Summary
Peptide neuromodulators are released from a unique organelle: the dense-core vesicle. Dense-core vesicles are generated at the trans-Golgi, and then sort cargo during maturation before being secreted. To identify proteins that act in this pathway, we performed a genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We identified two conserved Rab2-binding proteins: RUND-1, a RUN domain protein, and CCCP-1, a coiled-coil protein. RUND-1 and CCCP-1 colocalize with RAB-2 at the Golgi, and rab-2, rund-1 and cccp-1 mutants have similar defects in sorting soluble and transmembrane dense-core vesicle cargos. RUND-1 also interacts with the Rab2 GAP protein TBC-8 and the BAR domain protein RIC-19, a RAB-2 effector. In summary, a new pathway of conserved proteins controls the maturation of dense-core vesicles at the trans-Golgi network.
This paper examines the relationship between heavy drinking and aggression using quantitative and qualitative data from a Department of Health funded interview study of untreated heavy drinkers living in the largely urban English West Midlands region (n 5 403). Interviews consisted of a combination of forced choice questions and semi-structured discussion. Quantitative data showed high levels of verbal aggression, serious arguments and fights. Significant associations were found between alcohol-related aggression, lower age, number of very heavy drinking days and lower socioeconomic status. Thematic analysis of qualitative data showed that participants considered alcohol to be heavily implicated in aggressive behaviour, but differences exist between quantitative and qualitative findings in terms of the importance of gender. Participants associated aggression with masculinity and youth, but violence involving women and domestic violence were rarely discussed.
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