Evidence of association between interferon regulatory factor 5 gene polymorphisms and asthma

Asthma is a heterogeneous disorder hallmarked by chronic inflammation in the respiratory system. Exacerbations of asthma are correlated with respiratory infections. Considering the implication of interferon regulatory factor 5 (IRF5) in innate and adaptive immunity, we investigated the preferential transmission patterns of ten IRF5 gene polymorphisms in two asthmatic family cohorts. A common IRF5 haplotype was found to be associated with asthma and the severity of asthmatic symptoms. Stratified analysis of subgroups of asthmatic individuals revealed that the associations were more pronounced in nonatopic asthmatic individuals. In addition, the risk alleles of IRF5 polymorphisms for asthma were almost completely opposite to those for autoimmune disorders. Our study provides the first evidence of association between IRF5 and asthma, and sheds light on the related but potentially distinct roles of IRF5 alleles in the pathogenesis of asthma and autoimmune disorders.     

Covalent grafting of poly(L-lactide) to tune the in vitro degradation rate

The in vitro rate of degradation was purposely affected by covalently grafting the surface of poly(l-lactide) (PLLA). PLLA films were surface modified by our vapor-phase nondestructive photografting technique. Films were grafted for 20 min with one of the following monomers: acryl amide (AAm), N-vinyl pyrrolidone (VP), or acrylic acid (AA) and thereafter incubated in vitro in a phosphate-buffered saline solution at 37 degrees C for 154 days. The films were studied with contact angle measurements, SEM, ATR-FTIR, SEC, and DSC. The analyses verified that the in vitro rate of degradation was enhanced and that the grafted surface layer did remain covalently attached to the surface during the initial stages of incubation.     

Wood hydrolysate barriers: performance controlled via selective recovery

Films and coatings were produced from a noncellulosic polysaccharide-rich wood hydrolysate (WH), and the resulting oxygen barrier performance was improved by a selective choice of upgrading conditions. The WH was obtained from process water in the hydrothermal treatment of hardwood and subjected to one of three alternative upgrading treatments, resulting in xylan-rich fractions with significant differences in structure, composition, and properties of the recovered WH fractions, which in turn had a major impact on their performance with respect to tensile and oxygen barrier properties. The WH in the least upgraded state, the crudest fraction, produced films with the best performance in terms of oxygen permeability and was superior to corresponding films based on highly purified hemicellulose.     

Analysis of genetic variation in the GenomEUtwin project.

Multiallelic short tandem repeat polymorphisms, or microsatellites, are useful markers in genome wide scans to identify chromosomal regions containing genes underlying disease loci. The biallelic single nucleotide polymorphism (SNP) can be used to fine map previously identified large candidate regions or to test functional candidate genes by association analysis. In the GenomEUtwin project the population based impact of susceptibility genes for six multifactorial traits will be studied. A genome wide panel of informative human microsatellite markers will be analyzed by fluorescent capillary electrophoresis in well characterized twin and population samples. Contrary to microsatellites, selection of the most informative panels of SNPs is hampered by imperfect data on the allele frequencies and population distribution of SNPs markers in the databases. Therefore, selection of SNPs requires a substantial amount of bioinformatics, and, the SNPs need to be validated experimentally in the relevant populations prior to genotyping large sample sets. In the GenomEUtwin project, large scale genotyping of SNPs will be performed using the SNPstreamUHT and MassARRAY genotyping systems that are based on the primer extension reaction principle combined with fluorescent and mass spectrometric detection, respectively. Production of the genotyping data will be a joint effort by GenomEUtwin partners at the University of Helsinki, the National Public Health Institute in Helsinki, Finland and Uppsala University, Sweden. All genotyping data will be stored in a common database established specifically for the GenomEUtwin project, from where it can be accessed by the twin research centres that provided the samples for genotyping.     

Effects of 50-Hz magnetic field exposure on superoxide radical anion formation and HSP70 induction in human K562 cells

Epidemiological studies suggest a correlation between exposure to low-level extremely low-frequency (ELF) magnetic fields (MF) and certain cancers and neurodegenerative diseases. Experimental studies have not provided any mechanism for such effects, although at flux density levels significantly higher than the ones encountered in epidemiological studies, radical homoeostasis and levels of stress response proteins can be affected. Here, we report on the influence of MF exposure (50-Hz sine wave; 1 h; 0.025–0.10 mT; vertical or horizontal MF exposure direction) on different cellular parameters (proliferation, cell cycle distribution, superoxide radical anion, and HSP70 protein levels) in the human leukaemia cell line K562. The positive control heat treatment (42°C, 1 h) did not affect either cell proliferation or superoxide radical anion production but caused accumulation of cells in the G2 phase and increased the stress protein HSP70. MF exposure (0.10 mT, 1 h) did not affect either cell cycle kinetics or proliferation. Both vertical and horizontal MF exposures for 1 h caused significantly and transiently increased HSP70 levels (>twofold), at several flux densities, compared to sham controls and also compared to heat treatment. This exposure also increased (30–40%) the levels of the superoxide radical anion, comparable to the positive control PMA. Addition of free radical scavengers (melatonin or 1,10-phenantroline) inhibited the MF-induced increase in HSP70. In conclusion, an early response to ELF MF in K562 cells seems to be an increased amount of oxygen radicals, leading to HSP70 induction. Furthermore, the results suggest that there is a flux density threshold where 50-Hz MF exerts its effects on K562 cells, at or below 0.025 mT, and also that it is the MF, and not the induced electric field, which is the active parameter.     

Facile synthesis of degradable and electrically conductive polysaccharide hydrogels

Degradable and electrically conductive polysaccharide hydrogels (DECPHs) have been synthesized by functionalizing polysaccharide with conductive aniline oligomers. DECPHs based on chitosan (CS), aniline tetramer (AT), and glutaraldehyde were obtained by a facile one-pot reaction by using the amine group of CS and AT under mild conditions, which avoids the multistep reactions and tedious purification involved in the synthesis of degradable conductive hydrogels in our previous work. Interestingly, these one-pot hydrogels possess good film-forming properties, electrical conductivity, and a pH-sensitive swelling behavior. The chemical structure and morphology before and after swelling of the hydrogels were verified by FT-IR, NMR, and SEM. The conductivity of the hydrogels was tuned by adjusting the content of AT. The swelling ratio of the hydrogels was altered by the content of tetraaniline and cross-linker. The hydrogels underwent slow degradation in a buffer solution. The hydrogels obtained by this facile approach provide new possibilities in biomedical applications, for example, biodegradable conductive hydrogels, films, and scaffolds for cardiovascular tissue engineering and controlled drug delivery.     

Controllable degradation product migration from cross-linked biomedical polyester-ethers through predetermined alterations in copolymer composition

Uniformly degrading biomaterials with adjustable degradation product migration rates were customized by combining the advantages of cross-linked poly(epsilon-caprolactone) with the hydrophilic character of poly(1,5-dioxepan-2-one). Hydrolytic degradation of these random cross-linked networks using 2,2'-bis-(epsilon-caprolactone-4-yl) propane (BCP) as the cross-linking agent was studied for up to 546 days in phosphate buffer solution at pH 7.4 and 37 degrees C. The hydrophilicity of the materials was altered by varying the copolymer compositions. After different hydrolysis times the materials were characterized, and the degradation products were extracted from the buffer solution and analyzed. Fourier transform infrared spectroscopy, differential scanning calorimetry, atomic force microscopy, scanning electron microscopy, and gas chromatography-mass spectrometry were used to observe the changes taking place during the hydrolysis. From the results it was concluded that degradation profiles and migration of degradation products are controllable by tailoring the hydrophilicity of cross-linked polyester-ether networks.     

Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. Currently, ~8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR>1.3). In order to identify additional genes contributing to SLE susceptibility, we conducted a replication study in a UK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association analysis in the UK dataset and subsequent meta-analysis with the published data identified five SLE susceptibility genes reaching genome-wide levels of significance (P(comb)<5×10(-8)): NCF2 (P(comb) = 2.87×10(-11)), IKZF1 (P(comb) = 2.33×10(-9)), IRF8 (P(comb) = 1.24×10(-8)), IFIH1 (P(comb) = 1.63×10(-8)), and TYK2 (P(comb) = 3.88×10(-8)). Each of the five new loci identified here can be mapped into interferon signalling pathways, which are known to play a key role in the pathogenesis of SLE. These results increase the number of established susceptibility genes for lupus to ~30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease.     

Controlled synthesis of star-shaped L-lactide polymers using new spirocyclic tin initiators

The reaction between pentaerythritol ethoxylate compounds and dibutyltin oxide was developed as a route to synthesize two new spirocyclic tin initiators. The initiators were successfully synthesized and they were characterized by (1)H NMR and differential scanning calorimetry (DSC). The (1)H NMR spectra showed the characteristic signals for the methylene protons in the ether chains. Furthermore, the usefulness of the new initiators was examined in ring-opening polymerizations of L-lactide in chloroform at 60 degrees C. L-Lactide was polymerized at monomer-to-initiator ([M]/[I]) ratios between 20 and 500. The results indicated that the initiation was instantaneous and that the molecular weight distribution was very narrow, <1.13. The number average molecular weight could be controlled by the [M]/[I] ratio, and the yield was very high. (1)H NMR, size exclusion chromatography, and DSC were used to clarify the architecture. The expected results were obtained. The star-shaped polymers had a smaller hydrodynamic volume, and the melting point was lower than that obtained for the corresponding linear poly(L-lactide).     

Electron beam-induced graft polymerization of acrylic acid and immobilization of arginine-glycine-aspartic acid-containing peptide onto nanopatterned polycaprolactone

Electron beam- (EB-) induced graft polymerization of acrylic acid and the subsequent immobilization of arginine-glycine-aspartic acid (RGD) peptide onto nanopatterned polycaprolactone with parallel grooves is reported. A high concentration of carboxylic groups was introduced onto the polymer substrate by EB-induced polymerization of acrylic acid. In the coupling of the RGD peptide to the carboxylated polymer surface, a three-step peptide immobilization process was used. This process included the activation of surface carboxylic acid into an active ester intermediate by use of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), the introduction of disulfide groups by use of 2-(2-pyridinyldithio)ethanamine hydrochloride (PDEA), and final immobilization of the peptide via a thiol-disulfide exchange reaction. The extent of coupling was measured by UV spectroscopy. A preliminary study of the in vitro behavior of keratinocytes (NCTC 2544) cultured on the acrylic acid-grafted and RGD peptide-coupled surface showed that most cells grown on the coupled samples had a spread-rounded appearance, while the majority of cells tended to be elongated along the grooves on uncoupled substrates.