Repeating the Errors of Our Parents? Family-of-Origin Spouse Violence and Observed Conflict Management in Engaged Couples

Based on a developmental social learning analysis, it was hypothesized that observing parental violence predisposes partners to difficulties in managing couple conflict. Seventy-one engaged couples were assessed on their observation of parental violence in their family of origin. All couples were videotaped discussing two areas of current relationship conflict, and their cognitions during the interactions were assessed using a video-mediated recall procedure. Couples in which the male partner reported observing parental violence (male-exposed couples) showed more negative affect and communication during conflict discussions than couples in which neither partner reported observing parental violence (unexposed couples). Couples in which only the female partner reported observing parental violence (female- exposed couples) did not differ from unexposed couples in their affect or behavior. Female-exposed couples reported more negative cognitions than unexposed couples, but male-exposed couples did not differ from unexposed couples in their reported cognitions

Endocytic profiling of cancer cell models reveals critical factors influencing lipid nanoparticle mediated mRNA delivery and protein expression

Lipid nanoparticles have great potential for delivering nucleic acid-based therapeutics, but low efficiency limits their broad clinical translation. Differences in transfection capacity between in vitro models used for nanoparticle pre-clinical testing is poorly understood. To address this, using a clinically relevant lipid nanoparticle (LNP) delivering mRNA we highlight specific endosomal characteristics in in vitro tumour models that impact on protein expression. A 30-cell line LNP-mRNA transfection screen identified three cells lines having low, medium and high transfection that correlated with protein expression when they were analysed in tumour models. Endocytic profiling of these cell lines identified major differences in endolysosomal morphology, localisation, endocytic uptake, trafficking, recycling, and endolysosomal pH, identified using a novel pH probe. High transfecting cells showed rapid LNP uptake and trafficking through an organised endocytic pathway to lysosomes or rapid exocytosis. Low transfecting cells demonstrated slower endosomal LNP trafficking to lysosomes, and defective endocytic organisation and acidification. Our data establishes that efficient LNP-mRNA transfection relies on an early and narrow endosomal escape window prior to lysosomal sequestration and/or exocytosis. Endocytic profiling should form an important pre-clinical evaluation step for nucleic acid delivery systems to inform model selection and guide delivery system design for improved clinical translation