Genome-wide identification of direct HBx genomic targets

Background: The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV. Results: ChIP-Seq high throughput sequencing of HBx-bound fragments was used to obtain a high-resolution, unbiased, mapping of HBx binding sites across the genome in HBV replicating cells. Protein-coding genes and ncRNAs involved in cell metabolism, chromatin dynamics and cancer were enriched among HBx targets together with genes/ncRNAs known to modulate HBV replication. The direct transcriptional activation of genes/miRNAs that potentiate endocytosis (Ras-related in brain (RAB) GTPase family) and autophagy (autophagy related (ATG) genes, beclin-1, miR-33a) and the transcriptional repression of microRNAs (miR-138, miR-224, miR-576, miR-596) that directly target the HBV pgRNA and would inhibit HBV replication, contribute to HBx-mediated increase of HBV replication. Conclusions: Our ChIP-Seq analysis of HBx genome wide chromatin recruitment defined the repertoire of genes and ncRNAs directly targeted by HBx and led to the identification of new mechanisms by which HBx positively regulates cccDNA transcription and HBV replication

P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy

open access articleDuchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP–P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target

HBT technology and reliability for satellite applications, within the relatively new APOS project

The APOS (Advanced Power Subassemblies project addresses the devices (MMIC or discrete) used in the solid state power amplifiers (SSPA) that drive the transmit active antenna. These are key devices and their electrical and thermal performances have a major impact on both the satellite and the ground terminals. GaAs-based heterostructure bipolar transistor, due to their superior power/linearity performance, could be one of these enabling devices. This aspect will be addressed within the frame of this project through three main objectives : 1)To analyse the reliability of UMS HBT technology and demonstrate it meets the requirements of the commercial satellite markets. 2)To improve the power and thermal performances of HBT by developing a power flip- chip assembly technology using thermal bumps in the active area of the power device. 3)To benchmark the developed power HBT technology by using the power MMIC in a suitable active antenna module. This project consortium is formed by Alcatel Space, that will co-ordinate the project, United Monolithic Semiconductors (UMS), Thomson-CSF, Institute for Material Research at Limburg University Centrum (1MO-LUC), DESTIN and Institut d'Electronique et de Microelectronique du Nord (1EMN)

Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription

Objective The HBV HBx regulatory protein is required for transcription from the covalently closed circular DNA (cccDNA) minichromosome and affects the epigenetic control of both viral and host cellular chromatin. Design We explored, in relevant cellular models of HBV replication, the functional consequences of HBx interaction with DLEU2, a long non-coding RNA (lncRNA) expressed in the liver and increased in human hepatocellular carcinoma (HCC), in the regulation of host target genes and the HBV cccDNA. Results We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), the catalytic active subunit of the polycomb repressor complex 2 (PRC2) complex. Computational modelling and biochemical evidence suggest that HBx and EZH2 share two preferential binding sites in DLEU2 intron 1. HBx and DLEU2 co-recruitment on the cccDNA displaces EZH2 from the viral chromatin to boost transcription and viral replication. DLEU2-HBx association with target host promoters relieves EZH2 repression and leads to the transcriptional activation of a subset of EZH2/PRC2 target genes in HBV-infected cells and HBV-related HCCs. Conclusions Our results highlight the ability of HBx to bind RNA to impact on the epigenetic control of both viral cccDNA and host genes and provide a new key to understand the role of DLEU2 and EZH2 overexpression in HBV-related HCCs and HBx contribution to hepatocytes transformation

State of the Art 58W, 38% PAE X-Band AlGaN/GaN HEMTs microstrip MMIC Amplifiers

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Associations céréale-légumineuse multi-services

Depuis plusieurs décennies, l’évolution de l’agriculture en France est, dans un certain nombre de régions de grande culture et d’élevage marquée fortement par la simplification des assolements accompagnée d’un usage accru des intrants et la standardisation des itinéraires techniques. Le challenge est maintenant de concevoir des agroécosystèmes plus diversifiés dans l’objectif d’une gestion écologique des parcelles cultivées devant se traduire par une amélioration de la productivité et la stabilité des systèmes face à divers aléas et la fourniture de différents services éco-systémiques. Ce projet a exploré l’augmentation de la diversité cultivée au sein de la parcelle via des associations céréale-légumineuse. Il a montré la diversité des services que l’on peut en attendre en agriculture biologique et en agriculture conventionnelle, en système céréalier et en système d’élevage. Ces associations permettent de répondre à la fois à des enjeux de production, de réduction des intrants, de réduction des impacts environnementaux des cultures, de stabilité face à des aléas biotiques et abiotiques. Le coeur du projet a consisté a testé différents leviers d’actions pour aider à l’orientation des performances de ces associations pour différents objectifs. Les atouts et contraintes ’adoption à l’échelle des filières (notamment pour les collecteurs) ont été aussi mis en évidence et quantifiés

Associations céréale-légumineuses multi-services

Depuis plusieurs décennies, l’évolution de l’agriculture en France est, dans un certain nombre de régions de grande culture et d’élevage marquée fortement par la simplification des assolements accompagnée d’un usage accru des intrants et la standardisation des itinéraires techniques. Le challenge est maintenant de concevoir des agroécosystèmes plus diversifiés dans l’objectif d’une gestion écologique des parcelles cultivées devant se traduire par une amélioration de la productivité et la stabilité des systèmes face à divers aléas et la fourniture de différents services éco-systémiques. Ce projet a exploré l’augmentation de la diversité cultivée au sein de la parcelle via des associations céréale-légumineuse. Il a montré la diversité des services que l’on peut en attendre en agriculture biologique et en agriculture conventionnelle, en système céréalier et en système d’élevage. Ces associations permettent de répondre à la fois à des enjeux de production, de réduction des intrants, de réduction des impacts environnementaux des cultures, de stabilité face à des aléas biotiques et abiotiques. Le cœur du projet a consisté a testé différents leviers d’actions pour aider à l’orientation des performances de ces associations pour différents objectifs. Les atouts et contraintes d’adoption à l’échelle des filières (notamment pour les collecteurs) ont été aussi mis en évidence et quantifiés