610 research outputs found

    Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine

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    Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205-targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ- and interleukin 2-producing CD4 + T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ-dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities

    Trastorno bipolar y deterioro cognitivo

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    El presente trabajo tiene como objetivo demostrar la relación entre el trastorno bipolar y el deterioro cognitivo. Se comparó un grupo de 35 pacientes con diagnostico de trastorno bipolar según los criterios diagnósticos del DSM IV, versus un grupo control de personas mayores de 21 y menores de 60 años de edad que no presentaban antecedentes de tratamientos por psiquiatría. El instrumento que se aplicó en ambos grupos fue la ACE (Addenbrooke¨s cognitive examination) que evalúa seis dominios cognitivos como la orientación, atención, memoria, fluencia verbal, lenguaje y habilidades visuoespaciales.Facultad de Ciencias Médica

    The Virion Host Shut-Off (vhs) Protein Blocks a TLR-Independent Pathway of Herpes Simplex Virus Type 1 Recognition in Human and Mouse Dendritic Cells

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    Molecular pathways underlying the activation of dendritic cells (DCs) in response to Herpes Simplex Virus type 1 (HSV-1) are poorly understood. Removal of the HSV virion host shut-off (vhs) protein relieves a block to DC activation observed during wild-type infection. In this study, we utilized a potent DC stimulatory HSV-1 recombinant virus lacking vhs as a tool to investigate the mechanisms involved in the activation of DCs by HSV-1. We report that the release of pro-inflammatory cytokines by conventional DC (cDC) during HSV-1 infection is triggered by both virus replication-dependent and replication-independent pathways. Interestingly, while vhs is capable of inhibiting the release of cytokines during infection of human and mouse cDCs, the secretion of cytokines by plasmacytoid DC (pDC) is not affected by vhs. These data prompted us to postulate that infection of cDCs by HSV triggers a TLR independent pathway for cDC activation that is susceptible to blockage by the vhs protein. Using cDCs isolated from mice deficient in both the TLR adaptor protein MyD88 and TLR3, we show that HSV-1 and the vhs-deleted virus can activate cDCs independently of TLR signaling. In addition, virion-associated vhs fails to block cDC activation in response to treatment with TLR agonists, but it efficiently blocked cDC activation triggered by the paramyxoviruses Sendai Virus (SeV) and Newcastle Disease Virus (NDV). This block to SeV- and NDV-induced activation of cDC resulted in elevated SeV and NDV viral gene expression indicating that infection with HSV-1 enhances the cell's susceptibility to other pathogens through the action of vhs. Our results demonstrate for the first time that a viral protein contained in the tegument of HSV-1 can block the induction of DC activation by TLR-independent pathways of viral recognition

    Reporte ejecutivo del proceso de consultoría integral en una empresa de transformación de la madera y sus derivados, ubicada en el AMG

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    La empresa con la que se trabajó en consultoría procesa madera, fabrica muebles e instalaciones de diseño. Durante este periodo de otoño 2022 a través del PAP Consultoría para la Competitividad de realizó un proceso de diagnóstico colaborativo y sistémico, basados en un análisis externo, interno y de la estrategia, donde se utilizaron distintas herramientas que permitieron identificar las áreas de oportunidad en las cuales la empresa debe de poner atención para lograr estabilidad, mantenerse en el mercado actual y ser competitiva. Una vez analizados todos los factores, se definieron las áreas claves de desempeño y las capacidades empresariales que la empresa deberá desarrollar en los próximos periodos de PAP.ITESO, A.C

    Investigaciones arqueológicas en el centro de la provincia de Corrientes: primeros resultados de las prospecciones en el sistema Iberá

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    Las investigaciones arqueológicas en el centro de la provincia de Corrientes han sido escasas y discontinuas. Con el objetivo de revertir este panorama se iniciaron trabajos de campo en el sector sur y sursureste del macrosistema Iberá (Reserva Provincial Iberá y Parque Nacional Iberá). En este trabajo se presentan los resultados de las actividades de prospección y excavación desarrolladas. Como resultado de las mismas, se identificaron 11 áreas en las que los materiales arqueológicos se presentan en densidades variables y asociados a una matriz sedimentaria con alta proporción de conchillas. En líneas generales, estas se caracterizan por la presencia de material cerámico, lítico, restos óseos humanos y faunísticos, ornamentos, entre otros. A esta información, se integran y discuten los antecedentes para el sector, confirmando el alto potencial arqueológico del área. La evaluación de la red de permeabilidad del sector permitió identificar tres formas posibles de desplazamiento práctico entre la totalidad de los sitios hasta ahora identificados (n= 33)

    N-1,2,3-triazole-isatin derivatives for cholinesterase and β-amyloid aggregation inhibition: A comprehensive bioassay study

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    Our goal was the evaluation of a series of N-1,2,3-triazole-isatin derivatives for multi-target activity which included cholinesterase (ChE) inhibition and β-amyloid (Aβ) peptide anti-aggregation. The compounds have shown considerable promise as butyrylcholinesterase (BuChE) inhibitors. Although the inhibition of eel acet- ylcholinesterase (eeAChE) was weak, the inhibitions against equine BuChE (eqBuChE) and human BuChE (hBuChE) were more significant with a best inhibition against eqBuChE of 0.46 μM. In some cases, these mo- lecules gave better inhibitions for hBuChE than eqBuChE. For greater insights into their mode of action, mole- cular docking studies were carried out, followed by STD-NMR validation. In addition, some of these compounds showed weak Aβ anti-aggregation activity. Hepatotoxicity studies showed that they were non-hepatoxic and neurotoxicity studies using neurite out- growth experiments led to the conclusion that these compounds are only weakly neurotoxic

    The heritability and patterns of DNA methylation in normal human colorectum

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    DNA methylation (DNAm) has been linked to changes in chromatin structure, gene expression and disease. The DNAm level can be affected by genetic variation; although, how this differs by CpG dinucleotide density and genic location of the DNAm site is not well understood. Moreover, the effect of disease causing variants on the DNAm level in a tissue relevant to disease has yet to be fully elucidated. To this end, we investigated the phenotypic profiles, genetic effects and regional genomic heritability for 196080 DNAm sites in healthy colorectum tissue from 132 unrelated Colombian individuals. DNAm sites in regions of low-CpG density were more variable, on average more methylated and were more likely to be significantly heritable when compared with DNAm sites in regions of high-CpG density. DNAm sites located in intergenic regions had a higher mean DNAm level and were more likely to be heritable when compared with DNAm sites in the transcription start site (TSS) of a gene expressed in colon tissue. Within CpG-dense regions, the propensity of the DNAm level to be heritable was lower in the TSS of genes expressed in colon tissue than in the TSS of genes not expressed in colon tissue. In addition, regional genetic variation was associated with variation in local DNAm level no more frequently for DNAm sites within colorectal cancer risk regions than it was for DNAm sites outside such regions. Overall, DNAm sites located in different genomic contexts exhibited distinguishable profiles and may have a different biological function

    Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine

    Get PDF
    Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ– and interleukin 2–producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities

    We are more than EFL teachers-we are Educators: Emancipating EFL student-teachers through photovoice

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    The prevailing pedagogical orientations of English as a foreign language (EFL) education in Spain oppress learners intellectually in ways that are counterproductive to their learning. As a reaction to this, 129 EFL student-teachers (STs) took part during the 2013/14, 2014/15, and 2015/16 academic years in a workshop which drew on the methodology of participatory action research and on photovoice as a data-creating strategy, in order to emancipate these STs intellectually, boost their EFL development, and offer an alternative critical model for their future EFL teaching. The research was assessed collectively through a variety of qualitative strategies. Results showed that the photovoice workshop created a rich and meaningful context for EFL learning, one which enabled the STs to fully actualize their intellectual potential by producing knowledge collectively, thereby setting a memorable educational example for their own future teaching

    Valoración antropométrica y nutricional de estudiantes de Nutrición de la Universidad Maza

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    Siendo la obesidad la pandemia del siglo XXI, es necesario analizar cuál es la incidencia de la misma en personas especializadas en la temá- tica, de ahí la importancia de evaluar su prevalencia en estudiantes de Nutrición. Su objetivo es determinar la composición y peso corporal de alumnas de la carrera de Nutrición de la UMaza
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