Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell. These data were compared with gene expression profiles from HCV-infected chimpanzees.</p> <p>Results</p> <p>Transcriptome profiling of Huh-7 cells treated with 25-HC gave 47 downregulated genes, 16 of which are clearly related to the mevalonate pathway. Fewer genes were observed to be upregulated (22) in the presence of 25-HC and 5 genes were uniquely upregulated in the HCV replicon bearing cells. Comparison of these gene expression profiles with data collected during the initial rise in viremia in 4 previously characterized HCV-infected chimpanzees yielded 54 overlapping genes, 4 of which showed interesting differential regulation at the mRNA level in both systems. These genes are PROX1, INSIG-1, NK4, and UBD. The expression of these genes was perturbed with siRNAs and with overexpression vectors in HCV replicon cells, and the effect on HCV replication and translation was assessed. Both PROX1 and NK4 regulated HCV replication in conjunction with an antiviral state induced by 25-hydroxycholesterol.</p> <p>Conclusion</p> <p>Treatment of Huh-7 cells bearing HCV replicons with 25-HC leads to the downregulation of many key genes involved in the mevalonate pathway leading to an antiviral state within the host cell. Furthermore, dysregulation of a larger subset of genes not directly related to the mevalonate pathway occurs both in 25-HC-treated HCV replicon harbouring cells as well as during the initial rise in viremia in infected chimpanzees. Functional studies of 3 of these genes demonstrates that they do not directly act as antiviral gene products but that they indirectly contribute to the antiviral state in the host cell. These genes may also represent novel biomarkers for HCV infection, since they demonstrate an outcome-specific expression profile.</p

Rn 124, les sites de la déviation nord d'Auch (Gers) : rapport de fouille : DFS de sauvetage urgent

Fouille partielle d’un tronçon de la voie romaine Auch-Lectoure, constituée d’un ballast de galets et de matériaux divers. Utilisé depuis la première moitié du premier siècle de notre ère, la voie a été régulièrement rechargée. Elle est partiellement détruite à la fin du moyen-âge par un nouveau chemin, dont l’utilisation s’est prolongée jusqu’au XVIIIe. S

Rn 124, les sites de la déviation nord d'Auch (Gers) : rapport de fouille : DFS de sauvetage urgent

Fouille partielle d’un tronçon de la voie romaine Auch-Lectoure, constituée d’un ballast de galets et de matériaux divers. Utilisé depuis la première moitié du premier siècle de notre ère, la voie a été régulièrement rechargée. Elle est partiellement détruite à la fin du moyen-âge par un nouveau chemin, dont l’utilisation s’est prolongée jusqu’au XVIIIe. S

La villa rustique de Larajadé (Auch, Gers), un petit établissement rural aux portes d'Augusta Auscorum : l'approche archéologique

International audienc

A multisystem-compatible deep learning-based algorithm for detection and characterization of angiectasias in small-bowel capsule endoscopy. A proof-of-concept study.

International audienceBackground and aimsCurrent artificial intelligence (AI)-based solutions for capsule endoscopy (CE) interpretation are proprietary. We aimed to evaluate an AI solution trained on a specific CE system (Pillcam®, Medtronic) for the detection of angiectasias on images captured by a different proprietary system (MiroCam®, Intromedic).Material and methodsAn advanced AI solution (Axaro®, Augmented Endoscopy), previously trained on Pillcam® small bowell images, was evaluated on independent datasets with more than 1200 Pillcam® and MiroCam® still frames (equally distributed, with or without angiectasias). Images were reviewed by experts before and after AI interpretation.ResultsSensitivity for the diagnosis of angiectasia was 97.4% with Pillcam® images and 96.1% with Mirocam® images, with specificity of 98.8% and 97.8%, respectively. Performances regarding the delineation of regions of interest and the characterization of angiectasias were similar in both groups (all above 95%). Processing time was significantly shorter with Mirocam® (20.7 ms) than with Pillcam® images (24.6 ms, p<0.0001), possibly related to technical differences between systems.ConclusionThis proof-of-concept study on still images paves the way for the development of resource-sparing, “universal” CE databases and AI solutions for CE interpretation

Stations routières en Gaule romaine

Ce dossier ambitionne de renouveler la documentation sur les stations routières en Gaule romaine et dans les provinces voisines. Le sujet, qui intéresse autant l’histoire politique que l’histoire économique, méritait en effet un nouvel éclairage, à la lumière de données archéologiques récentes qui concernent une période comprise entre la fin de l’époque républicaine et l’Antiquité tardive. Les vocables employés dans les sources écrites pour désigner des établissements d’accueil des voyageurs, si difficiles à cerner soient-ils, sont mis à l’épreuve des faits archéologiques par les chercheurs. L’étude circonstanciée de l’architecture des établissements de bord de route, avec la mise en évidence de modèles architecturaux susceptibles de ressortir, pour certains, d’une politique d’équipement routier de l’État romain, constitue l’essentiel des contributions présentées dans ce dossier. Des recherches micro-régionales démontrent par ailleurs la fréquence et la variété des établissements d’accueil des voyageurs le long des routes des Gaules

An open-label randomized controlled trial of low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults (MSN Study).

International audienceFirst-line therapy of minimal change nephrotic syndrome (MCNS) in adults is extrapolated largely from pediatric studies and consists of high-dose oral corticosteroids. We assessed whether a low corticosteroid dose combined with mycophenolate sodium was superior to a standard oral corticosteroid regimen. We enrolled 116 adults with MCNS in an open-label randomized controlled trial involving 32 French centers. Participants randomly assigned to the test group (n=58) received low-dose prednisone (0.5 mg/kg/day, maximum 40 mg/day) plus enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks; those who did not achieve complete remission after week 8 were eligible for a second-line regimen (increase in the prednisone dose to 1 mg/kg/day with or without Cyclosporine). Participants randomly assigned to the control group (n=58) received conventional high-dose prednisone (1 mg/kg/day, maximum 80 mg/day) for 24 weeks. The primary endpoint of complete remission after four weeks of treatment was ascertained in 109 participants, with no significant difference between the test and control groups. Secondary outcomes, including remission after 8 and 24 weeks of treatment, did not differ between the two groups. During 52 weeks of follow-up, MCNS relapsed in 15 participants (23.1%) who had achieved the primary outcome. Median time to relapse was similar in the test and control groups (7.1 and 5.1 months, respectively), as was the incidence of serious adverse events. Five participants died from hemorrhage (n=2) or septic shock (n=3), including 2 participants in the test group and 3 in the control group. Thus, in adult patients, treatment with low-dose prednisone plus enteric-coated mycophenolate sodium was not superior to a standard high-dose prednisone regimen to induce complete remission of MCNS