The P2X7 receptor, a member of the P2X family of nucleotide-gated channels, is predominantly expressed by monocytic cells. The activation of this receptor has been associated with downstream-signalling cascades, resulting in the release of a number of inflammatory mediators. There are more than 815 single nucleotide polymorphisms (SNPs) that have been described in the human P2X7R gene, but only few have been functionally characterized. The main aim of this study is to determine whether P2X7R gene polymorphisms confer susceptibility to rheumatoid arthritis (RA). A total of 125 patients with RA and 158 healthy volunteers were enrolled in this study. DNA fragment was PCR amplified and sequenced on the AB 3130 Genetic Analyzer. No significant difference in allele frequencies of 489 C→T, 1096 C→G and 1513 A→C polymorphisms, among sporadic cases of RA and healthy controls was found. However, the 1513A/C genotype was significantly associated with the presence of rheumatoid factor and anti-MCV autoantibody in RA patients. Interestingly, the genotype frequency of 1068 A/A was 0.19 in the RA group and 0.09 in control group (P = 0.025). Consequently, this polymorphism (AA) is two folds greater in the RA group compared to controls. Moreover, this polymorphism was significantly associated with mean concentration of C-reactive protein in RA patients. In contrast, 946G→A and 1729 T→A were not detected in both groups. As a result, these two polymorphisms are uncommon in Omani Arab population. Polymorphism at position 1068 and 1513 in the P2X7R gene might contribute to the pathogenesis of RA. Moreover, the loss-of-function SNP at position 1096 C→G or the gain-of-function SNP at position 489 C→T of the P2X7 gene does not appear to be a susceptibility gene locus for the development of RA. Further studies are required to confirm this finding.

Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble -ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation. We will describe how these proteins are controlled in a range of regulated trafficking events, with particular emphasis on the insulin-stimulated delivery of glucose transporters to the surface of adipose and muscle cells. Here, we focus on a few examples of SNARE phosphorylation which exemplify distinct ways in which SNARE machinery phosphorylation may regulate membrane fusion.

Objective: This study aimed to establish reference ranges of serum concentrations of copper, zinc, retinol, α-tocopherol, copper:caeruloplasmin and copper:zinc ratios in a group of healthy Omani men and women. Materials and Methods: Assay techniques employed were atomic absorption spectrophotometry (copper and zinc), reverse-phase high-pressure liquid chromatography with isocratic elution (retinol and α-tocopherol), immunonephelometry (caeruloplasmin) and spectrophotometry (albumin and cholesterol). Results: The mean ± SD (µM) obtained for copper, zinc, retinol, and α-tocopherol were 15.9 ± 3.0, 14.2 ± 2.0, 1.45 ± 0.39 and 16.9 ± 4.4, respectively. The mean ± SD for copper:zinc and copper:caeruloplasmin ratios were 1.15 ± 0.30 µmol/mmol and 6.99 ± 0.84 µmol/g, respectively. Significantly higher (p < 0.0001) copper and caeruloplasmin concentrations, copper:zinc and copper:caeruloplasmin ratios and lower zinc, retinol, α-tocopherol, cholesterol concentrations and α-tocopherol:cholesterol ratio were present in women compared to men. Age appeared to be associated with copper and retinol concentrations, and copper:caeruloplasmin ratios in women; in men, the association was mostly moderate with caeruloplasmin, α-tocopherol, cholesterol concentrations and α-tocopherol:cholesterol ratios. Smokers had decreased albumin (p = 0.002), zinc (p = 0.023) concentrations, and copper:caeruloplasmin ratios (p = 0.002), increased α-tocopherol concentrations (p = 0.016) and α-tocopherol:cholesterol ratios (p = 0.021) compared with non-smokers. Deficiency incidence was ≤5% for all investigated parameters. Conclusions: Reference ranges of micronutrient concentrations and micromineral ratios were established for Omani subjects. The mean values of several micronutrients were lower than those reported for other populations and some showed gender effects.