960 resultados para 1604 Human Geography


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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.

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This paper describes a series of design games, specifically aimed at exploring shifts in human agency, how they are managed, and the impact this will have on the design of future context-aware applications. The games focussed on understanding information handling issues in dental practice with participants from the University of Queensland Dental School playing an active role in the activities. Participatory design activities reveal how technology solution impact on dental practices. By finding methods of representing technological possibilities in ways which can easily be understood we enhance the contribution that dentists can make to the design process.

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BACKGROUND: The murine ghrelin gene (Ghrl), originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0). We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. -----FINDINGS: 5' RACE revealed two transcription start sites (TSSs) in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR), we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. -----CONCLUSION: We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1) raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted.

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This paper represents a new theorization of the role of location-based games (LBGs) as potentially playing specific roles in peoples’ access to the culture of cities [22]. A LBG is a game that employs mobile technologies as tools for game play in real world environments. We argue that as a new genre in the field of mobile entertainment, research in this area tends to be preoccupied with the newness of the technology and its commercial possibilities. However, this overlooks its potential to contribute to cultural production. We argue that the potential to contribute to cultural production lies in the capacity of these experiences to enhance relationships between specific groups and new urban spaces. Given that developers can design LBGs to be played with everyday devices in everyday environments, what new creative opportunities are available to everyday people?

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This paper describes a series of design games, specifically aimed at exploring shifts in human agency in order to inform the design of context-aware applications. The games focused on understanding information handling issues in dental practice with participants from a university dental school playing an active role in the activities. Participatory design activities help participants to reveal potential implicit technical resources that can be presented explicitly in technologies in order to assist humans in managing their interactions with and amidst technical systems gracefully.

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Our brief is to investigate the role of community and lifestyle in the making of a globally successful knowledge city region. Our approach is essentially pragmatic. We start by broadly examining knowledge-based urban development from a number of different perspectives. The first view is historical. In this context knowledge work and knowledge workers are seen as vital parts of a new emergent mode of production reliant on the continual production of abstract knowledge. We briefly develop this perspective to encompass the work of Richard Florida who has, notedly, claimed: “Wherever talent goes, innovation, creativity, and economic growth are sure to follow.” Our next perspective examines concepts of knowledge and modes of its production to discover knowledge is not an unchanging object but a human activity that changes in form and content through history. The suggestion emerges that not only is the production of contemporary ‘knowledge’ organised in a specific (and new) manner but also the output of this networked production is a particular type of knowledge (i.e. techné). The third perspective locates knowledge production and its workers in the contemporary urban context. As such, it co-ordinates the knowledge city in the increasingly global structure of cities and develops a typology of different groups of knowledge workers in their preferred urban environment(s). We see emerging here a distinctive geography of knowledge production. It is an urban phenomenon. There is, in short, something about the nature of cities that knowledge workers find particularly attractive. In the next, essentially anthropological, perspective we start to explore the needs and desires of the individual knowledge worker. Beyond the needs basic to any modern human household an attempt is made to deduce, from a base understanding of knowledge work as mental labour, the compensatory cultural needs of the knowledge worker when not at work - and the expression of these needs in the urban fabric. Our final perspective consists of two case studies. In a review of the experiences of Austin, Texas and Singapore’s one-north precinct we collect empirical data on, respectively, a knowledge city that has sustained itself for over 50 years and an urban precinct newly launched into the global market for knowledge work and knowledge workers. Interwoven The Role of Community and Lifestyle in the Making of a Knowledge City Urban Research Program 8 through all perspectives, in the form of apposite citation, is that of ‘expert opinion’ gathered in a rudimentary poll of academic and industry sources. This opinion appears in text boxes while details of the survey can be found in Appendix A. In the conclusion of the report we interpret the wide range of evidence gathered above in a policy frame. It is our hope this report will leave the reader with a clearer picture of the decisive organisational, infrastructural, aesthetic and social dimensions of a knowledge precinct.

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As editors of the recently published Vocational psychological and organisational perspectives on career: Towards a multidisciplinary dialogue (Collin & Patton, 2009), we have considerable interest in this particular issue of the Australian Journal of Career Development. This short piece will first present the purpose and thesis of that book and, in the light of them, will then comment on the four papers. The book suggests that to understand the multidimensional and multilayered nature of career, “it has to be studied in a similarly multilayered and multi-perspectival way, and, indeed, it has been” (p. 3). Scholars have pointed out that there is a wide array of disciplines including economics, sociology, anthropology, geography, political science, various branches of psychology (e.g. industrial/organisational (I/O), vocational, counselling), psychiatry, education, organisation studies, organisational behaviour, personnel/human resource management, industrial relations, and more, all of which have something to say about career. Of these, the most influential, according to Peiperl and Arthur (2000), have been psychology, sociology, education and management. These many disciplinary perspectives on career constitute the rich field of career studies.