Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling

Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. Design: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p Results: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p= 1.3x10(-08), and rs842647 p= 5.26x10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. Conclusions: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappa B) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain similar to 40% of the heritability of coeliac disease

Measurements of 12C(→γ,pp) photon asymmetries for Eγ= 200–450 MeV

The 12C (→γ ,pp) reaction has been studied in the photon energy range 200-450 MeV at the Mainz microtron MAMI-C, where linearly polarised photons were energy-tagged using the Glasgow-Mainz Tagged Photon Spectrometer and protons were detected in the Crystal Ball detector. The photon asymmetry Σ has been measured over a wider Eγ range than previous measurements. The strongest asymmetries were found at low missing energies where direct emission of nucleon pairs is expected. Cuts on the difference in azimuthal angles of the two ejected protons increased the magnitude of the observed asymmetries. At low missing energies the Σ data exhibit a strong angular dependence, similar to deuteron photodisintegration

Surface-enhanced Raman spectroscopy using silver impregnated polycarbonate substrates

Novel substrates based on noble metal nanoparticles are currently the subject of extensive research in fields such as biological sensing, medicine, spectroscopy and nano-photonics due to the large electromagnetic fields generated in the vicinity of the metal surface via a surface plasmon resonance. The dependence of the resonance wavelength on the size, shape, local dielectric environment and interparticle spacing, enables engineering of the metal nanoparticle substrates to target specific requirements [1]. Here we report the fabrication of silver impregnated polycarbonate composites as substrates for surface enhanced Raman spectroscopy (SERS) where the plasmonic properties can be controlled via the reaction parameters. Although silver has superior plasmonic properties to other metals, it is often over looked for SERS substrates as it is highly prone to oxidation. The embedding of silver nanoparticles into polymer substrates offers substantial environmental protection, allowing for the construction of temporally stable plasmonic devices that can exploit the mechanical flexibility of the polymers and prevent particle agglomeration. These nanoparticle composites offer a number of advantages as SERS substrates as they are cheap, easily processed, and are bio-compatible

Clean preparation of nanoparticulate metals in porous supports: a supercritical route

Here we present the synthesis of nanometre sized silver particles which have been trapped within porous substrates; poly( styrene-divinylbenzene) beads and silica aerogels. This is the first time that supercritical carbon dioxide has been used to impregnate such porous materials with silver coordination complexes. In this paper we demonstrate that control over the resultant nanoparticles with respect to size, loading and distribution in the support material has been achieved by simple choice of the precursor complex. The solubility of the precursor complexes in the supercritical solvent is shown to be one of the key parameters in determining the size of the nanoparticles, their distribution and their homogeneity within the support matrix. Moreover, we demonstrate that the same methodology can be applied to two very different substrate materials. In the particular case of aerogels, conventional organic solvents could not be used to prepare nanoparticles because the surface tension of the solvent would lead to fracturing of the aerogel structure.Controlled decomposition of the coordination complexes in situ leads to metallic silver nanoparticles with a narrow size distribution, typically 10-100 nm that are homogeneously dispersed throughout the porous substrate. The whole process is carried out at near ambient temperature and no solvent residues are introduced into the porous media. The silver precursors are specifically designed to be both CO2 soluble and sufficiently labile to ensure facile decomposition to the metal. In-depth characterisation by X-ray diffraction and transmission electron microscopy has been applied to illustrate the homogeneous dispersion of particles throughout the composite material, determine the range and variation in particle size within the solid matrices and fully identify the resultant particles as metallic silver. This enables visualisation of dispersion and concentration, and control over particle size of the fabricated nanocomposite materials.</p