Estudio de las modificaciones conformacionales y su influencia en la actividad inmunológica de péptidos derivados de las familias de las proteínas spect-1 y -2, siap-1 y -2 de plasmodium falciparum

SPECT-1 y -2 y SIAP-1 y -2 son proteínas pertenecientes al esporozoíto de Plasmodium falciparum causante de la malaria más agresiva en los humanos. Estas proteínas están involucradas en el paso del parásito a través de las células del hospedero humano y en la invasión del hepatocito, haciéndolas blancos atractivos para ser estudiadas. Péptidos conservados de alta capacidad de unión (cHABPs) a células HeLa y HepG2 derivados de estas moléculas son no inmunogénicos porque son incapaces de generar una respuesta inmunitaria, pero son claves para el parásito porque cumplen una función importante durante la infección del hospedero humano. En este trabajo se encontró que algunos cHABPs pertenecientes a las proteínas SPECT-1 y -2, están posiblemente involucrados con la unión y formación de poros sobre la membrana de las células hospederas, ayudando al esporozoíto a abrirse paso través de las células del hospedero. Por otro lado, con el fin de cambiar el comportamiento inmunológico de cHABPs derivados de SPECT-1 y -2 y SIAP-1 y -2, se obtuvieron nuevos péptidos mediante el reemplazo de aminoácidos críticos por otros residuos cuya masa molecular sea similar, pero diferente en su polaridad. En este trabajo se reporta que dichas modificaciones promovieron cambios en la estructura secundaria (determinada por DC o 1H-RMN) de los péptidos modificados (mHABPs) cuando se comparó con la estructura de los cHABPs nativos; adicionalmente, estos mHABPs invirtieron su comportamiento inmunológico convirtiéndose en péptidos inmunogénicos inductores de anticuerpos. Lo que permite establecer la existencia de una relación entre la estructura que adoptan estos mHABPs con su actividad inmunológica. Además, algunos de los mHABPs estudiados aquí, pueden ser candidatos a ser incluidos en la vacuna contra la malaria químicamente sintetizada multi-epitope y multi-estadio que se está desarrollando en la Fundación Instituto de Inmunología de Colombia (FIDIC).

Development of designed site-directed pseudopeptide-peptido-mimetic immunogens as novel minimal subunit-vaccine candidates for malaria

Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the a-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immunotherapeutic effects for preventing and controlling malaria.

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.

Conceptual Rapprochement and the Analysis of the Historical, Normative and Jurisprudential Treatment of the Rural Workers, as Regards the Need for Special Protection

This article aims to present an approach to the issue of farm or rural zone workers, including a labour law study of agrarian legal decisions, so as to demonstrate their importance in respect to social, economic and cultural rights in Colombia. The study will serve to illustrate through the history, the applicable law and the jurisprudence, the different ways in which farmers have been treated from the time of the origin until the arrival of modern systems of industrialization. It calls into question the effectiveness of existing laws and the role of the courts, in spite of globalization, to maintain the minimum rights and guarantees of farm workers who are considered to be a vulnerable population. In conclusion, this study seeks to illustrate the current role of the Labor law and the National Health Service in the area of demonstrating of the existence or absence of mechanisms to protect workers in rural areas and the need to create some mechanisms that involve social justice given its prime importance in the Constitution of 1991.

Historical perspective of the Psychology of motivation

The psychology of motivation has a long tradition and history in psychology. In fact, we consider that, to a certain extent, understanding the history of the psychology of motivation is understanding great part of which has been psychology itself, since the main target of psychology was, and is, to try to explain behaviour, and the aim of psychology of motivation is to find out the causes of behaviour. In its long passage to the present time, there have been three perspectives that have monopolized most of the investigation: the biological, the behavioural and the cognitive. They are not excluding. Each one of them has been predominant in certain stages, although the same attention was paid to the other two. Nowadays, the biological and cognitive perspectives are those that receive greater attention from the investigators. The historical direction in the study of the psychology of motivation represents an important solution to know how the events that have given rise to the present consideration about the psychology of motivation were forged. To know the past helps us to understand the present, at the same time it allows us to hypothesise with great probability of success which will be the future in the study object.

Historical Development of Organochlorine Pesticides Legislation in Venezuela

Information about organochlorine pesticides legislation in Venezuela was recovered, using the search engine Google. Progress and setbacks was analyzed, with information about imports, exports, inventories, storage sites, controls and actions taken for disposal and participation in international conventions. The country appears to have adequate legislation, however, greater consistency of laws and decrees are required. Update the technical rule is necessary and increases the capacity to monitoring, identification and elimination of organochlorine pesticides.