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Chagas disease is a chronic infection that kills approximately 12,000 people a year. Mass migration of chronically infected and asymptomatic persons has caused globalization of Chagas disease and has made nonvectorial infection, including vertical and blood-borne transmission, more of a threat to human communities than vectorial infection. To control transmission, it is essential to test all pregnant women living in endemic countries and all pregnant women having migrated from, or having lived in, endemic countries. All children born to seropositive mothers should be tested not only within the first month of life but also at ~6 months and ~12 months of age. The diagnosis is made by identification of the parasite in blood before the age of 6 months and by identification of the parasite in blood and/or positive serology after 10 months of age. Follow up for a year is essential as a significant proportion of cases are initially negative and are only detected at a later stage. If the condition is diagnosed and treated early, the clinical response is excellent and the majority of cases are cured.

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The study of genomic organization and regulatory elements of rRNA genes in metazoan paradigmatic organisms has led to the most accepted model of rRNA gene organization in eukaryotes. Nevertheless, the rRNA genes of microbial eukaryotes have also been studied in considerable detail and their atypical structures have been considered as exceptions. However, it is likely that these organisms have preserved variations in the organization of a versatile gene that may be seen as living records of evolution. Here, we review the organization of the main rRNA transcription unit (rDNA) and the 5S rRNA genes (5S rDNA). These genes are reiterated in the genome of microbial eukaryotes and may be coded alone, in tandem repeats, linked to each other or linked to other genes. They may be found in the chromosome or extrachromosomally in linear or circular units. rDNA coding regions may contain introns, sequence insertions, protein-coding genes or additional spacers. The 5S rDNA can be found in tandem repeats or genetically linked to genes transcribed by RNA polymerases I, II or III. Available information from about a hundred microbial eukaryotes was used to review the unexpected diversity in the genomic organization of rRNA genes.

Previous work has shown the functions associated with activation of dopamine presynaptic receptors in some substantia nigra pars reticulata (SNr) afferents: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D1-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) Subthalamonigral terminals posses D1- and D2-class receptors where D1-class receptor activation enhances and D2-class receptor activation decreases excitatory postsynaptic currents. Here we report that pallidonigral afferents posses D2-class receptors (D3 and D4 types) that decrease inhibitory synaptic transmission via presynaptic modulation. No action of D1-class agonists was found on pallidonigral synapses. In contrast, administration of D1-receptor antagonists greatly decreased striatonigral IPSCs in the same preparation, suggesting that tonic dopamine levels help in maintaining the function of the striatonigral (direct) pathway. When both D3 and D4 type receptors were blocked, pallidonigral IPSCs increased in amplitude while striatonigral connections had no significant change, suggesting that tonic dopamine levels are repressing a powerful inhibition conveyed by pallidonigral synapses (a branch of the indirect pathway). We then blocked both D1- and D2-class receptors to acutely decrease direct pathway (striatonigral) and enhance indirect pathways (subthalamonigral and pallidonigral) synaptic force. The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models. These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.

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