La nucléoprotéine est nécessaire à l'immunogénicité des vecteurs vaccinaux basés sur les virus de la chorioméningite lymphocytaire recombinants (rLCMV)

Les vecteurs vaccinaux basés sur les rLCMV déficients en la glycoprotéine (rLCMV/deltaGP) induisent une réponse importante de la part des cellules T CD8+. Afin de mieux comprendre ses mécanismes moléculaires, nous avons généré un vecteur déficient en la nucléoprotéine (rLCMV/deltaNP). Contrairement à GP, NP est un facteur nécessaire pour la transcription virale et la réplication ("minimal trans-acting factor"). Nous avons démontré que, contrairement à rLCMV/deltaGP, rLCMV/deltaNP induit une réponse détectable de la part des cellules T CD8+ uniquement lorsqu'il est trans-complémenté par NP dans un hôte transgénique. L'expression génétique, qui dépend de NP, est donc essentielle à l'immunogénicité des vecteurs rLCMV

Developmental and metabolic brain alterations in rats exposed to bisphenol A during gestation and lactation.

In recent years, considerable research has focused on the biological effect of endocrine-disrupting chemicals. Bisphenol A (BPA) has been implicated as an endocrine-disrupting chemical (EDC) due to its ability to mimic the action of endogenous estrogenic hormones. The aim of this study was to assess the effect of perinatal exposure to BPA on cerebral structural development and metabolism after birth. BPA (1mg/l) was administered in the drinking water of pregnant dams from day 6 of gestation until pup weaning. At postnatal day 20, in vivo metabolite concentrations in the rat pup hippocampus were measured using high field proton magnetic resonance spectroscopy. Further, brain was assessed histologically for growth, gross morphology, glial and neuronal development and extent of myelination. Localized proton magnetic resonance spectroscopy ((1)H MRS) showed in the BPA-exposed rat a significant increase in glutamate concentration in the hippocampus as well as in the Glu/Asp ratio. Interestingly these two metabolites are metabolically linked together in the malate-aspartate metabolic shuttle. Quantitative histological analysis revealed that the density of NeuN-positive neurons in the hippocampus was decreased in the BPA-treated offspring when compared to controls. Conversely, the density of GFAP-positive astrocytes in the cingulum was increased in BPA-treated offspring. In conclusion, exposure to low-dose BPA during gestation and lactation leads to significant changes in the Glu/Asp ratio in the hippocampus, which may reflect impaired mitochondrial function and also result in neuronal and glial developmental alterations

Visualización de datos recopilados en redes vehiculares multisensor

El objetivo del este proyecto es crear un programa que muestre gráficamente datos relacionados a unas coordenadas, los cuales van a ser recogidos por sensores que transportan diferentes vehículos. Los datos recopilados pueden ser del tipo, nivel de humedad en ese punto, temperatura, nivel de CO2 en el aire, etc.Ingeniería en InformáticaInformatika Ingeniaritz

Heterologous arenavirus vector prime-boost overrules self-tolerance for efficient tumor-specific CD8 T cell attack

Therapeutic vaccination regimens inducing clinically effective tumor-specific CD8+ T lymphocyte (CTL) responses are an unmet medical need. We engineer two distantly related arenaviruses, Pichinde virus and lymphocytic choriomeningitis virus, for therapeutic cancer vaccination. In mice, life-replicating vector formats of these two viruses delivering a self-antigen in a heterologous prime-boost regimen induce tumor-specific CTL responses up to 50% of the circulating CD8 T cell pool. This CTL attack eliminates established solid tumors in a significant proportion of animals, accompanied by protection against tumor rechallenge. The magnitude of CTL responses is alarmin driven and requires combining two genealogically distantly related arenaviruses. Vector-neutralizing antibodies do not inhibit booster immunizations by the same vector or by closely related vectors. Rather, CTL immunodominance hierarchies favor vector backbone-targeted responses at the expense of self-reactive CTLs. These findings establish an arenavirus-based immunotherapy regimen that allows reshuffling of immunodominance hierarchies and breaking self-directed tolerance for efficient tumor control