Chromosome length and gene density contribute to micronuclear membrane stability.

Micronuclei are derived from missegregated chromosomes and frequently lose membrane integrity, leading to DNA damage, innate immune activation, and metastatic signaling. Here, we demonstrate that two characteristics of the trapped chromosome, length and gene density, are key contributors to micronuclei membrane stability and determine the timing of micronucleus rupture. We demonstrate that these results are not due to chromosome-specific differences in spindle position or initial protein recruitment during post-mitotic nuclear envelope assembly. Micronucleus size strongly correlates with lamin B1 levels and nuclear pore density in intact micronuclei, but, unexpectedly, lamin B1 levels do not completely predict nuclear lamina organization or membrane stability. Instead, small gene-dense micronuclei have decreased nuclear lamina gaps compared to large micronuclei, despite very low levels of lamin B1. Our data strongly suggest that nuclear envelope composition defects previously correlated with membrane rupture only partly explain membrane stability in micronuclei. We propose that an unknown factor linked to gene density has a separate function that inhibits the appearance of nuclear lamina gaps and delays membrane rupture until late in the cell cycle.

An exploration into "do-it-yourself" (DIY) e-liquid mixing: Users' motivations, practices and product laboratory analysis.

BACKGROUND: E-liquids are commercially available and manufactured, however some users of e-cigarettes prefer to prepare them at home (Do-it-Yourself; DIY) using individual ingredients. To date there is a paucity of research on how and why users make their own e-liquids. METHODS: Forty-one European and US based exclusive users of e-cigarettes (ex-smokers) were individually interviewed. Structured interviews focused on motivations for home-mixing, practices, buying habits and broader themes around reasons for long-term vaping. We also measured nicotine and solvent concentrations and analysed 33 DIY e-liquids collected from 16 participants for nicotine, solvents, flavourings, and potentially harmful chemicals. RESULTS: There were four main reasons for DIY: 1) economical (financial savings), 2) self-control over manufacturing process, 3) novelty, fun and 4) higher nicotine concentrations. Twelve out of 16 participants achieved nicotine concentration within 20% of their intended limit. Samples from five participants were above the EU Tobacco Products Directive's (TPD) 20 mg/ml nicotine concentration upper limit. Most samples contained more vegetable glycerine (VG) than propylene glycol (PG) and the most commonly used flavourings were dessert, e.g., vanilla and caramel. Chemical analysis also revealed presence of several potentially harmful chemicals and respiratory irritants, including cinnamaldehyde, benzaldehyde, and acetoin. CONCLUSION: DIY may offer users of e-cigarettes a long-term affordable practical method of vaping. Recommended safety advice needs to reflect actual and fast moving user behaviour.