometabolite, it helps tumor cells perform different functions, which helps solid hypoxic tumor cells spread to other parts of the body. Studies have shown that the acidic TME contains VEGF, Matrix metalloproteinases (MMPs), cathepsins, and transforming growth factor-ß (TGF-ß), all of which help spread in direct and indirect ways. Although each cytokine is important in its own manner in the TME, TGF-ß has received much attention for its role in metastatic transformation. Several studies have shown that lactate acidosis can cause TGF-ß expression in solid hypoxic cancers. TGF-ß has also been reported to increase the production of fatty acids, making cells more resistant to treatment. TGF-ß has also been shown to control the expression of VEGF and MMPs, which helps solid hypoxic tumors become more aggressive by helping them spread and create new blood vessels through an unknown process. The role of TGF-ß under physiological conditions has been described previously. In this study, we examined the role of TGF-ß, which is induced by lactate acidosis, in the spread of solid hypoxic cancer cells. We also found that TGF-ß and lactate work together to boost fatty acid production, which helps angiogenesis and invasiveness.

Exogenous ATP modulates PGE2 release in macrophages through sustained phosphorylation of CDK9 and p38 MAPK.

An important mediator of inflammation is prostaglandin E2 (PGE2 ), whose levels are determined by the activity of the enzyme cyclooxygenase (COX). Of the two isoforms of the enzyme, COX-2 has been shown to be induced in macrophages during inflammation. Although general COX inhibitors, belonging to the class of nonsteroidal anti-inflammatory drugs, or specific COX-2 inhibitors, called coxibs, are useful in the control of acute inflammation, adverse reactions were seen when used chronically in the treatment of rheumatoid arthritis or neurodegenerative diseases. Extracellular ATP (eATP) has been reported as a damage-associated molecular pattern signal. In this report, we show that eATP synergistically increases the levels of COX-2 enzyme and PGE2 in LPS-activated RAW264.7 macrophages and human monocytes. Activation of macrophages also occurred when cultured in media obtained from dying neurons that contained higher levels of ATP. We show that eATP increases the levels of COX-2 protein, which is sustained up to 36 h poststimulation. This is in turn due to sustained levels of phosphorylated, or activated, cyclin-dependent kinase 9 and p38 MAPK in ATP-treated cells compared to LPS-stimulated cells. The eATP-dependent increase in COX-2/PGE2 levels in LPS-activated RAW264.7 cells could be abolished using antagonists for purinergic P2X7 -and P2Y6 receptors. Similarly, the increase in COX-2/PGE2 levels in the peritoneum of LPS-treated mice could be significantly abolished in mice that were preinjected with the nonspecific P2 receptor antagonist, suramin. P2 receptor antagonists, therefore, should be explored in our search for an ideal anti-inflammatory candidate.

Prevalence and Predictors of Self-Reported Consistent Condom Usage among Male Clients of Female Sex Workers in Tamil Nadu, India.

Clients of female sex workers (FSWs) possess a high potential of transmitting HIV and other sexually transmitted infections from high risk FSWs to the general population. Promotion of safer sex practices among the clients is essential to limit the spread of HIV/AIDS epidemic. The aim of this study is to estimate the prevalence of consistent condom use (CCU) among clients of FSWs and to assess the factors associated with CCU in Tamil Nadu. 146 male respondents were recruited from the hotspots who reportedly had sex with FSWs in exchange for cash at least once in the past one month. Data were analyzed using bivariate and multivariate methods. Overall, 48.6 and 0.8 percent clients consistently used condoms in the past 12 months with FSWs and regular partners, respectively. Logistic regression showed that factors such as education, peers' use of condoms, and alcohol consumption significantly influenced clients' CCU with FSWs. Strategies for safe sex-behaviour are needed among clients of FSWs in order to limit the spread of HIV/AIDS epidemic in the general population. The role of peer-educators in experience sharing and awareness generation must also be emphasized.

Sexual behavior among unmarried business process outsourcing employees in Chennai: gender differences and correlates associated with it.

BACKGROUND: Premarital sex is often associated with high risk sexual behavior such as early age of initiation, multiple partners and inconsistent condom use. Evidence shows that such sexual behavior pre-disposes to sexually transmitted diseases including HIV. OBJECTIVES: This paper tried to investigate the correlates of premarital sexual behavior among male and female business process outsourcing (BPO) employees to highlight the gender differences that exist in relation to it. MATERIALS AND METHODS: Data were collected from 526 unmarried BPO employees during behavioral surveillance survey in Chennai, in the year 2009. RESULTS: The results showed that about one-third of respondents (males - 39.6%, females - 26.1%) had experienced premarital sex. Men reported having had their first sexual intercourse at 12 years and women at 16 years of age. While the prevalence of premarital sex was found to be high, the percentage using a condom during last sex was also high, especially, among the female employees (82.4%). Logistic regression showed that monthly individual income, work in shifts, migration, peer influence and friends with previous sexual experience were significant predictors of premarital sex among the male BPO employees. Visit to night clubs was significantly associated with a higher prevalence of premarital sex among the female employees. CONCLUSIONS: The study concludes that there is a significant gender dimension in the premarital sexual behavior among the BPO employees and that even as the sexual behavior of the young people is transitioning; their ability to negotiate safe sex behavior is also increasing. It is recommended to enhance efforts to advocate safe sex behavior among young adults employed in the BPO industry.

Knowledge of antiretrovirals in preventing parentto-child-transmission of HIV: a cross-sectional study among women living with HIV in Tamil Nadu, India.

BACKGROUND: India is amongst the top 10 countries in the world currently with the highest burden of pregnant women living with HIV and nearly 80% of these women do not receive antiretroviral (ARV) drugs to prevent parent-to-child transmission (PTCT) of HIV. The aim of this study was to estimate HIV-infected women's awareness on PTCT and knowledge of ARVs as a measure to prevent PTCT. METHODS: This was a descriptive, cross-sectional study in which a total of 986 women with HIV aged 18 years and above were interviewed in 13 high HIV prevalence districts of Tamil Nadu, South India. Data were analysed using descriptive, bivariate and multivariate methods. RESULTS: Nearly one fifth (18.8%) of the women with HIV had not heard of PTCT and 40% did not know that ARVs could prevent PTCT. In addition, 39.3% were not aware of the timing of PTCT; 50.4% reported intrauterine and intrapartum and 13.7% mentioned breastfeeding period as the possible timings of PTCT of HIV. Multivariate analysis showed that single/never married women had lower knowledge of PTCT. Also, those who had undergone a prior training on reproductive and child health (RCH) and those who discussed RCH issues with their partners were more likely to have higher knowledge. CONCLUSION: Considering the risk of HIV transmission from HIV-infected women to their children, the knowledge level of PTCT among them is low. Appropriate strategies to generate awareness among women with HIV need be introduced to help them make informed decisions.