Synthetic evaluation of standard and microwave-assisted solid phase peptide synthesis of a long chimeric peptide derived from four Plasmodium falciparum proteins

An 82-residue-long chimeric peptide was synthesised by solid phase peptide synthesis (SPPS), following the Fmoc protocol. Microwave (MW) radiation-assisted synthesis was compared to standard synthesis using low loading (0.20 mmol/g) of polyethylene glycol (PEG) resin. Similar synthetic difficulties were found when the chimeric peptide was obtained via these two reaction conditions, indicating that such difficulties were inherent to the sequence and could not be resolved using MW; by contrast, the number of coupling cycles and total reaction time became reduced whilst crude yield and percentage recovery after purification were higher for MW radiation-assisted synthesis. © 2018 by the authors

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions' immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides' (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo-electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.1

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

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

Hasta la fecha, la función de muchas proteínas de membrana hipotéticas de Mycobacterium tuberculosis aún se desconoce y su participación en las interacciones patógeno-huésped aún no se ha definido claramente. En este estudio, se evaluó la actividad biológica de los péptidos derivados de la proteína de membrana hipotética Rv0679c de M. tuberculosis y su participación en las interacciones patógeno-huésped. La transcripción del gen Rv0679c se estudió en 26 Mycobacteriumspp. Son. Los anticuerpos generados contra los supuestos epítopos de células B de Rv0679c se usaron en ensayos de inmunotransferencia y microscopía inmunoelectrónica. Los péptidos sintéticos que abarcan toda la longitud de la proteína fueron probados por su capacidad para unirse a las células A549 y U937. Los péptidos de unión de alta actividad (HABP) identificados en Rv0679c se probaron para determinar su capacidad para inhibir la invasión de micobacterias en las células.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

Mycobacterium tuberculosis H37Rv LpqG protein peptides can inhibit mycobacterial entry through specific interactions

Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease causing major mortality worldwide. As part of a systematic methodology for studying M. tuberculosis surface proteins which might be involved in host-pathogen interactions, our group found that LpqG surface protein (Rv3623) found in M. tuberculosis complex strains was located on the mycobacterial envelope and that peptide 16661 (21SGCDSHNSGSLGADPRQVTVY40) had high specific binding to U937 monocyte-derived macrophages and inhibited mycobacterial entry to such cells in a concentration-dependent way. A region having high specific binding to A549 alveolar epithelial cells was found which had low mycobacterial entry inhibition. As suggested in previous studies, relevant sequences in the host-pathogen interaction do not induce an immune response and peptides characterised as HABPs are poorly recognised by sera from individuals regardless of whether they have been in contact with M. tuberculosis. Our approach to designing a synthetic, multi-epitope anti-tuberculosis vaccine has been based on identifying sequences involved in different proteins' mycobacteria-target cell interaction and modifying their sequence to improve their immunogenic characteristics, meaning that peptide 16661 sequence should be considered in such design. © 2018 by the authors

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

Background. Malaria caused by Plasmodium vivax 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 Plasmodium falciparum, due in part to the difficulties of maintaining an in vitro culture of P. vivax. This study describes the identification of the P. falciparum thrombospondin-related apical merozoite protein homologue in P. vivax (PvTRAMP) and examines its potential to be further evaluated as vaccine candidate. Methods. The gene encoding PvTRAMP was identified through an extensive search of the databases hosting the genome sequence of P. vivax. Genes adjacent to pvtramp were identified in silico to determine the degree of similarity between the protein sequences encoded by equivalent chromosomic fragments in P. falciparum and Plasmodium knowlesi. The pvtramp gene was amplified from cDNA of P. vivax schizont stages, cloned and expressed in Escherichia coli. 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 P. vivax-infected individuals living in endemic areas was also assessed by ELISA. Results. The PfTRAMP homologue in P. vivax, 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 P. vivax. Conclusions. The results of this work support conducting further studies with PvTRAMP to evaluate its immunogenicity and protection-inducing ability in the Aotus animal model. © 2010 Mongui et al; licensee BioMed Central Ltd

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