Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

At work or play : a comparison of private property vehicle crashes with those occurring on public roads in north Queensland.

Objective: To define characteristics of vehicle crashes occurring on rural private property in north Queensland with an exploration of associated risk factors. Design: Descriptive analysis of private property crash data collected by the Rural and Remote Road Safety Study. Setting: Rural and remote north Queensland. Participants: A total of 305 vehicle controllers aged 16 years or over hospitalised at Atherton, Cairns, Mount Isa or Townsville for at least 24 hours as a result of a vehicle crash. Main outcome measure: A structured questionnaire completed by participants covering crash details, lifestyle and demographic characteristics, driving history, medical history, alcohol and drug use and attitudes to road use. Results: Overall, 27.9% of interviewees crashed on private property, with the highest proportion of private road crashes occurring in the North West Statistical Division (45%). Risk factors shown to be associated with private property crashes included male sex, riding off-road motorcycle or all-terrain vehicle, first-time driving at that site, lack of licence for vehicle type, recreational use and not wearing a helmet or seatbelt. Conclusions: Considerable trauma results from vehicle crashes on rural private property. These crashes are not included in most crash data sets, which are limited to public road crashes. Legislation and regulations applicable to private property vehicle use are largely focused on workplace health and safety, yet work-related crashes represent a minority of private property crashes in north Queensland.

User behaviours and intentions in digital media in Australia

This paper reports findings from a study of user behaviours and intentions towards online news and information in Australia, undertaken by the Queensland University of Technology Creative Industries Faculty and the Smart Services Cooperative Research Centre. It has used a literature review, online survey, focus groups and interviews to explore attitudes and behaviours towards online news and information. The literature review on consumer user of online media highlighted emerging technical opportunities, and flagged existing barriers to access experienced by consumers in the Australian digital media sector. The literature review highlighted multiple disconnects between consumer interests in online news and their ability to fulfil them. This presents an opportunity for news entities to appraise and resolve. Doing so may enhance their service offering, attract consumers and improve loyalty. These themes were further explored by the survey. The survey results revealed three typologies of user, described as ‘convenience’, ‘loyal’ and ‘customising’. Convenience users tend to access news by default, for example when they log out of email. Loyal users seek out a trusted brand such as mainstream news mastheads. Customising users tend to tailor news to their preferences, and be the first to use leading edge media. Respondents to the survey were then invited to participate in focus groups, which aimed to test the survey results. Consumer perceptions and attitudes are important factors in progression towards an information economy, because ultimately consumers are customers. By segmenting the online news market according to customer typology, media providers may identify new opportunities to attract and retain customers.

From conceptual process models to running systems: A holistic approach for the configuration of enterprise system processes

This paper proposes a method which aims at increasing the efficiency of enterprise system implementations. First, we argue that existing process modeling languages that feature different degrees of abstraction for different user groups exist and are used for different purposes which makes it necessary to integrate them. We describe how to do this using the meta models of the involved languages. Second, we argue that an integrated process model based on the integrated meta model needs to be configurable and elaborate on the enabling mechanisms. We introduce a business example using SAP modeling techniques to illustrate the proposed method.

Waking up with friends : breakfast news, Sunrise and the "televisual sphere"

This paper examines the Australian breakfast news program Sunrise. By drawing on interviews with both viewers and producers, as well as selected textual analysis, it examines the show, how it is "used" as a news source, and explores its role within the audience’s morning routines. By viewing the show as a part of what Baym has termed the "Televisual Sphere", it will argue against the common discourse that the program has simply followed a populist style in pursuit of higher ratings. Because of its success in communicating and connecting with viewers, it may be more constructive to consider Sunrise a very effective form of journalism which has been at the forefront of the recent trend towards increased levels of viewer input in television journalism.

Detection and Estimation of Nonstationary Power Transients

This chapter looks at issues of non-stationarity in determining when a transient has occurred and when it is possible to fit a linear model to a non-linear response. The first issue is associated with the detection of loss of damping of power system modes. When some control device such as an SVC fails, the operator needs to know whether the damping of key power system oscillation modes has deteriorated significantly. This question is posed here as an alarm detection problem rather than an identification problem to get a fast detection of a change. The second issue concerns when a significant disturbance has occurred and the operator is seeking to characterize the system oscillation. The disturbance initially is large giving a nonlinear response; this then decays and can then be smaller than the noise level ofnormal customer load changes. The difficulty is one of determining when a linear response can be reliably identified between the non-linear phase and the large noise phase of thesignal. The solution proposed in this chapter uses “Time-Frequency” analysis tools to assistthe extraction of the linear model.

Regulatory approaches to genetic testing in insurance

Rapid advancements in the field of genetic science have engendered considerable debate, speculation, misinformation and legislative action worldwide. While programs such as the Human Genome Project bring the prospect of seemingly miraculous medical advancements within imminent reach, they also create the potential for significant invasions of traditional areas of privacy and human dignity through laying the potential foundation for new forms of discrimination in insurance, employment and immigration regulation. The insurance industry, which has of course, traditionally been premised on discrimination as part of its underwriting process, is proving to be the frontline of this regulatory battle with extensive legislation, guidelines and debate marking its progress.

Ties that blind? How strong ties affect small business owner-managers’ perceived trustworthiness of their advisors

This research investigates how a strong personal relationship (strong tie) between a small business owner-manager and his professional or informal advisor affects the relationship between the advisor's recent performance and the owner-manager's perceptions of the advisor's trustworthiness in terms of ability, benevolence and integrity. A negative moderating effect could point to a 'tie that blinds': the owner-manager may be less critical in evaluating the advisor's perceived trustworthiness in light of their recent performance, because of the existing personal relationship. A conceptual model is constructed and examined with survey data comprising 153 young Finnish businesses. The results show that strong ties increase the owner-manager's perception of the advisor's integrity, disregarding their recent performance. For professional advisors, strong ties reduce the impact of recent performance in the owner-manager's evaluation of their ability. For informal advisors, a strong tie makes it more likely that their benevolence will be evaluated highly in light of their recent performance. While the results show that 'ties can blind' under certain circumstances, the limitations of the study raise the need for further research to specify these contextual factors and examine the causal link between the choice of advisor and business performance.

The 2008 declaration of independence by the Hong Kong Court and anomalies in the Hong Kong Company Law

Discusses two aspects of Hong Kong law: 1) the judgment of the Hong Kong Court of Final Appeal in A Solicitor v The Law Society of Hong Kong on whether Hong Kong courts were bound, post-1997, by pre-1997 House of Lords or Privy Council decisions, by pre-1997 decisions of their own, or by post-1997 overseas decisions from any jurisdiction; and 2) the need for clarification in the Hong Kong Companies Ordinance of whether a company can have a single legal representative, the ultra vires rule and the duties of company directors

More legislative traffic on the 'Doi Moi' superhighway : technology transfer, IP and competition law in Vietnam

Since 1986 Vietnam has been engaged in the transition from a centrally-controlled economy to a socialist-oriented market economy (the 'doi moi' renovation). The process for global economic integration has been slow given the magnitude of necessary reforms. Consequently technology entrepreneurs often discount Vietnam as a possible commercialization base which means that it is not realising its economic potential as a hub of technology transfer in the Asia-Pacific region. Three significant factors in the current uncertainty are Vietnam's laws on competition, intellectual property and technology transfer. Another problem is the lack of literature on these laws. This article first discusses the conceptual relationship between competition, intellectual property and technology transfer. Hopefully the article will provide some guidance for the technology entrepreneur considering foreign direct investment (FDI) in Vietnam. The bottom line is that these laws still need further reform to bolster entrepreneurial confidence.

An application of near-infrared and mid-infrared spectroscopy to the study of natural halotrichites : halotrichite, apjohnite and wupatkiite

Near-infrared (NIR) and Fourier transform infrared (FTIR) spectroscopy have been used to determine the mineralogical character of isomorphic substitutions for Mg2+ by divalent transition metals Fe, Mn, Co and Ni in natural halotrichite series. The minerals are characterised by d-d transitions in NIR region 12000-7500 cm-1. NIR spectrum of halotrichite reveals broad feature from 12000 to 7500 cm-1 with a splitting of two bands resulting from ferrous ion transition 5T2g ® 5Eg. The presence of overtones of OH- fundamentals near 7000 cm-1 confirms molecular water in the mineral structure of the halotrichite series. The appearance of the most intense peak at around 5132 cm-1 is a common feature in the three minerals and is derived from combination of OH- vibrations of water molecules and 2 water bending modes. The influence of cations like Mg2+, Fe2+, Mn2+, Co2+, Ni2+ shows on the spectra of halotrichites. Especially wupatkiite-OH stretching vibrations in which bands are distorted conspicuously to low wave numbers at 3270, 2904 and 2454 cm-1. The observation of high frequency 2 mode in the infrared spectrum at 1640 cm-1 indicates coordination of water molecules is strongly hydrogen bonded in natural halotrichites. The splittings of bands in 3 and 4 (SO4)2- stretching regions may be attributed to the reduction of symmetry from Td to C2v for sulphate ion. This work has shown the usefulness of NIR spectroscopy for the rapid identification and classification of the halotrichite minerals.