Investigation of a neuronal nitric oxide synthase gene (NOS1) polymorphism in a multiple sclerosis population

Multiple Sclerosis (MS) is a chronic neurological disease characterized by demyelination associated with infiltrating white blood cells in the central nervous system (CNS). Nitric oxide synthases (NOS) are a family of enzymes that control the production of nitric oxide. It is possible that neuronal NOS could be involved in MS pathophysiology and hence the nNOS gene is a potential candidate for involvement in disease susceptibility. The aim of this study was to determine whether allelic variation at the nNOS gene locus is associated with MS in an Australian cohort. DNA samples obtained from a Caucasian Australian population affected with MS and an unaffected control population, matched for gender, age and ethnicity, were genotyped for a microsatellite polymorphism in the promoter region of the nNOS gene. Allele frequencies were compared using chi-squared based statistical analyses with significance tested by Monte Carlo simulation. Allelic analysis of MS cases and controls produced a chi-squared value of 5.63 with simulated P = 0.96 (OR(max) = 1.41, 95% CI: 0.926-2.15). Similarly, a Mann-Whitney U analysis gave a non-significant P-value of 0.377 for allele distribution. No differences in allele frequencies were observed for gender or clinical course subtype (P > 0.05). Statistical analysis indicated that there is no association of this nNOS variant and MS and hence the gene does not appear to play a genetically significant role in disease susceptibility.

Investigation of an inducible nitric oxide synthase gene (NOS2A) polymorphism in a multiple sclerosis population

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting most commonly the Caucasian population. Nitric oxide (NO) is a biological signaling and effector molecule and is especially important during inflammation. Inducible nitric oxide synthase (iNOS) is one of the three enzymes responsible for generating NO. It has been reported that there is an excessive production of NO in MS concordant with an increased expression of iNOS in MS lesions. This study investigated the role of a bi-allelic tetranucleotide polymorphism located in the promoter region of the human iNOS (NOS2A) gene in MS susceptibility. A group of MS patients (n = 101) were genotyped and compared to an age- and sex-matched group of healthy controls (n = 101). The MS group was subdivided into three subtypes, namely relapsing-remitting MS (RR-MS), secondary-progressive MS (SP-MS) and primary-progressive MS (PP-MS). Results of a chi-squared analysis and a Fisher's exact test revealed that allele and genotype distributions between cases and controls were not significantly different for the total population (chi(2) = 3.4, P(genotype) = 0.15; chi(2) = 3.4, P(allele) = 0.082) and for each subtype of MS (P > 0.05). This suggests that there is no direct association of this iNOS gene variant with MS susceptibility.

Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds

Linkage disequilibrium (LD) mapping is commonly used as a fine mapping tool in human genome mapping and has been used with some success for initial disease gene isolation in certain isolated in-bred human populations. An understanding of the population history of domestic dog breeds suggests that LD mapping could be routinely utilized in this species for initial genome-wide scans. Such an approach offers significant advantages over traditional linkage analysis. Here, we demonstrate, using canine copper toxicosis in the Bedlington terrier as the model, that LD mapping could be reasonably expected to be a useful strategy in low-resolution, genome-wide scans in pure-bred dogs. Significant LD was demonstrated over distances up to 33.3 cM. It is very unlikely, for a number of reasons discussed, that this result could be extrapolated to the rest of the genome. It is, however, consistent with the expectation given the population structure of canine breeds and, in this breed at least, with the hypothesis that it may be possible to utilize LD in a genome-wide scan. In this study, LD mapping confirmed the location of the copper toxicosis in Bedlington terrier gene (CT-BT) and was able to do so in a population that was refractory to traditional linkage analysis.

The GSTM1 null genotype confers an increased risk for Solar Keratosis Development in an Australian Caucasian Population

Solar keratoses affect approximately 50% of Australian Caucasians aged over 40 y. Solar keratoses can undergo malignant transformation into squamous cell carcinoma followed by possible metastasis and are risk factors for basal cell carcinoma, melanoma, and squamous cell carcinoma. The glutathione-S-transferase genes play a part in detoxification of carcinogens and mutagens, including some produced by ultraviolet radiation. This study examined the role of glutathione-S-transferase M1, T1, P1, and Z1 gene polymorphisms in susceptibility to solar keratoses development. Using DNA samples from volunteers involved in the Nambour Skin Cancer Prevention Trial, allele and genotype frequencies were determined using polymerase chain reaction and restriction enzyme digestion. No significant differences were detected in glutathione-S-transferase P1 and glutathione-S-transferase Z1 allele or genotype frequencies; however, a significant association between glutathione-S-transferase M1 genotypes and solar keratoses development was detected (p=0.003) with null individuals having an approximate 2-fold increase in risk for solar keratoses development (odds ratio: 2.1; confidence interval: 1.3-3.5) and a significantly higher increase in risk in conjunction with high outdoor exposure (odds ratio: 3.4; confidence interval: 1.9-6.3). Also, a difference in glutathione-S-transferase T1 genotype frequencies was detected (p=0.039), although considering that multiple testing was undertaken, this was found not to be significant. Fair skin and inability to tan were found to be highly significant risk factors for solar keratoses development with odds ratios of 18.5 (confidence interval: 5.7-59.9) and 7.4 (confidence interval: 2.6-21.0), respectively. Overall, glutathione-S-transferase M1 conferred a significant increase in risk of solar keratoses development, particularly in the presence of high outdoor exposure and synergistically with known phenotypic risk factors of fair skin and inability to tan.

BoP and MNCs: where is the market and where the source of innovation?

ln 2004 Prahalad made managers aware of the great economic opportunity that the population at the BoP (Base of the Pyramid) could represent for business in the tom of new potential consumers. However, MNCs (Multi-National Corporations) have continued to fail in penetrating low income markets, arguably because applied strategies are often the same adopted at the top of the pyramid. Even in those few cases where products get re-envisioned, theie introduction in contexts of extreme poverty only induces new needs and develops new dependencies. At best the rearrangement of business models by MNCs has meant the realization of CSR (Corporate Social Responsibly) schemes that have validity from a marketing perspective, but still lack the crucial element of social embeddedness (London & Hart, 2004). Today the challenge is lo reach the lowest population tier with reinvented business models based on principles of value co-creation. Starting from a view of the potential consumer at the BoP as a ring of continuity in the value chain process – a resource that can itself produce value - this paper concludes proposing an alternative innovative approach to operate in developing markets that overturns the roles of MNCs and the BoP. The proposed perspective of ‘reversed' source of innovation and primary target market builds on two fundamental tenets: traditional knowledge is rich and greatly unexploded, and markets at the lop of the pyramid are saturated with unnecessary products / practices that have lost contact with the natural environment.

BoP and MNCs: where is the market and where the source of innovation?

ln 2004 Prahalad made managers aware of the great economic opportunity that the population at the BoP (Base of the Pyramid) could represent for business in the tom of new potential consumers. However, MNCs (Multi-National Corporations) have continued to fail in penetrating low income markets, arguably because applied strategies are often the same adopted at the top of the pyramid. Even in those few cases where products get re-envisioned, theie introduction in contexts of extreme poverty only induces new needs and develops new dependencies. At best the rearrangement of business models by MNCs has meant the realization of CSR (Corporate Social Responsibly) schemes that have validity from a marketing perspective, but still lack the crucial element of social embeddedness (London & Hart, 2004). Today the challenge is lo reach the lowest population tier with reinvented business models based on principles of value co-creation. Starting from a view of the potential consumer at the BoP as a ring of continuity in the value chain process – a resource that can itself produce value - this paper concludes proposing an alternative innovative approach to operate in developing markets that overturns the roles of MNCs and the BoP. The proposed perspective of ‘reversed' source of innovation and primary target market builds on two fundamental tenets: traditional knowledge is rich and greatly unexploded, and markets at the lop of the pyramid are saturated with unnecessary products / practices that have lost contact with the natural environment.

Re-contextualising and re-theorising cultural values in teacher education practices : a Samoan standpoint

This thesis explores the significance of Samoan cultural values in teacher education practices. The study examines the coexistence of traditional Samoan cultural values alongside values that have resulted through the influence of missionaries, colonisation, post-colonialism and globalisation.

Diurnal variation of small and large ion concentrations in an urban location

A Neutral cluster and Air Ion Spectrometer (NAIS) was used to monitor the concentration of airborne ions on 258 full days between Nov 2011 and Dec 2012 in Brisbane, Australia. The air was sampled from outside a window on the sixth floor of a building close to the city centre, approximately 100 m away from a busy freeway. The NAIS detects all ions and charged particles smaller than 42 nm. It was operated in a 4 min measurement cycle, with ion data recorded at 10 s intervals over 2 min during each cycle. The data were analysed to derive the diurnal variation of small, large and total ion concentrations in the environment. We adapt the definition of Horrak et al (2000) and classify small ions as molecular clusters smaller than 1.6 nm and large ions as charged particles larger than this size...

The null allele of GSTM1 does not affect susceptibility to solar keratoses in the Australian white population

Solar keratoses (SKs) are induced by exposure to UV radiation and are capable of undergoing transformation to squamous cell carcinoma (SCC).1 The two main factors influencing the occurrence of SK are the sensitivity of the skin to sunlight and the total duration of solar exposure. These factors are responsible for the high incidence of SK in Australia. Although the influence of genetic factors is not defined, there is evidence that the gene encoding the enzyme, glutathione S-transferase, may be implicated in cancer predisposition and therefore SK. Glutathione S-transferase Mu-1 (GSTM1) is an isoenzyme involved in the detoxification of carcinogens. The GSTM1 protein is completely absent in approximately 50% of white persons. This absence is caused by a homozygous gene deletion on chromosome 1p resulting in a null genotype.2 Katoh3 showed that the frequency of the GSTM1 null genotype was significantly higher in 85 patients with urothelial cancer (61.2%; p < 0.05), suggesting that the null genotype may increase cancer susceptibility. This finding was supported by Lafuente et al.4 who found evidence that persons who lack the GSTM1 gene have approximately twice the chance of experiencing malignant melanoma. Further research in the United Kingdom found that patients with two or more skin tumors of different types, basal cell carcinoma (BCC) and SCC, had a significantly higher frequency of GSTM1 null genotypes than controls (71%; p = 0.033). However the GSTM1 genotype in patients with only SCC was not excessive in this population.5 Persons residing in northern Australia have the highest incidence of nonmelanoma skin cancer (SCC and BCC) in the world6 and receive far greater solar exposure than persons residing in the United Kingdom. It is possible that the GSTM1 null genotype may affect susceptibility to SK, which may act as SCC precursors, in Australians exposed to these high levels of solar radiation.

Postdiagnosis personal growth in an Australian population of parents raising children with developmental disability

Background Parenting a child with a developmental disability presents a variety of long-term physical and emotional challenges. When exploring parent wellbeing, the disability field is dominated by a deficit model despite parents reportedly demonstrating coping and resilience. The current study is embedded in a salutogenic theory (Antonovsky, 1979) and explores the potential for parents of children diagnosed with a developmental disability to undergo positive changes. Method Participants were 6 fathers and 27 mothers who completed measures of distress and posttraumatic growth. Results Compared with a number of other Australian samples, participants reported significantly higher levels of posttraumatic growth. Reports of growth did not negate reports of distress. Results also indicated that constructs of distress and growth were independent. Conclusions The research has important implications for disability support services, reminding providers to be cognisant of the potential for growth, as well as distress, thereby permitting an atmosphere conducive to exploring such outcomes.

Making the train : re-conceptualising accessibility for intra-urban rail travel

Australian authorities have set ambitious policy objectives to shift Australia’s current transport profile of heavy reliance on private motor cars to sustainable modes. Improving accessibility of public transport is a central component of that objective. Past studies on accessibility to public transport focus on walking time and/or waiting time. However, travellers’ perceptions of the interface leg journeys may depend not only on these direct and tangible factors but also on social and psychological factors. This paper extends previous research that identified five salient perspectives of rail access by means of a statement sorting activity and cluster analysis with a small sample of rail passengers in three Australian cities (Zuniga et al, 2013). This study collects a new data set including 144 responses from Brisbane and Melbourne to an online survey made up of a Likert-scaled statement sorting exercise and questionnaire. It employs factor analysis to examine the statement rankings and uncovers seven underlying factors in the exploratory manner, i.e., station, safety, access, transfer, service attitude, traveler’s physical activity levels, and environmental concern. Respondents from groups stratified by rail use frequency are compared in terms of their scores of those factors. Findings from this study indicate a need to re-conceptualize accessibility to intra-urban rail travel in agreement with current policy agenda, and to target behavioral intervention to multiple dimensions of accessibility influencing passengers’ travel choices. Arguments in this paper are not limited to intra-urban rail transit, but may also be relevant to public transport in general.

Making the train : re-conceptualising accessibility for intra-urban rail travel

Australian authorities have set ambitious policy objectives to shift Australia’s current transport profile of heavy reliance on private motor cars to sustainable modes. Improving accessibility of public transport is a central component of that objective. Past studies on accessibility to public transport focus on walking time and/or waiting time. However, travellers’ perceptions of the interface leg journeys may depend not only on these direct and tangible factors but also on social and psychological factors. This paper extends previous research that identified five salient perspectives of rail access by means of a statement sorting activity and cluster analysis with a small sample of rail passengers in three Australian cities (Zuniga et al, 2013). This study collects a new data set including 144 responses from Brisbane and Melbourne to an online survey made up of a Likert-scaled statement sorting exercise and questionnaire. It employs factor analysis to examine the statement rankings and uncovers seven underlying factors in the exploratory manner, i.e., station, safety, access, transfer, service attitude, traveler’s physical activity levels, and environmental concern. Respondents from groups stratified by rail use frequency are compared in terms of their scores of those factors. Findings from this study indicate a need to re-conceptualize accessibility to intra-urban rail travel in agreement with current policy agenda, and to target behavioral intervention to multiple dimensions of accessibility influencing passengers’ travel choices. Arguments in this paper are not limited to intra-urban rail transit, but may also be relevant to public transport in general.

Common PPARγ variants C161T and Pro12Ala are not associated with inflammatory bowel disease in an Australian cohort

Background & Aims: Peroxisome proliferator-activated receptor (PPAR) γ is a transcription factor, highly expressed in colonic epithelial cells, adipose tissue and macrophages, with an important role in the regulation of inflammatory pathways. The common PPARγ variants C161T and Pro12Ala have recently been associated with Ulcerative Colitis (UC) and an extensive UC phenotype respectively, in a Chinese population. PPARγ Pro12Ala variant homozygotes appear to be protected from the development of Crohn's disease (CD) in European Caucasians. Methods: A case-control study was performed for both variants (CD n=575, UC n=306, Controls n=360) using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis in an Australian IBD cohort. A transmission disequilibrium test was also performed using CD trios for the PPARγ C161T variant. Genotype-phenotype analyses were also undertaken. Results: There was no significant difference in genotype distribution data or allele frequency between CD and UC patients and controls. There was no difference in allele transmission for the C161T variant. No significant relationship between the variants and disease location was observed. Conclusions: We were unable to replicate in a Caucasian cohort the recent association between PPARγ C161T and UC or between PPARγ Pro12Ala and an extensive UC phenotype in a Chinese population. There are significant ethnic differences in genetic susceptibility to IBD and its phenotypic expression.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.

Person re-identification using group information

After first observing a person, the task of person re-identification involves recognising an individual at different locations across a network of cameras at a later time. Traditionally, this task has been performed by first extracting appearance features of an individual and then matching these features to the previous observation. However, identifying an individual based solely on appearance can be ambiguous, particularly when people wear similar clothing (i.e. people dressed in uniforms in sporting and school settings). This task is made more difficult when the resolution of the input image is small as is typically the case in multi-camera networks. To circumvent these issues, we need to use other contextual cues. In this paper, we use "group" information as our contextual feature to aid in the re-identification of a person, which is heavily motivated by the fact that people generally move together as a collective group. To encode group context, we learn a linear mapping function to assign each person to a "role" or position within the group structure. We then combine the appearance and group context cues using a weighted summation. We demonstrate how this improves performance of person re-identification in a sports environment over appearance based-features.