The circadian clock consists of a feedback loop in which clock genes are rhythmically expressed, giving rise to cycling levels of RNA and proteins. Four of the five circadian genes identified to date influence responsiveness to freebase cocaine in the fruit fly, Drosophila melanogaster. Sensitization to repeated cocaine exposures, a phenomenon also seen in humans and animal models and associated with enhanced drug craving, is eliminated in flies mutant for period, clock, cycle, and doubletime, but not in flies lacking the gene timeless. Flies that do not sensitize owing to lack of these genes do not show the induction of tyrosine decarboxylase normally seen after cocaine exposure. These findings indicate unexpected roles for these genes in regulating cocaine sensitization and indicate that they function as regulators of tyrosine decarboxylase.

No abstract

Sensitization to repeated doses of psychostimulants is thought to be an important component underlying the addictive process in humans [1] [2] [3] [4]. In all vertebrate animal models, including humans [5], and even in fruit flies, sensitization is observed after repeated exposure to volatilized crack cocaine [6]. In vertebrates, sensitization is thought to be initiated by processes occurring in brain regions that contain dopamine cell bodies [2] [7]. Here, we show that modulated cell signaling in the Drosophila dopamine and serotonin neurons plays an essential role in cocaine sensitization. Targeted expression of either a stimulatory (Galpha(s)) or inhibitory (Galpha(i)) Galpha subunit, or tetanus toxin light chain (TNT) in dopamine and serotonin neurons of living flies blocked behavioral sensitization to repeated cocaine exposures. These flies showed alterations in their initial cocaine responsiveness that correlated with compensatory adaptations of postsynaptic receptor sensitivity. Finally, repeated drug stimulation of a nerve cord preparation that is postsynaptic to the brain amine cells failed to induce sensitization, further showing the importance of presynaptic modulation in sensitization.

Since the 1940s, French Guiana has implemented vector control to contain or eliminate malaria, yellow fever, and, recently, dengue, chikungunya, and Zika. Over time, strategies have evolved depending on the location, efficacy of the methods, development of insecticide resistance, and advances in vector control techniques. This review summarises the history of vector control in French Guiana by reporting the records found in the private archives of the Institute Pasteur in French Guiana and those accessible in libraries worldwide. This publication highlights successes and failures in vector control and identifies the constraints and expectations for vector control in this French overseas territory in the Americas.

The effective use of geospatial data and technologies to collect, manage, analyze, model, and visualize geographic data has great potential to improve data-driven decision-making for immunization programs. This article presents a theory of change for the use of geospatial technologies for immunization programming—a framework to illustrate the ways in which geospatial data and technologies can contribute to improved immunization outcomes and have a positive impact on childhood immunization coverage rates in low- and middle-income countries. The theory of change is the result of a review of the state of the evidence and literature; consultation with implementers, donors, and immunization and geospatial technology experts; and a review of country-level implementation experiences. The framework illustrates how the effective use of geospatial data and technologies can help immunization programs realize improvements in the number of children immunized by producing reliable estimates of target populations, identifying chronically missed settlements and locations with the highest number of zero-dose and under-immunized children, and guiding immunization managers with solutions to optimize resource distribution and location of health services. Through these direct effects on service delivery, geospatial data and technologies can contribute to the strengthening of the overall health system with equity in immunization coverage. Recent implementation of integrated geospatial data and technologies for the immunization program in Myanmar demonstrate the process that countries may experience on the path to achieving lasting systematic improvements. The theory of change presented here may serve as a guide for country program managers, implementers, donors, and other stakeholders to better understand how geospatial tools can support immunization programs and facilitate integrated service planning and equitable delivery through the unifying role of geography and geospatial data.