Association between single-nucleotide polymorphisms in growth factor genes and quality of life in men with prostate cancer and the general population

Purpose Improved survival for men with prostate cancer has led to increased attention to factors influencing quality of life (QOL). As protein levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) have been reported to be associated with QOL in people with cancer, we sought to identify whether single-nucleotide polymorphisms (SNPs) of these genes were associated with QOL in men with prostate cancer. Methods Multiple linear regression of two data sets (including approximately 750 men newly diagnosed with prostate cancer and 550 men from the general population) was used to investigate SNPs of VEGF and IGF-1 (10 SNPs in total) for associations with QOL (measured by the SF-36v2 health survey). Results Men with prostate cancer who carried the minor ‘T’ allele for IGF-1 SNP rs35767 had higher mean Role-Physical scale scores (≥0.3 SD) compared to non-carriers (p < 0.05). While this association was not identified in men from the general population, one IGF-1 SNP rs7965399 was associated with higher mean Bodily Pain scale scores in men from the general population that was not found in men with prostate cancer. Men from the general population who carried the rare ‘C’ allele had higher mean Bodily Pain scale scores (≥0.3 SD) than non-carriers (p < 0.05). Conclusions Through identifying SNPs that are associated with QOL in men with prostate cancer and men from the general population, this study adds to the mapping of complex interrelationships that influence QOL and suggests a role for IGF-I in physical QOL outcomes. Future research may identify biomarkers associated with increased risk of poor QOL that could assist in the provision of pre-emptive support for those identified at risk.

Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis

Objective: To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Design Case-control study. Setting Academic research. Subject(s) The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. Intervention(s) Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples. Main Outcome Measure(s) Allele frequency differences between cases and controls. Result(s) Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete linkage disequilibrium with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, which was highlighted in our previous study. Conclusion(s) Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases. © 2014 by American Society for Reproductive Medicine.

The structural basis of DNA binding by the single-stranded DNA-binding protein from Sulfolobus solfataricus

Canonical single-stranded DNA-binding proteins (SSBs) from the oligosaccharide/oligonucleotide-binding (OB) domain family are present in all known organisms and are critical for DNA replication, recombination and repair. The SSB from the hyperthermophilic crenarchaeote Sulfolobus solfataricus (SsoSSB) has a ‘simple’ domain organization consisting of a single DNA-binding OB fold coupled to a flexible C-terminal tail, in contrast with other SSBs in this family that incorporate up to four OB domains. Despite the large differences in the domain organization within the SSB family, the structure of the OB domain is remarkably similar all cellular life forms. However, there are significant differences in the molecular mechanism of ssDNA binding. We have determined the structure of the SsoSSB OB domain bound to ssDNA by NMR spectroscopy. We reveal that ssDNA recognition is modulated by base-stacking of three key aromatic residues, in contrast with the OB domains of human RPA and the recently discovered human homologue of SsoSSB, hSSB1. We also demonstrate that SsoSSB binds ssDNA with a footprint of five bases and with a defined binding polarity. These data elucidate the structural basis of DNA binding and shed light on the molecular mechanism by which these ‘simple’ SSBs interact with ssDNA.

Different approaches of applying single-objective binary genetic algorithm on the wind farm design

This paper discusses three different ways of applying the single-objective binary genetic algorithm into designing the wind farm. The introduction of different applications is through altering the binary encoding methods in GA codes. The first encoding method is the traditional one with fixed wind turbine positions. The second involves varying the initial positions from results of the first method, and it is achieved by using binary digits to represent the coordination of wind turbine on X or Y axis. The third is the mixing of the first encoding method with another one, which is by adding four more binary digits to represent one of the unavailable plots. The goal of this paper is to demonstrate how the single-objective binary algorithm can be applied and how the wind turbines are distributed under various conditions with best fitness. The main emphasis of discussion is focused on the scenario of wind direction varying from 0° to 45°. Results show that choosing the appropriate position of wind turbines is more significant than choosing the wind turbine numbers, considering that the former has a bigger influence on the whole farm fitness than the latter. And the farm has best performance of fitness values, farm efficiency, and total power with the direction between 20°to 30°.

Versatile single-layer sodium phosphidostannate(II): Strain-tunable electronic structure, excellent mechanical flexibility, and an ideal gap for photovoltaics

Density functional theory (DFT) calculations were performed to study the structural, mechanical, electrical, optical properties, and strain effects in single-layer sodium phosphidostannate(II) (NaSnP). We find the exfoliation of single-layer NaSnP from bulk form is highly feasible because the cleavage energy is comparable to graphite and MoS2. In addition, the breaking strain of the NaSnP monolayer is comparable to other widely studied 2D materials, indicating excellent mechanical flexibility of 2D NaSnP. Using the hybrid functional method, the calculated band gap of single-layer NaSnP is close to the ideal band gap of solar cell materials (1.5 eV), demonstrating great potential in future photovoltaic application. Furthermore, strain effect study shows that a moderate compression (2%) can trigger indirect-to-direct gap transition, which would enhance the ability of light absorption for the NaSnP monolayer. With sufficient compression (8%), the single-layer NaSnP can be tuned from semiconductor to metal, suggesting great applications in nanoelectronic devices based on strain engineering techniques.

Parameterization and reliability of single-leg balance test assessed with inertial sensors in stroke survivors: a cross-sectional study

Background and purpose There are no published studies on the parameterisation and reliability of the single-leg stance (SLS) test with inertial sensors in stroke patients. Purpose: to analyse the reliability (intra-observer/inter-observer) and sensitivity of inertial sensors used for the SLS test in stroke patients. Secondary objective: to compare the records of the two inertial sensors (trunk and lumbar) to detect any significant differences in the kinematic data obtained in the SLS test. Methods Design: cross-sectional study. While performing the SLS test, two inertial sensors were placed at lumbar (L5-S1) and trunk regions (T7–T8). Setting: Laboratory of Biomechanics (Health Science Faculty - University of Málaga). Participants: Four chronic stroke survivors (over 65 yrs old). Measurement: displacement and velocity, Rotation (X-axis), Flexion/Extension (Y-axis), Inclination (Z-axis); Resultant displacement and velocity (V): RV=(Vx2+Vy2+Vz2)−−−−−−−−−−−−−−−−−√ Along with SLS kinematic variables, descriptive analyses, differences between sensors locations and intra-observer and inter-observer reliability were also calculated. Results Differences between the sensors were significant only for left inclination velocity (p = 0.036) and extension displacement in the non-affected leg with eyes open (p = 0.038). Intra-observer reliability of the trunk sensor ranged from 0.889-0.921 for the displacement and 0.849-0.892 for velocity. Intra-observer reliability of the lumbar sensor was between 0.896-0.949 for the displacement and 0.873-0.894 for velocity. Inter-observer reliability of the trunk sensor was between 0.878-0.917 for the displacement and 0.847-0.884 for velocity. Inter-observer reliability of the lumbar sensor ranged from 0.870-0.940 for the displacement and 0.863-0.884 for velocity. Conclusion There were no significant differences between the kinematic records made by an inertial sensor during the development of the SLS testing between two inertial sensors placed in the lumbar and thoracic regions. In addition, inertial sensors. Have the potential to be reliable, valid and sensitive instruments for kinematic measurements during SLS testing but further research is needed.

Extending genetic linkage analysis to diffusion tensor images to map single gene effects on brain fiber architecture

We extended genetic linkage analysis - an analysis widely used in quantitative genetics - to 3D images to analyze single gene effects on brain fiber architecture. We collected 4 Tesla diffusion tensor images (DTI) and genotype data from 258 healthy adult twins and their non-twin siblings. After high-dimensional fluid registration, at each voxel we estimated the genetic linkage between the single nucleotide polymorphism (SNP), Val66Met (dbSNP number rs6265), of the BDNF gene (brain-derived neurotrophic factor) with fractional anisotropy (FA) derived from each subject's DTI scan, by fitting structural equation models (SEM) from quantitative genetics. We also examined how image filtering affects the effect sizes for genetic linkage by examining how the overall significance of voxelwise effects varied with respect to full width at half maximum (FWHM) of the Gaussian smoothing applied to the FA images. Raw FA maps with no smoothing yielded the greatest sensitivity to detect gene effects, when corrected for multiple comparisons using the false discovery rate (FDR) procedure. The BDNF polymorphism significantly contributed to the variation in FA in the posterior cingulate gyrus, where it accounted for around 90-95% of the total variance in FA. Our study generated the first maps to visualize the effect of the BDNF gene on brain fiber integrity, suggesting that common genetic variants may strongly determine white matter integrity.

Compliance with seafood safety standards within the Vietnamese finfish capture distribution chain

This thesis examined the level of food safety compliance with government regulations and investigated routes of microbiological contaminations in raw finfish within Vietnamese domestic seafood distribution chains. Findings from direct observation, microbiological analysis and employee surveys were synthesized to identify the main factors affecting food safety and hygiene practices of fish distributors. The studies produced clear recommendations for food safety management in the domestic distribution chains. The findings may contribute to national efforts to decrease the risks of fish-borne illness for consumers in Vietnam.

Single layer lead iodide: Computational exploration of structural, electronic and optical properties, strain induced band modulation and the role of spin-orbital-coupling

Graphitic like layered materials exhibit intriguing electronic structures and thus the search for new types of two-dimensional (2D) monolayer materials is of great interest for developing novel nano-devices. By using density functional theory (DFT) method, here we for the first time investigate the structure, stability, electronic and optical properties of monolayer lead iodide (PbI2). The stability of PbI2 monolayer is first confirmed by phonon dispersion calculation. Compared to the calculation using generalized gradient approximation, screened hybrid functional and spin–orbit coupling effects can not only predicts an accurate bandgap (2.63 eV), but also the correct position of valence and conduction band edges. The biaxial strain can tune its bandgap size in a wide range from 1 eV to 3 eV, which can be understood by the strain induced uniformly change of electric field between Pb and I atomic layer. The calculated imaginary part of the dielectric function of 2D graphene/PbI2 van der Waals type hetero-structure shows significant red shift of absorption edge compared to that of a pure monolayer PbI2. Our findings highlight a new interesting 2D material with potential applications in nanoelectronics and optoelectronics.

Transferability of cupped oyster EST (Expressed Sequence Tag)-derived SNP (Single Nucleotide Polymorphism) markers to related crassostrea and ostrea species

Single nucleotide polymorphisms (SNPs) are widely acknowledged as the marker of choice for many genetic and genomic applications because they show co-dominant inheritance, are highly abundant across genomes and are suitable for high-throughput genotyping. Here we evaluated the applicability of SNP markers developed from Crassostrea gigas and C. virginica expressed sequence tags (ESTs) in closely related Crassostrea and Ostrea species. A total of 213 putative interspecific level SNPs were identified from re-sequencing data in six amplicons, yielding on average of one interspecific level SNP per seven bp. High polymorphism levels were observed and the high success rate of transferability show that genic EST-derived SNP markers provide an efficient method for rapid marker development and SNP discovery in closely related oyster species. The six EST-SNP markers identified here will provide useful molecular tools for addressing questions in molecular ecology and evolution studies including for stock analysis (pedigree monitoring) in related oyster taxa.

Genomewide screens in ankylosing spondylitis

Efforts to identify genes other than HLA-B27 in AS have been driven by the strength of the evidence from genetic epidemiology studies indicating that HLA-B27, although a major gene in AS, is clearly not the only significant gene operating. This is the case for both genetic determinants of disease-susceptibility and phenotypic characteristics such as disease severity and associated disease features. In this chapter the genetic epidemiology of AS and the gene-mapping studies performed to date will be reviewed and the future direction of research in this field discussed.

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom

Objective - To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. Methods - HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. Results - The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10-99). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10-5), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HkA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. Conclusion - HLA-B27 and -B60 are associated with susceptibility to AS, but differences in BLA-B27 subtype do not affect susceptibility to AS in this white population.

Complete genome sequences of Helicoverpa armigera Single Nucleopolyhedrovirus Strains AC53 and H25EA1 from Australia

We report here the genome sequences of two alphabaculoviruses of Helicoverpa spp. from Australia: AC53, used in the biopesticides ViVUS and ViVUS Max, and H25EA1, used in in vitro production studies.

High-throughput sequencing of IL23R reveals a low-frequency, nonsynonymous single-nucleotide polymorphism that is associated with ankylosing spondylitis in a Han Chinese population

Objective Ankylosing spondylitis (AS) is a highly heritable common inflammatory arthritis that targets the spine and sacroiliac joints of the pelvis, causing pain and stiffness and leading eventually to joint fusion. Although previous studies have shown a strong association of IL23R with AS in white Europeans, similar studies in East Asian populations have shown no association with common variants of IL23R, suggesting either that IL23R variants have no role or that rare genetic variants contribute. The present study was undertaken to screen IL23R to identify rare variants associated with AS in Han Chinese. Methods A 170-kb region containing IL23R and its flanking regions was sequenced in 50 patients with AS and 50 ethnically matched healthy control subjects from a Han Chinese population. In addition, the 30-kb region of peak association in white Europeans was sequenced in 650 patients with AS and 1,300 healthy controls. Validation genotyping was undertaken in 846 patients with AS and 1,308 healthy controls. Results We identified 1,047 variants, of which 729 were not found in the dbSNP genomic build 130. Several potentially functional rare variants in IL23R were identified, including one nonsynonomous single-nucleotide polymorphism (nsSNP), Gly149Arg (position 67421184 GA on chromosome 1). Validation genotyping showed that the Gly149Arg variant was associated with AS (odds ratio 0.61, P = 0.0054). Conclusion This is the first study to implicate rare IL23R variants in the pathogenesis of AS. The results identified a low-frequency nsSNP with predicted loss-of-function effects that was protectively associated with AS in Han Chinese, suggesting that decreased function of the interleukin-23 (IL-23) receptor protects against AS. These findings further support the notion that IL-23 signaling has an important role in the pathogenesis of AS.

A linkage study across the T cell receptor A and T cell receptor B loci in families with rheumatoid arthritis

Objective. To examine whether the T cell receptor (TCR) A or TCRB loci exhibit linkage with disease in multiplex rheumatoid arthritis (RA) families. Methods. A linkage study was performed in 184 RA families from the UK Arthritis and Rheumatism Council Repository, each containing at least 1 affected sibpair. The microsatellites D14S50, TCRA, and D14S64 spanning the TCRA locus and D7S509, Vβ6.7, and D7S688 spanning the TCRB locus were used as DNA markers. The subjects were genotyped using a semiautomated polymerase chain reaction-based method. Two-point and multipoint linkage analyses were performed. Results. Nonparametric single-marker likelihood odds (LOD) scores were 0.49 (P = 0.07) for D14S50, 0.65 (P = 0.04) for TCRA, 0.07 (P = 0.29) for D14S64, 0.01 (P = 0.43) for D7S509, 0.0 (P = 0.50) for Vβ6.7, and 0.0 (P = 0.50) for D7S688. By multipoint analysis, there was no evidence of linkage at TCRB (LOD score 0), and the maximum LOD score at the TCRA locus was 0.37 (at D14S50). The presence of a susceptibility locus (LOD score < -2.0) was excluded, with lambda ≤ 1.8 at TCRA and ≤1.4 at TCRB. Conclusion. These linkage studies provide no significant evidence of a major germline-encoded TCRA or TCRB component of susceptibility to RA.