UQ Theses Collection (RHD) - UQ staff and students only - UQ eSpace

The Role of Microphthalmia Transcription Factor (Mitf) in Osteoclast Gene Regulation

Meadows, Nicholas Axel — 2008-11-21T00:00:00Z

Microphthalmia transcription factor (Mitf) has been shown to be a key regulator of osteoclast function by activating genes like TRAP and cathepsin K. Mitf is a member of the helix-loop-helix leucine zipper family of transcription factors and regulates its target genes by binding as a homo- or heterodimer to an E-box consensus sequence termed the M-Box (T/CANNTG/A). In order to identify the suite of genes that are regulated by Mitf in macrophages and osteoclasts, the level of Mitf activity has been modulated in the pre-osteoclastic macrophage cell line, RAW/C4. Stable transfectant cell lines expressing the Mitf-A isoform (RAW/C4-Mitf-A/pEF6) and the dominant negative isoform, mi (RAW/C4-mi/pEF6), under the control of the EF1a promoter, were prepared. Both the expression and function of the exogenous genes were validated using western blotting, immunocytochemical staining, Q-PCR and promoter-reporter transfection analysis. The genes differentially regulated by the alteration of the level of Mitf in these cells were expression profiled by microarray analysis. The 22 000 element murine Compugen array was hybridized with RNA prepared from the RAW/C4-Mitf/pEF6 and RAW/C4-mi/pEF6 cell lines before and after induction of osteoclast differentiation with RANKL. Genes identified include those either up- or down-regulated during osteoclast differentiation, as well as genes with differential expression as a result of overexpression of Mitf protein. A bioinformatic analysis was undertaken in parallel to identify candidate M-box-containing genes that may be Mitf targets. A large-scale Blast technique was developed to download 2 kb of DNA sequence 5 of the translation start site for all the genes on the Compugen array. These promoter regions were searched for the presence of M-boxes and a subset of potential Mitf target genes was compiled and compared with targets generated from the microarray analysis. This approach identified eight genes that were indicated to be Mitf regulated based on their expression profile and the presence of a M-box within their proximal promoter region. The expression of these genes was validated using Q-PCR and following a literature review of their functional biology, five genes remained. Ccl9, Clcn7, Eos, Fra1 and Ostm1 all met the stringent criteria necessary for selection for further investigation. A bioinformatic analysis of the promoter regions for these genes was undertaken to determine mouse-human evolutionary conservation and establish a common mechanism for transcriptional regulation of each gene. Common conserved transcription factor binding sites were identified and candidate M-boxes within their promoter regions were assayed for Mitf binding and transcription activation using a series of in vitro techniques on the cell lines. Electrophoretic mobility shift and promoter-reporter luciferase assays were performed on RAW/C4 cells to demonstrate binding site specificity and promoter activation by Mitf. Consequently osteopetrosis associated protein 1, Ostm1 and chloride channel 7, Clcn7 were identified as specific targets for Mitf transcriptional regulation. Primary cells were also used for Q-PCR and chromatin immunoprecipitation assays, which confirmed Mitf regulation of Clcn7. Both Ostm1 and Clcn7 have known mutations that can cause a failure of osteoclast activity and severe osteopetrosis, a phenotype characteristic of particular Mitf mutations. These findings validate the combined bioinformatic and microarray approach used to identify novel Mitf targets during osteoclastogenesis. The identification of two genes, whose expression appears to be regulated by Mitf, that are directly involved with osteoclast resorption suggests the role of Mitf in controlling bone resorption might be more significant than previously perceived. These results indicate that Mitf may be a master regulator of osteoclast bone resorption and genes regulated by Mitf during osteoclast activation may be considered therapeutic targets for the treatment of bone resorption disorders.

The role of MicroRNA in head and neck cancer

Anderson, Shane Robert — 2013-03-07T12:18:13Z

The role of microsatellite instability in Hepatocarcinogenesis

Macdonald, Graeme Alistair. — 2011-09-03T00:00:00Z

The Role of Middle Managers in Organisational Change

Herzig, Sharyn Elizabeth — 2008-11-21T00:00:00Z

Change is ever-present in todays fast-paced organisations (Lewis, 2000). Market demands, the introduction of new technologies and an internal push for growth are some of the major factors driving change in organisations. However the failure rate, reported as high as 50% (Majchrzak, 1988) to 70% (Burnes, 2002), needs to be addressed (Marks & Mirvis, 2000). In particular, adequate coverage has not been given to the role middle managers play in organisational change (Huy, 2002; McKinley & Scherer, 2000). Middle management can be broadly defined as managers holding positions between the first-level supervisors and the level of executives, below those who have company-wide responsibilities (Frohman & Johnson, 1992). In the 1990s, middle management was typically viewed as resistant to change (Wai-Kwong, Priem, & Cycyota, 2001). It is important to reduce negative views held of middle management and promote their positive input into organisational change processes. Middle managers have been identified as contributing to higher levels of organisational performance when involved in strategy-making (Wai-Kwong et al., 2001) and the positive emotional management of their employees (Huy, 2002). Thus, the aim of the current body of research was to make a contribution to the existing deficient literature on middle managers in organisational change by exploring the strategic role of middle managers. Factors which facilitate organisational change and several underlying psychological states were also investigated. In addition, a measure of perceived change success was developed. Three studies were undertaken to investigate the role of middle managers. Study 1 was an exploratory study investigating middle managers perceptions of their role in change. It was qualitative in nature and examined a number of different types of change. Study 2 also was from the point of view of middle managers, while Study 3 investigated the impact of middle managers roles on employees. Both Studies 2 and 3 were quantitative and focused on transitional change. Study 1 involved interviews with 40 middle managers from a range of organisations. Thematic analysis revealed that, at the pre-implementation stage, the psychological state of uncertainty experienced by middle managers focused on the strategic concept of the change. During implementation however, uncertainty related to the appropriate procedures to implement. Middle managers strategic role was classified into three categories labelled creators, designers, and implementers. Those with higher strategic input (i.e., the creators and designers), reported lower levels of uncertainty than those with low strategic input (i.e., implementers). The factors identified as being facilitators to uncertainty management (i.e., communication with senior management and their own staff, support from senior management, role conflict, and peer interaction) along with other psychological states (i.e., change efficacy and commitment) were expressed in themes in the qualitative study. From middle managers responses regarding their perceptions of change success, an outcome measure of change was developed and employed in Studies 2 and 3. Study 2 extends the findings of Study 1 by means of quantitative research. A questionnaire was utilised in a cross-sectional study of 123 middle managers to examine the role of middle management during organisational change at a large mining company. The change context was the implementation of Six Sigma projects. Change outcome variables included perceived change success and importance placed on Six Sigma values. In addition, an independent measure of success was provided by the company via an internal audit. Using hierarchical multiple regression, factors which facilitated the implementation of projects by middle managers were examined (including communication with leaders, support from leaders, communication with employees, peer interaction and training). The psychological states (uncertainty, change efficacy and commitment) were found to play a mediating role in some relationships between the facilitators and the change outcomes. Also of interest was the role middle managers adopted during change, determined by strategic design input and Six Sigma project member role. Analysis of variance (ANOVAs) revealed that higher levels of strategic input and higher level Six Sigma roles were associated with more positive perceptions of a number of factors (e.g., more positive perceptions of communication, support, perceived change success and reduced strategic uncertainty) compared to those middle managers with lower levels of strategic input and lower level Six Sigma roles. A third study was conducted to further examine the findings related to communication with employees and to further explore the effect middle managers have on employees during change. One hundred and six employees were surveyed at one point in time regarding their past experiences of technological change at a tourism organisation. A series of hierarchical multiple regression analyses revealed that, at the pre-implementation stage of change, communication from middle managers was positively related to employees perceptions of change success. This relationship was partially mediated by employee readiness for change. During implementation, transformational leadership and transactional leadership were introduced as factors of theoretical interest and both were found to be positively related to employees perceptions of change success and this relationship was mediated by communication from middle managers. Overall, these studies support the important positive role of middle managers in organisational change, including creating a readiness for change in employees and leading to more successful perceptions of change for both middle managers and employees. The findings suggest that a greater strategic involvement of middle managers was associated with more successful change outcomes. Also identified were numerous important facilitators to the role of middle managers and their relationship to psychological states. Another key contribution was the development of the organisational change outcome measure, titled perceived change success. The relevance of this measure for future research is discussed.

The role of mononuclear phagocytes in dengue immunopathogenesis

Bhatia, Kanika Devi. — 2007-08-24T00:00:00Z

The role of mosquitoes in the emergence of Japanese encephalitis virus in Australia

van den Hurk, Andrew Francis. — 2007-08-24T00:00:00Z

The role of multicultural festivals in a society in transition: From being ethnically homogeneous to becoming multicultural

Insun Sunny Lee — 2012-03-28T00:00:00Z

While there are numerous studies focusing on various aspects of festivals in general, research on particular types of festivals, including multicultural festivals, remains limited. However, with the emerging cultural diversity of many societies worldwide, the importance of building well-integrated multicultural societies, as well as understanding this process, is increasing. Multicultural festivals have emerged in many locations, in particular in societies still at the beginning of becoming multi-ethnic, as a useful instrument for promoting social harmony and integration. The evaluation on this role, however, remains poorly explored. This study aimed to explore the role of multicultural festivals in a society in transit from being ethnically homogeneous to multicultural, and to offer insights into the contribution of multicultural festivals as an instrument within a multicultural policy to the development of successful multiculturalism. To evaluate the role of multicultural festivals as an instrument for the development of multiculturalism, the experiences and benefits visitors gain from attending a multicultural festival, and how these experiences and benefits contribute to building better multiculturalism must be considered. By adopting a Benefits-Based Management (BBM) framework to the multicultural festival field, this study explores the festival experiences that visitors had at a multicultural festival, the benefits gained from those festival experiences, and what particular experience leads to which benefit. To achieve the aim and objectives of this study, a mixed method research approach was used in the research design. Quantitative data were collected and analysed in the first phase, followed by qualitative interviews that helped to elaborate the initial findings. In the first phase, a total of 420 valid questionnaires from 176 Koreans and 244 ethnic minorities were collected at three multicultural festivals: the ‘Open multicultural festival’, ‘Siheung multicultural festival’ and ‘Colourful multicultural festival’, in South Korea, from April to June 2010. In the second phase of the qualitative study, a total of 44 visitors, 24 Korean and 20 ethnic minority visitors, were interviewed after the festival from April to June 2010. Findings from the quantitative data revealed that visitors had emotional experience as the most common experience, followed by social and learning experiences at multicultural festivals, and transformational benefit was identified as the greatest benefit the majority of visitors gained, followed by cognitive, social and affective benefits. It was also found that different visitors across the ethnic and behavioural variables had different experiences and benefits. Visitors gained transformational benefit mostly from social experience at a multicultural festival, cognitive benefit from emotional and social experiences, affective benefit from social experience, and social benefit from having learning and emotional experiences. It also appeared that the impacts of experiences on benefits were different for different ethnic and behavioural groups. By demonstrating the use of multicultural festivals as a socio-political strategy for the development of successful multiculturalism, this study encourages governments and policy makers to consider multicultural festivals as an important instrument for the development of successful multiculturalism. Identifying visitor experiences and benefits from a visit to a multicultural festival can be used as a barometer to measure the development of multiculturalism, and may indeed demonstrate that such festivals assist in enhancing social integration. The understanding of what experience leads to which benefit is of use in the management of festivals, providing additional information to event organisers for the planning and implementation of strategies to strengthen specific visitor benefits at future festivals. This study also has significance examining the festival experience and benefit from visitor perspective by adopting a BBM approach to the festival context, the multicultural festival setting in particular. Testing a BBM approach to festivals in this study with quantitative data enables research on understanding festival visitor experience to be advanced, and qualitative study in this study contributes to expand the knowledge and understanding of visitor experiences and benefit at multicultural festivals in a society in transition from being ethnically homogeneous to becoming multicultural in particular. As the findings of this study are delimited to multicultural festivals in societies in transit from ethnically homogeneous to becoming multicultural, future research may compare the roles of multicultural festivals in different societies, one in a society in transit to becoming a multicultural society, and one in a society in which multiculturalism is well established. As the BBM approach has been initially applied to the festival context in this study, continued applications of the BBM approach in a broad range of festivals and events are also valid topic for future festival visitor studies.

The role of Neogenin during neurogenesis and migration in the embryonic forebrain

Stacey Cole — 2010-10-13T00:00:00Z

The proliferation and differentiation of neural progenitors during neurogenesis, and their subsequent migration and positioning within the embryonic forebrain, are key processes of cortical development. The neuronal progenitors of the cortex are the radial glia, which give rise to pyramidal neurons that then migrate towards the outer surface. In the ventral forebrain, progenitors give rise to interneurons that migrate tangentially into the developing cortex and integrate into the circuitry of the brain. Abnormal neuronal migration is the underlying cause of several human disorders, including lissencephaly and epilepsy. Neogenin is a member of the immunoglobulin (Ig) superfamily and is closely related to the axon guidance receptor Deleted in Colorectal Cancer (DCC). Neogenin has been identified as a receptor for members of the Netrin and Repulsive Guidance Molecule (RGM) ligand families, and has been shown to regulate a range of developmental processes including axon guidance, neural tube closure, and mammary gland development. In this thesis we investigate the role of Neogenin during development of the mouse forebrain. The precise mRNA expression and protein localisation patterns of Neogenin in the developing forebrain are described, with Neogenin detected in both progenitor and neuronal populations. We also characterise the Neogenin (Neo1Gt) loss-of-function mouse, where it was shown that the Neogenin mutation in these animals was hypomorphic, with full-length protein detected in embryonic mice homozygous for the mutation. As a result, we determined that these animals displayed variable phenotypic defects with low penetrance in the developing forebrain. It was also shown that Neogenin played a role in neuronal differentiation. In vitro, Neogenin regulated interneuron differentiation in the presence of RGMa, a ligand for Neogenin, with an increase in interneuron number when cells were cultured in the presence of high levels of the ligand. Furthermore, this thesis also demonstrated that RGMa was involved in the regulation of neurite outgrowth in neuronal cultures. Finally, using an explant assay this study demonstrated that RGMa induced a chemorepulsive response in interneurons migrating from the medial ganglionic eminences. This suggests that Neogenin plays a role in interneuron migration in the ventral forebrain. To determine the precise role of Neogenin during neurogenesis and migration, further work utilising siRNA Neogenin knockdown in an optimised lentivirus system would be required. This would confirm a role for Neogenin in neuronal differentiation, migration and neurite outgrowth in the developing mammalian forebrain.

The role of neogenin in the adult brain: neuronal migration, differentiation and implications for adult neurogenesis

Dana Bradford — 2011-03-06T00:00:00Z

The ability of the adult brain to produce neurons is well established. The molecular mechanisms controlling differentiation to a neural fate and those guiding migration of neurons from a proliferative zone to their final destination are still poorly understood. The largest proliferative region in the adult brain is the subventricular zone (SVZ) where cells differentiate into neuronal precursors. These new neurons migrate along the rostral migratory stream (RMS) and integrate into the neuronal circuitry of the olfactory bulb. Therefore the RMS is an ideal system in which to study neuronal differentiation and cell migration. Neogenin is a multi-functional receptor with diverse developmental roles including axon guidance, differentiation and migration. Neogenin has been shown to interact with two ligand families — Netrins, which are classic guidance cues well described in embryogenesis, and the Repulsive Guidance Molecules (RGMs) which have recently reported roles in axon guidance. This Thesis addresses the functional role of neogenin in the adult mouse forebrain and cerebellum. Defects in differentiation in neogenin loss of function mice (neogt/gt) are described and their mechanisms discussed. Neogenin is expressed on neural stem cells and progenitor cells in the SVZ. In vitro analysis of these cells showed significantly fewer neurons generated from neogt/gt mice, demonstrating a role for neogenin in neuronal differentiation. In vitro and in vivo, the subpopulation of neurons affected was found to be the adult-born calretinin-positive granule cell population. A corresponding decrease in granule cell layer density in both the olfactory bulb and cerebellum of neogt/gt mice was also observed. Further analysis suggests that RGMa is a candidate ligand for regulating this effect. Neuroblasts in the RMS also express neogenin, suggesting neogenin may have a role in cell migration along the RMS. The expression pattern of netrin-1 in the adult forebrain coupled with disrupted migration in mice heterozygous for the netrin-1 mutation indicates a potential role for netrin-1 in guiding migration in this system. Finally, preliminary studies in human forebrain tissue show the expression of neogenin and RGMa are conserved, suggesting their function is the same in human brains.

The role of neutrophil primining and neutrophil antibodies in the pathogenesis of Transfusion-Related Acute Lung Injury (TRALI)

Yoke Lin Fung — 2008-10-28T00:00:00Z

THE ROLE OF NMYC AND CMYC IN SKIN DEVELOPMENT AND IN HEDGEHOG PATHWAY-INDUCED TUMORIGENESIS

RHONDA HUI PING KAN — 2012-02-08T00:00:00Z

Members of the Myc family of proteins namely Nmyc, Cmyc and Lmyc are a group of basic helix-loop-helix transcription factors which have been implicated in the regulation of a plethora of cellular functions and whose dysregulated expression has been associated with a wide variety of human diseases. Given that the endogenous role of Myc family members in the skin has been poorly defined, particularly that of Nmyc, the role of Nmyc and Cmyc in postnatal skin development and homeostasis was first investigated. This was genetically tested via conditional deletion of Nmyc and/or Cmyc in the skin using the epithelial-specific K14Cre recombinase. While Nmyc and Cmyc expression levels were significantly reduced, Nmyc and/or Cmyc deficient mice exhibited normal postnatal skin histology with normal hair follicle (HF) cycling and did not result in transcriptional upregulation of other Myc family members. Hedgehog (Hh) signalling is required for proper embryonic development and postnatal homeostasis and its dysregulation is associated with a growing list of congenital disorders and human cancers including basal cell carcinoma (BCC). The majority of sporadic/familial forms of human BCCs have been linked to mutations in the HH signal receptor, PATCHED 1(PTCH1), which results in constitutive HH pathway activation. Nmyc has previously been shown to be ectopically expressed throughout BCC-like lesions that developed upon loss of Ptch1 activity in the skin. Further detailed investigation into Nmyc expression in Ptch1 deleted skin confirmed that Nmyc is upregulated specifically in late, but not initial, stages of BCC development. However, the functional significance of elevated Nmyc expression in Hh pathway-induced BCC is still unclear. Therefore, to examine the requirement for Nmyc and its cellular homologue Cmyc at different stages of BCC development, Nmyc and/or Cmyc were simultaneously deleted together with Ptch1 in the mouse skin using K14Cre. Deletion of Nmyc alone did not rescue the phenotypes of hyperproliferation, expansion of progenitor cell compartment and BCC-like lesion formation, which occur following loss of Ptch1 activity. Similarly, removal of Cmyc alone did not modify the early effects induced by loss of Ptch1. However, its function in the progression of BCC development could not be determined given these mice do not survive into adulthood. Transcriptional analyses in the skin of K14Cre;Nmyc;Ptch1 and K14Cre;Cmyc;Ptch1 mice identified increased expression of other Myc family members to compensate for their individual loss. Interestingly, although inactivation of both Nmyc and Cmyc did not attenuate the early Ptch1 deficient phenotype, their combined loss strongly suppresses the progression of BCC lesion formation namely by limiting the expansion and hyperproliferation of the epidermal progenitor cell compartment. In addition to the well-established cell autonomous role of mutation-driven activation of Hh pathway in cancers, there is accumulating evidence to support the importance of the stromal environment in supporting Hh pathway-induced tumour growth and progression. However, at the time when this project commenced, very little was known about the participation of the Hh pathway in regulating epithelial-mesenchymal interaction in BCC development. The paucity of knowledge about this interaction is mainly attributed to the fact that the analysis of such complex reciprocal interactions is difficult in vivo. Therefore, the aim of this part of the project was to establish an in vitro organotypic skin co-culture model which serves as a powerful tool to elucidate the role of Hh signalling in epithelial-mesenchymal interaction in the skin. Using a combined approach of an organotypic co-culture model and Ptch1 deleted cells, it was found that Hh pathway activation in either the epidermal or dermal compartment alone was unable to trigger the development of characteristic BCC-like lesions. Based on this observation, it was predicted that BCC development likely requires a complex reciprocal tumour-stroma interaction. In summary, this thesis demonstrates for the first time that although Nmyc and Cmyc are not functionally required in postnatal skin under homeostatic (physiological) conditions, overall Myc expression levels are critical determinants in driving progression, but not initiation, of Hh pathway-induced BCC tumour development.

The Role of Non-Structural Protein NS2A in Flavivirus Assembly and Secretion

Jason Leung — 2010-08-14T00:00:00Z

Flaviviruses are a group of medically relevant pathogens, known to cause serious disease in animals and humans. The previously defined roles of the flavivirus non-structural protein 2A (NS2A) in RNA replication, and modulation of the host antiviral response, has recently been extended to include virus assembly and secretion. In West Nile virus subtype Kunjin (KUN), an Isoleucine (I)-to-Asparagine (N) substitution at position 59 of the NS2A protein blocked the production of secreted virus particles in cells electroporated with viral RNA carrying this mutation. In this study, prolonged incubation of mutant KUN NS2A-I59N replicon RNA, in an inducible BHK-derived packaging cell line (expressing KUN structural proteins C, prM, and E), generated escape mutants that rescued the secretion of infectious virus-like particles. Sequencing identified three groups of revertants that included (i) reversions to wild-type, hydrophobic Ile, (ii) pseudorevertants to more hydrophobic residues (Ser, Thr, and Tyr) at codon 59, and (iii) pseudorevertants retaining Asn at NS2A codon 59, but containing a compensatory mutation (Thr-to-Pro) at NS2A codon 149. Engineering hydrophobic residues at NS2A position 59, or the compensatory T149P mutation into NS2A-I59N replicon RNA, restored the assembly of secreted virus-like particles in packaging cells. T149P mutation also rescued virus production when introduced into the full-length KUN RNA containing an NS2A-I59N mutation. Immunofluorescence and electron microscopy analyses of NS2A-I59N replicon-expressing cells showed a distinct lack of virus-induced membranes normally present in cells expressing wild-type replicon RNA. The compensatory mutation NS2A-T149P restored the induction of membrane structures to a level similar to those observed during wild-type replication. These results further confirm the role of NS2A in virus assembly, demonstrate the importance of hydrophobic residues at codon 59 in this process, implicate the involvement of NS2A in the biogenesis of virus-induced membranes, and suggest a vital role for these induced membranes in virus assembly. To further our understanding of how mutations within NS2A are able to affect the induction of virus-induced membranes, leading to a block in virus assembly, the membrane topology of KUN NS2A was investigated. Using a plasmid encoding NS1 and NS2A proteins with C-terminal c-myc and FLAG epitopes, NS2A proteins containing N-linked acceptor sites and C-terminal truncations were generated. Assays were performed to identify the subcellular localization of specific sequences within NS2A by Western blot and immunofluorescence analyses. While the membrane topology could not be determined experimentally, the findings of this study support the assertion that cleavage at the NS1/NS2A junction requires the majority, if not all of the NS2A protein for proper processing to occur, and suggests that the interaction between hydrophilic loops and -helical transmembrane segments plays an important role in the formation and stability of the flavivirus NS2A protein topology. Based on the knowledge of polyprotein processing events, and utilizing a range of software packages, a topology model of NS2A was predicted. The likelihood of additional sequences within NS2A affecting the ability to induce virus-specific membranes, and facilitate virion assembly, has led to the development of an invasive bacterial screening system, as a delivery vehicle to screen libraries of mutated KUN replicon clones. Using these invasive bacteria to deliver mutated KUN replicons into BHK-derived packaging cells, mutations causing a deficiency in either RNA replication or encapsidation can be identified by performing -gal assays on cells maintained in the presence, or absence of Doxycycline (suppressing the expression of structural proteins), respectively. Furthermore, this system was adapted for use in a 96-well plate format, allowing for high-throughput screening. Thus, KUN replicon clones capable of RNA replication, but unable to assemble and secrete virus-like particles can be identified and further analyzed, in the hope of mapping amino acid residues and motifs involved in encapsidation of flavivirus RNA. Finally, a range of hypotheses are discussed, explaining the possible mechanisms by which NS2A is involved in flavivirus assembly. A number of future directions and applications are also presented.

The role of norms in intergroup discrimination : a social identity pesrspective

Wellen, Jackie Melissa. — 2007-08-24T00:00:00Z

The role of nuclear factor one (NFI) in cortical development

Mason, Sharon Anne — 2012-09-27T00:00:00Z

The role of obesity in the development and progression of chronic liver diseases

Hickman, Ingrid Joy — 2007-08-24T00:00:00Z

The role of Patched1 during development of the mouse cerebellum and regulation of neural stem cells in medulloblastoma

Jonathan Robson — 2010-12-24T00:00:00Z

The Sonic Hedgehog (Shh) signalling pathway plays a critical role in the development of many organs including the brain, lungs and skin. Of particular interest to this project, aberrant activity of the Shh pathway has been shown to be involved in the development of the paediatric cerebellar tumour medulloblastoma, typically through loss of function of the Shh receptor Patched 1 (Ptc1). Binding of Shh to Ptc1, or ablation of Ptc1 function, results in Smoothened (Smo) activation resulting in the activation of a number of downstream transcription factors responsible for cell proliferation and migration. In addition to its role in cerebellar development the Shh/Ptc1 pathway has also been associated with neural stem cell regulation although direct assessment of this relationship is difficult given the lack of in vivo neural stem cell markers. The aim of this project was to quantitatively assess the effect increased Shh/Ptc1 pathway activity has on neural stem cells via in vitro stem and progenitor cell assays, and determine if neural stem cells are the cell of origin of medulloblastoma. In order to determine how the Shh/Ptc1 pathway regulates neural stem cell fates Ptc1 function was ablated in the neocortex and subventricular zones of the developing mouse embryo through the use of an inducible Nestin Cre recombinase/Ptc1 conditional transgenic mouse line. Using in vitro neural stem cell assays it was identified that constitutive activation of the Shh/Ptc1 pathway in the neocortex and subventricular zone of the developing brain resulted in increased stem and progenitor cell numbers in vivo. Concomitant with an increase in Gli1 expression in the neocortex, an increase in the rate of symmetric neural stem cell division was observed. While sufficient to increase stem cell and progenitor cell numbers, increased activity of the Shh/Ptc1 pathway was not sufficient to rescue the loss of stem cells observed in neocortices devoid of Notch1 signalling. Although studies are beginning to elucidate the role of the Shh/Ptc1 signalling pathway in medulloblastoma formation little is known about the primary cell type responsible for tumour initiation. The observation that Shh/Ptc1 constitutive activation increased both stem and progenitor cell numbers and increased the rate of cell division prompted us to investigate the possibility that Ptc1 ablated neural stem cells may be a cellular origin of medulloblastoma, whereby the Shh/Ptc1 pathway maintains neural cells in a stem like fate. To identify the relationship between neural stem cells and medulloblastoma formation Ptc1 function was ablated in the developing cerebellum under the control of GFAP Cre recombinase which resulted in constitutive activation of the Shh/Ptc1 pathway in the cerebellar stem cell compartment, leading to medulloblastoma. It was shown that homozygous loss of Ptc1 in the cerebellar ventricular zone and developing external granule layer resulted in increased cell proliferation concomitant with increased Gli1 expression. Neural stem-like cells were isolated from the adult Ptc1 deleted medulloblastoma but not from equivalently aged wild type mice. Unlike primary Ptc1 deleted cells, isolated neurospheres from Ptc1 deleted medulloblastomas failed to recapitulate tumour formation in vivo. In contrast to primary Ptc1 deleted cells, Ptc1 deleted neurospheres showed significantly decreased Shh/Ptc1 pathway expression concomitant with a loss of primary cilia in vitro. To further investigate the possibility of a cancer stem cell as a cell of origin of medulloblastoma the primary Ptc1 deleted cell population was assayed for cancer stem cell markers through Fluorescent Activated Cell Sorting (FACS) of a panel of CD antibodies. This project identified 5 antibodies, CD38, CD44, CD90.2, CD117 and CD121b to have lower binding detection in Ptc1 deleted medulloblastoma compared to wild type cerebella and 3 antibodies, CD1d, CD24 and CD81 which have greater binding detection in Ptc1 deleted medulloblastomas compared to wild type cerebella. Of these, CD24 positive cells were identified to have increased tumour forming potential compared to CD24 negative cells identifying a possible medulloblastoma initiation marker in Ptc1 deleted stem/progenitor cells. Co-localised with CD15, a recently hypothesised neural stem cell marker, the CD24 positive population was found to be split into two distinct cell populations which led to the hypothesis that CD24/CD15 co-expression may identify the tumour forming cell population in medulloblastoma. Collectively these data suggest that medulloblastoma resulting from aberrant Shh/Ptc1 signalling may be due to a persistent stem-like cell whose tumorigenic potential depends on the presence of primary cilia and may be detected in vivo through specific expression profiles of cell surface markers.

The role of patched1 in mammalian facial dysmorphology

Metzis, Vicki — 2012-10-31T00:00:00Z

The role of p120-ctn in regulating E-cadherin-mediated adhesion

Marita Kathleen Goodwin — 2007-08-24T00:00:00Z

The role of Peroxisome proliferator-activated receptors in the rat brain

Smith, Steven Andrew — 2007-08-24T00:00:00Z

THE ROLE OF PHASE VARIABLE TYPE III RESTRICTION-MODIFICATION SYSTEMS IN GENE REGULATION

Srikhanta, Yogitha — 2008-11-21T00:00:00Z

Phase variation, the high frequency reversible switching of gene expression, is a common feature of host-adapted bacterial pathogens and is generally associated with genes encoding surface factors. Phase variation results in genetically and phenotypically diverse populations, providing a strategy for rapid adaptation to changes within the host environment and evading immune responses. However, in a growing number of host-adapted pathogens, phase variation has been found to occur in genes encoding methyltransferases (mod genes) associated with type III restrictionmodification (R-M) systems. R-M systems traditionally confer protection against foreign DNA, and several roles have been proposed for phase variable R-M systems based on DNA restriction function. The existence of phase variable methyltransferases raises the possibility of further functions for R-M systems such as gene regulation. In this thesis the role of a phase variable methyltransferase (mod) associated with a type III R-M system of Haemophilus influenzae strain Rd was investigated. Microarray expression analysis comparing a wild-type strain expressing mod to a mod knockout mutant strain, revealed altered expression of 15 genes under Mod control, some of which were virulence associated. This key finding confirmed that this phase variable methyltransferase coordinates the random switching of expression of multiple genes. Phylogenetic studies were used to analyse phase variable mod genes associated with type III R-M systems in the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae revealing that these organisms have two distinct mod genes - modA and modB. There are also distinct alleles of modA and modB that differ only in their DNA recognition domain. Phylogenetic analysis was also used to create an up-to-date list of potentially phase variable type III R-M systems present within other host-adapted organisms. To confirm whether phase variable methyltransferases controlled gene expression in other pathogens, the phase variable modA genes of Neisseria were studied. Mutant strains lacking the modA11, modA12 or modA13 genes were made and their phenotype analysed. Microarray analysis revealed that in all three modA alleles multiple genes were either up- or down-regulated, some of which were virulence associated. For example, in N. meningitidis (modA11), 80 genes were differentially expressed including the vaccine antigen candidates lactoferrin binding proteins A and B. Functional studies in N. gonorrhoeae confirmed that wild-type FA1090 modA13 ON and FA1090modA13::kan mutant strains have distinct phenotypes in antimicrobial resistance, a primary human cervical epithelial cell model of infection and biofilm formation. In summary, this thesis provides experimental confirmation that in three important human pathogens, H. influenzae, N. meningitidis and N. gonorrhoeae, alteration of expression of a type III DNA-methyltransferase causes switching of multiple genes. This novel genetic system has been termed the phasevarion (phase variable regulon). The wide distribution of phase variable mod genes indicates that this may be a common strategy used by host-adapted bacterial pathogens to randomly switch between distinct differentiated cell types.

THE ROLE OF PROTEASE IN UNLOCKING THE NUTRITIVE VALUE OF SORGHUM GRAIN FOR PIGS

Avril Finn — 2011-10-18T00:00:00Z

In Australia, and especially Queensland, sorghum is an important animal feed grain due to its drought resistance and heat tolerance. In many instances sorghum is thought to have a lower nutritive value compared to other cereal grains by pig producers due to poor pig performance when fed the grain with respect to rate of gain (ROG), average daily intake (ADI) and feed conversion ratio (FCR). An experiment was conducted on 640 Large White pigs (7.0 to 9.2 kgs) to evaluate the effects of different grain types and cultivars on performance of weaned pigs. The pigs were fed complete diets for 21 days containing 65% of one of 32 test grains (11 sorghum, 9 wheat, 7 barley and 5 triticale) with a calculated DE of 14 MJ/kg and lysine content of 0.90 g/MJ DE. Overall, sorghum was shown to have a significantly (P<0.05) negative effect on pig performance when compared to wheat, barley and triticale. However, it was also shown that some sorghum cultivars could perform just as well as the other grain types. To determine whether pig performance was affected by animal age, a second experiment was conducted on 120 Large White male pigs (16 to 25 kgs) to evaluate the effects of different sorghum cultivars. The pigs were fed complete diets for 21 days containing 82% of one of 10 sorghum grains (one yellow and nine red) with a calculated DE of 14 MJ/kg and lysine content of 1.13 g/MJ DE. Grower pigs fed different varieties of sorghum grains showed statistically significant (P<0.05) differences in ROG, but not ADI or FCR. The performance of the grower pigs compared to the weaner pigs on the same 10 test sorghum grains showed no correlation which leads to the conclusion that the age of a pig can affect its growth performance when fed the same grain. However, in contrast to the modest growth performance of pigs fed sorghum, the total digestible energy (DE) of sorghum is either similar or higher than some grains e.g. wheat. Therefore a third experiment was conducted on 42 Large White male pigs (32 to 37 kgs) to investigate whether DE values in grower pigs from both apparent ileal digested (AID) energy and apparent total tract digested (ATTD) energy measurements vary between different cereal grains. The pigs were fed complete diets containing 95% of each of the 32 grains used earlier with a calculated DE of 13 MJ/kg and lysine content of 0.70 g/MJ DE. There were highly significant (P<0.001) differences in the DE between grain types. The highest DE was from sorghum and wheat, followed by triticale, and the lowest for barley. Grain cultivar had a highly significant effect (P<0.001) on the ATTD energy for the diet on an as received (AR) basis, and the ATTD energy for the grain as an ingredient on an AR and dry matter (DM) basis. However, grain cultivar had no effect on the AID energy for the diet. There was also a significant (P<0.05) effect of the grain variety on the ratio of the diet AID to ATTD with wheat having the highest ratio followed by sorghum, triticale, and barley. One reason for poorer pig performance, when fed sorghum may be due to starch/protein interactions in the endosperm matrix restricting digestion of both starch and (kafirin) protein. Therefore an in vitro experiment was conducted using two sorghum cultivars, the yellow seeded Liberty and a red seed coat hybrid (Red1) to determine the efficacy of specific exogenous enzymes on the digestion of sorghum kafirins. Five exogenous enzymes, xylanase, beta-glucanase, protease, amylase and phytase were used in combination and individually. Enzymes were added to hammer milled whole grain then a protein extraction and sodium dodecyl sulfate polycrylamide gel electrophoresis (SDS-PAGE) analysis was undertaken, which showed that digestion of sorghum α-, β- and γ-kafirins was improved by the addition of protease either on its own or in combination with other enzymes. However, in combination with xylanase, beta-glucanase and amylase it appeared to lose its efficacy. Due to the positive effect of exogenous protease in vitro, an in vivo experiment with 144 Large White male pigs (7 to 9 kgs) was conducted to evaluate the addition of protease enzyme at four different levels (0ppm, 50ppm, 100ppm and 500ppm) to a complete diet containing 65% of either Liberty (yellow), Buster (red) sorghum and a wheat control, with a calculated digestible energy (DE) of 14.57 MJ/kg and an available lysine content of 1.55 g/MJ DE. At 0-21 days, for the highest protease level (500ppm) both sorghums performed better than in the absence of protease, and similarly to the wheat control in terms of FCR. In conclusion, although sorghum and wheat show higher AID and ATTD energy compared to triticale and barley, sorghum typically gives poorer pig performance than wheat, barley and triticale. However, selection of appropriate sorghum cultivars and, particularly, treatment with exogenous protease show promise as means of obtaining pig growth performance and feed conversion efficiency similar to or better than that of other cereals used in Australia.

The role of retinoic acid receptor related orphan nuclear receptor ROR[alpha]1 in muscle differentiation

Lau, Wai Fun Patrick — 2010-12-07T00:00:00Z

The role of RSVP distractors in the effect of concurrent extraneous cognitive load on AB task performance

Samantha Howard — 2011-04-08T00:00:00Z

The attentional blink (AB) is the impaired ability to identify a second target (e.g., letter) presented among a rapid serial visual presentation (RSVP) of distractors (e.g., digits) when the second target (T2) occurs within approximately 500 ms of a correctly identified first target (T1). One of the more intriguing findings to emerge from recent AB literature is that an observer will show a significantly reduced AB and overall better target accuracy if they simultaneously perform a task that is extraneous to the RSVP (Olivers & Nieuwenhuis, 2005; 2006). Contemporary accounts of this ‘additional task benefit’ emphasise the role of distractors, with the most recent theories highlighting the importance of the processes occurring at T1+1 distractor selection (Olivers & Meeter, 2009; Olivers, van der Stigchel, & Hulleman, 2007). The purpose of this thesis is to test the following three general questions 1) whether the T1+1 distractor item plays a crucial role in the additional task benefit, 2) whether the additional task benefit is sensitive to the level of discriminability between targets and distractors, and 3) whether distractors are essential for demonstrating the additional task benefit. A preliminary set of experiments replicated Olivers and Nieuwenhuis’ (2006) finding of an additional task benefit on target identification accuracy in a standard AB task. In a set of follow-up AB experiments, RSVP targets were four-letter words and distractors were orthographically acceptable (word-similar) or orthographically unacceptable (word-dissimilar) non-words. The findings indicated that a low degree of discriminability between targets and distractors is pivotal for showing the beneficial effect of secondary task load. It was also shown that reducing the effectiveness of the T1+1 mask through distractor repetition eliminates the additional task benefit. These findings were extended in two final experiments demonstrating an additional task benefit when there were no distractors between T1 and T2, but no additional task benefit in an RSVP of successive target stimuli. These results suggest that the effect of secondary task load principally depends on the presence of T1 and an adequate temporal frame in which this initial target may be processed before the onset of T2. Taken together, the project’s findings are inconsistent with contemporary distractor-based models of the secondary task benefit on AB task performance. Instead, the findings match recent accounts of the AB, which emphasise the dynamics of attentional processes involved in target selection.

The role of series elasticity and biarticular muscles in lower extremity movements : a study of muscle mechanics using an EMG-to-force model

Barrett, R. S. — 2007-08-24T00:00:00Z

The role of serine proteases in angiogenesis

Sit, Mae-Le. — 2007-08-24T00:00:00Z

The role of Slit2 in kidney development

Piper, Michael John — 2007-08-24T00:00:00Z

The Role of Sox18 in Blood Vessel Development

Meredith Downes — 2008-11-06T00:00:00Z

The Role of Stated Organizational Values in Times of Change and Crisis

Stewart Arnold — 2010-03-18T00:00:00Z

Weick (2006) calls for researchers to investigate how employees ‘hold it together’ during periods when organizational routine and order are challenged. This thesis focuses on employee experiences during two types of organizational upheaval: periods of planned, large-scale organizational change and periods of organizational crisis triggered by external events. In both conditions, employees can react negatively. This leads to failure to cope with the current situation and with future situations that pose similar threats and challenges. On the other hand, if employees can make sense of a threatening, challenging situation, the outcomes are more positive for them as individuals and for the organization as a whole. Weick’s (1988) concept of sensemaking is used as a guiding framework for investigating the experiences, attitudes, and actions reported by employees in times of organizational change and crisis. The general assertion of the thesis is that the espoused and enacted values of an organization provide sensemaking cues to employees in difficult times. More specifically, the role of stated organizational values is examined. Organizational values are often stated as a set of principles that provide guidance for employees, particularly as part of a managing-by-values approach. The context for the research program is the healthcare industry, because values are very important for healthcare employees. Moreover, healthcare organizations must continue to function optimally during challenging conditions. Three research studies are reported. Study 1 was conducted in an Australian public hospital that was undergoing large-scale change. Thirty-five employees from a range of occupations were interviewed midway through the five-year period of change. Thematic analysis of their interviews revealed that employees mostly reported negative experiences of the change program. Furthermore, employees made sense of the change program by focusing on specific cues in their situation. One such cue was the organization’s strongly promoted set of ‘core values’. The stated values were seen to be a visible symbol of the hospital’s principles, but there were negative perceptions about how well these principles were enacted. Study 2 was conducted in a public hospital in Singapore exposed to a crisis situation due to the SARS virus in 2003. Thirty-one employees from a range of occupations were interviewed four months after the outbreak had ended. Twenty of these participants returned for a second interview, one week after the first interview. A card sort procedure and thematic analysis of the interview data were used to investigate employees’ experiences of the crisis. Results revealed that employees made sense of the crisis through identification with their profession and their organization. They also perceived that the hospital’s actions during the crisis were consistent with its written set of organizational values. In addition, employees identified a number of organizational citizenship behaviors (OCBs) that they had shown during the crisis. Study 3 was conducted at three hospitals in Singapore. A pilot study involved 24 employees from a public hospital. They engaged in a focus group discussion about professionalism and they refined a set of hospital-specific employee behaviors that could potentially be classified as OCBs. The main study involved survey completion by a stratified sample of employees from another public hospital (n= 214) and from a private hospital (n=184). All respondents were invited to complete a second survey (measuring related variables) three weeks after the first survey. Analysis of 301 usable survey responses revealed findings that contribute to different literatures. Firstly, asking respondents to rate OCBs according to whether they were voluntary, unrewarded, and beneficial to the organization, revealed that many OCB items used in previous research were not perceived as being ‘true OCBs’ by the survey respondents. Furthermore, despite the use of many possible OCB dimensions, the true OCB items were factor analyzed into just two factors. One factor reflected OCBOs, which are behaviors directed towards the organization as a whole, while the other factor reflected OCBIs, which are behaviors directed towards other individuals. A second contribution is the suggestion that employees’ sense of ‘professionalism’ is a single construct. Survey respondents did not distinguish between professional identification and professional commitment in the same way as organizational identification and commitment were differentiated. Professionalism was weakly related to tendency to engage in OCBOs and more strongly related to tendency to engage in OCBIs. Finally, the main contribution to the values literature is the development of the concept of ‘organizational values integrity’ (OVI). This is conceptualized as the perceived alignment between organizational actions and organizational words, especially those words espoused in values statements. Structural equation modeling revealed that OVI influenced organizational identification and organizational commitment, which both mediated the impact of OVI on OCBOs. Furthermore, OVI had a direct impact on OCBOs. Overall, this thesis highlights employee perceptions that the organization acts in ways that are aligned to its stated values as important influences on employee attitudes and OCBs, particularly in difficult times. Implications for managerial practice and further research are discussed.

The role of summer dormancy in improving survival of temperate perennial pasture grasses in drought-prone environments

Norton, Mark Roger — 2008-11-21T00:00:00Z

The poor survival of perennial pasture grasses is a major constraint to agricultural systems where summers are characterised by long, severe droughts and high temperatures. The search for grasses with superior tolerance to these conditions has resulted in a re-awakening of interest in the summer dormancy trait leading to the recent release of several summer dormant cultivars. This has led to renewed questioning about the nature of summer dormancy particularly as the definition of the trait is unclear. Therefore, this research has aimed to strengthen understanding of summer dormancy in the pasture grasses Dactylis glomerata L. (cocksfoot), Festuca arundinacea Schreb. (tall fescue) and Phalaris aquatica L. (phalaris) by studying two cultivars contrasting in the expression of summer dormancy from each species. A range of field trials in the south of France aimed to identify key physiological mechanisms whereby summer dormancy enhances survival over long, dry summers by concentrating on the effects of different levels of summer water supply and plant maturity. Field trials in that region also compared and evaluated several methods to measure the intensity of summer dormancy and developed a new method based on herbage production from irrigated summer culture. Growth chamber trials with small pots studied the relationship between temperature and the expression of summer dormancy by comparing the growth response to a range of temperatures of two cohorts of plants contrasting in exposure to conditions aimed to induce summer dormancy. Finally, winter research conducted in pots in the glasshouse subjected plants to drying cycles to study dehydration tolerance and avoidance and related these to the expression of the summer dormancy which had been observed in the summer field studies. The component mechanisms of summer dormancy were clearly expressed under full summer irrigation by reproductive plants which had been vernalised and although present in younger, spring-sown plants they were approx. 40% less intense while the tall fescue cv only expressed dormancy if subjected to prior drought. Expression began in late spring/early summer and included growth cessation and herbage senescence resulting in substantially less summer evapotranspiration in the dormant tall fescue and cocksfoot swards compared to their summer active counterparts. The dormant cocksfoot under drought dehydrated to -6.7 MPa and even under irrigation dehydration to -3 MPa occurred . In contrast, under irrigation the dormant tall fescue and phalaris cvs remained hydrated. Dehydrin expression increased in all cvs as water deficit intensified but while expression declined after a storm in the non-dormant cvs (in response to increased water status), levels remained uniformly high in the three dormant cvs. The summer dormant tall fescue maintained full sward cover after summer droughts of 116 and 144 days whereas cover in the summer active cv fell by approx. 25%. Similar sward loss (22%) occurred in a summer active cocksfoot, in contrast to the summer dormant cv after a 144 day drought. No survival advantage for the summer dormant cv was measured in phalaris although this seemed to be due to unique field trial site characteristics. Five methods for summer dormancy measurement varying according to summer water availability, i.e., full irrigation, mid-summer storm and complete drought, and assessment method, viz., herbage production measurement or visual estimation of herbage senescence, were compared and evaluated. A method using the herbage harvested from irrigated summer culture was developed. Summer dormancy is best measured under non-limiting moisture, because assessing the trait under complete drought can result in false scores, e.g. Medly cocksfoot was moderately dormant under drought (6/10), but non-dormant under full summer irrigation or after a storm (1-2/10). Dormancy was scored equally well by measuring herbage production or by visually assessing the level of herbage senescence. The examination of the effect of temperature on summer dormancy questioned whether dormancy is independent of temperature or is simply a decline in growth in response to high summer temperatures. In cocksfoot the decline associated with summer dormancy (approx. 100%) was independent from any which occurred as a result of high temperatures. In tall fescue, despite indications that dormancy was a separate effect it was not possible to definitively separate the effects of rising temperature from prior dormancy induction suggesting the need for further research. Inconsistent and inconclusive results occurred in phalaris suggesting that small pot culture is inappropriate for studying dormancy in this species. Subjecting plants to drying cycles in a winter glasshouse environment demonstrated that dehydration tolerance, dehydration avoidance and summer dormancy are separate responses able to be independently expressed. In cocksfoot and tall fescue two highly dehydration-avoiding cvs also expressed high levels of dormancy in summer as reproductive plants although a summer active cocksfoot was also highly dehydration-avoiding. In contrast, the highly summer dormant phalaris cvs showed no greater levels of dehydration avoidance/tolerance than much less dormant cvs. The research has identified key mechanisms of drought survival as being component, defining characteristics of summer dormancy and has also demonstrated robust screening methods to extend utilisation of the trait in plant improvement.

The role of suppressors of cytokine signalling (SOCS) in prolactin action

Tam, Sau Ping — 2007-08-24T18:20:17Z

The role of synapse formation on motoneuron survival during embryonic development

Banks, Glen B. — 2011-08-09T00:00:00Z

The role of the Activator Protein-2 transcription factor family in human skin and its appendages

Popa, Claudia — 2007-08-24T00:00:00Z

The Role of the Internet in the Lives of People with Traumatic Brain Injury

Jennifer Egan — 2010-06-17T00:00:00Z

Psychosocial factors represent complex and enduring challenges for people with a traumatic brain injury (TBI), their families and health and rehabilitation systems, particularly in relation to social isolation, change/loss of role and identity issues. Traditional rehabilitation approaches to psychosocial issues target cognitive rehabilitation and psychological adjustment of the individual with a TBI, which reflect the medical model of health. However, the International Classification of Functioning, Disability and Health (ICF) ushers a new era in TBI research and practice, which advances the conceptualisation of disability, to include the impact of environmental factors. The ICF identifies the Internet as one such environmental factor, which has the potential to facilitate or impede social participation of people with a disability. Empirical studies suggest the potential of the Internet to empower people with disabilities, via opportunities for social connection; social support; social role participation and identity experimentation. However, research has focused on people with sensory, physical, and mental health issues, with little known of the potential of the Internet for people with a TBI. This area of deficit warrants investigation, in view of the potential of the Internet to address many dimensions of psychosocial concern following TBI. This study explores the role of the Internet in the lives of people with a TBI, with a focus on the potential of the Internet to influence psychosocial recovery. Psychosocial recovery is conceptualised as the reconstruction of a positive identity, as found in subjective accounts of people with a TBI (Lewington, 1996), and strongly supported in the mental health consumer literature. Using a social constructionist approach, this study explores how people with a TBI use the Internet and how they make meaning of their Internet experience. This approach acknowledges the socially situated nature of Internet use and validates the subjective accounts of people with a TBI, whose perspectives are underrepresented in the rehabilitation literature. This study also trials the method of email-facilitated qualitative interviewing, to address face-to-face interviewing barriers, relating to cognitive-linguistic impairments (Lloyd, Gatherer, & Kalsy, 2006; Paterson & Scott-Findley, 2002). Thus, the Internet is the focus of the enquiry and the mediator of the method. The findings highlight the positive potential of the Internet to facilitate social participation for people with a TBI. Participants reported that features such as asynchronicity, reduced cues and anonymity made the Internet an accessible and usable technology, for social connection; social support; social role participation and identity reconstruction. A major theme emerging from the data was control of self, which this study conceptually linked to identity reconstruction and psychosocial recovery. Findings allayed concerns regarding the negative potential of the Internet to increase social isolation of vulnerable people, as participants regarded face-to-face relationships as more fulfilling than online friendships, supporting classic communication theories (Rice, 1987; Rice & Love, 1987), which propose that the Internet is a less personal medium than face-to-face communication, due to the feature of reduced cues. The findings of the method indicated that email facilitated qualitative interviewing addressed face-to-face interviewing barriers related to cognitive linguistic impairments; mobility factors; chronic health issues and environmental stimuli. Most participants indicated that asynchronicity, reduced cues, and anonymity facilitated control of communication, cognition and identity, thus enabling interview participation. The method had also advantages for the researcher, including time for reflection and the ability to yield richer data than in face-to-face contexts. However, the method was resource intensive, requiring information technology proficiency, familiarly with the impact of cognitive-linguistic impairments in online contexts and counselling experience. In addition, ethical guidelines required the involvement of a support person for the emotional protection of participants. This study makes two contributions to knowledge. One contribution relates to the potential of the Internet as an ICF environmental factor to address long-term psychosocial concerns, in addition to positively influencing psychosocial recovery from TBI, as reported by participants. This study contributes to a new era of research, which considers the impact of environmental factors on the experience of TBI, as framed by the ICF. The second contribution relates to the method of email facilitated qualitative interviewing, which advances knowledge of interviewing barriers for people with a TBI and addresses calls for innovative methods with this population. The findings of the method bring into question long held assumptions about the capacity of people with a TBI to participate in research and have implications for research design in qualitative and quantitative methodologies.

The role of the judge in civil trials : a comparison of German and Australian processes

Gregory, Shannon Therese — 2012-10-10T00:00:00Z

The role of the national government in facilitating innovation within the tourism industry: a case from Norway

Mei, Xiang Ying — 2012-09-05T20:35:10Z

THE ROLE OF THE PLANT CELL WALL ON THE BIOACCESSIBILITY AND BIOAVAILABILITY OF ANTHOCYANINS AND PHENOLIC ACIDS RELEASED FROM FRUITS AND VEGETABLES.

Anneline Padayachee — 2012-06-28T00:00:00Z

Fruits and vegetables are well known sources of vitamins, minerals and fibre as well as polyphenolic compounds and other phytonutrients. Extensive research into the chemoprotective benefits of plant-based foods has found that such compounds and their metabolites have antioxidant, anti-inflammatory and/or anti-carcinogenic properties. Whilst the health benefits associated with high dietary intake of fruit and vegetable polyphenols is a well researched field, the role of the plant cell wall on the bioaccessibility of these compounds is not. Polyphenolic and other nutrient compounds are located within the vacuole of plant cells surrounded by a lipid membrane and thereby separated from the plant cell wall which encapsulates the cell. In order for polyphenols and other nutrients to be bioavailable (i.e. absorbed during digestion through the gastrointestinal tract), they must first become bioaccessible (i.e. released from the plant cell ready to be absorbed by the body). In order for nutrients to be bioaccessible, the plant cell wall needs to be breached with the consequent possibility of binding between nutrients and plant cell walls. This thesis explores the nature of interactions between plant cell walls and two important classes of polyphenolic phytonutrients, anthocyanins and phenolic acids. The main structural constituent of the fruit and vegetable cell wall is cellulose, which is surrounded by a matrix of pectin and hemicelluloses, and at times lignin. Lignin directly affects the textural and palatability qualities of plant foods, and is generally not present in large amounts in fruits and vegetables. Cellulose fibres are tough and insoluble, and hence able to resist substantial force and provide support to the plant cells, whilst pectin increases the flexibility through formation of a co-extensive network with the rigid cellulose fibre network. The degree of methyl esterification (DE) of carboxyl groups is commonly used to differentiate pectins and to control network formation. The role of cell walls in polyphenol bioaccessibility has not been researched extensively. Rupture of the cell wall during mastication or processing (e.g. pureeing or juicing) results in polyphenols being released from the cell vacuole with consequent contact with cell walls for the first time, with the potential for binding interactions to occur. The human upper gastrointestinal tract (stomach and small intestine (S.I.) is unable to digest plant cell walls. Therefore if polyphenols bound to plant cell walls at the point of ingestion are not released from the cell wall material during transit through the gastric and small intestinal digestive phases, they will be carried by the cell walls to the large intestine where they may be released by bacterial fermentation of cell wall polymers and potentially further metabolised by bacteria before being either absorbed or excreted. This research fills several major gaps in current knowledge by: 1) identifying potential mechanisms for polyphenol-plant cell wall interactions; 2) assessing the bioaccessibility of polyphenols in a real vegetable system; and 3) examining the release of plant cell wall-bound polyphenols during gastric and S.I. digestion and the potential delivery of polyphenols to the colon. The extent of anthocyanin and phenolic acid interaction with cell wall components was investigated by monitoring the rate of polyphenol depletion from diluted purple carrot juice concentrate in the presence of pure cellulose or cellulose-pectin composites containing either low DE or high DE pectins, produced by the bacterium Gluconacetobacter xylinus. Binding of anthocyanins to plant cell wall components seems to be a 2-stage process with initially (1 hour) a limited amount (13-18%) of anthocyanins bound to the surface of the cellulose or cellulose-pectin composite. Whilst anthocyanins bound to both cellulose and pectin, more were bound to pectin. With prolonged exposure (7 days) to cell wall material, a gradual increase in anthocyanin binding occurred with approximately 35% binding to cellulose and the high DE composite and up to 80% binding to the low DE composite. This may be due to anthocyanins stacking on top of a base layer. Support for localised deposition of anthocyanins was found from confocal microscopy which showed apparent local high concentrations of anthocyanins alongside regions with much less, if any, bound anthocyanins. There does not seem to be molecular selectivity as depletion from solution of individual anthocyanin molecules is similar throughout the binding process. Phenolic acid depletion from solution in the presence of model cell walls also occurred. However unlike anthocyanins, more phenolic acids were bound to the pure cellulose initially than to the cellulose-pectin composites. Phenolic acid depletion was rapid, with approximately 20% phenolic acids binding to cell wall components within the first hour. This gradually increased to approximately 35% (low DE composite) and 50% (high DE composite and pure cellulose) over 14 days contact time. Additionally phenolic acid depletion from different concentrations of diluted purple carrot juice concentrate was similar indicating that cell walls may have a limited saturation level for binding phenolic acids. Conversely, doubling the concentration of free anthocyanins available led to at least twice as much binding with cell wall components. This indicates that whilst anthocyanin binding is slow, it may not be limited by available binding sites. Extrapolation of data from these model systems to carrot puree suggests that significant amounts of anthocyanins and phenolic acids could bind to the plant cell wall, potentially restricting their bioavailability in the S.I. In order to ascertain the potential extent of polyphenol delivery to the large intestine via plant fibre in a real food system, polyphenols bound to cell wall material in a black carrot puree were subjected to simulated gastric and small intestinal digestion. It was found that the majority of available hydrophilic polyphenols derived from black carrots bound to the PCW matter with only ~ 36 % of the total phenolic acids (~ 1.2 mg/g puree) and 30 % of anthocyanins (1.3 mg/g puree) in the black carrot puree being released into the liquid phase. Approximately 30 % of the bound phenolic acids and anthocyanins could be extracted with acidified methanol. However, only <5 % of anthocyanins and phenolic acids were released during simulated gastric and small intestinal digestion. This is in agreement with results from the model cell wall system where the majority of bound polyphenols remained bound after simulated gastric and small intestinal digestion indicating that the binding mechanism between polyphenols and cell wall components is sufficiently strong to resist pH changes during the digestive process. This may be due to a 3-phase mechanism with initial random binding of anthocyanins and phenolic acids to cellulose fibres followed by further deposition of anthocyanins and phenolic acids, finally resulting in penetration into the internal cavity of the fibre of at least some polyphenols. As almost all polyphenols bound to cell wall components remain bound during simulated gastric and small intestinal digestion, they would be expected to be delivered to the large intestine where fermentation and metabolism by gut bacteria can occur. The extent of release and uptake of polyphenols bound to cell walls by gut bacteria fermentation and the effect on large bowel health should be addressed in future studies.

The role of the short stature homeobox-containing gene in skeletal growth and development

Munns, Craig Frank John — 2007-08-24T00:00:00Z

The role of the ubiquitin protein ligase, Nedd4-2, in neuronal development

Prudence Donovan — 2012-03-28T00:00:00Z

Correct ontogeny of the nervous system is reliant upon exquisite regulation of exogenous growth factors and their cellular reception. Integration of a myriad of signalling pathways during the development of the nervous system results in up to 100 billion nerve cells differentiating and migrating to take the their place in the elegant neuronal network that underpins brain homeostasis. The importance of such receptor ligand interactions to the proper initiation of neuronal differentiation, outgrowth and innervation has been demonstrated using a variety of structure- function studies, analysis of knockout animal models, protein-protein interactions and behavioural studies. Despite this, at present, knowledge concerning how such a vast array of signalling pathways are coordinately regulated to achieve the appropriate temporal and spatial regulation of neurogenic proteins is deficient. Modulation of the functional protein output of cell can be regulated by ubiquitination. Attachment of ubiquitin to a target protein is a post-translation modification carried out primarily by ubiquitin protein ligases that bind to consensus motifs on target proteins and conjugate ubiquitin chains to lysine residues within that protein. This process is known to label proteins for recycling or degradation in the proteasome. Thereby providing a mechanism for the removal and attenuation of a proteins signalling potential-when and where it is required. Such a modification is rapid and provides regulation of a protein that is context dependent and easily reversible, therefore providing a on/off switching mechanism, appropriate to the formation complex networks, as seen during neuronal development. Nedd4-2 is an ubiquitin protein ligase that is developmentally regulated; the protein was first identified from a subtractive cDNA library as developmentally down-regulated transcript in the brain. The expression of Nedd4-2 peaks at the time of neurogenesis and is maintained at significantly lower levels in the adult brain. Presently, the knowledge concerning the regulation of Nedd4-2, protein recruitment by Nedd4-2 and how this regulates neuronal development is lacking. Early studies of protein recruitment by Nedd4-2 indicated that it binds to target proteins through a consensus PY motif, despite a small list of proteins being identified and characterized as targets of Nedd4-2 mediated proteolytic degradation; the role of Nedd4-2 has largely not been characterized in the mammalian brain. Therefore, the key focus of this thesis was to examine the role of Nedd4-2, in neuronal development by defining and pinpointing where and how Nedd4-2 influences initiation of neurite development,differentiation and survival. The work presented in this thesis addresses this by establishing the importance of Nedd4-2 expression in regulating neurite outgrowth in PC12 cells. Studies presented here indicate that Nedd4-2 acts to negatively regulate neurite development in PC12 cells, furthermore it is demonstrated that neurogenic proteins such as NGF and Ras differentially regulate Nedd4-2. This work was extended into an in vivo model, made possible by the generation of Nedd4-2 knockout mice. These studies demonstrated the importance of Nedd4-2 in maintaining homeostasis, indicating that complete abrogation of Nedd4-2 expression is peri-natal lethal. Histological assessment of key brain regions developing at this time indicates that the absence of Nedd4-2 is accompanied by deranged development of cortical areas in the brain. To gain insight into molecular mechanisms that mediate the phenotype observed in both the in vitro and in vivo modelling of Nedd4-2 during development an in silico screen was performed to develop a definitive list of putative binding candidates, this revealed the extent of the potential role for Nedd4-2 in regulating biological processes. Most notably, it was shown that PY containing proteins are enriched in pathways that regulate axon guidance receptors and the cytoskeleton. Of this list, it was demonstrated for the first time that Nedd4-2 binds to the axon guidance receptor, Neogenin and that Neogenin is ubiquitinated most likely in a Nedd4-2 dependent manner, highlighting the importance of Nedd4-2 in regulating the cell surface expression of proteins. Furthermore, prediction of the Nedd4-2 interactome led to the identification and characterization of MAP2 as a novel Nedd4-2 binding protein. These studies gave rise to the novel observation that Nedd4-2 is a potent regulator of the neuronally expressed MAP2 and indicate that Nedd4-2 can effect the differentiation and branching behaviour of nascent neurons possibly through destabilization of tubulin polymerization. Taken together this thesis demonstrates that Nedd4-2 is an important negative or rate-limiting regulator of neuronal differentiation and development in the embryonic brain, dorsal root ganglia and in PC12 cells. Furthermore, it is suggested that ubiquitin-mediated regulation of Nedd4-2 ligands such as MAP2 and Neogenin may be the effectors of the phenotype observed in the Nedd4- 2 knockout mice. This thesis also contributes to the broader understanding of how complex and convergent signalling networks are discretely regulated to achieve proper development and homeostasis.

The Role of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in Haematopoiesis

Yi Shen — 2011-03-23T00:00:00Z

Haematopoietic stem cells (HSC) give rise to haematopoietic progenitor cells (HPC) which terminally differentiate into all blood cell types. HSC can reconstitute the haematopoietic system following damage and reside in specific micro-domains of the bone marrow (BM) known as niches. HSC niches are preferentially located at the interface between the bone and BM (endosteum) and are abundant in long bones. Molecules expressed in these niches provide the extrinsic cues that control HSC quiescence, self-renewal or differentiation by asymmetric division. Many proteins found in these niches are involved in the egress of HSC into the blood during mobilisation. These proteins include proteases such as neutrophil elastase, cathepsin-G and matrix metalloproteinases (MMP), as well as their inhibitors, α1-antitrypsin (serpina1) and tissue inhibitor of metalloproteinases (TIMP)-1 to -4. TIMP-3 is a less studied member of the TIMP family. It not only regulates MMP activity but also the activity of sheddases (and thus plays a role in cytokine maturation), prevents vascular endothelial growth factor binding to its receptor 2, inhibits cancer proliferation and can cause sorsby fundus dystrophy. Despite its many interesting functions, TIMP-3’s role in haematopoiesis and mobilisation has not been well documented. By qRT-PCR and reverse zymography, I have determined that TIMP-3 mRNA is expressed at a 10-fold higher level at the endosteum when compared to central BM. Multipotent stromal cells (MSC), endothelial cells and mature osteoblasts (OB) expressed high levels of TIMP-3. Erythroid progenitors, megakaryocyte progenitors and mature megakaryocytes expressed TIMP-3 mRNA at much lower levels than stromal cells, while all other haematopoietic cells expressed extremely low to undetectable levels of TIMP-3 mRNA. Immunohistofluorescence on paraffin embedded bone sections with a rabbit anti-human TIMP-3 antibody (which cross-reacts with mouse TIMP-3) validated TIMP-3 protein expression in endothelial cells, OB and megakaryocytes. Interestingly, TIMP-3 mRNA and protein expression decreased with granulocyte-colony stimulating factor induced mobilisation. To investigate TIMP-3 function, human TIMP-3 (huTIMP-3) cDNA was over-expressed in mouse HSC via retroviral transduction using MND-X-IRES-eGFP (MXIE) retroviral vector. In mice transplanted with HSC transduced with MXIE retroviral vector containing huTIMP-3 cDNA, the frequency of B-cells and T-cells over-expressing huTIMP-3 were significantly reduced in blood and BM when compared to mice transplanted with HSC transduced with control empty vector. Conversely, the frequency of huTIMP-3 expressing myeloid cells was significantly higher in the blood, BM and spleen. Blood leukocytes and splenocytes of mice over-expressing huTIMP-3 in haematopoietic cells exhibited significantly greater colony forming ability. The presence of huTIMP-3 also increased Lineage-Sca-1+Kit+ stem cell proliferation both in vivo and in vitro. Interestingly as well, long term over-expression of huTIMP-3 resulted in calcification of bones with markedly decreased BM content and ultimately death.

The role of Tomosyn in insulin-regulated GLUT4 trafficking

Widberg, Charlotte Heidi. — 2011-12-22T00:00:00Z

The role of trust in community acceptance of urban water management schemes: A social-psychological model of the characteristics and determinants of trust and acceptance

Victoria Ross — 2010-06-04T00:00:00Z

Given the important role that trust plays in acceptance of water management schemes, the current research investigated the characteristics and determinants of trust by developing a social-psychological model of trust in the area of water management and reuse. The research advanced a theoretical understanding of trust by using social identity theory and the relational model of trust as a framework and providing a systematic examination of the relationships between the variables in the hypothesised trust model. The proposed trust model was tested across three potentially different perceived risk contexts; low, medium and high. Analysis through path modelling provided strong support for the hypothesised model. In all three contexts trust in the water authority was a significant predictor of acceptance of the water management scheme, and risk perceptions mediated the relationship between trust and acceptance. In other words higher levels of trust in the authority were associated with lower perceptions of risk, which were in turn associated with higher levels of acceptance. In Study 4, which was set in the high perceived risk context of the proposed indirect potable reuse scheme in Toowoomba, perceptions of risk had the strongest direct effect on acceptance of the scheme, and the trust, risk and acceptance relationship was stronger than it was in the other studies. The relational variables of procedural fairness, identification with one’s community, ingroup membership of the water authority and a social bond (shared values) with the water authority were all found to impact on trust, either directly or indirectly. In addition, the instrumental variable of the credibility of the authority (measured as technical competence and a lack of vested interests) was found to have a significant impact on trust. Taken together, the results provide support for social identity theory and the relational model of trust as a framework for understanding trust in authorities. The results are also consistent with literature that suggests that the relational and instrumental models of trust are not incompatible (e.g., Edwards & Kidd, 2003; Tyler & Kramer, 1996). The findings from this research program clearly have a practical application for improving acceptance of water management schemes. The combined results demonstrate the importance of trust in the water authority in reducing perceived risk and thus increasing acceptance of schemes. The results highlight the need for water authorities and policy makers to build public trust through procedural fairness, building a sense of the water authority as a member of the community, and through demonstrating technical competence and concern for the interests of the public.

The Role of Ultraviolet Radiation in Molecular Pathways to Melanoma

Hacker, Elke — 2008-11-21T00:00:00Z

A great deal of cancer research is aimed at describing the precise mechanisms that allow cells to become transformed. Many genes have been associated with melanoma and the majority of the functions of these genes pertain to three pathways Ras/Raf/MAPK, Ink4a/Cdk4-cyclin/pRb and ARF/Mdm2/p53. Over-expression of Hras in melanocytes, combined with a single neonatal UVR dose is sufficient to induce melanoma in pigmented mice. These lesions were small in situ cutaneous melanomas. To assess the role of the pRb pathway in melanoma mice, over expressing Hras were combined with activated Cdk4 mutants. These animals develop melanoma spontaneously, with a penetrance of 58%, which rose to 83% after neonatal ultraviolet radiation (UVR). Furthermore, the entire UVRtreated cohort that developed melanoma had multiple cutaneous lesions and 92% had metastatic tumours. In this model Hras activation alone is sufficient to predispose melanocytes to UVR-induced transformation, while mutant Cdk4 is more important for tumour progression, producing larger more aggressive, metastatic melanomas. To further assess the Ink4a/Cdk4-cyclin/pRb pathway in this disease a melanocytespecific deletion of the Rb1 gene was constructed. This model allowed for the culturing of Rb1-null melanocytes. Rb1-null melanocytes were studied and found to proliferate more rapidly than controls and to have a decreased requirement for mitogens. Expression arrays were performed to identify differences between the small in situ TPras lesions and those more aggressive Cdk4[superscript]R24C/R24C/TPras melanomas. We observed up regulation of Tcfeb, Ednrb, Tcfap2b and Gpr155 and down regulation of Plagl1 in Cdk4[superscript]R24C/R24C/TPras lesions. The overlay of expression and aCGH analysis showed dysfunction of various genes that are involved in regulating p53 and DNA repair pathways in the Cdk4[superscript]R24C/R24C/TPras tumours (Plagl1, Abcc10, Hsp90aa1 and Htatip). We also observed aberrations of several genes that regulate p21 (E2F2 and Htatip) and identified several potential markers of melanoma progression (Pax7, Dpp3, cdc42, Fgf22, Nme2, Esm1, Ednrb, Mum1 and Notch4). We also identified several genetic changes in Cdk4[superscript]R24C/R24C/TPras tumours that were specific to either UVR-induced or spontaneously derived lesions and identified a number of candidate genes (Hsp90aa1, Gzmk, Esm1, Bop1, Rapgef3, Htatip and Dpp3). This study has identified numerous novel candidate genes and also confirmed the importance of various melanoma-associated genes in this disease.

The role of universities in the development of regional innovation systems in Australia

Gunasekara, Chrys. — 2007-08-24T00:00:00Z

THE ROLE OF UNPLANNED HUMAN SETTLEMENTS IN LAND COVER CHANGE: A CASE STUDY OF THE CHYULU HILLS SQUATTERS- KENYA

Grace Muriuki — 2011-03-21T00:00:00Z

Investigations in this thesis advance our understanding on the role of unplanned human settlements in land cover change. Despite its complexity, the fundamental causes of land cover change are well known, and comprise biophysical, economic, policy/institutional and demographic factors. Of these, population growth and migration are implicated as the most significant. In future almost all land cover change will occur in rural areas which are experiencing rapid increases in population and migration, already a critical concern for conservation programs worldwide. Squatters are immigrants who illegally establish residence in areas deemed unsettled or with poorly-defined tenure. Their land use decisions tend to be risk-minimization strategies, influenced by their socio-economic characteristics and lack of long-term stakes in the land they occupy. This reduces their motivation to invest in and conserve resources, and they often become exceptional land degraders. In order to reduce their impact on landscapes and minimise the conflicts associated with their settlements, there is need for targeted research on their role in land cover change. I contribute knowledge to this problem using the Chyulu Hills as a case study. First, I reviewed current knowledge on migration and land cover change and the influential structural constructs that guide research in this field. Based on this review, I evaluated the dynamics of squatter migration to the Chyulu Hills, and the history of conflicts of squatters with the protected areas. Combining community surveys with statistical analysis, I revealed the proximate and underlying causes of the migration. I found that squatter movements to Chyulu Hills were widespread and long term, and that squatters are drawn from all over Kenya. Household socioeconomic and policy-related factors such as provision of schools, land tenure security and issuance of free land had a strong influence on squatter migration. Land and settlement policies were also implicated in migration and squatting. Most significantly, I established a high prevalence of secondary migration, where squatters migrated repeatedly to maximise their livelihood opportunities. The responsiveness of squatters to policy stimuli highlighted its potential to regulate or influence squatter mobility in rural landscapes. Next, I combined remote sensing/GIS tools, community surveys and landscape metrics to evaluate the rates and patterns of land cover change in the Chyulu Hills between 1967 and 1999, a period of high squatter migration. I found rapid changes in land cover over the 32 years of squatter settlements. The total proportion of native vegetation (dense forests, open forests and shrublands) decreased from 91% to 36%. In the same period, dense forests declined by 8.7% while cultivation expanded by approximately 40%. I explained these changes in the context of policy and management of land and the protected areas of Tsavo and Chyulu Hills. Squatter problems were related to land alienation during the British colonization of Kenya. I found preferential patterns of village establishment in or near dense forests. Landscape fragmentation confirmed the spontaneous nature of squatter settlements, and it is not clear yet how these transformations might affect the wildlife that uses it as a dispersal area. The community knowledge of the patterns and processes of land cover change, assessed using an adapted semi-quantitative tool known as proportional piling, agreed well with quantitative GIS measures of land cover change. Following this, I tested alternative postulates of the role of biophysical, household socioeconomic, access and institutional factors in the variation in remnant vegetation in villages in Chyulu Hills. Using Generalised Linear Models, model averaging and hierarchical partitioning analyses, I selected the best set of models within a 95% confidence interval, and ranked the relative importance of the explanatory factors in the variation in remnant vegetation. I found that squatter presence and their associated characteristics of short stays in villages, larger households and younger household heads were the most significant factors in remnant vegetation variations. This was supported by results of hierarchical partitioning. I then analyzed the policy on management of squatters and protected areas. For the most part, squatter management is ad hoc and reactionary, biased towards urban squatters, and largely limited to site and services improvements. I argued that this arose from a multiplicity of governance institutions and policies for natural resource management with overlapping mandates, rigid conservation management paradigms, and lack of provisions for participatory engagement of all stakeholders. I proposed the promotion of enabling policy environments that embrace participatory opportunities supported by building squatter human and social capital. Long-term land use planning should consider alternative livelihood sources that are less dependent on land as viable opportunities for reducing landscape changes and conflicts associated with squatters in rural areas. I recommend further research that integrates a broader spectrum of exogenous and contextual factors such as national policies, droughts and pandemics such as HIV/AIDS that influence household socioeconomics in rural land cover change. I also propose predictive studies that build potential future scenarios and that utilise finer temporal and spatial resolutions.

The roles of manganese and manganese transport systems in the response to oxidative stress in Neisseria gonorrhoeae and Streptococcus pneumoniae

Tseng, Hsing-Ju (Hilda) — 2007-08-24T00:00:00Z

The "rules of engagement": Social conventions surrounding the communication of criticism

Carla Jeffries — 2012-04-27T00:00:00Z

Criticism is important because it carries the potential for growth and positive change. Criticism holds the potential to identify weaknesses and suboptimal behaviours and, if acknowledged and integrated, can lead to the positive transformation of an individual or a group. Despite the therapeutic benefits of criticism, communicating critical feedback is a difficult behaviour. Criticism is frequently experienced as threatening and, when delivered or “taken” badly, can lead to a cascade of negative consequences (damaged self-esteem, hurt, conflict, withdrawal). Because it carries so much potential for hurt, the delivery of negative feedback is bounded by complex codes of etiquette. The present thesis aims to provide the first comprehensive map of these “rules of engagement” and to explore their psychological underpinnings and consequences. Chapter 2 describes the extant literature pertaining to the communication of interpersonal criticism. It then presents a survey study (N = 849) examining the extent to which people view the communication of criticism as more or less appropriate across various targets and in various contexts. We found evidence that respondents calibrate their feedback as a function of (a) the psychological resilience of the target, (b) whether the target is mutable, (c) whether the target deserves punishment, and (d) whether the target lies outside or within the boundary of one’s extended self. The effects are robust across age and gender. Cross-cultural differences in the endorsement of some rules were identified. Chapter 3 presents a study (N = 263) that disentangles the extent to which the withholding of negative feedback is motivated by a desire to protect the self as opposed to a desire to protect the target from the damaging social consequences of criticism. We found that participants provided more negative essay feedback if they thought that their assessments were anonymous than if they anticipated providing feedback face-to-face with the essay writer. Feedback was most negative when the feedback was not to be delivered to the essay writer at all. This effect only emerged among participants who were low in self-liking (but was unrelated to perceptions of self-competency). Manipulations of the self-esteem of the essay writer had no effect at all on evaluations. The data lend strong support for a self-protection motive and more modest support for an other-protection motive for withholding negative feedback. Chapter 4 presents two studies investigating the normative protection of low status groups from criticism. Study 1 (N = 816) identified the “David and Goliath” rule – the tendency for people to perceive members of “David” groups (groups with low power or status) as more “off-limits” to criticism than “Goliath” groups (groups with high power or status). We identified the existence of the David and Goliath rule across five national samples (Study 1). However the rule was endorsed more strongly in Western than in Chinese cultures, an effect mediated by cultural differences in power distance. Study 2 (N = 302) identified the psychological underpinnings of this rule in an Australian sample. Lower social dominance orientation (SDO; Pratto, Sidanius, Stallworth, & Malle, 1994) was associated with greater endorsement of the rule, an effect mediated through the differential attribution of stereotypes. Specifically, those low in SDO were more likely to attribute traits of warmth and incompetence to David versus Goliath groups, a pattern of stereotypes that was related to the protection of David groups from criticism. In Chapter 5, three studies investigated whether men and women are viewed as more or less appropriate to criticize. In Studies 1 (N = 502) and 2 (N = 129) we identified the tendency for people in both community and student samples to view women as more “off-limits” to criticism than men; coined the gender rule. This effect was moderated by participant gender with male participants endorsing the gender rule to a greater extent than female participants. Study 3 (N = 163) demonstrated that the gender rule is not a broad brush tendency with all women receiving protection from criticism. Consistent with work on stereotype content, both male and female targets occupying communal roles (high warmth-low competence) received less negative feedback than male and female targets in agentic roles (low warmth-high competence). These differences in performance evaluations could not be explained by differences in performance expectations or endorsement of benevolent or hostile sexism. In sum, this thesis demonstrates that there are rules that govern the delivery of criticism. We argue that the ironic consequence of “protecting” certain individuals and groups against criticism is that these people and groups are not given the same opportunities to learn and grow from their mistakes. The potential for miscommunication – and the perverse implications of withholding criticism – are discussed in Chapter 6.

The scalability and validity of four visual perceptual instruments : a comparison using the Rasch Measurement Model

Brown, G. Ted — 2007-08-24T00:00:00Z

The Science and Policy of Greenhouse Gas Management: A study of Australian and British stakeholder understanding, demands and expectations within the anthropogenic climate change discourse

Graham Farebrother — 2011-11-15T00:00:00Z

This study examines the science and policy interactions of greenhouse gas management (GHG) in Australia and the UK. It takes an historic approach, detailing how human recognition of Earth System impacts developed. As perturbations to different aspects of the Earth System were increasingly recognised, concerns grew for the sustainability of the natural world, and consequently for the sustainability of the economic system that underpins human societies. Over time, impacts and problems of increasing complexity have been identified, and it has become evident that an ad hoc manner of economic advance cannot be perpetuated. Much global and nation state effort is currently dedicated to designing and implementing policies to mitigate and manage the expected far-reaching impacts associated with anthropogenic climate change (ACC). The ACC discourse has progressed rapidly in recent times. Speculation of human interference in the Earth’s climate began in the 19th century; this speculation progressed into warnings in the 1930s, followed by quantitative measurements of atmospheric perturbation in the 1950s. Fears of anthropogenic disruption to the Earth System in the form of climate change have since resulted in international agreements, underpinned by concepts of sustainable development, and the precautionary principle. During the second half of the 20th century, civil society grew in strength and adopted a more powerful role in decision making processes and governance within many nation states; a process that has been actively encouraged through the activities of the United Nations. This change, in conjunction with a growing Green ethic, driven by the observation of environmental damage and impacts, has enveloped many aspects of human activity. As the level of industrialisation has increased in both scope and geographic range, environmental impacts have grown from local to regional to global and, with the onset of predictive computer modelling, bleak scenarios of future conditions have ensued. A growing knowledge base pertaining to various aspects of ACC has merged with both the expectations of an increasingly more powerful civil society, and an increasingly pervasive Green ethic. Following the introduction of the United Nations Framework Convention on Climate Change in 1992, GHG management has been at the fore of global and nation state policy discussions. The ACC discourse has since become increasingly embroiled with issues of sustainability; equity between developed and developing countries; and, the maintenance and promotion of the economic positions of various developed countries and trading blocs. Because of the broad association of GHGs with a variety of human activities, the discourse is seen by many as an umbrella cause. The goal of reducing anthropogenic GHG perturbation of the atmosphere has been coopted to heighten the awareness of many environmental and social problems, and to underpin the promotion of a range of vested interests. To understand the role of science in the development of GHG management policies, this study examines stakeholder understanding, perceptions, and expectations of both climate change science and mitigation policies. Interviews conducted in the UK and Australia, that targeted vocal and affected stakeholders, suggested that a high level of expectation is associated with the outcomes of GHG management policies; beyond the direct minimisation of climate interference, other environmental and societal improvements are expected. The ACC discourse is associated with a broad swath of issues that are found within contemporary society and deemed to be in need of resolution. The discourse is not only linked to existing and well known issues such as tropical rainforest deforestation, developing country poverty alleviation, biodiversity decline, and waste management but also to emerging problems including resource decline, rampant consumerism, falling human health standards, environmental degradation, and low levels of societal wellbeing. These associations are shown to be strong even when stakeholders have limited knowledge of, or even regard for, the underlying science of ACC. As a consequence of these many and varied associations, that have different sets of emphases from different elements of civil society, and in different locations, instigating universally acceptable GHG management policy is suggested as being problematic. Findings from this research suggest that if a greater focus on quantifiable environmental and societal improvement was a component of localised GHG management policies, then their acceptance and uptake by civil society would be eased and enhanced. The study shows that many less than ideal conditions and norms have developed within different societies and that a focal point is widely recognised as being useful or even necessary to help identify and rectify such problems. At both local and global levels, because of its direct association with Earth System impacts and the links to unsustainable forms of human behaviour, GHG management could be such a focal point if it is appropriately used.

The search for meaning in music education: Reflections on difference and practice.

Cuskelly, James Martin — 2008-11-21T00:00:00Z

This thesis investigates issues of meaning in music and the ways in which music education can be organised and delivered to maximise the experience of meaning for students. Two key questions are pursued within this thesis. Firstly, what is the nature of meaning in music, both as it is reported by educators and students, and evidenced in the literature? Secondly, in what ways can music education curriculum be organised to maximise this experience of meaning for students, specifically in the core areas of listening, composing and performing? In recognizing the various ways in which concepts of musical meaning are employed within music education and in an attempt to clarify and more accurately define what is intended when referring to meaning in music, three specific terms-signification, responsification and socialification-are suggested. The use of these terms also provides important points of reference throughout the discussion. Employing an autobiographical and phenomenological approach alongside a critical analysis of music education philosophies, this study investigates the lived experiences of teachers and students in terms of meaning in music. The inclusion of personal histories-my own and the stories of the students whom I teach-within the methodological framework provides a unique vehicle for the capture of data given the highly personalised nature of much of the material to hand. Further, a consideration of the lived experience of teachers and students in light of contemporary research and thinking serves to firmly anchor the discussion within the educational context. This research has found that issues of meaning are layered, multifaceted and interrelated, that there are numerous elements that contribute to meaning and that what is significant in music may be diverse, varying from individual to individual, from group to group. Musical meaning may be highly personalized and /or culturally delineated, and meaning in music may not remain static; it may vary across experiences or over time. This research has identified particular practices and approaches which significantly influence the development of meaning in music; such educative practices are worthy of sustained consideration by those within the field.

THE SELF EVALUATION MAINTENANCE MODEL IN ADOLESCENT SIBLING AND TWIN RELATIONSHIPS

Blakeley-Smith, Anita Maria — 2008-11-21T00:00:00Z

The project was designed to examine how nontwin and twin sibling adolescents deal with situations of competition and comparison between them. Using the Self Evaluation Maintenance Model (Tesser, 1988) as a framework, this project explored the reactions and strategies that adolescent nontwin and twin adolescents employ in order to maintain a positive selfevaluation. In addition, the potential mediating factors of sibling relationship quality and perceptions of differential parental treatment on adolescents reactions to competition and comparison to their self esteem was also investigated. Three studies were conducted. All three studies investigated the relevance of the SEM model to understanding nontwin and twin adolescents reactions to situations of competition and comparison, but employed different methodologies and samples. Study 1 involved both members of the sibling pair completing a questionnaire that included their emotional and behavioural reactions to selfgenerated situations of competition and comparison, counterbalanced by closeness, relevance and performance. In this study, closeness referred to either a sibling or friend comparator. Four hundred and sixty (232 pairs of) same sex nontwin and twin adolescents aged between 13 and 17 took part in Study 1. The results revealed that both sibling nontwin and twin adolescents were motivated to maintain a positive self evaluation. In line with the SEM model, both the comparison and reflection processes were evident for emotional reactions. However, closeness of the competitor did not interact with selfrelevance of the task to affect performance as predicted. Self evaluation was enhanced when both nontwin and twin adolescents were outperformed on tasks of low rather than high self relevance, indicating the presence of the reflection process. However, nontwin adolescents reported being more positive about being outperformed by their sibling than their friend suggesting that siblings may consider their friendships to be the closer relationship to them. Closeness of the competitor did not affect positive reactions to competition and comparison for twin adolescents. For negative emotional reactions and behavioural reactions, closeness of the competitor did not interact with relevance to affect performance for either nontwin or twin adolescents as predicted. Birth order was found to affect self evaluation, even in twin relationships. Both younger nontwin and twin adolescents were more able to preserve self evaluation when outperformed by their older sibling, while older nontwin and twin adolescents found being outperformed by their younger sibling to be particularly difficult. Zygosity effects were only found for positive but not negative emotional reactions. Contrary to expectations, perceptions of differential parental treatment did not mediate emotional reactions to self esteem for adolescents. Sibling relationship quality did not mediate emotional reactions to self esteem for nontwin adolescents. When outperformed by their twin, sibling relationship conflict and sibling relationship warmth was found to mediate emotional reactions to self esteem for monozygotic twins and dizygotic twins respectively. A subsample of Study 1 participants completed Study 2. The participants in Study 2 were one hundred and six (53 pairs of) nontwin and twin same sex adolescents. Study 2 explored nontwin and twin adolescent siblings emotional reactions to situations of competition and comparison in an experiential context, again using the SEM model (Tesser, 1988) as a framework. Sibling pairs were asked to orally discuss situations where they had competed with or compared themselves to their sibling/twin, to view themselves completing this discussion and then to complete a series of questions relating to Tessers (1988) SEM model. Subjects completed the same questions for each of the four SEM conditions, counterbalanced by performance on the task and relevance of the task. As adolescents only competed against a close competitor (i.e. their sibling), the relevance of the task was the determining factor as to whether the processes of reflection and comparison would be utilised. The comparison and reflection processes were indicated for both positive and negative emotional reactions for nontwin and twin adolescents. Unlike Study 1, birth order, zygosity effects and mediating effects of sibling relationship quality were not found. Study 3 involved comparison of nontwin and twin adolescents in terms of self evaluation maintenance within the framework of the SEM model in both the retrospective and experiential context. In this study, closeness was assessed in terms of genetic similarity. Monozygotic twins showed the most positive emotional reactions to performance against their twin than dizygotic twins and siblings in both contexts. For retrospectively recalled situations, siblings, rather than twins, reported the most negative reactions to being outperformed on highly self relevant tasks compared to monozygotic and dizygotic twins. This project found that the SEM model (Tesser, 1988) provided a more valid framework for explaining both twin and nontwin adolescent siblings self evaluation maintenance than a strictly social comparison approach. The results of all three studies were interpreted as being generally consistent with the SEM model. The results contribute new insights into differences in self evaluation maintenance between nontwin and twin adolescent siblings and provide direction for future research into the potential role of birth order, sibling relationship quality and attachment in adolescents self evaluation maintenance.