Investigation of the role of the GABRG2 gene variant in migraine

Migraine is the most common neurological disorder worldwide affecting about 12% of the worldwide population. This disorder has been classed into two main types of migraine—with and without aura. While a number of factors can influence the onset of migraine, a major factor is that of genetics. The GABAA gene encodes for the GABAA receptor. Along with other receptors, the GABAA receptor is involved in the mediation of neuronal activities. In this study, a GABRG2 gene (GABAA receptor gamma-2-subunit) SNP (rs211037) was genotyped on a migraine case–control population of 546 (273 affected and an equal number of healthy) individuals. Using specifically designed primers, a high resolution melt (HRM) assay was carried out in the genotyping process. After genotyping, results were compared in the case and control populations. Analysis of results showed no significant differences in the allele frequencies between case and control populations. Similarly no differences were detected for subtypes or for a specific gender of migraine (p > 0.05). Although this gene has been previously found to be involved in febrile seizures and there is some co-morbidity between epilepsy and migraine, we decided to investigate this marker for involvement in migraine. The results did not support a role for the tested GABRG2 variant in migraine.

Towards a model for student selection in clinical psychology

Background Selection of candidates for clinical psychology programmes is arguably the most important decision made in determining the clinical psychology workforce. However, there are few models to inform the development of selection tools to support selection procedures. The study, using a factor analytic structure, has operationalised the model predicting applicants' capabilities. Method Eighty-eight clinical applicants for entry into a postgraduate clinical psychology programme were assessed on a series of tasks measuring eight capabilities: guided reflection, communication skills, ethical decision making, writing, conceptual reasoning, empathy, and awareness of mind and self-observation. Results Factor analysis revealed three capabilities: labelled “awareness” accounting for 35.71% of variance; “reflection” accounting for 20.56%; and “reasoning” accounting for 18.24% of variance. Fourth year grade point average (GPA) did not correlate with performance on any of the selection capabilities other than a weak correlation with performance on the ethics capability. Conclusions Eight selection capabilities are identified for the selection of candidates independent of GPA. While the model is tentative, it is hoped that the findings will stimulate the development and validation of assessment procedures with good predictive validity which will benefit the training of clinical psychologists and, ultimately, effective service delivery.

Investigation of Association between PFO complicated by cryptogenic stroke and a common variant of the cardiac transcription factor GATA4

Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke.

Analysis of the MTHFR C677T variant with migraine phenotypes

Background The methylenetetrahydrofolate reductase (MTHFR) gene variant C677T has been implicated as a genetic risk factor in migraine susceptibility, particularly in Migraine with Aura. Migraine, with and without aura (MA and MO) have many diagnostic characteristics in common. It is postulated that migraine symptomatic characteristics might themselves be influenced by MTHFR. Here we analysed the clinical profile, migraine symptoms, triggers and treatments of 267 migraineurs previously genotyped for the MTHFR C677T variant. The chi-square test was used to analyse all potential relationships between genotype and migraine clinical variables. Regression analyses were performed to assess the association of C677T with all migraine clinical variables after adjusting for gender. Findings The homozygous TT genotype was significantly associated with MA (P < 0.0001) and unilateral head pain (P = 0.002). While the CT genotype was significantly associated with physical activity discomfort (P < 0.001) and stress as a migraine trigger (P = 0.002). Females with the TT genotype were significantly associated with unilateral head pain (P < 0.001) and females with the CT genotype were significantly associated with nausea (P < 0.001), osmophobia (P = 0.002), and the use of natural remedy for migraine treatment (P = 0.003). Conversely, male migraineurs with the TT genotype experienced higher incidences of bilateral head pain (63% vs 34%) and were less likely to use a natural remedy as a migraine treatment compared to female migraineurs (5% vs 20%). Conclusions MTHFR genotype is associated with specific clinical variables of migraine including unilateral head pain, physical activity discomfort and stress.

Evolution of lure response in tephritid fruit flies : phytochemicals as drivers of sexual selection

The males of many Bactrocera species (Diptera: Tephritidae) respond strongly and positively to a small number of plant-derived chemicals (=male lures). Males that have imbibed the lures commonly have a mating advantage over unfed males, but no female benefits have been demonstrated for females mating with lure-fed males. It has been hypothesized that the strong lure response is a case of runaway selection, where males receive direct benefits and females receive indirect benefits via 'sexy sons', or a case of sensory bias where females have a lower threshold response to lures. To test these hypotheses we studied the effects of lure feeding on male mating, remating and longevity; while for females that had mated with lure-fed males we recorded mating refractoriness, fecundity, egg viability and longevity. We used Bactrocera tryoni as our test animal and as lures the naturally occurring zingerone and chemically related, but synthetic chemical cuelure. Feeding on lures provided direct male benefits in greater mating success and increased multiple mating. For the first time, we recorded direct female effects: increased fecundity and reduced remating receptivity. Egg viability did not differ in females mated with lure-fed or unfed males. The life span of males and females exposed to lures was reduced. These results reveal direct, current-generation fitness benefits for both males and females, although the male benefits appear greater. We discuss that while lure response is indeed likely to be a sexual selection trait, there is no need to invoke runaway selection to explain its evolution.

Association study of a functional variant in intron 8 of the dopamine transporter gene and migraine susceptibility

Migraine is a common, genetically influenced neurovascular disorder. The dopamine transporter gene is a candidate for migraine association studies. This study tested a functionally linked variable number tandem repeat (VNTR) in intron 8 of the dopamine transporter gene (DATInt8) in 550 migraine cases (401 with aura, 149 without aura) and 550 non-migraine controls. Chi-squared analysis of the DATInt8 revealed that the allele and genotype frequency distributions for migraine cases (including subtype analysis) and controls were not different (P > 0.1). These findings offer no evidence for an association of the DATInt8 with migraine with and without aura and therefore do not implicate the dopamine transporter gene as a modifier of migraine risk.

Genetic response to combined family selection for improved mean harvest weight in giant freshwater prawn (Macrobrachium rosenbergii) in Vietnam

We estimated genetic changes in body and carcass weight traits in a giant freshwater prawn (GFP) (Macrobrachium rosenbergii) population selected for increased body weight at harvest in Vietnam. The data set consisted of 18,387 individual body and 1730 carcass weight records, as well as full pedigree information collected over four generations. Average selection response (per generation) in body weight at harvest (transformed to square root) estimated as the difference between the Selection line and the Control group was 7.4% calculated from least squares mean (LSMs), 7.0% from estimated breeding values (EBVs) and 4.4% calculated from EBVs between two consecutive generations. Favorable correlated selection responses (estimated from LSMs) were found for other body traits including: total length, cephalothorax length, abdominal length, cephalothorax width, and abdominal width (12.1%, 14.5%, 10.4%, 15.5% and 13.3% over three selection generations, respectively). Data in the second generation of selection showed positive correlated responses for carcass weight traits including: abdominal weight, exoskeleton-off weight, and telson-off weight of 8.8%, 8.6% and 8.8%, respectively. We conclude that body weight at harvest responded well to the application of combined (between and within) family selection and correlated responses in carcass weight traits were favorable.

The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura

Background The C677T variant in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that may also be affected by genetically influenced hyperhomocysteinaemia. To determine whether the C677T variant in the MTHFR gene is associated with migraine susceptibility we utilised unrelated and family-based case-control study designs. Methods A total of 652 Caucasian migraine cases were investigated in this study. The MTHFR C677T variant was genotyped in 270 unrelated migraine cases and 270 controls as well as 382 affected subjects from 92 multiplex pedigrees. Results In the unrelated case-control sample we observed an over-representation of the 677T allele in migraine patients compared to controls, specifically for the MA subtype (40% vs. 33%) (χ2 = 5.70, P = 0.017). The Armitage test for trend indicated a significant dosage effect of the risk allele (T) for MA (χ2 = 5.72, P = 0.017). This linear trend was also present in the independent family-based sample (χ2 = 4.25, Padjusted = 0.039). Overall, our results indicate that the T/T genotype confers a modest, yet significant, increase in risk for the MA subtype (odds ratio: 2.0 – 2.5). No increased risk for the MO subtype was observed (P > 0.05). Conclusions In Caucasians, the C677T variant in the MTHFR gene influences susceptibility to MA, but not MO. Investigation into the enzyme activity of MTHFR and the role of homocysteine in the pathophysiology of migraine is warranted.

The methylentetrahydrofolate reductase gene variant (C677T) as a risk factor for essential hypertension in Caucasians

Essential hypertension (EH) is a common, multifactorial disorder likely to be influenced by multiple genes of modest effect. The methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation is functionally important, being strongly associated with reduced enzyme activity and increased plasma levels of homocysteine. Mild hyperhomocysteinemia is a known risk factor for cardiovascular disease (CVD) and hypothesised also to be involved in hypertension pathophysiology. The present study was performed to determine the prevalence of the 677T mutation in Australian Caucasian patients diagnosed with EH and to test whether the C677T variant is associated with the disorder. A case-control cohort, consisting of 250 EH patients and 250 age, sex and racially matched normotensive controls, were used for the association study. Comparison of C677T allele frequencies revealed a higher proportion of the mutant allele (T) in the EH group (40%) compared to unaffected controls (34%) (p=0.07). Furthermore, genotypic results indicated that the prevalence of the homozygous mutant genotype (T/T) in the affected group was higher than that of controls (14%:10%) (p=0.17). Interestingly, conditional logistic regression showed that the MTHFR C677T mutation conferred a mild, yet significant increase in risk of essential hypertension after adjusting for body mass index (odds ratio=1.57, 95% confidence interval: 1.04-2.37, p=0.03). These findings require further investigation in large independent samples, but suggest that essential hypertension, like CVD, may be mildly influenced by the MTHFR C677T variant.

G-protein β3 subunit gene (GNB3) variant in causation of essential hypertension

Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein β3 subunit gene (GNB3) induces formation of a splice variant (Gβ3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (χ2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105±7, 109±16, and 128±28 mm Hg (mean±SD) for CC, CT, and 7T, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein β3 subunit gene in the causation of essential hypertension.

An interpretive field study of packaged software selection processes

Packaged software is pre-built with the intention of licensing it to users in domestic settings and work organisations. This thesis focuses upon the work organisation where packaged software has been characterised as one of the latest ‘solutions’ to the problems of information systems. The study investigates the packaged software selection process that has, to date, been largely viewed as objective and rational. In contrast, this interpretive study is based on a 21⁄2 year long field study of organisational experiences with packaged software selection at T.Co, a consultancy organisation based in the United Kingdom. Emerging from the iterative process of case study and action research is an alternative theory of packaged software selection. The research argues that packaged software selection is far from the rationalistic and linear process that previous studies suggest. Instead, the study finds that aspects of the traditional process of selection incorporating the activities of gathering requirements, evaluation and selection based on ‘best fit’ may or may not take place. Furthermore, even where these aspects occur they may not have equal weight or impact upon implementation and usage as may be expected. This is due to the influence of those multiple realities which originate from the organisational and market environments within which packages are created, selected and used, the lack of homogeneity in organisational contexts and the variously interpreted characteristics of the package in question.

Association of a low density lipoprotein receptor microsatellite variant with obesity

OBJECTIVE To determine whether a microsatellite polymorphism located towards the 3' end of the low density lipoprotein receptor gene (LDLR) is associated with obesity. DESIGN A cross-sectional case-control study. SUBJECTS One hundred and seven obese individuals, defined as a body mass index (BMI) ≤ 26 kg/m2, and 163 lean individuals, defined as a BMI < 26 kg/m2. MEASUREMENTS BMI, blood pressure, serum lipids, alleles of LDLR microsatellite (106 bp, 108 bp and 112 bp). RESULTS There was a significant association between variants of the LDLR microsatellite and obesity, in the overall tested population, due to a contributing effect in females (χ2 = 12.3, P = 0.002), but not in males (χ2 = 0.3, P = 0.87). In females, individuals with the 106 bp allele were more likely to be lean, while individuals with the 112 bp and/or 108 bp alleles tended to be obese. CONCLUSIONS These results suggest that in females, LDLR may play a role in the development of obesity.

A genetic variant located in miR-423 is associated with reduced breast cancer risk

Background/Aim: Since microRNAs (miRNAs) act as translational regulators of multiple genes, single nucleotide polymorphisms (SNP) in them can have potentially wide-ranging effects. Using an association approach, this research examined the effects of the rs6505162 SNP, an A>C polymorphism located in the premiRNA region of miR-423, on breast cancer development. Materials and Methods: Caucasian Australian women with breast cancer and controls matched for age and ethnicity were genotyped for rs6505162 and their genotypic and allelic frequencies analysed for significant differences. Results: Analysis indicated that there were significant differences between the case and control populations (χ 2=6.70, p=0.035), with the CC genotype conferring reduced risk of breast cancer development (odds ratio=0.50 95% confidence interval=0.27-0.92, p=0.03). Conclusion: Further functional research is required to determine the mechanism of action of this SNP on miRNA function.

Selection of energy storage system for a regenerative dynamic dynamometer

This paper presents a design technique of a fully regenerative dynamic dynamometer. It incorporates an energy storage system to absorb the energy variation due to dynamometer transients. This allows the minimum power electronics requirement at the grid to supply the losses. The simulation results of the full system over a driving cycle show the amount of energy required to complete a driving cycle, therefore the size of the energy storage system can be determined.

Design optimisation of ironless motors based on magnet selection

This paper considers the design of a radial flux permanent magnet iron less core brushless DC motor for use in an electric wheel drive with an integrated epicyclic gear reduction. The motor has been designed for a continuous output torque of 30 Nm and peak rating of 60 Nm with a maximum operating speed of 7000 RPM. In the design of brushless DC motors with a toothed iron stator the peak air-gap magnetic flux density is typically chosen to be close to that of the remanence value of the magnets used. This paper demonstrates that for an ironless motor the optimal peak air-gap flux density is closer to the maximum energy product of the magnets used. The use of a radial flux topology allows for high frequency operation and can be shown to give high specific power output while maintaining a relatively low magnet mass. Two-dimensional finite element analysis is used to predict the air-gap flux density. The motor design is based around commonly available NdFeB bar magnet size