Repertoire, Genealogy and Genomic Organization of Cruzipain and Homologous Genes in Trypanosoma cruzi, T. cruzi-Like and Other Trypanosome Species

Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches

Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection

Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome ( approximately 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods

Handling separable non-convexities using disjunctive cuts

International audienceD'Ambrosio, Lee, and Wächter (2009, 2012) introduced an algorithmic approach for handling separable non-convexities in the context of global optimization. That algorithmic framework calculates lower bounds (on the optimal min objective value) by solving a sequence of convex MINLPs. We propose a method for addressing the same setting, but employing disjunctive cuts (generated via LP), and solving instead a sequence of convex NLPs. We present computational results which demonstrate the viability of our approach

Prevalência do transtorno de déficit de atenção/hiperatividade numa escola pública primária Attention deficit/hyperactivity disorder prevalence in an inner city elementary school

OBJETIVO: Definir a prevalência do transtorno de déficit de atenção/hiperatividade (TDAH) numa amostra de crianças escolares de uma única escola primária pública. MÉTODO: A população do estudo foi composta por todos os alunos das classes de alfabetização à quarta série de uma escola. No primeiro estágio da pesquisa, as professoras e os pais preencheram um questionário padronizado de 18 sintomas definidos no DSM-IV. No segundo estágio, os alunos com triagem positiva foram convidados para um atendimento na escola. Após assinatura de consentimento esclarecido, preencheram-se o questionário de sintomas do DSM-IV, uma anamnese dirigida e um questionário psicossocial concebido para a pesquisa e realizaram-se exames físico e neurológico completos. O diagnóstico de TDAH admitia três subtipos: hiperativo predominante (H), desatento predominante (TDA), ou misto (TDA+ H). RESULTADOS: De 403 alunos avaliados no início, 108 tiveram triagem positiva. Destes, avaliaram-se 101 alunos. Havia 68 meninos e 33 meninas. A idade mediana foi 9 anos (faixa, 6-15 anos; desvio padrão, 1,99). O diagnóstico de TDAH foi definido em 69 alunos (17,1%), incluindo 27 crianças (39,1%) com TDA sem H, 26 crianças (37,7%) com TDA + H e 16 (23,2%) com H sem TDA. Dentre as crianças diagnosticadas, 45 (65,2%) eram meninos e 24 (34,8%) meninas (razão 1,9:1). CONCLUSÃO: A prevalência de TDAH em 403 crianças escolares de uma escola primária pública foi 17,1%.<br>OBJECTIVE: To define the prevalence of attention deficit/hyperactivity disorder (ADHD) in a sample school-aged children from a public elementary school. METHOD: The study population was composed of all pupils who attended the first five grades at a public state school. During the first stage, school teachers and parents filled a standardized questionnaire of 18 ADHD symptoms defined at DSM-IV. In the second stage, children who screened positive and their parents were invited for a medical visit at school. After signature of an informed consent, the following procedures were done: DSM-IV symptoms questionnaire, oriented history, physical exam and neurologic exam. ADHD diagnosis was subdivided into three types: predominantly hyperactive (H), predominantly inattentive (ADD), and mixed type ADD + H. RESULTS: Among 403 pupils recruited in the first stage, 108 screened positive. Of these, 101 were assessed. There were 68 boys and 33 girls. Median age was 9 years (Range, 6-15 years; standard deviation, 1.99). ADHD diagnosis was defined for 69 pupils (17.1%), including 27 children (39.1%) with ADD, 26 children (37.7%) with ADD + H, and 16 children (23.2%) with H without ADD. Among children who received a diagnosis of ADHD, 45 (65.2%) were boys and 24 (34.8%) were girls (ratio 1.9:1). CONCLUSION: ADHD prevalence in a sample of 403 school-aged children from a public elementary school was 17.1%