Lysine-based surfactants in nanovesicle formulations: the role of cationic charge position and hydrophobicity in in vitro cytotoxicity and intracellular delivery

Understanding nanomaterial interactions within cells is of increasing importance for assessing their toxicity and cellular transport. Here, we developed nanovesicles containing bioactive cationic lysine-based amphiphiles, and assessed whether these cationic compounds increase the likelihood of intracellular delivery and modulate toxicity. We found different cytotoxic responses among the formulations, depending on surfactant, cell line and endpoint assayed. The induction of mitochondrial dysfunction, oxidative stress and apoptosis were the general mechanisms underlying cytotoxicity. Fluorescence microscopy analysis demonstrated that nanovesicles were internalized by HeLa cells, and evidenced that their ability to release endocytosed materials into cell cytoplasm depends on the structural parameters of amphiphiles. The cationic charge position and hydrophobicity of surfactants determine the nanovesicle interactions within the cell and, thus, the resulting toxicity and intracellular behavior after cell uptake of the nanomaterial. The insights into some toxicity mechanisms of these new nanomaterials contribute to reducing the uncertainty surrounding their potential health hazards

Life Course Offending Pathways Across Gender and Race/Ethnicity

Purpose This paper aims to refine our understanding of life course offending patterns across gender and race/ethnicity and to advance work in this area by examining how gender and race/ethnicity interact to influence life course offending patterns. Methods We use criminal justice system data to construct a longitudinal offending cohort that includes all individuals born in 1983/1984 with at least one court finalization for a criminal offense in the state of Queensland between the ages of 10 and 25 years. The data include 41,280 offenders (25.6 % female; 8.9 % Indigenous Australian) responsible for 209,872 offenses (M?=?5.08, SD?=?12.31). Coupling these data with state-level census data for those born in 1983/1984 (N?=?129,782), we estimate cohort offending rates overall and disaggregated by gender and race/ethnicity both independently and jointly. Focusing on the offenders, we use semiparametric group-based modeling to identify the number and longitudinal distributions of offending trajectories within the cohort and compare how subgroups defined by gender, Indigenous status, and their combination sort into these trajectories. Results Most of the birth cohort has little to no contact with the criminal justice system through age 25. However, patterns are not uniform across gender or race/ethnicity, with males and Indigenous Australians most likely to fit the serious and chronic offending trajectories. Gender and race/ethnicity also interact to influence offending patterns with non-Indigenous females significantly more likely than any other group to avoid system contact, while Indigenous males have comparatively exaggerated rates of contact. Moreover, Indigenous females offend in ways more similar to non-Indigenous males than females and, in some instances, evidence even more serious offending. Conclusions Developmental and life course models should highlight not just the operant developmental dynamics across key life stages or the relevant age-graded risk and protective factors at play, but also how gender and race/ethnicity condition these processes both independently and jointly.Arts, Education & Law Group, School of Criminology and Criminal JusticeNo Full Tex