Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8(+) T cell response.

Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8(+) T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3133-DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2(+) TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second β-chain complementarity-determining region (CDR2β). Extensive mutagenesis studies of three distinct TRBV11-2(+) TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2β loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs

Extremely high frequencies of alpha-globin gene deletion in Madang and on Kar Kar Island, Papua New Guinea.

Extremely high frequencies of the deletion form of alpha(+)-thalassemia (-alpha/), as studied by the DNA mapping technique, were found in the population of Madang, a coastal province in the north of Papua New Guinea (PNG) and in the population of Kar Kar, an island situated near Madang. Ninety-seven percent of the population tested from Madang and 89% of that from Kar Kar Island were either alpha(+)-thalassemia heterozygotes or homozygotes. By contrast, no examples of the deletion form were detected in the Eastern Highlands of PNG. The haplotype frequencies of alpha(+)-thalassemia (-alpha/) in Madang and Kar Kar Island were found to be 81.33% and 66.67%, respectively. A more detailed analysis of the gene deletion revealed that in both populations 96% were of the 4.2 kilobase (kb) type and 4% were of the 3.7-kb type. Thus, this group is the only example in which the 4.2-kb deletion is predominant over 3.7-kb defect. The presence in high frequencies of alpha(+)-thalassemia in the coastal area of Madang and on the neighboring island, where malaria has long been holoendemic or hyperendemic, and its virtual absence from the nonmalarious highlands of PNG suggest the role of malaria as the selective factor in maintaining alpha(+)-thalassemia. If this selective pressure is still operating, and since alpha(+)-thalassemia has no apparent homozygous disadvantage, the abnormal haplotype (-alpha/) will be in the process of fixation in this population

Adaptação e avaliação de uma intervenção cognitivo-comportamental para meninos vítimas de violência sexual

Objetivou-se adaptar e avaliar um modelo de intervenção cognitivo-comportamental para meninos vítimas de Violência Sexual (VS), derivado de um modelo avaliado com meninas. A dissertação é composta por um artigo teórico sobre VS contra meninos, um capítulo que descreve o processo de adaptação do modelo, um relato de experiência sobre a produção e utilização de um documentário sobre VS contra meninos utilizado na aplicação do modelo adaptado e um artigo com os resultados dessa aplicação. Três meninos vítimas de VS com idades entre oito e 16 anos foram avaliados antes e após a intervenção por meio de instrumentos psicológicos quanto a sintomas comumente presentes em vítimas de VS. A aplicação do modelo adaptado foi avaliada por três juízes independentes por meio de seis indicadores. As avaliações sintomatológicas dos participantes e a da aplicação do modelo adaptado se constituem como evidências iniciais sobre sua ação terapêutica.This work aimed to adapt and assess a cognitive-behavioral intervention model for boys who are victims of sexual violence that was derived from a model that evaluated girls. The master thesis consists of a theoretical article about sexual violence against boys; a chapter describing the process of adapting the model; a report on the experience of producing and using the documentary about sexual violence against boys while applying the adapted model; and an article with the results from this application. Three boys between the ages of eight and 16 who had been victims of sexual violence were evaluated, through psychological instruments before and after the intervention, in terms of symptoms common to sexual violence victims. Three independent judges evaluated the application of the adapted model through six indicators. The evaluations of the participants’ symptoms as well as of the adapted model’s application provide initial proof of therapeutic effectiveness