Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Implementation Failures as Learning Pathologies

This is the author accepted manuscript. The final version is available from Palgrave Macmillan via the DOI in this recordIn many ways, the study of implementation is the study of policy failure. After all, scholarly preoccupation with the causes of policy pathologies motivated the first wave of implementation studies in the post-war decades (Derthick 1972; Pressman and Wildavsky 1973). Examination of policy learning has followed a similar trajectory. The first (and now classic) studies linking learning and policy change were central to the serious efforts to create a systematic approach to policy sciences (Deutsch 1966; Heclo 1974; Lindblom 1965). Recent developments re-appraising policy learning, and in particular spotlighting its varieties and its limitations, enable a clearer connection with implementation fiascos (Howlett 2012; Dunlop and Radaelli 2013, 2018). New conceptualisations of policy learning point to the importance of scope conditions which render learning deep or shallow, functional or dysfunctional (Dunlop 2017). In this chapter, the implementation failure-policy learning nexus is explored at three analytical levels: micro level of individual policy actors; meso level of groups and organisational bodies; and finally, the macro, systemic level