Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA)

Introduction

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent.

Methods

A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated.

Results

In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA.

Conclusions

The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.     

Optimization of a Dual Mechanism Gastrofloatable and Gastroadhesive Delivery System for Narrow Absorption Window Drugs

In order to overcome poor bioavailability of narrow absorption window drugs, a gastrosphere system comprising two mechanisms of gastric retention, namely buoyancy and gastroadhesion, has been investigated in this study employing poly(lactic-co-glycolic acid) (PLGA), polyacrylic acid (PAA), alginate, pectin, and a model drug metformin hydrochloride. Fifteen formulations were obtained using a Box–Behnken statistical design. The gastrosphere yield was above 80% in all cases; however, due to the high water solubility of metformin, drug entrapment efficacy was between 18% and 54%. Mean dissolution time and gastroadhesive strength were used as the formulation responses in order to optimize the formulation. Furthermore, the molecular mechanics force field simulations were performed to corroborate the experimental findings. Drug release profiles revealed three different release kinetics, namely, burst, first-order and zero-order release. Varying gastroadhesive results were obtained, and were highly sensitive to changes in polymer concentrations. FTIR revealed that strong bonds of PAA and PLGA were retained within the gastrosphere. Surface area and porosity analysis provided supporting evidence that the lyophilization process resulted in a significant increase in the porosity. Analysis of the surface morphology by SEM revealed that air pockets were spread over the entire surface of the gastrosphere, providing a visual proof of the high porosity and hence low density of the gastrosphere. The spatial disposition and energetic profile of the sterically constrained and geometrically optimized multi-polymeric complex of alginate, pectin, PAA, and PLGA corroborated the experimental results in terms of in vitro drug release and gastroadhesive strength of the fabricated gastrospheres.     

Differential response of single and co-inoculation of <Emphasis Type="Italic">Rhizobium leguminosarum</Emphasis> and <Emphasis Type="Italic">Mesorhizobium ciceri</Emphasis> for inducing water deficit stress tolerance in wheat

Limited soil water availability is a major threat to agricultural productivity because it inhibits plant growth and yields. Various strategies have been adopted to mitigate water deficit stress in plants; however, using extremophilic microbes with plant growth promoting traits could be an environmentally friendly and cost-effective approach to improve crop stress resilience. Rhizobia are well known for their symbiotic association with legumes, but they can also improve the fitness of non-legumes under stressed conditions. Thus, different rhizobial strains were isolated from nodules of two legumes (lentil and chickpea) and tested for osmoadaptation at four different polyethylene glycol (PEG-6000) levels, i.e., ? 0.05, ? 0.65, ? 1.57, and ? 2.17 MPa. Two stress-tolerant rhizobial strains, SRL5 and SRC8, were selected to evaluate their potential to induce tolerance against water deficits in wheat grown at four different percentages of field capacity (FC; 40, 60, 80, and 100%). Rhizobial inoculation improved physiological parameters and growth of wheat under water deficit; however, co-inoculation of selected rhizobia was better than sole application. Grain yield was most limited at the highest level of water deficit but sole inoculation with SRC8 and SRL5 improved yield by 24% and 19%, respectively. Combined inoculation increased grain yield by up to 48% compared to the uninoculated control. Thus, rhizobia from different legumes possess enormous potential for improving the resilience of cereals (non-legumes) to water deficit stress. Moreover, co-inoculation of rhizobia could be more beneficial than their sole application.     

Investigation of Embedded Si/C System Exposed to a Hybrid Reaction of Centrifugal-Assisted Thermite Method

A novel method is proposed to study the behavior and phase formation of a Si+C compacted pellet under centrifugal acceleration in a hybrid reaction. Si+C as elemental mixture in the form of a pellet is embedded in a centrifugal tube. The pellet assembly and tube are exposed to the sudden thermal energy of a thermite reaction resulted in a hybrid reaction. The hybrid reaction of thermite and Si+C produced unique phases. X-ray diffraction pattern (XRD) as well as microstructural and elemental analyses are then investigated. XRD pattern showed formation of materials with possible electronic and magnetic properties. The cooling rate and the molten particle viscosity mathematical model of the process are meant to assist in understanding the physical and chemical phenomena took place during and after reaction. The results analysis revealed that up to 85% of materials converted into secondary products as ceramics-matrix composite.     

Morphological and molecular characterization of sweet,grain and forage sorghum (Sorghum bicolor L.) genotypes grown under temperate climatic conditions

Abstract

In the present study, we used 12 genotypes of sorghum originated from different countries (five sweet, four grain and three forage). These different genotypes and types of sorghum were evaluated for the agro-morphological traits that are associated with the estimated sugar and bioethanol yield to estimate their phenotypic diversity. Analysis of variance showed significant differences between different types of sorghum for all the evaluated traits. Sweet sorghum genotypes, however, showed better performance with respect to all studied traits than the other genotypes. A positive significant correlation was observed between plant height, leaf number, leaf area, biomass yield, cane and bagasse yields, and the predicted bioethanol yield. Both, cluster and principal component analysis were performed to group the genotypes according to their agro-morphological and molecular similarity coefficients. For analytical approaches, the Iranian grain and forage genotypes clustered separately from the other genotypes. The clustering patterns obtained from the molecular dominant markers had higher discriminatory power than using morphological characters to separate sweet genotypes from the forage and grain sorghum ones. The results clearly indicated that sweet sorghum can be grown in Germany and maintains its superiority in biomass production and sugar yield over grain and forage sorghum types.     

Occurrence of phosphate-solubilizing bacteria in some Iraqi soils

The phosphate-solubilizing bacteria (PSB) were enumerated in 52 soil samples collected from agricultural areas at Baghdad. The results revealed that more than 90% of the samples were inhabited with indigenous PSB. The number varied and ranged from 0.012–28.4×10⁴ cell g^–1 soil. The correlations between PSB counts and electrical conductivity, available phosphorus, cation-exchange capacity, soil moisture, organic matter and pH were insignificant. Both abundance and numbers of PSB were more pronounced in descending order under vegetables, legumes, grasses, cereal and orchard trees.     

Isolation of poly(3-hydroxybutyrate-<Emphasis Type="Italic">co</Emphasis>-4-hydroxybutyrate) producer from Malaysian environment using γ-butyrolactone as carbon source

Samples from various natural environments in Peninsular Malaysia were screened for microorganisms that are capable of producing poly(3-hydroxybutyrate-co-4-hydroxybutyrate). A total of 663 isolates were isolated and 119 out of these isolates were identified as possible PHA producers based on Nile red staining methods. All these potential producers emitted pink fluorescence when grown on solid mineral salts medium (MSM) containing Nile red and exposed to UV light. The isolates obtained in this study were cultivated in MSM containing γ-butyrolactone as the carbon source. Gas chromatography (GC) analysis confirmed that 95 out of the 119 isolates were PHA producers. Among the 95 positive isolates, 77 isolates produced only P(3HB) homopolymer and 18 isolates produced PHA containing 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB) monomers. Of these 18 isolates, USMAA1020 was screened as the best P(3HB-co-4HB) producer based on GC analysis. For further confirmation, PHA was extracted from the isolate and analyzed by GC as well as nuclear magnetic resonance (NMR). Results from both analyses confirmed that this isolate was capable of producing PHA containing 3HB and 4HB. Based on, biochemical characterization, 16S rRNA sequencing, DNA base composition, cellular fatty acids analysis and DNA–DNA hybridization, it is clearly indicated that this isolate belongs to the genus Cupriavidus. Poly(3HB-co-4HB) was synthesized by this bacterium in one-stage, two-stage and three-stage cultivation using γ-butyrolactone as the carbon source. The highest 4HB composition of 82 mol% was obtained through three-stage cultivation.     

Effects of polyculture and monoculture farming in oil palm smallholdings on tropical fruit‐feeding butterfly diversity

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