Quantitative in vitro to in vivo extrapolation of genotoxicity data provides protective estimates of in vivo dose.

Genotoxicity assessment is a critical component in the development and evaluation of chemicals. Traditional genotoxicity assays (i.e.

Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy.

Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that metal response element binding transcription factor 2/polycomblike 2 (MTF2/PCL2) plays a fundamental role in the polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML.

Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis.

Polycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 to specific genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions.

Genotypes of Mycobacterium bovis strains isolated from domestic animals and wildlife in Canada in 1985-2015.

Two internationally recognised and standardised genotyping methods, mycobacterial interspersed repetitive unit and variable number tandem repeat analysis (MIRU-VNTR) and spoligotyping, were applied to characterise genetic variations among 137 Mycobacterium bovis isolates recovered from Canadian domestic and wild animals during 1985-2015. Spoligotyping generated seven types that were discriminated further into12 MIRU-VNTR types. The discriminatory power indexes were estimated as 0.

Comparing BMD-derived genotoxic potency estimations across variants of the transgenic rodent gene mutation assay.

There is growing interest in quantitative analysis of in vivo genetic toxicity dose-response data, and use of point-of-departure (PoD) metrics such as the benchmark dose (BMD) for human health risk assessment (HHRA). Currently, multiple transgenic rodent (TGR) assay variants, employing different rodent strains and reporter transgenes, are used for the assessment of chemically-induced genotoxic effects in vivo. However, regulatory issues arise when different PoD values (e.