SummaryAccurately predicting an outcome requires that animals learn supporting and conflicting evidence from sequential experience. In mammals and invertebrates, learned fear responses can be suppressed by experiencing predictive cues without punishment, a process called memory extinction. Here, we show that extinction of aversive memories in Drosophila requires specific dopaminergic neurons, which indicate that omission of punishment is remembered as a positive experience. Functional imaging revealed co-existence of intracellular calcium traces in different places in the mushroom body output neuron network for both the original aversive memory and a new appetitive extinction memory. Light and ultrastructural anatomy are consistent with parallel competing memories being combined within mushroom body output neurons that direct avoidance. Indeed, extinction-evoked plasticity in a pair of these neurons neutralizes the potentiated odor response imposed in the network by aversive learning. Therefore, flies track the accuracy of learned expectations by accumulating and integrating memories of conflicting events.

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Adolescence is a time for exploration and risk-taking; in today's urban environment, with the twin threats of substance abuse and HIV/AIDS, the stakes are particularly high. This paper describes a community-based participatory research project to design, implement, and evaluate a faith-based substance abuse and HIV/AIDS prevention program for African-American adolescents. A coalition of university-based investigators and African-American church member stakeholders collaborated on all aspects of Project BRIDGE, the 3-year intervention to reduce substance abuse and HIV/AIDS in African-American adolescents. Our results support the use of community-based participatory research to create desirable change in this setting. Adolescents who participated in Project BRIDGE reported significantly less marijuana and other drug use and more fear of AIDS than a comparison group. Project BRIDGE has been designated an official ministry of the church and the program has been extended to others in the larger metropolitan community. The church now has a well-trained volunteer staff University faculty developed skills in negotiating with community-based settings. The coalition remains strong with plans for continued collaborative activities.

Pigment gallstones are a common clinical complication of sickle cell (SS) disease. Genetic variation in the promoter of uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) underlies Gilbert syndrome, a chronic form of unconjugated hyperbilirubinemia, and appears to be a risk factor for gallstone formation. We investigated the association between UGT1A1 (TA) n genotype, hyperbilirubinemia, and gallstones in a sample of Jamaicans with SS disease. Subjects were from the Jamaican Sickle Cell Cohort Study (cohort sample, n ‫؍‬ 209) and the Sickle Cell Clinic at the University of the West Indies, Kingston, Jamaica (clinic sample, n ‫؍‬ 357). The UGT1A1 (TA) n promoter region was sequenced in 541 SS disease subjects and 111 healthy controls (control sample). Indirect bilirubin levels for (TA) 7 /(TA) 7 and (TA) 7 /(TA) 8 genotypes were elevated compared with (TA) 6 /(TA) 6 (clinic sample, P < 10 ؊5 ; cohort sample, P < 10 ؊3