Otx2 Gene Deletion in Adult Mouse Retina Induces Rapid RPE Dystrophy and Slow Photoreceptor Degeneration

International audienceBACKGROUND: Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE), a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells. METHODOLOGY/PRINCIPAL FINDINGS: Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease. CONCLUSIONS: Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE

Force Measurements of TCR/pMHC Recognition at T Cell Surface

The rupture forces and adhesion frequencies of single recognition complexes between an affinity selected peptide/MHC complex and a TCR at a murine hybridoma surface were measured using Atomic Force Microscopy. When the CD8 coreceptor is absent, the adhesion frequency depends on the nature of the peptide but the rupture force does not. When CD8 is present, no effect of the nature of the peptide is observed. CD8 is proposed to act as a time and distance lock, enabling the shorter TCR molecule to bridge the pMHC and have time to finely read the peptide. Ultimately, such experiments could help the dissection of the sequential steps by which the TCR reads the peptide/MHC complex in order to control T cell activation

Dissertation sur les parties sensibles du corps animal : suivi d'un mémoire sur les avantages que procurent les frictions mercurielles dans le traitement de quelques epilepsies idiopatiques ...

par Mr. E. J. P. HoussetAus dem Vorbesitz der Naturforschenden Gesellschaft in Züric

In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal

International audienceNon-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), represents the hepatic manifestation of obesity and metabolic syndrome. Due to the spread of the obesity epidemic, NAFLD is becoming the most common chronic liver disease and one of the principal indications for liver transplantation. However, no pharmacological treatment is currently approved to prevent the outbreak of NASH, which leads to fibrosis and cirrhosis. Preclinical research is required to improve our knowledge of NAFLD physiopathology and to identify new therapeutic targets. In the present review, we summarize advances in NAFLD preclinical models from cellular models, including new bioengineered platforms, to in vivo models, with a particular focus on genetic and dietary mouse models. We aim to discuss the advantages and limits of these different models

Étrennes aux trois Andrés, ou Apologie du "Précis historique sur l'année séculaire de la délivrance de la ville d'Auxerre", contre les observations d'un anonime insérées dans le "Journal de Verdun" du mois d'octobre 1769. [Signé : Housset.]

Appartient à l’ensemble documentaire : Bourgogn1Avec mode text

Des philosophes devant la mort

Sous la direction de Bertrand Quentin. Textes issus de communications données lors de la journée d'étude du 24 mai 2014, organisée par le Laboratoire interdisciplinaire d'études du politique Hannah Arendt de Paris Est (LIPHA Paris-Est).International audienceL’homme des sociétés contemporaines souhaiterait que la science se charge de résoudre ses problèmes métaphysiques mais il sent bien face à la mort qu’il y a maldonne. C’est ici que les philosophes du passé peuvent nous être utiles. La manière dont ils ont posé la question de la mort peut clairement être réinvestie dans les problématiques de notre époque L’ouvrage nous montre comment différents philosophes approchent cette question redoutable. Les contrastes seront saisissants entre Stoïciens, saint Augustin, Descartes ou Levinas. La pensée négro-africaine est également convoquée. Au bout de ce parcours, on découvrira qu’il y a chez l’homme la possibilité par la pensée et les mœurs de retirer à la mort une certaine part de son âcreté, même s’il restera aussi en elle quelque chose de rédhibitoirement inassimilable