Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Vos

The subjective well-being political paradox: Evidence from Latin America

The subjective well-being political paradox describes the observation that individuals are on average more satisfied with their lives in welfare states than under right-leaning (conservative) governments, which are less likely to promote welfare policies; however, at the individual level, people who identify as leaning politically more to the right show higher levels of life satisfaction than those who describe themselves as leaning to the left. This subjective well-being political paradox has previously been observed in Europe. The present study investigates whether this paradox can also be found across 18 Latin American countries by using data from 9 waves of the Latinobarómetro survey. In addition to life satisfaction, we further consider respondents’ self-rated ability to meet their financial needs in a satisfactory manner, which can be seen as a proxy for satisfaction with income. Latin America is an interesting region to study this question because of its political history and the emergence of left-leaning governments during the last fifteen years. We find that people report higher life satisfaction and a better ability to meet their financial needs under left-leaning governments compared to centre and right-leaning governments. In contrast, conservative individuals report higher financial and overall well-being than liberal individuals, which confirms the subjective well-being political paradox that was also found in Europe. Our analysis includes controls for macroeconomic indicators, such as inflation and unemployment rates and GDP per capita as well as socio-demographic factors

DNA pooling: A tool for large-scale association studies

DNA pooling is a practical way to reduce the cost of large-scale association studies to identify susceptibility loci for common diseases. Pooling allows allele frequencies in groups of individuals to be measured using far fewer PCR reactions and genotyping assays than are used when genotyping individuals. Here, we discuss recent developments in quantitative genotyping assays and in the design and analysis of pooling studies. Sophisticated pooling designs are being developed that can take account of hidden population stratification, confounders and inter-loci interactions, and that allow the analysis of haplotypes.link_to_subscribed_fulltex

Long-Term Cigarette Smoking Trajectories Among HIV-Seropositive and Seronegative MSM in the Multicenter AIDS Cohort Study

OBJECTIVE: To examine the association between demographic characteristics and long-term smoking trajectory group membership among HIV-seropositive and HIV-seronegative men who have sex with men (MSM). METHODS: A cohort of 6,552 MSM from the Multicenter AIDS Cohort Study (MACS) were asked detailed information about their smoking history since their last follow-up. Group-based trajectory modeling was used to examine smoking behavior and identify trajectory group membership. Because participants enrolled after 2001 were more likely to be younger, HIV-seronegative, non-Hispanic black, and have a high school diploma or less, we also assessed time of enrollment in our analysis. RESULTS: Participants were grouped into 4 distinct smoking trajectory groups: persistent nonsmoker (n=3,737 [55.9%]), persistent light smoker (n=663 [11.0%]), heavy smoker to nonsmoker (n=531 [10.0%]), and persistent heavy smoker (n=1,604 [23.1%]). Compared with persistent nonsmokers, persistent heavy smokers were associated with being enrolled in 2001 and later (adjusted odds ratio [aOR], 2.35; 95% CI, 2.12-2.58), having a high school diploma or less (aOR, 3.22; 95% CI, 3.05-3.39), and being HIV-seropositive (aOR, 1.17; 95% CI, 1.01-1.34). These associations were statistically significant across all trajectory groups for time of enrollment and education but not for HIV serostatus. CONCLUSIONS: The overall decrease of smoking as shown by our trajectory groups is consistent with the national trend. Characteristics associated with smoking group trajectory membership should be considered in the development of targeted smoking cessation interventions among MSM and people living with HIV