Aging and Immortality in a Cell Proliferation Model

We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.Comment: 6 pages, 1 figure, 2-column revtex4 format; version 2: final published form; contains various improvements in response to referee comment

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

HIV testing is associated with increased knowledge and reductions in sexual risk behaviours among men in Cape Town, South Africa

HIV testing benefits those who test positive, allowing them to receive treatment, but the benefits for those who test negative remain controversial. We evaluated the impact of testing on HIV knowledge and sexual risk among men in South Africa. Men were recruited from townships outside Cape Town and completed a survey that assessed testing history, knowledge, and sexual behaviours. Among the 820 participants, 516 (63%) reported being tested (82% tested negative, 6% tested positive, and 12% unknown). Compared to those who had never been tested for HIV, men who tested for HIV were more knowledgeable about HIV transmission, but did not differ on sexual risk behaviour. Knowledge moderated the effect of testing on sexual risk such that men reported fewer sexual partners (incidence rate ratio (IRR) = 0.91, 95% CI = 0.84, 0.98) and fewer unprotected anal sex events (IRR = 0.81, 95% CI = 0.66, 1.00) if they had been tested for HIV and were knowledgeable about HIV transmission. For men testing HIV-negative, knowledge predicted fewer sexual risk behaviours. Previous HIV testing is associated with enhanced knowledge, which moderates sexual risk behaviour among South African men living in Cape Town. Results suggest that HIV testing may increase knowledge and lead to reductions in sexual risk even when results are negative.

Heterosexual anal intercourse and HIV infection risks in the context of alcohol serving venues, Cape Town, South Africa

The most efficient sexual behavior for HIV transmission is unprotected receptive anal intercourse. However, it is unclear what role heterosexual unprotected anal sex is playing in the worlds worst HIV epidemics of southern Africa. The objective is to examine the prevalence of heterosexual unprotected anal intercourse among men and women who drink at informal alcohol serving establishments (shebeens) in South Africa. Cross-sectional surveys were collected from a convenience sample of 5037 patrons of 10 shebeens in a peri-urban township of Cape Town, South Africa. Analyses concentrated on establishing the rates of unprotected anal intercourse practiced by men and women as well as the factors associated with practicing anal intercourse. We found that 15% of men and 11% of women reported anal intercourse in the previous month, with 8% of men and 7% of women practicing any unprotected anal intercourse. Multiple logistic regression showed that younger age, having primary and casual sex partners, and meeting sex partners at shebeens were independently associated with engaging in anal intercourse. Mathematical modeling showed that individual risks are significantly impacted by anal intercourse but probably not to the degree needed to drive a generalized HIV epidemic. Anal intercourse likely plays a significant role in HIV infections among a small minority of South Africans who patronize alcohol serving establishments. Heterosexual anal intercourse, the most risky sexual behavior for HIV transmission, should not be ignored in HIV prevention for South African heterosexuals. However, this relatively infrequent behavior should not become the focus of prevention efforts.

Exploring the relationships among food insecurity, alcohol use, and sexual risk taking among men and women living in South African townships

South African townships have among the highest rates of HIV infection in the world. Considerable research on understanding the high rates of HIV transmission in this country has identified alcohol use as a critical factor in driving the HIV epidemic. Although the relationship between alcohol use and sexual risk-taking is well documented, less is known about how other factors, such as food insecurity, might be important in understanding alcohol's role in sexual risk-taking. Furthermore, prior research has highlighted how patterns of alcohol use and sexual risk-taking tend to vary by gender. We examined how food insecurity is related to both alcohol use and sexual risk-taking. We administered anonymous community surveys to men (n = 1,137) and women (n = 458) residing within four contiguous Black African townships outside of Cape Town, South Africa. In multivariate linear regression, we found that food insecurity was related to having higher numbers of male sex partners and condom-protected sex acts among women only. These relationships, however, were fully mediated by women's alcohol use. Among men, we found that food insecurity was negatively related to unprotected sex; that is, men with greater food security reported more unprotected sex acts. Unlike the results found among women, this relationship was not mediated by alcohol use. Food insecurity appears to be an important factor in understanding patterns of sexual risk-taking in regards to gender and alcohol use, and may serve as an important point of intervention for reducing HIV transmission rates.