Hacer realidad un derecho: una experiencia de inclusión de alumnado con discapacidad cognitiva en una institución educativa

La inclusión del alumnado con algún tipo de discapacidad es uno de los retos pendientes en el ámbito escolar. El presente estudio tiene como objetivo comprender las experiencias subjetivas de los estudiantes con discapacidad cognitiva leve, padres de familia, pares y docentes, frente al proceso de inclusión escolar en una institución educativa de la ciudad de Neiva. Es un estudio cualitativo-etnográfico que utilizó la observación participante y el dibujo libre en 27 personas distribuidas en 6 grupos (entidades gubernamentales, grupo de apoyo, profesores, padres de familia, estudiantes con discapacidad e iguales). Los resultados evidencian que son las entidades gubernamentales las encargadas de garantizar el derecho a la educación y a la inclusión escolar desde la normatividad reconociendo que existen dificultades en la implementación de estos programas. Las demás personas involucradas en el proceso requieren tener mucho compromiso para que la inclusión pueda realizarseen un ambiente de igualdad quepermita la construcción del proyecto de vida. Los estudiantes con discapacidad cognitiva se sienten bien ya que tienen la oportunidad de iniciar un proceso de socialización con los pares los cuales los han aceptado, acogido y establecido un trato con igualdad.Inclusion in schools has been a topic of great interest because the statistics demonstrate a low level of educational inclusion. Therefore, this study aims to understand the subjective experiences of students with Mild Cognitive Disability, parents, peers and teachers to the process of school inclusion in the Educational Institution from the city of Neiva. It is a qualitative ethnographic study, used participant observation and the free drawing in 27 people in 6 groups (government agencies, support groups, teachers, parents, students with disabilities and peers). The results demonstrate that Governmental Entities are responsible for ensuring the right to education and school inclusion from the normativity recognizing that there are difficulties in implementing these programs. The other people involved in the process need to be very commitment to inclusion that can be carried out in an environment of equality that allows the construction of life project. Students with Cognitive Disabilities are feeling good because they have the opportunity to start a process of socialization with peers which have accepted them, welcomed and established equality treatment

Using the PfEMP1 Head Structure Binding Motif to Deal a Blow at Severe Malaria

Plasmodium falciparum (Pf) malaria causes 200 million cases worldwide, 8 million being severe and complicated leading to similar to 1 million deaths and similar to 100,000 abortions annually. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) has been implicated in cytoadherence and infected erythrocyte rosette formation, associated with cerebral malaria; chondroitin sulphate-A attachment and infected erythrocyte sequestration related to pregnancy-associated malaria and other severe forms of disease. An endothelial cell high activity binding peptide is described in several of this similar to 300 kDa hypervariable protein's domains displaying a conserved motif (GACxPxRRxxLC); it established H-bonds with other binding peptides to mediate red blood cell group A and chondroitin sulphate attachment. This motif (when properly modified) induced PfEMP1-specific strain-transcending, fully-protective immunity for the first time in experimental challenge in Aotus monkeys, opening the way forward for a long sought-after vaccine against severe malaria

Incidencia de la psicomotricidad global en el desarrollo integral del ni?o en el nivel preescolar

115 P?ginasEl presente trabajo de investigaci?n se desarrolla dentro del enfoque cualitativo, lo que permite un acercamiento a la realidad para entenderla, encontrar problem?ticas que afectan a la comunidad y plantear posibles soluciones. La investigaci?n es de car?cter descriptivo, en esta se utilizaron diferentes t?cnicas e instrumentos que conllevan a la identificaci?n de las necesidades de la poblaci?n objeto de estudio; permitiendo una mejor claridad frente al proceso. El objetivo central de este proyecto fue desarrollar estrategias que fortalezcan los procesos psicomotrices en los ni?os y ni?as del grado preescolar de la Instituci?n Educativa Fe y Alegr?a ubicada en el municipio de Ibagu?. Este fortalecimiento psicomotriz se hizo a trav?s del uso de actividades te?rico pr?cticas recreativas que permiten evidenciar la importancia de estos procesos, donde se favorece el conocimiento, dominio y utilizaci?n del cuerpo respecto a la propia persona y al entorno. Como producto enriquecedor se elabora un proyecto de aula llamado ?Reconozcamos nuestro cuerpo? que busca satisfacer las necesidades identificadas mediante juegos motores reglados, dramatizaci?n, actividades de expresi?n, ejercicios corporales, gimnasia mental, plegado, dactilopintura, moldeado, y actividades l?dicas que articulen mente y cuerpo de los ni?os. En el dise?o de la propuesta pedag?gica se plantea un manual de estrategias de activaci?n a la destreza motriz aplicable al proceso de ense?anza y de aprendizaje a fin de afianzar continuamente el desarrollo de t?cnicas para una adecuada motricidad, coordinaci?n y firmeza motriz en los ni?os mejorando la calidad de los procesos formativos en el aula.ABSTRACT. This research is developed within the qualitative approach, allowing an approach to reality to understand, find problems affecting the community and propose possible solutions. The research is descriptive, different techniques and tools that lead to the identification of the needs of the population under study were used. The main objective of this project was to develop strategies to strengthen the psychomotor processes in children of preschool grade of School Fe y Alegr?a located in the town of Ibague. This psychomotor building was done through the use of recreational activities theoretical practices that reveal the importance of these processes, where knowledge, mastery and use of body to the person themselves and the environment are favored. Product enriching classroom project called "Let's recognize our body" that seeks to meet the needs identified by regulated motor games, drama, expressive activities, physical exercises, mental gymnastics, bending, finger paint, molding, and recreational activities that articulate mind is made and bodies of children. In designing the pedagogical approach manual activation strategies to motor skills applicable to the process of teaching and learning in order to continuously strengthen the development of techniques for proper motor, motor coordination and strength in children poses improving quality of educational processes in the classroom.ADVERTENCIA. El Instituto de Educaci?n a Distancia-IDEAD de la Universidad del Tolima, el director del trabajo y el jurado calificador, no son responsables de los conceptos ni de las ideas expuestas por el autor del presente trabajo. (Art?culo 16, Acuerdo 032 de 1976 y Art?culo 29, acuerdo 064 de 1991, Consejo Acad?mico de la Universidad del Tolima).Las autoras Laura Magnolia Ardila Beltr?n identificada con C?dula de Ciudadan?a No. 1110.468.882 de Ibagu?, Indira Yahaira C?ceres Vanegas con C?dula de Ciudadan?a No. 1110.496.959 de Ibagu? y Yury Maried Mart?nez Perdomo con C?dula No. 107.5210.608 de Neiva, autorizan a la Universidad del Tolima la reproducci?n total o parcial de este documento con la debida cita de reconocimiento de la autor?a y cede a la misma los derechos patrimoniales con fines de investigaci?n, docencia e institucionales consagrados en el Art?culo 72 de la Ley 23 de 1982 y las normas que la constituyen o modifiquen. (Acuerdo No.0066 de 2003 del Consejo de la Universidad del Tolima).INTRODUCCION 18 1 PLANTEAMIENTO DEL PROBLEMA 21 1.1 DESCRIPCI?N DEL PROBLEMA 21 1.2 FORMULACI?N DEL PROBLEMA 22 2 OBJETIVOS 23 2.1 OBJETIVO GENERAL 23 2.2 OBJETIVOS ESPEC?FICOS 23 3 JUSTIFICACI?N 24 4 MARCO REFERENCIAL 27 4.1 ANTECEDENTES 27 4.2 MARCO TEORICO 31 4.2.1 Evoluci?n hist?rica de la psicomotricidad 31 4.2.2 Situaci?n actual y concepto de la psicomotricidad 35 4.2.3 Psicomotricidad y educaci?n 37 4.3 MARCO CONTEXTUAL 41 4.3.1 Familia 42 4.3.2 Docente 47 4.3.3 Ni?os 51 4.4 MARCO LEGAL 53 4.4.1 A nivel internacional 54 4.4.2 A nivel nacional 56 4.4.3 A nivel local 61 4.4.4 A nivel institucional 63 5 METODOLOGIA 67 5.1 ESTRUCTURA METODOL?GICA 65 5.1.1 Descripci?n Fase 1 70 5.1.2 Descripci?n Fase 2 74 5.2 AN?LISIS DE RESULTADOS 77 5.2.2 Confiabilidad 77 5.3 EVALUACI?N Y SEGUIMIENTO 78 5.3.1 Fase 1: Caracterizaci?n de las pr?cticas que se ejercen y de los discursos que circulan sobre la educaci?n de los ni?os y ni?as menores de siete a?os 78 5.3.2 Fase 2: Los sentidos Pedag?gicos de los proyectos de intervenci?n 81 6 PROYECTO DE INTERVENCION 85 6.1 ESQUEMA GENERAL 85 6.2 ACTIVIDADES INTEGRADORAS DEL PROYECTO DE INTERVENCION 87 6.2.1 Actividades integradoras para directivos y docentes 87 6.2.2 Actividades integradoras para padres de familia 89 6.2.3 Actividades integradoras para ni?os 90 6.3 EXPERIENCIA PEDAGOGICA 92 7 CONCLUSIONES 95 8 RECOMENDACIONES 96 REFERENCIAS 98 ANEXOS 10

Identification and characterization of the Plasmodium vivax thrombospondin-related apical merozoite protein

<p>Abstract</p> <p>Background</p> <p>Malaria caused by <it>Plasmodium vivax </it>is a major public health problem worldwide that affects 70-80 million people in the Middle East, Asia, Western Pacific, South America and the Caribbean. Despite its epidemiological importance, few antigens from this parasite species have been characterized to date compared to <it>Plasmodium falciparum</it>, due in part to the difficulties of maintaining an <it>in vitro </it>culture of <it>P. vivax</it>. This study describes the identification of the <it>P. falciparum </it>thrombospondin-related apical merozoite protein homologue in <it>P. vivax </it>(PvTRAMP) and examines its potential to be further evaluated as vaccine candidate.</p> <p>Methods</p> <p>The gene encoding PvTRAMP was identified through an extensive search of the databases hosting the genome sequence of <it>P. vivax</it>. Genes adjacent to <it>pvtramp </it>were identified <it>in silico </it>to determine the degree of similarity between the protein sequences encoded by equivalent chromosomic fragments in <it>P. falciparum </it>and <it>Plasmodium knowlesi</it>. The <it>pvtramp </it>gene was amplified from cDNA of <it>P. vivax </it>schizont stages, cloned and expressed in <it>Escherichia coli</it>. Anti-PvTRAMP antisera was obtained by inoculating rabbits with PvTRAMP B cell epitopes produced as synthetic peptides in order to assess its recognition in parasite lysates by Western blot and in intact parasites by indirect immunofluorescence. The recognition of recombinant PvTRAMP by sera from <it>P. vivax-</it>infected individuals living in endemic areas was also assessed by ELISA.</p> <p>Results</p> <p>The PfTRAMP homologue in <it>P. vivax</it>, here denoted as PvTRAMP, is a 340-amino-acid long antigen encoded by a single exon that could have a potential role in cytoadherence, as indicated by the presence of a thrombospondin structural homology repeat (TSR) domain. According to its transcription and expression profile, PvTRAMP is initially located at the parasite's apical end and later on the parasite surface. Recombinant PvTRAMP is recognized by sera from infected patients, therefore, indicating that it is targeted by the immune system during a natural infection with <it>P. vivax.</it></p> <p>Conclusions</p> <p>The results of this work support conducting further studies with PvTRAMP to evaluate its immunogenicity and protection-inducing ability in the <it>Aotus </it>animal model.</p

α-Helix peptides designed from EBV-gH protein display higher antigenicity and induction of monocyte apoptosis than the native peptide

We tested the hypothesis that stabilizing α-helix of Epstein–Barr virus gH-derived peptide 11438 used for binding human cells will increase its biological activity. Non-stable α-helix of peptide 11438 was unfolded in an entropy-driven process, despite the opposing effect of the enthalpy factor. Adding and/or changing amino acids in peptide 11438 allowed the designing of peptides 33207, 33208 and 33210; peptides 33208 and 33210 displayed higher helical content due to a decreased unfolding entropy change as was determined by AGADIR, molecular dynamics and circular dichroism analysis. Peptides 33207, 33208 and 33210 inhibited EBV invasion of peripheral blood mononuclear cells and displayed epitopes more similar to native protein than peptide 11438; these peptides could be useful for detecting antibodies induced by native gH protein since they displayed high reactivity with anti-EBV antibodies. Anti-peptide 33207 antibodies showed higher reactivity with EBV than anti-peptide 11438 antibodies being useful for inducing antibodies against EBV. Anti-peptide 33210 antibodies inhibit EBV invasion of epithelial cells better than anti-peptide 11438 antibodies. Peptide 33210 bound to normal T lymphocytes and Raji cells stronger than peptide 11438 and also induced apoptosis of monocytes and Raji cells but not of normal T cells in a similar way to EBV-gH. Peptide 33210 inhibited the monocytes’ development toward dendritic cells better than EBV and peptide 11438. In conclusion, stabilizing the α-helix in peptides 33208 and 33210 designed from peptide 11438 increased the antigenicity and the ability of the antibodies induced by peptides of inhibiting EBV invasion of host cells

Mycobacterium tuberculosis Rv0679c protein sequences involved in host-cell infection: Potential TB vaccine candidate antigen

BACKGROUND: To date, the function of many hypothetical membrane proteins of Mycobacterium tuberculosis is still unknown and their involvement in pathogen-host interactions has not been yet clearly defined. In this study, the biological activity of peptides derived from the hypothetical membrane protein Rv0679c of M. tuberculosis and their involvement in pathogen-host interactions was assessed. Transcription of the Rv0679c gene was studied in 26 Mycobacterium spp. Strains. Antibodies raised against putative B-cell epitopes of Rv0679c were used in Western blot and immunoelectron microscopy assays. Synthetic peptides spanning the entire length of the protein were tested for their ability to bind to A549 and U937 cells. High-activity binding peptides (HABPs) identified in Rv0679c were tested for their ability to inhibit mycobacterial invasion into cells. RESULTS: The gene encoding Rv0679c was detected in all strains of the M. tuberculosis complex (MTC), but was only transcribed in M. tuberculosis H37Rv, M. tuberculosis H37Ra and M. africanum. Anti-Rv0679c antibodies specifically recognized the protein in M. tuberculosis H37Rv sonicate and showed its localization on mycobacterial surface. Four HABPs inhibited invasion of M. tuberculosis to target cells by up to 75%. CONCLUSIONS: The results indicate that Rv0679c HABPs and in particular HABP 30979 could be playing an important role during M. tuberculosis invasion of host cells, and therefore could be interesting research targets for studies aimed at developing strategies to control tuberculosis

Lectura de contexto y abordaje psicosocial desde los enfoques narrativos. Popayán, Medellín y La Sierra Cauca.

… «cuando llegaron los paramilitares y le dieron a la gente 24 horas para desocupar el territorio donde estábamos. Me tocó correr con ellas, acosando, porque había mucha gente corriendo. Dejamos casa, gallinas, marranos: todo lo dejé por allá perdido. Eso fue muy triste…cuando íbamos a tomar chocolatito, llegaron los paras y me preguntaron qué hacía ahí. Yo pensaba que nos iban a matar, a nosotras que no debíamos nada». (Relato tomado del libro Voces: historias de violencia y esperanza en Colombia.) La violencia sociopolítica que ha vivido Colombia ha generado no solo en el colectivo sino en lo individual daños psicológicos, físicos y materiales en las comunidades sin medir su origen, religión, etnia, edad, condición política, etc. Las dificultades que se han vivido han generado malestar obstruyendo el proyecto de vida de comunidades y personas prevaleciendo la injusticia y la destrucción de sueños y posibilidades de vida. El conflicto armado ha generado el desplazamiento forzado, la mutilación por minas personales y hasta la muerte, masacres y toda una cadena de sufrimientos afectando gravemente al país. Este trabajo contiene reflexiones acerca de algunos casos reales que han vivido las victimas los cuales nos posicionan como estudiantes de psicología frente a la realidad de las víctimas, sus vivencias y realidades. Es entender como desde la perspectiva narrativa como técnica de acompañamiento es posible que la acción psicosocial permita el abordaje mediante la propuesta de estrategias adecuadas para facilitar la potencialización de las víctimas y de esta manera los afrontamientos frente a sus situaciones de dolor sean superadas permitiendo una vida digna, llena de esperanza y puedan avanzar hacia nuevos caminos de tranquilidad y superación colectiva, familiar e individual. La aplicación de esta técnica permite profundizar en nuestro quehacer profesional y lograr de esta manera contribuir a la recuperación de tejido social que tanto necesita nuestro país.«when the paramilitaries arrived and gave the people 24 hours to vacate the territory where we were. I had to run with them, harassing them, because there were a lot of people running. We left house, chickens, pigs: everything I left there was lost. That was very sad ... when we were going to take chocolate, the paramilitaries arrived and asked me what I was doing there. I thought they were going to kill us, we did not owe anything. " (Story taken from the book Voices: stories of violence and hope in Colombia.) The sociopolitical violence that Colombia has experienced has generated not only in the collective but in the individual psychological, physical and material damages in the communities without measuring their origin, religion, ethnicity, age, political condition, etc. The difficulties that have been experienced have generated discomfort obstructing the life project of communities and people, prevailing injustice and the destruction of dreams and life possibilities. The armed conflict has generated forced displacement, mutilation by personal mines and even death, massacres and a whole chain of suffering seriously affecting the country. This work contains reflections about some real cases that the victims have lived which position us as students of psychology in face of the reality of the victims, their experiences and realities. It is to understand how from the narrative perspective as a support technique it is possible that the psychosocial action allows the approach by proposing adequate strategies to facilitate the empowerment of the victims and in this way the confrontations facing their pain situations are overcome allowing a life worthy, full of hope and can move towards new paths of tranquility and collective, family and individual improvement. The application of this technique allows us to deepen our professional work and in this way contribute to the recovery of the social fabric that our country so badly needs

T cell peptides derived from invasive stages of Schistosoma mansoni as potential schistosomiasis vaccine

Schistosomiasis is a parasitic disease that affects 143 million people in endemic countries. This work analyzed overexpressed sequences from the cercaria phase to the early schistosomulum phase using bioinformatics tools to predict host interaction and selected proteins for predicting T cell epitopes. The final peptides were chemically synthesized, and their toxicity was evaluated in vitro. Peptides were formulated in the Adjuvant Adaptation (ADAD) vaccination system and injected into BALB/c mice that were challenged with S. mansoni cercariae to assess protection and immunogenicity. A total of 39 highly expressed S.mansoni proteins were identified as being of potential interest. Three T cell peptides predicted to bind MHC mouse and human class II were synthesized and formulated for vaccination. SmGSP and SmIKE reduced the number of eggs trapped in the liver by more than 50% in challenged BALB/c mice. The liver of mice vaccinated with either SmGSP or SmTNP had a significantly reduced affected liver surface. Transcriptome-based T cell peptides elicit partial protection and could be candidates for a multiantigen vaccine

Síntesis de constructos de multicopias peptídicas de secuencias derivadas de la proteína apical sushi protein (asp) de plasmodium falciparum: caracterización fisicoquímica y estudios de inmunogenicidad

La malaria continúa siendo uno de los problemas de salud pública de mayor relevancia a nivel mundial. En la actualidad más del 40% de la población mundial que habita en las regiones tropicales y subtropicales son endémicas de esta enfermedad. Pese a las estrategias propuestas por entidades como la OMS y OPS, en el último año se registraron 216 millones de casos clínicos de malaria y cerca de 655.000 decesos por esta causa, mayoritariamente mujeres embarazadas y niños menores de cinco años de edad. Este problema se ha visto ostensiblemente agravado por múltiples circunstancias, entre estas los fuertes cambios climáticos de los últimos años que han permitido la colonización de nuevos territorios anteriormente carentes de malaria, la resistencia por parte del Plasmodium (agente causal de la enfermedad) a los diferentes esquemas de antibióticos empleados para su control y así mismo la resistencia de la hembra del mosquito Anopheles (vector de transmisión de la enfermedad) a los insecticidas más usados. Por lo anterior la búsqueda de nuevas estrategias tanto terapéuticas como inmunoprofilácticas sigue siendo una prioridad global. En la actualidad alrededor de 150 diferentes prototipos de vacuna contra la malaria se encuentran en diferentes fases de investigación sin resultados alentadores respecto a la prevención de la enfermedad. Sin embargo un esfuerzo importante realizado en los años ochenta, liderado por el Profesor Manuel Elkin Patarroyo y su equipo condujo a la obtención de la primera vacuna sintética contra esta enfermedad denominada SPf66, cuya eficacia protectora contra la enfermedad fue en promedio entre 30 a 50% en los diferentes estudios clínicos realizados en diferentes lugares del mundo. Desde entonces, este equipo de investigación ha venido ahondando en el estudio de los complejos mecanismos de infección empleados por el Plasmodium falciparum (especie de malaria letal al humano) para el desarrollo de una nueva generación de vacuna sintética multiestadío, multiantigénica y definida fisicoquímicamente como unidades macromoleculares. Como parte importante de este engranaje, hemos planteado en este trabajo la obtención de constructos macromoleculares sintéticos totalmente definidos. Para ello nos basamos en el diseño racional de inmunógenos modificados estratégicamente, provenientes de regiones no polimórficas de antígenos relevantes del Plasmodium que evidencien motivos o sitios clave para su unión a las células blanco del patógeno en estadios sanguíneos, en este caso al glóbulo rojo. Este tipo de modificaciones a nivel de estructura primaria de los antígenos nativos incluye la detección de posibles marcos de lectura por parte del HLA. Teniendo en cuenta lo anterior, seleccionamos un antígeno expresado en los organelos apicales de los estadios merozoito y esquizonte maduro del parasito denominado Apical Sushi Protein (PfASP), denominado así por poseer dominios tipo Sushi caracterizados por contener puentes disulfuro semejantes a los encontrados en moléculas de la cascada del complemento del sistema inmunológico humano. Una vez determinados cuatro péptidos con alta capacidad de unión a glóbulos rojos (denominados HABPs por High Activity Binding Peptides) codificados como 34259, 34270, 34273 y 34290 ubicados en diferentes lugares dentro de la estructura de 731 aminoácidos de PfASP, estos se sintetizaron como polímeros no controlados vía Cisteínas y se sometieron a evaluación de diferentes propiedades biológicas, entre ellas su capacidad citotóxica, hemolítica, antigénica y además fueron evaluados funcionalmente por su capacidad de evidenciar control de la infección por malaria en un modelo animal experimental de roedores previamente vacunados con estos polímeros y sus análogos modificados estratégicamente, esto teniendo en cuenta la alta semejanza estructural entre la proteína humana PfASP y secuencias ortólogas en Plasmodium berghei y Plasmodium yoelii. Con las secuencias de PfASP que evidenciaron perfiles de actividad funcional más relevantes, se decidió diseñar y elaborar constructos macromoleculares definidos tetraméricamente empleando varias estrategias para su posterior análisis, entre estas la síntesis de polímeros no controlados vía Cisteínas, constructos lineales obtenidos por condensación de bloque, dobles dímeros convencionales o asimétricos y finalmente dobles dímeros simétricos en los cuales se funcionalizaron residuos de lisina en el núcleo de propagación de este nuevo tipo de dendrímeros con el propósito de equiparar tanto las distancias como la reactividad de las funciones amino primaria respecto al carbono alpha. A algunos de los constructos se incorporaron secuencias blanco sustrato de Catepsinas (enzimas presentes a nivel lisosomal en las células profesionales fagocíticas APC) con el propósito de tratar de guiar la presentación antigénica de estos análogos sintéticos. Estos compuestos se obtuvieron con rendimientos diferenciales en cantidades suficientes para los ensayos de actividad funcional. Con esta batería de análogos sintéticos se realizaron nuevamente estudios de actividad citotóxica, hemolítica, antigénica e inmunogénica en ensayos de protección en grupos de animales experimentales, ratones BALB/c. Se encontró que algunos de estos constructos, como son los Dobles Dímeros Simétricos y Constructos Lineales por Condensación que contenían las secuencias blanco de Catepsinas y otros espaciadores como ácido aminohexanóico, evidenciaron controlar de manera eficiente los niveles de infección en los animales desafiados con las dos cepas de malaria murina. Los linfocitos B presentes en el bazo de aquellos animales que evidenciaron controlar la infección por malaria se sometieron a análisis del perfil de citoquinas secretadas y se encontró que en algunos casos la respuesta fue coherente con perfiles definidos Th2, otros Th1 preferencialmente y algunos una relación equiparable Th1-Th2, indicando la capacidad inmuno-estimuladora de este tipo de compuestos definidos fisicoquímicamente y evidenciando su papel en el campo de nuevas vacunas contra la malaria diseñadas racionalmente.Abstract. Malaria is still one of the most important public health problems worldwide. Currently, over 40% of the world population living in tropical and subtropical regions is endemic for this disease. In spite of all strategies proposed by organizations such as WHO —World Health Organization— and PAHO —Panamerican Health Organization—, for the last year 216 million clinical cases of malaria were registered and nearly 655,000 deaths due to this cause, mainly pregnant women and children under five years of edge. This problem has been visibly worsened by multiple circumstances among them, the strong climate changes over recent years, which have allowed the colonization of new territories where malaria was not present before, resistant evolved mechanisms by Plasmodium species —the causative agent of this disease— to antibiotics and that of the female Anopheles mosquito (the malaria transmission vector) to insecticides such as DDT. Therefore, the search for new therapeutic and immunoprophylactic strategies for this deathly disease remains a global priority. Currently, about 150 different prototypes of malaria vaccines are at different stages of research without promising results regarding the prevention of the disease. However, a significant effort in the eighties, headed by Professor Manuel Elkin Patarroyo and his team, led the development of the first synthetic vaccine called SPf66 against this disease, whose protective efficacy was averaged between 30-50% in different clinical trials conducted in different parts of the world. Since then, this research team has been delving into the study of the complex infection mechanisms used by Plasmodium falciparum —lethal species for human beings— as the basis for developing a new generation of a multistage and multiantigenic and completely physicochemically defined vaccine presented as a macromolecular unit. As an important part of this gear, we have proposed obtaining of fully defined synthetic macromolecular constructs. In order to do this, we rely on the rational design of strategically modified immunogens. Such immunogens belong to non-polymorphic regions of the Plasmodium’s blood states relevant antigens characterized by harbouring high binding motifs to the pathogen’s target cells. Such site-directed mutations at the native antigens primary structure level have considered potential HLA reading frames. Taking the above considerations into account, we have selected a specific antigen expressed on the apical organelles of the merozoite as well as in mature schizont stages of the parasite known as Apical Sushi Protein (PfASP), because of their Sushi domains which are characterized by disulfide bridges similar to those found in the complement cascade molecules of the human immunological system. Having identified four High Activity Binding Peptides (HABPs), they were coded as 34259, 34270, 34273 and 34290 respectively and all of them are located at different places in the 731 aminoacids of the PfASP. These were synthesized as uncontrolled polymers via cysteine reactivity and were subjected to the evaluation of different biological properties, including their cytotoxic, hemolytic and antigenic activity. Besides, they were functionally evaluated to determine if they were able to control the malaria infection in an experimental animal model, in which mice were previously immunized with these polymers and their strategically modified analogues, considering the high structural similarity between the human PfASP and its orthologous sequences in the Plasmodium berghei and Plasmodium yoelii. Upon detection of those PfASP sequences that showed profiles with most relevant functional activity, it was decided to design and develop tetramerically defined macromolecular constructs by using several strategies for further analysis, among these uncontrolled polymer synthesis via cysteine reactivity, linear constructs obtained by blocks condensation, conventional or asymmetric double dimers and finally symmetrical double dimers in which lysine residues were functionalized at the spreading nucleus of this new type of dendrimers, in order to equalize both distances and reactivity of these two primary amino functions in relation to the alpha carbon. Cathepsins substrate target sequences —enzymes present at a lysosomal level in the antigen-presenting cells— were incorporated onto some constructs primary structure in order to guide the antigen presentation of these synthetic analogues by APC— antigen presenting cells. These compounds were obtained in differential overall yields in sufficient amounts to conduct the functional activity trials. With this set of synthetic analogues, cytotoxic, hemolytic, antigenic and immunologic activity studies were conducted in protection trials in experimental animal groups of BALB/c mice. Some of these constructs, such as Symmetric Double Dimers and Linear Condensed Constructs which contained the target sequences of Cathepsins and other spacers such as aminohexanoic acid, were found to control efficiently the infection levels in animals exposed to the two strains of rodent malaria. B cells present in the spleen cells of those animals which were able to control the malaria infection were subjected to an analysis of secreted cytokines. The results show that, in some cases, the response was consistent with Th2 profiles, other Th1 preferentially and others having an equivalent Th1-Th2 ratio which indicates the immuno-stimulatory capacity of this novel type of physicochemically defined compounds revealing thus their role in rationally designed new malaria vaccinesDoctorad