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.

Investigating feelings towards mathematics among Chinese kindergarten children

Prior to entering schooling settings, many children exhibit intuitive knowledge of mathematics and many have mastered basic addition combinations. However, often as a result of formal instruction, some children begin to dislike or fear mathematics. In this study, children at a kindergarten in China took a smiley-face survey to determine how their feelings and beliefs about mathematics were affected throughout their kindergarten years.Results suggest that even children in this study have a better number sense and mathematics achievement, they appear to develop mathematics anxiety in Chinese cultural context.

Celebrity capital as a strategic asset : implications for new venture strategies

Despite an increase in businesses started by celebrities, we have limited understanding as to how celebrity entrepreneurs benefit new ventures. Drawing on a reputational capital perspective, we develop the notion of celebrity capital and show how it can be used to uniquely differentiate the venture and to overcome liabilities of newness. We discuss how celebrity capital can negatively influence the venture when negative information about the celebrity surfaces and in terms of limiting the scope of the venture. We discuss the different strategic implications of celebrity capital for ventures using celebrity entrepreneurs versus endorsers.

Identifying effective leadership practices for implementing a new mathematics curriculum in Taipei

This study explores successful junior high school principals’ leadership practices for implementing the reformed mathematics curriculum in Taipei. Avolio and Bass’s (2002) full range leadership theory was used to record data through interviews and observations of five Taipei “Grade A” junior high school principals. Findings revealed that specific leadership practices linked to management by exception-active and contingent reward (transaction leadership), and individualised consideration and idealised influence (transformational) were considered effective for implementing reform measures. Ensuring principals are aware of effective measures may further assist reform agendas.

Comparing the ethical predisposition of university students in five English-speaking countries : an examination of 14 questionable business practices

Recent years have seen intense scrutiny focused on the reported ethical breaches of enterprises across the globe. At the forefront of the accompanying criticism are the actions of giant American firms such as WorldCom, Arthur Anderson, and Enron. However, such deviations from acceptable standards of conduct have not been confined to the American market. Australia endured its era of “corporate excess” in the 1980s [Milton-Smith, 1997]. As a result, a spate of ethics-based research was undertaken in the early 1990s. More recently, China has been identified as a major venue for behavior deemed to be unacceptable, even unsafe. Issues such as counterfeit fashion items, software, and automobile parts have been a concern for several years [Gonzalez, 2007]. Perhaps more disconcerting are the recent recalls of children’s products, many of which were produced for leading toy companies such as Mattel and Fisher-Price, because of the use of dangerous lead-based paint. As one might anticipate, news reports and consumer protection agencies have been quick to condemn any action that falls within the “controversial” category. Indeed, many segments of society characterize such actions as unethical behavior. One result of this increased level of concern is the higher level of attention given to ethics in higher education programs. Even accreditation bodies such as AACSB have virtually mandated the integration of ethics into the curriculum. As a consequence, academicians have ramped up their ethics-based research agendas.

The Google online marketing challenge and research opportunities

The Google Online Marketing Challenge is an ongoing collaboration between Google and academics, to give students experiential learning. The Challenge gives student teams US$200 in AdWords, Google’s flagship advertising product, to develop online marketing campaigns for actual businesses. The end result is an engaging in-class exercise that provides students and professors with an exciting and pedagogically rigorous competition. Results from surveys at the end of the Challenge reveal positive appraisals from the three—students, businesses, and professors—main constituents; general agreement between students and instructors regarding learning outcomes; and a few points of difference between students and instructors. In addition to describing the Challenge and its outcomes, this article reviews the postparticipation questionnaires and subsequent datasets. The questionnaires and results are publicly available, and this article invites educators to mine the datasets, share their results, and offer suggestions for future iterations of the Challenge.

Students’ perceptions of a blended web-based learning environment

The enhanced accessibility, affordability and capability of the Internet has created enormous possibilities in terms of designing, developing and implementing innovative teaching methods in the classroom. As existing pedagogies are revamped and new ones are added, there is a need to assess the effectiveness of these approaches from the students’ perspective. For more than three decades, proven qualitative and quantitative research methods associated with learning environments research have yielded productive results for educators. This article presents the findings of a study in which Getsmart, a teacher-designed website, was blended into science and physics lessons at an Australian high school. Students’ perceptions of this environment were investigated, together with differences in the perceptions of students in junior and senior years of schooling. The article also explores the impact of teachers in such an environment. The investigation undertaken in this study also gave an indication of how effective Getsmart was as a teaching model in such environments.

Aligning school reform and teacher education reform in the middle years : an Australian case study

This paper discusses the development of a new Bachelor of Education (Middle Years of Schooling) at The University of Queensland, Australia. The middle years of schooling have increasingly been the focus of education reform initiatives in Australia, but this has not been accompanied by significant increases in the number of teacher education institutions offering specialised middle schooling-level teacher preparation programmes. Considering the rapidly changing social and economic context and the emergent state of middle schooling in Australia, the programme represented a conceptual and practical opportunity and challenge for The University of Queensland team. Working collaboratively, the team sought to design a teacher education preservice programme that was both responsive and generative: that is, responsive to local school contexts and to current education research and reform at national and international levels; and generative of cutting-edge theories and practices associated with middle schooling, teachers' work, and teacher education. This paper focuses on one component of the Middle Years of Schooling Teacher Education programme at The University of Queensland; namely, the practicum. We first present the underlying principles of the practicum programme and then examine "dilemmas" that emerged early in the practicum. These issues and tensions were associated with the ideals of "middle years" philosophy and the pragmatics of school reform associated with that approach. Within this context, we explore what it means to be both responsive and generative, and describe how we as teacher educators negotiated the extremes these terms implied.

Blur limits for defocus, astigmatism and trefoil

We investigated the limits at which blur due to defocus, crossed-cylinder astigmatism, and trefoil became noticeable, troublesome or objectionable. Black letter targets (0.1, 0.35 and 0.6 logMAR) were presented on white backgrounds. Subjects were cyclopleged and had effectively 5 mm pupils. Blur was induced with a deformable, adaptive-optics mirror operating under open-loop conditions. Mean defocus blur limits of six subjects with uncorrected intrinsic higher-order ocular aberrations ranged from 0.18 ± 0.08 D (noticeable blur criterion, 0.1 logMAR) to 1.01 ± 0.27 D (objectionable blur criterion, 0.6 logMAR. Crossed-cylinder astigmatic blur limits were approximately 90% of those for defocus, but with considerable meridional influences. In two of the subjects, the intrinsic aberrations of the eye were subsequently corrected before the defocus and astigmatic blur were added. This resulted in only minor reductions in their blur limits. When assessed with trefoil blur and corrected intrinsic ocular aberrations, the ratio of objectionable to noticeable blur limits in these two subjects was much higher for trefoil (3.5) than for defocus (2.5) and astigmatism (2.2).

Limits of spherical blur determined with an adaptive optics mirror

We extended an earlier study (Vision Research, 45, 1967–1974, 2005) in which we investigated limits at which induced blur of letter targets becomes noticeable, troublesome and objectionable. Here we used a deformable adaptive optics mirror to vary spherical defocus for conditions of a white background with correction of astigmatism; a white background with reduction of all aberrations other than defocus; and a monochromatic background with reduction of all aberrations other than defocus. We used seven cyclopleged subjects, lines of three high-contrast letters as targets, 3–6 mm artificial pupils, and 0.1–0.6 logMAR letter sizes. Subjects used a method of adjustment to control the defocus component of the mirror to set the 'just noticeable', 'just troublesome' and 'just objectionable' defocus levels. For the white-no adaptive optics condition combined with 0.1 logMAR letter size, mean 'noticeable' blur limits were ±0.30, ±0.24 and ±0.23 D at 3, 4 and 6 mm pupils, respectively. White-adaptive optics and monochromatic-adaptive optics conditions reduced blur limits by 8% and 20%, respectively. Increasing pupil size from 3–6 mm decreased blur limits by 29%, and increasing letter size increased blur limits by 79%. Ratios of troublesome to noticeable, and of objectionable to noticeable, blur limits were 1.9 and 2.7 times, respectively. The study shows that the deformable mirror can be used to vary defocus in vision experiments. Overall, the results of noticeable, troublesome and objectionable blur agreed well with those of the previous study. Attempting to reduce higher-order aberrations or chromatic aberrations, reduced blur limits to only a small extent.

Resistance training for obese, type 2 diabetic adults: A review of the evidence

In both developed and developing countries, increased prevalence of obesity has been strongly associated with increased incidence of type 2 diabetes mellitus (T2DM) in the adult population. Previous research has emphasized the importance of physical activity in the prevention and management of obesity and T2DM, and generic exercise guidelines originally developed for the wider population have been adapted for these specific populations. However, the guidelines traditionally focus on aerobic training without due consideration to other exercise modalities. Recent reviews on resistance training in the T2DM population have not compared this modality with others including aerobic training, or considered the implications of resistance training for individuals suffering from both obesity and T2DM. In short, the optimal mix of exercise modalities in the prescription of exercise has not been identified for it benefits to the metabolic, body composition and muscular health markers common in obesity and T2DM. Similarly, the underlying physical, social and psychological barriers to adopting and maintaining exercise, with the potential to undermine the efficacy of exercise interventions, have not been addressed in earlier reviews. Because it is well established that aerobic exercise has profound effects on obesity and T2DM risk, the purpose of this review was to address the importance of resistance training to obese adults with T2DM.