Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior

Prevalence and predictors of chronic kidney disease of undetermined causes (CKDu) in Western Kenya’s “sugar belt”: a cross-sectional study

Abstract Background Epidemics of chronic kidney disease of undetermined causes (CKDu) among young male agricultural workers have been observed in many tropical regions. Western Kenya has similar climatic and occupational characteristics as many of those areas. The study objectives were to characterize prevalence and predictors of CKDu, such as, HIV, a known cause of CKD, in a sugarcane growing region of Kenya; and to estimate prevalence of CKDu across occupational categories and evaluate if physically demanding work or sugarcane work are associated with reduced eGFR. Methods The Disadvantaged Populations eGFR Epidemiology Study (DEGREE) protocol was followed in a cross-sectional study conducted in Kisumu County, Western Kenya. Multivariate logistic regression was performed to identify predictors of reduced eGFR. Results Among 782 adults the prevalence of eGFR < 90 was 9.85%. Among the 612 participants without diabetes, hypertension, and heavy proteinuria the prevalence of eGFR < 90 was 8.99% (95%CI 6.8%, 11.5%) and 0.33% (95%CI 0.04%, 1.2%) had eGFR < 60. Among the 508 participants without known risk factors for reduced eGFR (including HIV), the prevalence of eGFR < 90 was 5.12% (95%CI 3.4%, 7.4%); none had eGFR < 60. Significant risk factors for reduced eGFR were sublocation, age, body mass index, and HIV. No association was found between reduced eGFR and work in the sugarcane industry, as a cane cutter, or in physically demanding occupations. Conclusion CKDu is not a common public health problem in this population, and possibly this region. We recommend that future studies should consider HIV to be a known cause of reduced eGFR. Factors other than equatorial climate and work in agriculture may be important determinants of CKDu epidemics