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Human exposure to polycyclic aromatic hydrocarbons (PAH) is a significant public health problem that will worsen with a warming climate and increased large-scale wildfires. Here, we characterize an epigenetic memory at the cytochrome P450 1 A (CYP1A) gene in wild Fundulus heteroclitus that have adapted to chronic, extreme PAH pollution. In wild-type fish, CYP1A is highly induced by PAH. In PAH-tolerant fish, CYP1A induction is blunted. Since CYP1A metabolically activates PAH, this memory protects these fish from PAH-mediated cancer. However, PAH-tolerant fish reared in clean water recover CYP1A inducibility, indicating a non-genetic effect. We observed epigenetic control of this reversible memory of generational PAH stress in F1 PAH-tolerant embryos. We detected a bivalent domain in the CYP1A promoter enhancer comprising both activating and repressive histone post-translational modifications. Activating modifications, relative to repressive ones, showed greater increases in response to PAH in sensitive embryos, relative to tolerant, consistent with greater gene activation. PAH-tolerant adult fish showed persistent induction of CYP1A long after exposure cessation, which is consistent with defective CYP1A shutoff. These results indicate that PAH-tolerant fish have epigenetic protection against PAH-induced cancer in early life that degrades in response to continuous gene activation. [ABSTRACT FROM AUTHOR]

I. Introduction Social media (1) has taken the world by storm. (2) As of 2016, over three billion people in the world are active Internet users, (1) and over two [...]

The mutagenesis of various complexes, including lysine 62, asparagine 64 and conserved region 1 is found to highly reduce the activity of the human ecto-ATPase (NTPDase) that contains several conserved motifs and lysine and arginine residues. The results show that most of the residues in the complex are essential for protein expression and that the substitution of such acidic residues by alanine leads to a decreased divalent ion binding.

In this study we examined the effects of exposure to the antiandrogenic fungicide vindozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of [...]

Background: The changing diabetes in children (CDiC) project is a public‐private partnership implemented by Novo Nordisk, to improve access to diabetes care for children with type 1 diabetes. This paper outlines the findings from an evaluation of CDiC in Bangladesh and Kenya, assessing whether CDiC has achieved its objectives in each of six core program components. Research design and methods: The Rapid Assessment Protocol for Insulin Access (RAPIA) framework was used to analyze the path of insulin provision and the healthcare infrastructure in place for diagnosis and treatment of diabetes. The RAPIA facilitates a mixed‐methods approach to multiple levels of data collection and systems analysis. Information is collected through questionnaires, in‐depth interviews and focus group discussions, site visits, and document reviews, engaging a wide range of stakeholders (N = 127). All transcripts were analyzed thematically. Results: The CDiC scheme provides a stable supply of free insulin to children in implementing facilities in Kenya and Bangladesh, and offers a comprehensive package of pediatric diabetes care. However, some elements of the CDiC program were not functioning as originally intended. Transitions away from donor funding and toward government ownership are a particular concern, as patients may incur additional treatment costs, while services offered may be reduced. Additionally, despite subsidized treatment costs, indirect costs remain a substantial barrier to care. Conclusion: Public‐private partnerships such as the CDiC program can improve access to life‐saving medicines. However, our analysis found several limitations, including concerns over the sustainability of the project in both countries. Any program reliant on external funding and delivered in a high‐turnover staffing environment will be vulnerable to sustainability concerns. [ABSTRACT FROM AUTHOR]