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“Late onset Alzheimer’s disease (LOAD) is typical of the majority of Alzheimer’s disease (AD) cases (similar to 90%), and has no clear genetic association. Previous studies from our lab suggest

that an epigenetic component could be involved. Developmental exposure p38 MAPK inhibitor of primates and rodents to lead (Pb) predetermined the expression of AD-related genes, such as the amyloid-beta precursor protein (A beta PP), later in life. In addition to A beta PP, the preponderance of genes that were reprogrammed was rich in CpG dinucleotides implicating DNA methylation and chromatin restructuring in their regulation. To examine the involvement of epigenetic intermediates in Pb-induced alterations in gene expression, differentiated SH-SY5Y cells were exposed to a series of Pb concentrations (5-100 mu M) for 48 h and were analyzed for the protein expression of A beta PP, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), specificity protein

1 and 3 (Sp1, Sp3) and epigenetic intermediates like DNA methyltransferase 1, 3a (Dnmt1, Dnmt3a) and methyl CpG binding protein 2 (MeCP2) involved in DNA methylation six days after the exposure had ceased. Western blot analysis indicated a significant latent elevation in AD biomarkers as well as the transcription factors Sp1 and Sp3, accompanied by a significant ML323 concentration reduction in the protein levels of DNA methylating enzymes. RT-PCR analysis of Dnmt1, Dnmt3a and MeCP2 indicated a significant down-regulation mTOR inhibitor of the mRNA levels. These data suggest that Pb interferes with DNA methylating capacity in these cells, thus altering the expression of AD-related genes.”
“Background: In Uganda, malaria and lymphatic filariasis (causative agent Wuchereria bancrofti) are transmitted by the same vector species of Anopheles mosquitoes, and thus are likely to share common environmental risk factors and overlap in geographical space. In a comprehensive nationwide survey in 2000-2003 the geographical distribution of W. bancrofti was assessed by screening school-aged children for circulating filarial antigens (CFA). Concurrently, blood

smears were examined for malaria parasites. In this study, the resultant malariological data are analysed for the first time and the CFA data re-analysed in order to identify risk factors, produce age-stratified prevalence maps for each infection, and to define the geographical patterns of Plasmodium sp. and W. bancrofti co-endemicity.

Methods: Logistic regression models were fitted separately for Plasmodium sp. and W. bancrofti within a Bayesian framework. Models contained covariates representing individual-level demographic effects, school-level environmental effects and location-based random effects. Several models were fitted assuming different random effects to allow for spatial structuring and to capture potential non-linearity in the malaria-and filariasis-environment relation.