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.     

Porosity and pore size regulate the degradation product profile of polylactide

Porosity and pore size regulated the degradation rate and the release of low molar mass degradation products from porous polylactide (PLA) scaffolds. PLA scaffolds with porosities above 90% and different pore size ranges were subjected to hydrolytic degradation and compared to their solid analog. The solid film degraded fastest and the degradation rate of the porous structures decreased with decreasing pore size. Degradation products were detected earlier from the solid films compared to the porous structures as a result of the additional migration path within the porous structures. An intermediate degradation rate profile was observed when the pore size range was broadened. The morphology of the scaffolds changed during hydrolysis where the larger pore size scaffolds showed sharp pore edges and cavities on the scaffold surface. In the scaffolds with smaller pores, the pore size decreased during degradation and a solid surface was formed on the top of the scaffold. Porosity and pore size, thus, influenced the degradation and the release of degradation products that should be taken into consideration when designing porous scaffolds for tissue engineering.     

Tuning the polylactide hydrolysis rate by plasticizer architecture and hydrophilicity without introducing new migrants

The possibility to tune the hydrolytic degradation rate of polylactide by plasticizer architecture and hydrophilicity without introduction of new degradation products was investigated by subjecting polylactide with cyclic oligolactide and linear oligolactic acid additives to hydrolytic degradation at 37 and 60 °C for up to 39 weeks. The more hydrophilic oligolactic acid plasticizer led to larger water uptake and rapid migration of plasticizer from the films into the aging water. This resulted in a porous material more susceptible to further hydrolysis. During hydrolysis at 37 °C the mass loss was generally 10-20% higher for the material containing linear oligolactic acid plasticizers. The hydrolysis accelerating effect of the linear oligolactic acid is probably counteracted by the higher degree of crystallinity in the films containing oligolactic acid additives. The degradation process was monitored by measurements of mass loss, water uptake, molar mass changes, material composition changes, surface changes, and thermal properties. The water-soluble degradation products were analyzed by following pH changes and identified by electrospray ionization-mass spectrometry (ESI-MS). The time frame for formation of water-soluble products was influenced by the architecture and hydrophilicity of the plasticizer. Furthermore, the advantage with oligolactide and oligolactic acid plasticizers was clearly demonstrated as they do not introduce any new migrants into the degradation product patterns.     

Hemicellulose-based multifunctional macroinitiator for single-electron-transfer mediated living radical polymerization

A multifunctional macroinitiator for single-electron-transfer mediated living radical polymerization (SET-LRP) was designed from acetylated galactoglucomannan (AcGGM) by α-bromoisobutyric acid functionalization of the anomeric hydroxyl groups on the heteropolysaccharide backbone. This macroinitiator, with a degree of substitution of 0.15, was used in the SET-LRP of methyl acrylate, catalyzed by Cu(0)/Me(6)-TREN in DMSO, DMF, or DMSO/H(2)O in various concentrations. Kinetic analyses confirm high conversions of up to 99.98% and a living behavior of the SET-LRP process providing high molecular weight hemicelluloses/methyl acrylate hybrid copolymers with a brush-like architecture.     

Macromolecular design of aliphatic polyesters with maintained mechanical properties and a rapid, customized degradation profile

An innovative type of triblock copolymer that maintains and even increases the mechanical properties of poly(l-lactide) (PLLA) and poly(ε-caprolactone) (PCL) with a controlled, predictable, and rapid degradation profile has been synthesized. Elastic triblock copolymers were formed from the hydrophobic and crystalline PLLA and PCL with an amorphous and hydrophilic middle block of poly(but-2-ene-1,4-diyl malonate) (PBM). The polymers were subjected to degradation in PBS at 37 °C for up to 91 days. Prior to degradation, ductility of the PLLA-PBM-PLLA was approximately 4 times greater than that of the homopolymer of PLLA, whereas the modulus and tensile stress at break were unchanged. A rapid initial hydrolysis in the amorphous PBM middle block changed the microstructure from triblock to diblock with a significant reduction in ductility and molecular weight. The macromolecular structure of the triblock copolymer of PLLA and PBM generates a more flexible and easier material to handle during implant, with the advantage of a customized degradation profile, demonstrating its potential use in future biomedical applications.     

Extremely low-frequency magnetic field exposure and protection against UV-induced death in chicken embryos

We report on a study where 4-day old chicken embryos from different flocks were pre-treated with 50 Hz magnetic fields (MF) prior to a 60-min UV-C exposure (1.7 mW/cm(2)) to investigate the possible protective effect of MF exposure on UV-induced embryo death. Different flux densities (0.010, 0.025, 0.050, 0.10, and 0.20 mT), field directions (vertical and horizontal), as well as MF exposure times (10, 20, and 60 min) were employed. We did not find any significant effects by MF exposure, irrespective of exposure time, flux density, or field direction on the survival of embryos. Neither could we find any flock dependency on sensitivity to MF exposure.     

Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity

Objective: Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl‐coenzyme A‐desaturase (SCD), is related to obesity. Further, SCD1‐deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans. Research Methods and Procedures: The study population was 1143 elderly Swedish men taking part of a population‐based cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis. Results: Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (β) = 1.19, p = 0.007] and waist circumference (β = ?4.4, p = 0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference. Conclusion: This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.     

Cold-tolerant (psychrotrophic) moulds and blue stain fungi from softwood in Sweden. Growth rates in relation to pH and temperature

Seventy isolates of moulds and blue stain fungi ( Zygomycota and Deuteromycota ), isolated from discoloured outdoor softwood in Sweden, comprising of 27 different species, (the two largest genera Penicillium and Cladosporium ) were investigated for their linear growth at three different start-pH values (5, 7 and 9.5) at two temperatures (2°C and 24°C) on malt extract agar (MEA). At 24°C all isolates showed growth at all three start-pH values except for one isolate which did not grow at initial-pH 9.5. After 21 days at 2°C at the three start pH-values, only six isolates showed no growth indicating that 64 of the isolates were cold-tolerant (psychrotrophic). Of these 64 strains, 58 showed growth at an initial pH of 9.5. Lower pH optima at 2°C than at 24°C were found for most of the isolates. The reduction of the linear growth at initial pH 9.5 in relation to the growth at optimal pH was more pronounced (higher) at the low temperature.     

Solvent-free vapor-phase photografting of acrylamide onto poly(ethylene terephthalate)

Poly(ethylene terphthalate) (PET) films were photografted under reduced pressure in a solvent-free vapor of acrylamide and a co-initiator, benzophenone. Characterization of grafted samples by ESCA and contact angles showed that the grafting increased with grafting time and temperature. The amide groups obtained by the acrylamide grafting were converted into amine groups by the Hofmann rearrangement to be used in coupling reactions. The amine groups were confirmed by reaction with pentafluorobenzoyl chloride, which provides a fluorine label for ESCA. Surface grafting of polymeric substrates in the vapor phase induced by plasma or high energy and UV irradiation is reviewed.