Direct arylations on water: synthesis of 2,5-disubstituted oxazoles balsoxin and texaline

An efficient two-step palladium catalysed synthesis of 2,5-disubstituted oxazoles is reported

C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance

In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity

Chemical sensor networks for gas detection and environmental monitoring

This paper reviews the principles and prospects for optical fibre based measurement techniques for determining gas concentrations. Most of these exploit the precision and versatility of tuneable diode laser spectroscopy in the near infrared. We demonstrate the potential offered by large area multipoint totally passive networks and establish the performance potential which these may offer in hostile environments. These benefits include more than adequate sensitivity for most applications, automatic recalibration of both zero point and scale factor and the ability to precisely determine line shape information and in some cases perform detailed line spectrum analysis to determine concentration, pressure and temperature simultaneously. We also briefly describe the principles and application of photo acoustic spectroscopy and outline the performance improvements which tuneable diode laser systems also offer in this context. These studies have illustrated that, in appropriate niche applications, fibre based gas measurement systems offer substantial long term engineering potential

Identification and biological characterization of 6-aryl-7-isopropylquinazolinones as novel TRPV1 antagonists that are effective in models of chronic pain

Vanilloid receptor 1 (VR1, TRPV1) is a cation-selective ion channel that is expressed on primary afferent neurons and is upregulated following inflammation and nerve damage. Blockers of this channel may have utility in the treatment of chronic nociceptive and neuropathic pain. Here, we describe the optimization from a high throughput screening hit, of a series of 6-aryl-7-isopropylquinazolinones that are TRPV1 antagonists in vitro. We also demonstrate that one compound is active in vivo against capsaicin-induced hyperalgesia and in models of neuropathic and nociceptive pain in the rat