Rôle de la reptine dans le carcinome hépatocellulaire humain

Le carcinome hépatocellulaire (CHC) est la tumeur maligne du foie la plus fréquente. Une analyse protéomique de 4 CHC réalisée dans notre laboratoire a mis en évidence la surexpression de la Reptine. Cette protéine est une ATPase connue pour interagir avec la b-caténine et c-Myc, deux oncogènes du CHC. Une surexpression des transcrits de la Reptine a été retrouvée dans 75 % des CHC et un taux élevé d'ARNm Reptine a été corrélé à un mauvais pronostic. Aucune mutation de la séquence codante de la Reptine n'a été retrouvée. Afin de comprendre la fonction de la Reptine dans la carcinogenèse hépatique, nous avons modulé son expression dans la lignée de CHC humaine HuH7. Une réduction majeure de l'expression de la Reptine a provoqué un arrêt de la prolifération et une apoptose. Réciproquement, la surexpression stable de la Reptine obtenue a conféré aux cellules une résistance à l'apoptose. Les cellules surexprimant la Reptine proliféraient aussi davantage en agar mou et donnaient naissance à des tumeurs plus rapidement progressives après injection à des souris immunodéprimées. Ces résultats sont en faveur d'un rôle important pour cette protéine dans la carcinogenèse. Afin d'évaluer la possibilité que la Reptine puisse être une cible thérapeutique, nous avons mis au point une lignée HuH7 qui exprime de façon conditionnelle un shRNA Reptine. Cette lignée a ensuite été injectée en sous cutané à des souris immunodéprimées. Lorsque les tumeurs ont atteint un volume défini, nous avons induit l'expression de shRNA Reptine, ce qui a provoqué l'inhibition de la croissance tumorale. Ces résultats confortent l'idée que la Reptine puisse être une cible thérapeutique dans le CHC.Hepatocellular carcinoma (HCC) is the most common primary liver cancer. A proteomic analysis of 4 HCC realized in our lab led to the discovery of Reptin expression. Reptin is an ATPase which is able to interact with b-catenin and c-Myc, two oncogenes of HCC. An overexpression of Reptin transcripts was found in 75 % of HCC and it was associated with a poor prognosis. No mutation was identified in the coding sequence of Reptin. In order to study the role of Reptin in HCC, we modulated its expression in the HuH7 human HCC cell line. Downregulation of Reptin reduced cell growth and increased apoptosis. Conversely, HuH7 cells with stable overexpression of Reptin had an increased resistance to apoptosis, grew better in soft agar and gave rise to significantly larger tumors when injected to immunocompromised mice. These results argue for a major role of Reptin in liver carcinogenesis. In order to define whether Reptin was a potential therapeutic target, we developed a cell line expressing inducible Reptin shRNA. This cell line was injected to immunocompromised mice. When tumors reached a defined volume, we induced the expression of the Reptin shRNA. This caused an inhibition of tumor growth. These results suggest that Reptin could be a therapeutic target inHCC.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Mise en Oeuvre et modélisation d'une chaine d'acquisition sur une carte de prototypage mixte analogique-numérique

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Channel waveguide lasers in bulk Tm:LiYF 4 produced by deep diamond-saw dicing

International audienceWe report on a novel approach to fabricate channel (ridge) waveguides (WGs) in bulk crystals using precision diamond saw dicing. The channels feature a high depth-to-width aspect ratio (deep dicing). The proof-of-the-concept is shown for a Tm3+:LiYF4 fluoride crystal. Channels with a depth of 200 µm and widths of 10–50 µm are diced and characterized by confocal laser microscopy revealing a r.m.s. roughness of the walls well below 100 nm. The channels obtained possess waveguiding properties at ∼815 nm with almost no leakage of the guided mode having a vertical stripe intensity profile into the bulk crystal volume and relatively low propagation losses (0.20-0.43 dB/cm). Laser operation is achieved in quasi-CW regime by pumping at 780 nm. The maximum peak output power reaches 0.68 W at ∼1.91 µm with a slope efficiency of 53.3% (in σ-polarization). The proposed concept is applicable to a variety of laser crystals with different rare-earth dopants

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Spectral induced polarization data of rocks and porous media with graphit

Can horses discriminate human body odors from joy and fear contexts?

International audienceAnimals are commonly believed to detect human emotions through smell, in link with the primitive and ubiquitous characteristics of chemoreception. Indeed, the brain areas dedicated to odor processing are among the oldest structures in mammalian evolution, and chemosignals may play a role in interspecific communication. However, few studies have conclusively demonstrated that animals can perceive human emotions through smell. To determine whether horses can discriminate between human odors of fear and joy, a habituation-discrimination protocol was used. Horses were exposed to sweat odors from humans who declared they had experienced fear or joy while viewing a comedy or a horror film, respectively. A first odor was presented twice in subsequent trials (habituation), and then the same odor and a novel odor were presented simultaneously (discrimination). Both odors came from the same donor. Experimenters presenting the odors or coding the behavioral responses of horses to odors were blind to the condition. Horses sniffed the novel odor more than the repeated odor, indicating that they discriminated between the human odors produced in fear and joy contexts. Moreover, asymmetric nostril use and differences in habituation speed further imply differences in the emotional processing of the two odours by horses

Les chevaux peuvent-ils percevoir nos émotions via nos odeurs ?: Capacité de discrimination des odeurs humaines de joie et de peur par les chevaux

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Horses discriminate human body odours from joy and fear contexts

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Horses discriminate human body odours from joy and fear contexts

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