Disruption of microtubule stability in mammalian cells may lead to genotoxicity and carcinogenesis. The ability to screen for microtubule destabilization or stabilization is therefore a useful and efficient approach to aid in the design of molecules that are safe for human health. In this study, we developed a high-throughput 384-well assay combining immunocytochemistry with high-content imaging to assess microtubule disruption in the metabolically competent human liver cell line: HepaRG.
View Article and Find Full Text PDFRegulatory genetic toxicology focuses on DNA damage and subsequent gene mutations. However, genotoxic agents can also affect epigenetic marks, and incorporation of epigenetic data into the regulatory framework may thus enhance the accuracy of risk assessment. Additionally, epigenetic alterations may identify non-genotoxic carcinogens that are not captured with the current battery of tests.
View Article and Find Full Text PDFThe development of safe crop protection products is a complex process that traditionally relies on intensive animal use for hazard identification. Methods that capture toxicity in early stages of agrochemical discovery programs enable a more efficient and sustainable product development pipeline. Here, we explored whether the zebrafish model can be leveraged to identify mammalian-relevant toxicity.
View Article and Find Full Text PDFBackground: Prior studies have shown that individuals and their peers often have similar substance use behaviors, but the mechanisms driving these similarities - particularly in rural settings, are not well understood. The primary objectives of this analysis are to (1) identify factors that contribute to relationship turnover and maintenance within a rural network of persons who use drugs (PWUD), (2) determine whether assimilation and/or homophily shape participants use of injection drugs, heroin, and stimulants (methamphetamine and cocaine), and (3) assess the extent that these mechanisms influence networks ties and/or behaviors and whether these effects vary across time.
Methods: Sociometric network data were collected from a cohort of PWUD in rural Eastern Kentucky at baseline (2008-2010) and at four follow-up visits conducted approximately semiannually.