The role of the purinergic P2X(7 )receptor in inflammation

The inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X(7 )receptor (P2X(7)R) is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X(7)R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X(7)R in inflammation, immunity and its potential role in disease will be reviewed and discussed

The role of the purinergic P2X(7 )receptor in inflammation

The inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X(7 )receptor (P2X(7)R) is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X(7)R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X(7)R in inflammation, immunity and its potential role in disease will be reviewed and discussed

The HIPASS Catalogue - II. Completeness, Reliability, and Parameter Accuracy

The HI Parkes All Sky Survey (HIPASS) is a blind extragalactic HI 21-cm emission line survey covering the whole southern sky from declination -90 to +25. The HIPASS catalogue (HICAT), containing 4315 HI-selected galaxies from the region south of declination +2, is presented in Meyer et al. (2004a, Paper I). This paper describes in detail the completeness and reliability of HICAT, which are calculated from the recovery rate of synthetic sources and follow-up observations, respectively. HICAT is found to be 99 per cent complete at a peak flux of 84 mJy and an integrated flux of 9.4 Jy km/s. The overall reliability is 95 per cent, but rises to 99 per cent for sources with peak fluxes >58 mJy or integrated flux > 8.2 Jy km/s. Expressions are derived for the uncertainties on the most important HICAT parameters: peak flux, integrated flux, velocity width, and recessional velocity. The errors on HICAT parameters are dominated by the noise in the HIPASS data, rather than by the parametrization procedure.Comment: Accepted for publication in MNRAS. 12 pages, 11 figures. Paper with higher resolution figures can be downloaded from http://hipass.aus-vo.or

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

A calibrated diversity assay for nucleic acid libraries using DiStRO—a Diversity Standard of Random Oligonucleotides

We have determined diversities exceeding 1012 different sequences in an annealing and melting assay using synthetic randomized oligonucleotides as a standard. For such high diversities, the annealing kinetics differ from those observed for low diversities, favouring the remelting curve after annealing as the best indicator of complexity. Direct comparisons of nucleic acid pools obtained from an aptamer selection demonstrate that even highly complex populations can be evaluated by using DiStRO, without the need of complicated calculations

The characterization of the distant blazar GB6 J1239+0443 from flaring and low activity periods

In 2008 AGILE and Fermi detected gamma-ray flaring activity from the unidentified EGRET source 3EG J1236+0457, recently associated with a flat spectrum radio quasar GB6 J1239+0443 at z=1.762. The optical counterpart of the gamma-ray source underwent a flux enhancement of a factor 15-30 in 6 years, and of ~10 in six months. We interpret this flare-up in terms of a transition from an accretion-disk dominated emission to a synchrotron-jet dominated one. We analysed a Sloan Digital Sky Survey (SDSS) archival optical spectrum taken during a period of low radio and optical activity of the source. We estimated the mass of the central black hole using the width of the CIV emission line. In our work, we have also investigated SDSS archival optical photometric data and UV GALEX observations to estimate the thermal-disk emission contribution of GB6 J1239+0443. Our analysis of the gamma-ray data taken during the flaring episodes indicates a flat gamma-ray spectrum, with an extension of up to 15 GeV, with no statistically-relevant sign of absorption from the broad line region, suggesting that the blazar-zone is located beyond the broad line region. This result is confirmed by the modeling of the broad-band spectral energy distribution (well constrained by the available multiwavelength data) of the flaring activity periods and by the accretion disk luminosity and black hole mass estimated by us using archival data.Comment: 30 pages, 7 figures, 4 tables MNRAS Accepted on 2012 June 1