Surface antigens in Plasmodium falciparum malaria : PfEMP1 and SURFIN4.2

Plasmodium falciparum malaria is an infectious disease that on despite of the ongoing eradication efforts is still endemic in more than 100 countries, sometimes causing severe disease that leads to the death of around half a million people per year. Malaria pathology is tightly associated with the parasite cycle inside the human red blood cells (RBCs). Central to this cycle is the initial invasion by the merozoite and the extensive RBC modifications induced by the parasite, transporting proteins to the RBC cytoplasm and membrane. The P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) transported to the surface of the parasitized RBC (pRBC) and the surface-associated interspersed protein 4.2 (SURFIN4.2) present both at the pRBC surface as well as at the merozoite apex and surface, are the major focus of this thesis. PfEMP1 is the major surface antigen and mediates rosetting (binding of parasitized RBCs (pRBCs) to two or more RBCs), a parasite phenotype associated with the development of severe disease. The most N-terminal segment of this protein (the NTSDBL1α domain) has been identified as the ligand for rosetting and naturally acquired antibodies targeting this particular protein protect against severe disease development. In this study we wanted to address the specific regions in PfEMP1 and in other protein targets recognized by rosette-disrupting antibodies (generated upon immunization with recombinant PfEMP1 or naturally acquired during P. falciparum infection). We also wanted to explore other functional roles of these antibodies. A panel of antibodies (monoclonal and polyclonal) against rosette-mediating NTS-DBL1α domains was produced by animal immunization. The antibodies were analyzed with particular attention to their capacity to recognize the surface of the pRBC, disrupt the rosettes formed by homologous parasites and induce phagocytosis by monocytic cells. Additionally, the specific epitopes recognized by the majority of these antibodies were successfully mapped to a specific region of subdomain 3 (SD3) of the DBL1α domain, regardless of the parasite strain used. These results suggested this region as a major target of anti-rosetting antibodies. Most of these antibodies also induced opsonization for phagocytosis, a role that could be of great importance during pRBCs clearance in vivo. Interestingly, some of the antibodies with high opsonizing activity did not disrupt rosettes, indicating that other epitopes besides those involved in rosetting are exposed on the pRBC surface and are able to induce functional antibodies that could provide protection. The naturally acquired antibodies in sera from children living in a malaria endemic region were also investigated. The ability of these antibodies to recognize three parasite-derived surface proteins (PfEMP1, RIFIN-A and SURFIN4.2) was assessed. Different variables were also measured in the presence of these sera samples, including rosetting rate, surface reactivity and opsonization for phagocytosis on a rosetting model parasite grown in group O or group A RBCs. The data showed that the acquired immune response developed during natural infection could recognize the pRBC surface and more importantly could induce pRBC phagocytosis and in a few cases disrupt the rosettes formed by a heterologous parasite model. These activities however had limited access to the pRBCs inside a rosette formed with group A RBCs, where these cells act as a shield for the pRBCs, protecting it from antibodies’ recognition therefore impairing their effector function. This study also suggested that SURFIN4.2 previously identified at the pRBC surface could be involved in rosette formation, either as a direct ligand or as an accessory element for rosette strengthening. The suggestion of SURFIN4.2 as a possible mediator in rosetting prompted us to deepen the study of this protein, however, the initial results steered the approach to this protein from the rosetting phenomenon towards a more striking and understudied role of this protein during the invasion process. Using antibodies against the N-terminus, the protein was observed at the surface of the merozoite but more strikingly also in the neck of the rhoptries. The protein was shed into culture supernatant upon schizont rupture and was associated with GLURP (Glutamate Rich Protein) and RON-4 (Rhoptry Neck Protein 4) to form a complex we named SURGE (SURFIN4.2-RON-4-GLURP complEx). Importantly, SURFIN4.2 was detected at the apex of the merozoite during merozoite initial attachment and active invasion into the RBCs. The exact functional role of SURGE remains to be determined, but the presence of RON-4, a protein confined to the moving junction (MJ), strongly suggests a role in strengthening the stable contact between the merozoite apex and the RBC, possibly as and additional RBC adhesion molecule. Supporting the involvement of the protein complex during the invasion process, antibodies against the N-terminus of SURFIN4.2 partially inhibited invasion

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER- negative loci combined account for ~11% of familial relative risk for ER- negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

Nematodes

A fist of nematodes associated with the roots of beans and other plants is given in table form, the species of Meloidogyne and Pratylenchus being the most common in bean crops in the Americas. Meloidogyne species are prevalent in light sandy soils with good drainage. Length of survival in the soil depends on the nematode species, stage of development of the pathogen, soil type, moisture, and aeration. Color illustrations are given of the symptoms and damage caused by nematode feeding on root systems. They often appear on aerial plant parts which become chlorotic, stunted, burned at the leaf edges, and finally wilt. Crop rotation, deep plowing, the use of fallow, weed control, and flooding for 1-2 wk reduce nematode populations. Chemical control is effective but expensive and requires special equipment for soil applications. Control by plant resistance is the most efficient strategy. (CIAT)En forma de cuadro se presenta una lista de los nematodos que se asocian frecuentemente con las raices de frijol y otras plantas, siendo las especies de Meloidogyne y Pratylenchus las mas comunes en los cultivos de frijol en America. Las especies de Meloidogyne predominan en suelos arenosos livianos bien drenados. El periodo de supervivencia en el suelo depende de la especie de nematodo, el estado de desarrollo del patogeno, el tipo de suelo, la humedad y la temp. Se dan ilustraciones a color de los sintomas y danos ocasionados por los nematodos al alimentarse de los sistemas radicales. Estos se encuentran a menudo en las partes aereas de las plantas, las cuales se vuelven cloroticas, raquiticas, presentan quemazones en los bordes de las hojas y terminan marchitandose. La rotacion de cultivos, el arado profundo, el uso de barbecho, el control de malezas y las inundaciones durante 1-2 semanas disminuyen la poblacion de nematodos. El control quimico, aunque efectivo, es costoso y requiere equipo especial para hacer las aplicaciones al suelo. La estrategia mas efectiva es el control mediante el uso de var. resistentes. (CIAT

Estudio comparativo de metodologías para reubicación optima de transformadores de distribución en redes de nivel de tensión 1

Los sistemas de distribución son los encargados de recibir la energía proveniente de los sistemas de transmisión (o subtransmisión) y entregarla a los diferentes tipos de usuarios, con niveles adecuados de calidad, continuidad y confiabilidad. Dado que en estos sistemas es donde se presentan los mayores índices de pérdidas de los sistemas eléctricos, los esfuerzos de las compañías de distribución están encaminados a mejorar sus características operativas, y por consiguiente, la reducción de las pérdidas técnicas y no técnicas. Por esta razón, las empresas distribuidoras de energía eléctrica requieren operar los sistemas con criterios técnicos de economía, confiabilidad y seguridad apropiados para garantizar la calidad del servicio a los clientes, cumpliendo con las normas técnicas exigidas y mínimo tiempo de interrupción del servicio, buscando siempre tener el menor índice posible de pérdidas en el sistema. Para mejorar la operación y eficiencia de los sistemas de distribución han aparecido nuevas estrategias que surgen de acuerdo a requerimientos técnicos, regulatorios o económicos. Con el fin de minimizar las pérdidas técnicas en estos sistemas se han empleado diversas metodologías como balance de fases, instalación de condensadores, reguladores de tensión, repotenciación de conductores, reubicación de transformadores y reconfiguración, entre otros

Reading aloud as an instructional strategy to develop elementary school children’s reading skills in a foreign language

La presente investigación aborda el análisis de diferente información obtenida después de la aplicación de lectura en voz alta como una estrategia instructiva en una escuela de carácter público en Colombia. A través de diferentes métodos para la recolección y análisis de los datos como observaciones, entrevistas y diarios de campo, los resultados arrojaron que esta estrategia es efectiva para aprender vocabulario con el soporte de imágenes y cognados verdaderos; generar motivación e interés hacia la lectura en una lengua extranjera, siempre y cuando se involucren aspectos de la cultura o el contexto del lector; y por último, una oportunidad para reflexionar en torno a la instrucción y el papel que cumple sobre los presentes y futuros docentes, brindando un modelo pedagógico que sea apropiado para desarrollar las habilidades establecidas dentro del Marco Común Europeo, referencia teórica acogida por el Ministerio de Educación Nacional de Colombia en su plan de Fortalecimiento de las competencias comunicativas en una segunda lengua, inglés, en este caso.This research addresses the analysis of different information obtained after the application of reading aloud as an instructional strategy in a public school in Colombia. Through various methods for collecting and analyzing data as observations, interviews and field diaries, the results showed that this strategy is effective in vocabulary learning while supported by images and true cognates; generating motivation and interest in reading a foreign language, as long as they involve aspects of culture or context of the reader, and lastly, a chance to reflect on the training and the role of the present and future teachers, providing a pedagogical model that is appropriate to develop the skills set within the Common European Framework, theoretical reference hosted by the Ministry of National Education of Colombia in its plan to strengthen communication skills in a second language, English in this case

Evaluacion de los analisis de suelos de las zonas productoras de yuca en Colombia

The results are given of physicochemical analyses of soils and estimated cassava yields for five production zones in Colombia. There was little correlation between yield and the factors studied. Yields tended to increase as P increased; and there was a positive response to K in 2 zones and Ca/Mg in 2 others. However, there were contradictory results with K and pH in three of the zones. Other factors affecting yield should be studied to find the reasons for this discrepancy. (CIAT

Variación del proteoma de las micropartículas plaquetarias dependiendo del estímulo: papel de las proteínas de señalización

Comunicaciones a congreso