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

Design of GaN-based balanced cascode cells for wide-band distributed power amplifier

International audienceThis paper reports on the design of a cascode GaN HEMT cell dedicated to 4-18 GHz flip-chip distributed power amplifier. The active device is a 8x50 mum AlGaN/GaN HEMT grown on SiC substrate. The GaN-based die which integrates the active cascode cell and its matching elements is flip-chipped via electrical bumps onto an AIN substrate. The matching elements of the balanced cascode cell are composed of series capacitances on the gate of both transistors with additional resistances to insure stability and bias path. The series capacitor on the gate of the 1st transistor is added for the distributed amplifier optimisation while the series capacitor on the gate of the 2 nd transistor is dedicate

An advanced sheep (Ovis aries, 2n = 54) cytogenetic map and assignment of 88 new autosomal loci by fluorescence in situ hybridization and R-banding

Presented herein is an updated sheep cytogenetic map that contains 452 loci (291 type I and 161 type II) assigned to specific chromosome bands or regions on standard R-banded ideograms. This map, which significantly extends our knowledge of the physical organization of the ovine genome, includes new assignments for 88 autosomal loci, including 74 type I loci (known genes) and 14 type II loci (SSRs/microsatellite marker/STSs), by FISH-mapping and R-banding. Comparison of the ovine map to the cattle and goat cytogenetic maps showed that common loci were located within homologous chromosomes and chromosome bands, confirming the high level of conservation of autosomes among ruminant species. Eleven loci that were FISH-mapped in sheep (B3GAT2, ASCC3, RARSL, BRD2, POLR1C, PPP2R5D, TNRC5, BAT2, BAT4, CDC5L and OLA-DRA) are unassigned in cattle and goat. Eleven other loci (D3S32, D1S86, BMS2621, SFXN5, D5S3, D5S68, CSKB1, D7S49, D9S15, D9S55 and D29S35) were assigned to specific ovine chromosome (OAR) bands but have only been assigned to chromosomes in cattle and goat

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

High power HBT technologies : present and trends

The HBT technology is now mature and offers a great variety of RF products for telecom applications, specially power amplifiers for which a high level of linearity is requested. The reliability has been the limiting factor in the supplying of high power amplifiers and nowadays only medium HPA are available in catalogue. Also, regarding the huge quantities of papers published in the mid 90s relating the interest of this technology for high PAE / Power, very few of the competitors have been successful. In Europe, open foundry services are available through UMS for high power applications ranging up to Ku band. New advances in term of thermal management / electrical behaviour and topology have been pushed ahead tending towards the limit of high power density. An improved version is underway to set up a doubling of the output power by cell (2.5W in X- Band). To address the market of the base stations, very high power transistors have been designed. Also, the Collector-Up DHBT offer potential improvement in term o high power at high frequency (1W at 40 GHz)

InGaP Power HBTs : Basic power cells for High Power transistors

Power HBT Technology offers today the best compromise for high power – high efficiency amplifiers up to Ku band. Many improvements have been published in the past to offer a better behaviour in terms of thermal heating and microwave performances. Since the reliability limiting factors have been solved, significant improvements could be proposed to get more power. In this paper, we report on the proposal of new elementary cells used in multi-finger transistors. Based on these, compact very high power amplifiers could be considered

Single and double heterojunction bipolar transistors in collector-up topology

For the first time, DC- and RF characteristics of single and double heterojunction bipolar transistors (S-HBT and D-HBT respectively) in collector-up topology are measured and compared. Both devices are realized in InGaP/GaAs technology and offer high common emitter breakdown voltage (BVceo > 16V) and high maximum oscillation frequency (fmax > 115GHz

Accurate Characterization of S-Band HBT Power Amplifier using simultaneously S parameters and Load-Pull Measurements

This paper emphasizes for the first time the link existing between some small-signal power gain circles and the output load of maximum power in GaAs HBTs. We use the locus of power gain, named Minimum Conjugate- Termination Power, which have the value MSG/2K. MSG is maximum stable gain and K the stability factor. This method has been applied to the measurements by load-pull of 30W S-Band HBT power bar. By varying the bias of the amplifier, it is possible using only S-parameters data to localize accurately and quickly the locus of the power load