Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?

Introduction

C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.

Methods

Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.

Results

Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10⁻⁸) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).

Conclusions

Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease.     

Solvothermal Preparation of ZnO Nanorods as Anode Material for Improved Cycle Life Zn/AgO Batteries

Nano materials with high surface area increase the kinetics and extent of the redox reactions, thus resulting in high power and energy densities. In this study high surface area zinc oxide nanorods have been synthesized by surfactant free ethylene glycol assisted solvothermal method. The nanorods thus prepared have diameters in the submicron range (300∼500 nm) with high aspect ratio. They have uniform geometry and well aligned direction. These nanorods are characterized by XRD, SEM, Specific Surface Area Analysis, solubility in alkaline medium, EDX analysis and galvanostatic charge/discharge studies in Zn/AgO batteries. The prepared zinc oxide nanorods have low solubility in alkaline medium with higher structural stability, which imparts the improved cycle life stability to Zn/AgO cells.     

Association between Traffic-Related Air Pollution,Subclinical Inflammation and Impaired Glucose Metabolism: Results from the SALIA Study

Background

Environmental and lifestyle factors regulate the expression and release of immune mediators. It has been hypothesised that ambient air pollution may be such an external factor and that the association between air pollution and impaired glucose metabolism may be attributable to inflammatory processes. Therefore, we assessed the associations between air pollution, circulating immune mediators and impaired glucose metabolism.

Methods

We analysed concentrations of 14 pro- and anti-inflammatory immune mediators as well as fasting glucose and insulin levels in plasma of 363 women from the Study on the influence of Air pollution on Lung function, Inflammation and Aging (SALIA, Germany). Exposure data for a group of pollutants such as nitrogen oxides (NO₂, NO_x) and different fractions of particulate matter were available for the participants'' residences. We calculated the association between the pollutants and impaired glucose metabolism by multiple regression models.

Results

The study participants had a mean age of 74.1 (SD 2.6) years and 48% showed impaired glucose metabolism based on impaired fasting glucose or previously diagnosed type 2 diabetes. Only long-term exposure NO₂ and NO_x concentrations showed positive associations (NO₂: OR 1.465, 95% CI 1.049-2.046, NO_x: OR 1.409, 95% CI 1.010-1.967) per increased interquartile range of NO₂ (14.65 µg/m³) or NO_x (43.16 µg/m³), respectively, but statistical significance was lost after correction for multiple comparisons. Additional adjustment for circulating immune mediators or the use of anti-inflammatory medication had hardly any impact on the observed ORs.

Conclusions

Our results suggest that exposure to nitrogen oxides may contribute to impaired glucose metabolism, but the associations did not reach statistical significance so that further studies with larger sample sizes are required to substantiate our findings. Our data do not preclude a role of inflammatory mechanisms in adipose or other tissues which may not be reflected by immune mediators in plasma.     

Inhibiting Cycloxygenase and Ornithine Decarboxylase by Diclofenac and Alpha-Difluoromethylornithine Blocks Cutaneous SCCs by Targeting Akt-ERK Axis

Non-melanoma skin cancer (NMSC) is the most common type of skin cancer in Caucasian populations. Its increasing incidence has been a major public health concern. Elevated expressions of ODC and COX-2 are associated with both murine and human NMSCs. Inhibition of these molecular targets singly employing their respective small molecule inhibitors showed limited success. Here, we show that combined blockade of ODC and COX-2 using their potent inhibitors, DFMO and diclofenac respectively abrogates growth of A431 epidermal xenograft tumors in nu/nu mice by more than 90%. The tumor growth inhibition was associated with a diminution in the proliferation and enhancement in apoptosis. The proliferation markers such as PCNA and cyclin D1 were reduced. TUNEL-positive apoptotic cells and cleaved caspase-3 were increased in the residual tumors. These agents also manifested direct target-unrelated effects. Reduced expression of phosphorylated MAPKAP-2, ERK, and Akt (ser⁴⁷³ & thr³⁰⁸) were noticed. The mechanism by which combined inhibition of ODC/COX attenuated tumor growth and invasion involved reduction in EMT. Akt activation by ODC+COX-2 over-expression was the key player in this regard as Akt inhibition manifested effects similar to those observed by the combined inhibition of ODC+COX-2 whereas forced over-expression of Akt resisted against DFMO+diclofenac treatment. These data suggest that ODC+COX-2 over-expression together leads to pathogenesis of aggressive and invasive cutaneous carcinomas by activating Akt signaling pathway, which through augmenting EMT contributes to tumor invasion.     

A new genus and two new species of trypanorhynch cestodes (Tentaculariidae) from the sharks Carcharhinus sorrah (Müller & Henle) and Sphyrna lewini (Griffith & Smith) from off the coasts of Malaysia and Mexico

Two new tentaculariid species were found infecting carcharhiniform sharks from off the coasts of Malaysian Borneo and the southwestern coast of the Baja California Sur, Mexico. Both new species exhibit a homeoacanthous heteromorphous basal and a homeoacanthous homeomorphous metabasal armature. Since this hook arrangement is unique within the tentaculariids and the taxonomy in this group deeply depends on the tentacular armature, Reimeriella n. g. is erected to accommodate R. varioacantha n. sp. ex Carcharhinus sorrah (Müller & Henle) and R. mexicoensis n. sp. ex Sphyrna lewini (Griffith & Smith). Unlike R. mexicoensis n. sp., R. varioacantha n. sp. has a pars bothrialis not overlapping the pars bulbosa and the number of testes is higher. Reimeriella mexicoensis n. sp. possesses very large uncinate to falcate hooks in the basal armature, while in R. varioacantha n. sp. these hooks are almost the same in size as the remaining hooks in both the basal and metabasal armature. The latter species is the first tentaculariid species where the metabasal armature very closely resembles an eutetrarhynchid with a heteroacanthous typical homeomorphous metabasal armature and a high number of spiniform hooks per half spiral row (10–11 vs 6–7 in R. mexicoensis n. sp.) in the metabasal and apical armature. This pattern provides further morphological evidence for the close relationship of the Eutetrarhynchoidea and the Tentacularioidea. Reimeriella varioacantha n. sp. enriches the trypanorhynch fauna from off the coast of Malaysian Borneo while R. mexicoensis n. sp. is a novel record of a tentaculariid trypanorhynch from the Mexican Pacific.

     

ES5 is involved in the regulation of phosphatidylserine synthesis and impacts on early senescence in rice (Oryza sativa L.)

Leaf senescence, which affects plant growth and yield in rice, is an ideal target for crop improvement and remarkable advances have been made to identify the mechanism underlying this process. We have characterized an early senile mutant es5 (early leaf senescence 5) in rice exhibiting leaf yellowing phenotype after the 4-leaf stage. This phenotype was confirmed by the higher accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), the disintegration of chloroplasts, reduction in chlorophyll content and photosynthetic rate and up-regulation of senescence-associated genes (SAGs) like Osh36, OsI57, and OsI85. Positional cloning revealed that the es5 phenotype is the result of one base substitution in ES5, encoding phosphatidylserine synthase (PSS) family protein, which is involved in the base-exchange type reaction to synthesize the minor membrane phospholipid phosphatidylserine. Functional complementation of ES5 in the es5 plants completely restored the wild-type phenotype. Ultra-high-performance liquid chromatography (UHPLC) analysis showed that es5 plants had increased levels of phosphatidylserine (PS) and decreased level of phosphatidylcholine (PC). These results provide evidence about the role of PS in rice leaf senescence.

     

LED light mediates phenolic accumulation and enhances antioxidant activity in Melissa officinalis L. under drought stress condition

The popularity of lemon balm in conventional medicine is suggested by the existence of two groups of compounds, namely essential oil and phenylpropanoids pathway derivatives. One of the promising approaches to improve tolerance to drought stress induced oxidative damage in seedlings grown in greenhouses and plant growth chambers is replacing the traditional and high-cost light technologies by recently developed light emitting diodes (LED). In this experiment, we analyzed the role of various LED lights including red (R), blue (B), red (70%) + blue (30%) (RB), and white (W) as well as normal greenhouse light (as control) to stimulate defense mechanisms against drought stress in two genotypes of Melissa officinalis L. The present study demonstrates that pre-treatment with LEDs with high-intensity output for 4 weeks alleviated harmful effects of drought stress in the two genotypes. Under drought stress, RB LED pre-treated plantlets of the two genotypes exhibited the highest relative growth index of shoot and root and total phenolic and anthocyanin content compared to those irradiated with other LEDs and greenhouse lights. The highest amount of malondialdehyde level was detected in R LED exposed plants. In response to drought, LED-exposed plants especially RB light-irradiated plants of the two genotypes maintained significantly higher antioxidant and phenylalanine ammonia-lyase (PAL) enzyme activities and higher expression level of the PAL1 and 4CL-1 genes compared to those irradiated with greenhouse light. We concluded that RB LED light provides a better growth condition and resistance to drought stress for the two genotypes of lemon balm by the highest antioxidant activity and the least amount of damage to the cell membranes. Our data suggest that LED light pre-treatments as moderate stress activate antioxidant systems, enhance the scavenging of ROS and induce drought stress tolerance in the two genotypes of lemon balm plants.

     

The Effects of Selenium Supplementation on Clinical Symptoms and Gene Expression Related to Inflammation and Vascular Endothelial Growth Factor in Infertile Women Candidate for In Vitro Fertilization

Biological Trace Element Research - This study was performed to determine the effects of selenium supplementation on clinical symptoms and gene expression related to inflammatory markers in...     

Urinary Metal Levels with Relation to Age,Occupation, and Smoking Habits of Male Inhabitants of Eastern Iran

Biological Trace Element Research - In low-income and middle-income countries such as Iran, smoking is becoming increasingly popular, especially among young people. This has led to additional...     

LC-MS/MS-based metabolic profiling of Escherichia coli under heterologous gene expression stress

Escherichia coli is frequently exploited for genetic manipulations and heterologous gene expression studies. We have evaluated the metabolic profile of E. coli strain BL21 (DE3) RIL CodonPlus after genetic modifications and subjecting to the production of recombinant protein. Three genetically variable E. coli cell types were studied, normal cells (susceptible to antibiotics) cultured in simple LB medium, cells harboring ampicillin-resistant plasmid pET21a (+), grown under antibiotic stress, and cells having recombinant plasmid pET21a (+) ligated with bacterial lactate dehydrogenase gene grown under ampicillin and standard isopropyl thiogalactoside (IPTG)-induced gene expression conditions. A total of 592 metabolites were identified through liquid chromatography-mass spectrometry/mass spectrometry analysis, feature and peak detection using XCMS and CAMERA followed by precursor identification by METLIN-based procedures. Overall, 107 metabolites were found differentially regulated among genetically modified cells. Quantitative analysis has shown a significant modulation in DHNA-CoA, p-aminobenzoic acid, and citrulline levels, indicating an alteration in vitamin K, folic acid biosynthesis, and urea cycle of E. coli cells during heterologous gene expression. Modulations in energy metabolites including NADH, AMP, ADP, ATP, carbohydrate, terpenoids, fatty acid metabolites, diadenosine tetraphosphate (Ap4A), and l -carnitine advocate major metabolic rearrangements. Our study provides a broader insight into the metabolic adaptations of bacterial cells during gene manipulation experiments that can be prolonged to improve the yield of heterologous gene products and concomitant production of valuable biomolecules.