Analisis del desplazamiento de la carga en vendimiadoras mediante el metodo de los elementos discretos

El pesado dinámico de las tolvas en una vendimiadora se ve afectado por diversas fuentes de variación. Una de ellas es el desplazamiento de la carga en su interior, debido principalmente a las inclinaciones del terreno a las que está expuesta la máquina. Este trabajo se ha realizado para cuantificar cómo se ve afectada la señal de la célula de carga en función de las inclinaciones de la máquina. El trabajo se ha dividido en dos partes: pruebas experimentales y modelización. La primera parte ha consistido en la realización de pruebas de laboratorio en las que la máquina vendimiadora, equipada con los correspondientes sensores y utilizando esferas de hidrogel como material para llenar la tolvas, fue sometida a distintas inclinaciones. En la segunda parte del trabajo se ha desarrollado un modelo de elementos discretos para simular el comportamiento de las esferas en el interior de la tolva y su efecto sobre la distribución de la carga. En un primer análisis de los datos se ha concluido que inclinaciones del terreno inferiores a 5° tendrían un efecto mínimo sobre el desplazamiento de la carga, y en consecuencia sobre la señal de la célula de carg

Effect of retinol dehydrogenase gene transfer in a novel rat model of Stargardt disease

International audienceDysfunction of the ATPase-binding Cassette Transporter protein (ABCA4) can lead to early onset macular degeneration, in particular to Stargardt disease. To enable translational research into this form of blindness, we evaluated the effect of Cas9-induced disruptions of the ABCA4 gene to potentially generate new transgenic rat models of the disease. We show that deletion of the short exon preceding the second nucleotide-binding domain is sufficient to drastically knock down protein levels and results in accumulation of retinoid dimers similar to that associated with Stargardt disease. Overexpression of the retinol dehydrogenase enzymes RDH8 and RDH12 can to a limited extent offset the increase in the bisretinoid levels in the Abca4(Ex42-/)- KO rats possibly by restricting the time window in which retinal can dimerize before being reduced to retinol. However, in vivo imaging shows that overexpression of RDH8 can induce retinal degeneration. This may be due to the depletion in the outer segment of the cofactor NADPH, needed for RDH function. The translational potential of RDH therapy as well as other Stargardt disease therapies can be tested using the Abca4 knockdown rat model

Long-term expression of melanopsin and channelrhodopsin causes no gross alterations in the dystrophic dog retina

International audienceSeveral preclinical studies have investigated the potential of algal channelrhodopsin and human melanopsin as optogenetic tools for vision restoration. In the present study, we assessed the potentially deleterious effects of long-term expression of these optogenes on the diseased retina in a large animal model of retinal degeneration, the RPE65-deficient Briard dog model of Leber congenital amaurosis. Intravitreal injection of adeno-associated virus vectors expressing channelrhodopsin and melanopsin had no effect on retinal thickness over a 16-month period post injection. Our data support the safety of the optogenetic approach for the treatment of blindness

Long-term expression of melanopsin and channelrhodopsin causes no gross alterations in the dystrophic dog retina

International audienceSeveral preclinical studies have investigated the potential of algal channelrhodopsin and human melanopsin as optogenetic tools for vision restoration. In the present study, we assessed the potentially deleterious effects of long-term expression of these optogenes on the diseased retina in a large animal model of retinal degeneration, the RPE65-deficient Briard dog model of Leber congenital amaurosis. Intravitreal injection of adeno-associated virus vectors expressing channelrhodopsin and melanopsin had no effect on retinal thickness over a 16-month period post injection. Our data support the safety of the optogenetic approach for the treatment of blindness

Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior

A single nucleotide polymorphism (SNP) in the human μ-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in a variety of drug addiction and pain sensitivity phenotypes; however, the extent of these adaptations and the mechanisms underlying these associations remain elusive. To clarify the functional mechanisms linking the OPRM1 A118G SNP to addiction and analgesia phenotypes, we derived a mouse model possessing the equivalent nucleotide/amino acid substitution in the Oprm1 gene. Mice harboring this SNP (A112G) demonstrated several phenotypic similarities to humans carrying the A118G SNP, including reduced mRNA expression and morphine-mediated antinociception. We found additional phenotypes associated with this SNP including significant reductions of receptor protein levels, morphine-mediated hyperactivity, and the development of locomotor sensitization in mice harboring the G112 allele. In addition, we found sex-specific reductions in the rewarding properties of morphine and the aversive components of naloxone-precipitated morphine withdrawal. Further cross-species analysis will allow us to investigate mechanisms and adaptations present in humans carrying this SNP

Gender-stratified gene and gene-treatment interactions in smoking cessation

We conducted gender-stratified analyses on a systems-based candidate gene study of 53 regions involved in nicotinic response and the brain-reward pathway in two randomized clinical trials of smoking cessation treatments (placebo, bupropion, transdermal an