3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria

T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DR beta 1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of V beta 12 and V beta 6 TCR gene families in 67% of HLA-DR beta 1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DR beta 1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

Structural Chromosomal Alterations Induced by Dietary Bioflavonoids in Fanconi Anemia Lymphocytes

Introduction Fanconi anemia is an autosomal recessive disease characterized by a variety of congenital abnormalities, progressive bone marrow failure, increased chromosomal instability and higher risk to acute myeloid leukemia, solid tumors. This entity can be considered an appropriate biological model to analyze natural substances with possible genotoxic effect. The aims of this study were to describe and quantify structural chromosomal aberrations induced by 5 flavones, 2 isoflavones and a topoisomerase II chemotherapeutic inhibitor in Fanconi anemia lymphocytes in order to determine chromosomal numbers changes and/ or type of chromosomal damage. Materials and methods Chromosomes stimulated by phytohaemagglutinin M, from Fanconi anemia lymphocytes, were analysed by conventional cytogenetic culture. For each chemical substance and controls, one hundred metaphases were evaluated. Chromosomal alterations were documented by photography and imaging analyzer. To statistical analysis was used chi square test to identify significant differences between frequencies of chromosomal damage of basal and exposed cell cultured a P value less than 0.05. Results There were 431 chromosomal alterations in 1000 metaphases analysed; genistein was the more genotoxic bioflavonoid, followed in descendent order by genistin, fisetin, kaempferol, quercetin, baicalein and miricetin. Chromosomal aberrations observed were: chromatid breaks, chromosomal breaks, cromatid and chromosomal gaps, quadriratials exchanges, dicentrics chromosome and complex rearrangements. Conclusion Bioflavonoids as genistein, genistin and fisetin, which are commonly present in the human diet, showed statistical significance in the number of chromosomal aberrations in Fanconi anemia lymphocytes, regarding the basal damage.

Las tecnologías de la información y las comunicaciones – tic - como herramientas de desarrollo económico y su impacto en la erradicación de la pobreza extrema y el hambre

Este documento evalúa el impacto de las TIC como herramientas de desarrollo económico en la erradicación de la pobreza extrema y el hambre, mediante un análisis comparativo de los países que han presentado un avance económico y social a partir de la adopción de las TIC, y su relación con la cifras de pobreza y Hambre. En la primera parte se desarrolla la relación de las TIC como oportunidades para avanzar en un proceso de cambio económico y social, se plantean los objetivos, la justificación y los alcances de la investigación. En la segunda parte se hace alusión al marco teórico, situación de la pobreza y el Hambre, causas, consecuencias e importancia de las TIC para el desarrollo económico y social, marco legislativo, índices de crecimiento en los diferentes países y su correlación con los indicadores económicos. En la tercera parte se realiza el marco metodológico de la investigación, análisis de los diferentes indicadores, índice de desarrollo tecnológico IDT, producto interno bruto PIB, indicador de pobreza PPA e indicador de índice global de hambre IGH; que describen la situación de los países objeto del estudio. En la cuarta parte se realiza la discusión de la investigación, y se presentan las conclusiones; determinando el estado directo o inverso en cuanto la erradicación de la pobreza extrema y el hambre mediante la implementación de las TIC, definiendo la aplicabilidad y pertinencia de estas en el desarrollo económico de los países que presentan un alto índice de pobreza extrema y hambre.