16 research outputs found
Analysis of Complement C3 Gene Reveals Susceptibility to Severe Preeclampsia
Preeclampsia (PE) is a common vascular disease of pregnancy with genetic predisposition. Dysregulation of the complement system has been implicated, but molecular mechanisms are incompletely understood. In this study, we determined the potential linkage of severe PE to the most central complement gene, C3. Three cohorts of Finnish patients and controls were recruited for a genetic case-control study. Participants were genotyped using Sequenom genotyping and Sanger sequencing. Initially, we studied 259 Finnish patients with severe PE and 426 controls from the Southern Finland PE and the Finnish population-based PE cohorts. We used a custom-made single nucleotide polymorphism (SNP) genotyping assay consisting of 98 SNPs in 18 genes that encode components of the complement system. Following the primary screening, C3 was selected as the candidate gene and consequently Sanger sequenced. Fourteen SNPs from C3 were also genotyped by a Sequenom panel in 960 patients with severe PE and 705 controls, including already sequenced individuals. Three of the 43 SNPs observed within C3 were associated with severe PE: rs2287845 (p = 0.038, OR = 1.158), rs366510 (p = 0.039, OR = 1.158), and rs2287848 (p = 0.041, OR = 1.155). We also discovered 16 SNP haplotypes with extreme linkage disequilibrium in the middle of the gene with a protective (p = 0.044, OR = 0.628) or a predisposing (p = 0.011, OR = 2.110) effect to severe PE depending on the allele combination. Genetic variants associated with PE are located in key domains of C3 and could thereby influence the function of C3. This is, as far as we are aware, the first candidate gene in the complement system with an association to a clinically relevant PE subphenotype, severe PE. The result highlights a potential role for the complement system in the pathogenesis of PE and may help in defining prognostic and therapeutic subgroups of preeclamptic women
Disposable (bio)chemical integrated optical waveguide sensors implemented on roll-to-roll produced platforms
Abstract
To enable wide spread dissemination of sensors in cost-critical applications and resource poor settings, methods to implement sensor chips using low-cost materials and mass-manufacturing methods are developed. In this paper we demonstrate that disposable polymeric integrated Young interferometer (YI) sensor chips, implemented on roll-to-roll mass-manufactured waveguides, are applicable for analyte specific sensing of small molecules and for multi-analyte detection of biomolecules. For the chemical sensing of small molecules, a sensor chip was functionalized with a molecularly imprinted polymer (MIP). We demonstrate that the MIP receptor layer is compatible with a polymer-based evanescent wave sensor for direct refractive index sensing. For multi-analyte detection of biomolecules, antibody-based receptor layers were patterned by inkjet printing onto the sensor surface demonstrating the applicability of the method with integrated YI chips. Demonstration of the analyte specific chemical- and biosensing with disposable polymeric YI sensor chips opens new possibilities to implement low-cost (bio)chemical sensors
The effects of submaximal exercise and cold exposure on blood coagulation parameters in coronary artery disease patients
Abstract
Background: Both exercise and cold exposure increase blood coagulation potential but their combined effects are not known. The purpose of the present study was to assess blood coagulation factors in response to submaximal exercise in the cold environment among patients with stable coronary artery disease (CAD).
Methods: Sixteen men (61.1 ± 7.1 years) with stable CAD participated in three 30-min experimental conditions (seated rest in − 15 °C and exercise in both + 22 °C and − 15 °C) in random order. The employed exercise consisted of brisk walking (66–69% of maximal heart rate). Factor VII (FVII), fibrinogen, D-dimer and von Willebrand factor (vWF) were analyzed from blood samples obtained before, immediately and one hour after each experiment.
Results: On average, FVII activity (95% confidence interval, CI) was 123 (108–143) %, 123 (106–140) %, 121 (103–139) % (baseline, recovery 1, recovery 2), fibrinogen concentration (95% CI) 3.81 (3.49–4.12) g/l, 3.71 (3.34–4.08) g/l, 3.65 (3.26–4.05) g/l, D-dimer concentration (95% CI) 0.42 (0.28–0.56) µg/ml, 0.42 (0.29-.55) µg/ml and 0.39 (0.29–0.49) µg/ml, and vWF activity (95% CI) 184 (135–232) %, 170 (128–212) % and 173 (129–217) % after exercise in the cold. Average FVII activity varied from 122 to 123%, fibrinogen concentration from 3.71 to 3.75 g/l, D-dimer concentration from 0.35 to 0.51 µg/ml and von Willebrand factor activity from 168 to 175% immediately after each three experimental condition.
Conclusions: Our findings suggest that submaximal lower body exercise carried out in a cold environment does not significantly affect blood coagulation parameters among patients with stable CAD
Surface-enhanced Raman spectroscopy for identification and discrimination of beverage spoilage yeasts using patterned substrates and gold nanoparticles
Abstract
In the beverage industry, the detection of spoilage yeasts such as Wickerhamomyces anomalus and Brettanomyces bruxellensis can be labourious and time-consuming. In the present study, a simple and repeatable technique was developed for rapid yeast detection using a combination of patterned gold-coated surface-enhanced Raman spectroscopy (SERS) substrates and gold nanoparticles. W. anomalus and B. bruxellensis showed several characteristic peaks, enabling the discrimination of these yeasts without chemometric analysis. The control yeast used as an indicator yeast, Rhodotorula mucilaginosa, showed 7 cell wall-related peaks originating from lipids and haemoproteins. Analysing W. anomalus SERS spectra with differently sized and shaped gold nanoparticles revealed the benefit of using either large, spherical, chemically synthesised gold nanoparticles or small, laser-synthesised, gold-silicon nanoparticles for yeast detection. Additionally, the spectra showed differences in SERS signal construction for small molecules and biological cells, as the nanoparticles with best response in biological cell detection did not excel in small molecule detection. The use of small composite gold-silicon nanoparticles in combination with the SERS substrate gave distinctive spectra for all detected yeast species
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Abstract
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids