Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements.

Regulatory agencies around the world have committed to reducing or eliminating animal testing for establishing chemical safety. Adverse outcome pathways can facilitate replacement by providing a mechanistic framework for identifying the appropriate non-animal methods and connecting them to apical adverse outcomes. This study separated 11,992 chemicals with curated rat oral acute toxicity information into clusters of structurally similar compounds.

Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea.

TET/JBP enzymes oxidize 5-methylpyrimidines in DNA. In mammals, the oxidized methylcytosines (oxi-mCs) function as epigenetic marks and likely intermediates in DNA demethylation. Here we present a method based on diglucosylation of 5-hydroxymethylcytosine (5hmC) to simultaneously map 5hmC, 5-formylcytosine, and 5-carboxylcytosine at near-base-pair resolution.

Regulation of IL-2 gene expression by Siva and FOXP3 in human T cells.

Background: Severe autoinflammatory diseases are associated with mutations in the Foxp3 locus in both mice and humans. Foxp3 is required for the development, function, and maintenance of regulatory T cells (Tregs), a subset of CD4 cells that suppress T cell activation and inflammatory processes. Siva is a pro-apoptotic gene that is expressed across a range of tissues, including CD4 T cells.