Doctoral Theses - Restricted Access

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Physicochemical Properties of Red Seaweed (Pyropia spp.) Protein Extracts from Laboratory-scale and Pilot Plant-scale Extractions
(ResearchSpace@Auckland, 2023) Zhang, Bohan; Quek, Siew-Young
Human Determinants of Motor Vehicle Driver Injury in a New Zealand Cohort Study Involving 108 741 Person-Years of Follow-Up
(ResearchSpace@Auckland, 2000) Whitlock, Gary; MacMahon, S; Norton, R
Background Motor vehicle driver injury is a leading cause of injury, disability and premature death in New Zealand, but only limited data are available about the risks associated with several potentially important human determinants of driver injury. Objective The objective of this research was to investigate associations of driver injury with socioeconomic status (as indicated by educational level, occupational status and neighbourhood income), marital status, handedness, body weight and snoring status. Design A cohort study with prospective and retrospective outcomes Participants 10 525 participants were recruited from two sources: a nationwide multiindustry workforce (n = 8008) and a random sample of the Auckland metropolitan electoral rolls (n = 2517). Twenty eight percent of the study participants were females, 10% were Maori, 5% were Pacific Islands people, and 85% were European or other ethnicity. The ages at baseline ranged from 16 to 88 years (mean 44 years). Data Collection and Analysis Driver injury was defined as an injury received while driving a motor vehicle (e.g. a car or motorcycle) and severe enough to cause death or hospitalisation. Outcome data for the period from January 1988 to June 1998 were obtained from the New Zealand Health Information Service. Baseline data on exposures and confounders were collected in 1992-93. Data on educational level, occupation (coded using the International Socioeconomic Index), domicile address (used to identify median neighbourhood income), social marital status, handedness and snoring status were obtained at baseline by questionnaire. Body weight was measured at baseline by research assistants. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportion hazards regression. The HRs reported below were all adjusted for age and gender, except those for body weight, which were adjusted for gender and alcohol intake (there was little evidence of confounding by age). Results 139 driver injury cases were observed during 108 741 person-years of follow-up. Increased relative risks of driver injury were observed among participants in the lowest approximate quartile of occupational status (HR: 4.17; 95% CI: 2.31-7.55), participants who had attended secondary school for two to three years (HR: 2.15; 95% CI: 1.37-3.37) or for less than two years (HR: 2.26; 95% CI: 1.34-3.81), never-married participants (HR: 1.97; 95% CI: 1.29-3.01), participants who weighed less than 70 kilograms (HR: 2.24; 95% CI: 1.34-3.77), and participants who weighed more than 110 kilograms (HR: 2.18; 95% CI: 0.99-4.83). There was little evidence that driver mJury risk was associated with neighbourhood mcome, handedness or snoring status. Conclusions Occupational status, educational level and marital status appear to be determinants of driver injury. Body weight may also be a determinant of driver injury, but further research is required to corroborate or refute this hypothesis. This study did not have sufficient statistical power to exclude the possibility of weak associations with neighbourhood income, handedness or snoring status. The absence of an association with snoring status may have been partly or totally accounted for by misclassification of that variable. These findings identify high-risk groups to which driver injury countermeasures could potentially be targeted.
Writing on the Loose: Reading Florian Illies's Generation golf, Maurice G. Dantec's Périphériques, Joschka Fischer's Mein langer Lauf zu mir selbst, and Frédéric Beigbeder's Windows on the world as examples of creative nonfiction
(ResearchSpace@Auckland, 2010) Kölling, Angela; Associate Professor Mike Hanne; Associate Professor Bernadette Luciano
This thesis brings together four diverse contemporary works, Generation Golf (2000) by Florian Illies, Périphériques (2003) by Maurice G. Dantec, Mein langer Lauf zu mir selbst (1999) by Joschka Fischer, and Windows on the World (2003) by Frédéric Beigbeder; and in so doing it demonstrates that these two German and two French authors combine belletrist endeavours with critical socio-political arguments in a way that corresponds to the literary form which Anglo-American writers refer to as 'creative nonfiction'. In particular, it shows that the authors recognisably share the desire to pull together critical social commentary in nonfiction form with the moral and aesthetic enterprise of the modern novelist. Current scholarship appreciates hybrid forms such as literary journalism, autofiction, nonfiction novels because they raise important formal, ethical and ontological questions. However, while they evaluate the relationship between fact and fiction in contemporary French and German writing of this kind, most scholars separate questions regarding the social merits of a text from its literary ones. This thesis adopts the creative nonfiction approach because it recognises that hybrid forms assume sharp, socio-literary positions. It defines creative nonfiction in the form of seven dynamics, which identify the distinct literary techniques that the authors use as a means to reject the constraints of weary intellectual conventions. Looking at these texts through the pluralist lens of creative nonfiction reveals that they make useful contributions to our understanding of the relationship between nonfiction and culture. Through their factual accuracy, these texts become acute documents of history and, through their literary versatility, they surpass the imaginative constraints of fact - hence this study carries the title 'Writing on the Loose'. Hybrid forms remind us that truth is an elusive concept and creative nonfiction invites us to consider this elusiveness as a valuable resource which allows us to re-imagine ourselves and our social communities.
Maui's sons: a genealogy of return
(ResearchSpace@Auckland, 2009) Kauvaka, Lea Lani K.; Coxon, Eve; Anae, Melani
Since 1996, the United States government has been removing record numbers of immigrants who have been convicted of crimes and misdemeanours. These counterflows of migrants have inspired heated debate and moral panic in several 'third world' regions, including the island region of the Caribbean and the Oceanic states of Tonga and Samoa. An interdisciplinary approach rooted to a genealogical program is needed to understand the ways in which the 'criminal deportee' discourse functions as a trope of the master narrative of 'third world' economic labour migration. In this genealogical program, I have sought to excavate statements surrounding discursive identities such as the the sixteenth century Spanish picaro fiction, the nineteenth century thug of India, and the twentieth century cinematic American gangster and North American thug in order to better understand the discursive textures of criminal subjectivities. This research has been approached through a talanoa (talk story) mode of fieldwork in Tonga and has been woven through a life writing mode of representation - a loom which has particular resonance in the academic development of Pacific Studies as an interdisciplinary, often self-reflexive, scholarship. Through this mode I interweave memory work, film criticism, autobiographical writing, and fragments from conversations which all serve to display a particular perspective of the journeys, exiles and returns involved with late-twentieth century movements of Tongan people. In an effort towards re-articulating this genealogical map with a bid for an Oceanic reading, woven throughout is an invocation of and appeal to the legend of Maui, Oceanic tapu-breaker, trickster and ancestor of the tangata moana (the peoples of the sea). It is a story meant to offer the ha (breath of life) for healing and reintegration of forced return migrants.
Enfance et déracinement: Nathalie Sarraute, Romain Gary
(ResearchSpace@Auckland, 2010) Diver, Ruth Louise; Bayard, Pierre; Ramsay, Raylene L.; Hanne, Michael
Cette thèse examine les enjeux associés au déracinement culturel vécu dans l’enfance et ses effets sur la créativité dans la vie adulte. Elle applique les acquis de la psychologie interculturelle et de domaines rapprochés à l’étude de deux auteurs français d’origine juive russe, Nathalie Sarraute et Romain Gary, dont les liens à leurs cultures d’origine n’ont pas jusqu’à présent fait l’objet d’études approfondies. Notre analyse des traces dans le discours autobiographique et l’oeuvre de fiction de ces deux auteurs de la présence de leurs cultures d’origine, d’accueil et de celles de l’expérience du déracinement révèle des phénomènes analogues : comment les propos autobiographiques deviennent un moyen de positionnement au sein de la culture d’accueil ; comment leur oeuvre de fiction expose une attitude critique commune envers cette culture d’adoption ; comment les facteurs culturels influent sur la réception de leur oeuvre ; comment la réception agit sur le discours autobiographique ; comment la créativité est mise en oeuvre pour interroger les enjeux de l’identité personnelle. Cette thèse montre comment, malgré la rareté des représentations manifestes des cultures d’origine dans leur fiction et leur discours autobiographique, l’influence de la tradition littéraire russe (et de l’humour juif, dans le cas de Gary) est cruciale pour la lecture de leur oeuvre, et pour rendre compte de son caractère innovant dans le champ littéraire français : l’oeuvre de Sarraute peut être perçue comme étant écrite contre Tolstoï et comme prolongeant les explorations des relations humaines de Dostoïevski ; l’oeuvre de Gary montre sa dette envers la culture yiddish et les modèles russes de mystification dans sa création d’Émile Ajar. En outre, cette recherche découvre que certaines différences dans la démarche artistique des deux auteurs sont attribuables à des stratégies identitaires contrastées endossées comme moyen de dissimulation d’une interrogation ou d’un vide identitaire communs, causés par l’expérience traumatisante du déracinement dans l’enfance. Ces stratégies identitaires peuvent se résumer comme silence et anonymat dans le cas de Sarraute, et dissimulation et invention dans le cas de Gary, et peuvent être perçues comme les caractéristiques constantes non seulement des contenus mais aussi de la production de leur oeuvre littéraire. Notre examen de la fiction et du discours autobiographique de ces deux auteurs sur une longue période offre de nouveaux apports au domaine de la psychologie interculturelle : il confirme le caractère traumatisant du déracinement culturel vécu pendant l’enfance et ses effets persistants dans la vie adulte, la complexité des processus d’acculturation, y compris le rôle des relations de groupes, et la difficulté et l’intérêt de la représentation ou de l’expression de tels traumatismes par la créativité littéraire.
Regulation of stem cell development by Runx transcription factors
(ResearchSpace@Auckland, 2009) Lam, Enid Yi Ni; Dr Maria Vega Flores; Prof Kathy Crosier
The origin of haematopoietic stem cells (HSCs) and the relative roles of the yolk sac and the aorta-gonad-mesonephros (AGM) region in the establishment of definitive haematopoiesis are controversial. Definitive HSCs were thought to originate from the AGM, while contribution from the yolk sac was restricted to the primitive blood. However, recent mammalian studies have demonstrated a contribution of yolk sac progenitors to the formation of definitive erythroid and myeloid lineages. This is supported by the recent discovery in zebrafish of erythromyeloid progenitors (EMPs) that arise within the posterior blood island (PBI), before emergence of HSCs in the AGM. The cell type that gives rise to HSCs is also unknown, with possible contributions from a bipotential haemangioblast, the haemogenic endothelium and the mesenchyme. The Runx transcription factors are important regulators of development in a number of organ systems. Runx1 is essential for the development of definitive HSCs and is transcribed from two promoters, P1 and P2, generating two major Runx1 isoforms. To further understand the role of Runx1 in HSC biology and the roles of the two isoforms during the establishment of definitive haematopoiesis, transgenic runx1 promoter reporter zebrafish were generated. The Tg(runx1P1:EGFP) line displays fluorescence in the PBI, where EMPs develop. The Tg(runx1P2:EGFP) line marks definitive HSCs in the AGM that are shown, by lineage tracing, to later populate the pronephros and thymus. Direct tracking of marked cells from the PBI in the runx1P1 transgenic confirms the two definitive blood lineages are distinct. Time-lapse imaging of a compound Tg(runx1P2:EGFP)/ Tg(kdrl:nls-mCherry) embryo expressing the red fluorescent protein mCherry in endothelial cells shows the emergence of HSCs from endothelial cells. This is the first demonstration of the direct generation of definitive HSCs from the haemogenic endothelium in a living embryo. The differential expression and functions of Runx3 isoforms were analysed. Depletion of Runx3P2 delays the entry of primitive erythrocytes into the circulation, and blocks the initiation of definitive haematopoiesis. Runx3P1 is expressed in the gut endoderm of the embryo and may function in regulating the activity of signalling pathways controlling angiogenesis through the Hedgehog and BMP signalling pathways.
The Embedded Faith Journeys of Generations X and Y within New Zealand Church Communities
(ResearchSpace@Auckland, 2008) Johnstone, Carlton Graeme; Dr. Tracey McIntosh; Dr. Martin Sutherland
Generations X and Y have been described as constituting a ‘black hole’ in congregational life. The literature emphasises that generations X and Y are interested in spirituality but not institutional religion. There is now a substantial body of literature arguing that generations X and Y find churches ‘irrelevant’, ‘absent of God’, ‘too rigid’, and ‘laughably out of touch’ with their lives. This thesis argues that generational accounts of religion often fail to make an important distinction between the churched and unchurched in relation to generational distinctiveness. This is a distinction often drawn by sociologists of religion, pointing to two quite different cultures, one communally orientated towards faith communities and the other orientated towards personal freedom and a privatised spiritual quest. Generations X and Y in this thesis refer to a generational unit who share a particular type of faith: owned and embedded within a church community. Employing a methodological approach of in-depth religious life story interviews this thesis is a sociological investigation into the way Christian faith journeys of GenX and GenY are embedded within New Zealand church communities. It is argued that their faith does not make sense outside of this embeddedness. Embedded faith provides a framework for making sense of the participants’ religious biographies. Embedded faith is contrasted to a more privatised understanding of faith and religion popular within sociology of religion. The active dimension of embedded faith is demonstrated through an exploration of modes of engagement with worship and preaching. This thesis builds upon qualitative studies that continue to demonstrate the salience of the collective act of religious involvement and social belonging. One of the challenges of embedded faith however, is finding a church to embed it within. This thesis provides understanding and insight into the relationship between embedded faith and church switching. It explores the way that church switching is an intentional act of disembedding and re-embedding faith and the reasons for this practice.
Torrent of Portyngale: a critical edition
(ResearchSpace@Auckland, 2009) Montgomery, Keith David; Nicholson, Roger
Torrent of Portyngale is a late medieval romance, preserved in a single manuscript, MS Chetham’s 8009. It is a complex mix of romance themes: adventure, loss and restoration, family and social status, piety and hypocrisy, woven around the love between Torrent, the orphaned son of a Portuguese earl, and Desonell, heir to the throne of Portugal. Cohesion to so wide a range of thematic material comes from the author’s careful elucidation of the religious and moral significance of the text’s events. While popular literature with a didactic purpose is not uncommon in medieval literature and elsewhere in romance (cf. Sir Amadace), modern criticism has failed to fully appreciate the purposeful combination of the two in Torrent of Portyngale. Torrent is perhaps the most critically neglected member of the Middle English verse romances. This is, in part, due to the state of the text, which suffers from extensive scribal corruption. The first modern edition, by James Halliwell (1842), was also careless and did little to create a good impression. The poem’s most recent editor, Eric Adam (1887), appreciated the shortcomings of Halliwell’s work and sought to restore Torrent. He incorporated evidence from fragmentary early prints of the text and drew on the fruits of nineteenth–century romance scholarship. Despite his good editorial intentions, however, it is now clear that he also made errors and editorial decisions that have coloured the way in which Torrent has been viewed since. The substantial body of twentieth and twenty–first century scholarship on Middle English romance and medieval studies in general has diminished the value of Adam’s edition to the point where it may be regarded as obsolete and a new edition long overdue. This fresh edition of Torrent has been prepared from microfilm of the manuscript. It re–examines the text’s phonology, morphology, syntax, dialect and vocabulary, to indentify and evaluate overlooked clues to help answer such fundamental questions as its date (scholars have dated it from the mid– fourteenth century to the first half of the fifteenth century) and provenance (it has been mapped from East Anglia to South Lancashire). Both the unflattering reputation that Torrent of Portyngale has gathered in modern times and the long–held notion that it is lacking in originality are challenged by the thorough re–examination of the state of the text, its scribes and their practices and evaluating them against prior and current romance scholarship. This new analysis provides a window through which Torrent can be viewed and valued as a product of its time, allowing it to be judged more accurately against its contemporaries and offering many new insights into a text that was clearly once popular.
Therapeutic potential of neural progenitor cell transplantation in a rat model of Huntington’s Disease
(ResearchSpace@Auckland, 2009) Vazey, Elena Maria; Prof Janusz Lipski; Stephanie Hughes
Huntington’s disease [HD] is a debilitating adult onset inherited neurodegenerative disorder with primary degeneration in the striatum and widespread secondary degeneration throughout the brain. There are currently no clinical treatments to prevent onset, delay progression or replace lost neurons. Striatal cell transplantation strategies under clinical evaluation appear viable and effective for the treatment of HD. However, the future of regenerative medicine lies in developing renewable, expandable multipotent neural cell sources for transplantation. This Thesis has investigated a range of novel developments for enhancing the therapeutic potential of neural progenitor cell transplantation in a quinolinic acid [QA] lesion rat model of HD using two cell sources, adult neural progenitor cells and human embryonic stem cell [hESC] derived neural progenitor cells. Chapter Three identified a novel method for in vitro lithium priming of adult neural progenitor cells which enhances their neurogenic potential at the expense of glial formation. Chapter Four demonstrated that lithium priming of adult neural progenitor cells altered their phenotypic fate in vivo after transplantation, enhancing regional specific differentiation and efferent projection formation. The therapeutic potential of this strategy was demonstrated by accelerated acquisition of motor function benefits in the QA model. Chapter Five then demonstrated the ability for post transplantation environmental enrichment to modify therapeutic functional outcomes in the QA lesion model, and through lithium priming and enrichment demonstrated that adult neural progenitors are amenable to combinatorial interventions which can alter their phenotypic fate and enhance anatomical integration. Chapter Six investigated the in vivo effects of in vitro noggin priming of hESC derived neural progenitor cells and identified enhanced safety and neuronal differentiation in the QA lesioned striatum after noggin priming. Furthermore Chapter Seven provided evidence for functional reconstruction and therapeutic functional benefits from transplantation of noggin primed hESC derived neural progenitor cells and also highlighted the need for systematic evaluations of hESC derived transplants to optimise their safety in vivo. These results are beneficial in demonstrating the realistic therapeutic potential held by these two cell sources. They demonstrate how transient interventions can enhance therapeutic outcomes of neural progenitor cell transplantation for HD and have developed the understanding of neural progenitor cell transplantation as a therapeutic tool, bringing transplantation from different cell sources closer to eventual translation for HD sufferers.
A methodology for business processes identification: developing instruments for an effective enterprise system project
(ResearchSpace@Auckland, 2006) Berkowitz, Zeev
Since the mid 1990s, thousands of companies around the world have implemented Enterprise Systems (ES), which are considered to be the most important development in the corporate use of information technology. By providing computerized support to business processes spanning both the enterprise and the supply chain, these systems have become an indispensable tool utilized by organizations to accomplish and maintain efficient and effective operational performance. However, there are many cases in which ES implementation has failed in terms of the required time and budget, and more importantly, in terms of functionality and performance. One of the main causes of these failures is the misidentification and improper selection of business processes to be implemented into the ES, which are a crucial element of the system's implementation life cycle. In order to achieve effective implementation, a ‘necessary and sufficient’ set of business processes must be designed and implemented. Implementing an excessive set of business processes is costly; yet implementing an insufficient set is ruinous. The heuristic identification of the set of business processes, based on requirement elicitation, is flawed; there is no guarantee that all the necessary processes have been captured (Type I error), and/or that superfluous processes have been selected for implementation (Type II error). The existing implementation methods do not include a methodology to address this vital issue. This thesis aims to resolve this problem and to provide a methodology that will generate a necessary and sufficient set of business processes in a given organization, based on its specific characteristics, which will be used as a baseline for implementing an ES. A proper definition of the business processes and their associated properties is proposed and detailed. The properties are then used as parameters to generate the complete set of all the possible business processes in the organization; from this set, necessary and sufficient processes are selected. The methodology exposes the fundamental level of business processes, which are then used as a baseline for further phases in the implementation process. The proposed methodology has been tested through the analysis of companies that have implemented ES. In each of these cases, the identification of business processes utilizing the proposed methodology has proven to provide superior results to those obtained through all other implemented practices, producing a better approximation of their existing business processes.
Evaluation of an Online English learning program
(ResearchSpace@Auckland, 2009) Ho, Yi-Chieh; Ellis, Rod
Along with the rapid growth of computer technology, the need for CALL evaluation has become increasingly important; however, its implementation remains problematic for a number of reasons including teachers’ lack of experience and adequate skills (Hubbard, 2006), lack of mutually agreed-upon adequate criteria (Hubbard, 2006), and lack of higher-level evaluative skills to evaluate media online (Oosterhof, Conrad, & Ely, 2008). This study describes the classroom-based evaluation of a CALL program. It was undertaken in a Taiwan technological institute, with participants (N = 39) from second-year night-time junior college. The aims were to evaluate the effectiveness of the English Discoveries Online (EDO) program, to identify changes for more effective future use and sound criteria for CALL evaluation. The program’s key features include self-directed courses, self-access out of class, regularly updated materials delivered through the Internet, Web-literacy development, the Teacher Management System, and support tools. Effectiveness was determined by examining self-access learning out of class, motivation, Web-literacy, English proficiency, and the above key features. Both quantitative and qualitative methods were used. The evaluation followed Alderson’s (1992) framework for planning, Weir and Roberts (1994) for design and implementation, and Ellis’ (1997a & b) three types of evaluation for data collection. Instruments included: questionnaires, checklists, an observation record of student behaviors, a monitoring record of the computer screens, reports, individual student records on self-access, and student e-mails sent to the teacher-researcher. The results showed that students considered the EDO helpful for learning English, for enhancing their computer knowledge and English learning interest out of class. There was no significant change in students’ motivation and Web-literacy. There was a significant improvement in students’ pre- and post-test scores in reading and writing. More positive rather than negative comments were given about the key features of the program in students’ reports. Overall, 91% of the class considered the program effective. The findings indicate that this program has a place in English teaching in this Taiwan context. Implications and limitations, as well as lessons learned as a teacher and an evaluator, are discussed.
Neuronal changes in the cerebral cortex of human brain in Huntington’s Disease
(ResearchSpace@Auckland, 2006) Thu, Doris C. V.
Huntington's disease (HD) is characterised by a major loss of neurons mainly in the basal ganglia but recent evidence by Macdonald and Halliday (2002) and others have shown that the cerebral cortex is also affected. In this study, neuronal changes in the primary motor cortex (Brodmann's area 4), primary sensory cortex (Brodmann's area 3), anterior cingulate cortex (Brodmann's area 24) and superior frontal cortex (Brodmann's area 8) were investigated in 16 HD cases and 15 age, sex and postmortem-delay matched normal cases. Immunohistochemical techniques and light microscopy were used to compare the pattern of neuronal loss between the normal and HD cortices. The total neuronal population (NeuN) and pyramidal subpopulation (SMI32) in a subvolume of specific Brodmann's areas were investigated using unbiased stereological counting techniques. The results demonstrated a marked neuronal reduction in these cortical regions in HD compared to normal cases, and this reduction was greater as the "striatal" neuropathological grade increased in the primary motor and primary sensory cortex. However, in the anterior cingulate and superior frontal cortex, marked reduction was also demonstrated in the early grade cases. Despite this, there is also a large variation in the pattern of cell loss between HD cases of the same neuropathological grade, prompting the hypothesis that other factors may be influencing the extent of cell degeneration. To investigate this, the HD cases in this study were grouped into "mainly motor", "mainly mood" and "mixed" symptomatology groups. The results have shown that regardless of their striatal neuropathological grade, the pattern of cell loss in the cerebral cortex is correlated to the various clinical symptomatologies of HD. Another major finding is the demonstration of marked dystrophic changes in the remaining pyramidal neurons in HD cortex, suggesting major ongoing neuronal dysfunction. In addition, cortical interneurons (calbindin, calretinin and parvalbumin) are also shown to be affected in HD. These overall findings, together with the demonstration that there is no statistically significant correlation between the extent of neuronal cell death in the cortex and the CAG expansion number in the HD IT15 gene, show that HD is a heterogeneous disease where the pattern of cell loss in the cerebral cortex is as variable as the pattern of symptomatology. These findings provide a major contribution to the scientific understanding of the pathogenesis of HD in the human brain.
Chemical and microbial transformations of some lanosterol derivatives
(ResearchSpace@Auckland, 1969) Bartley, John Peter; Professor L.H. Briggs; Dr P.S. Rutledge
Attempts have been made to transform lanosterol, by both chemical and microbial means, into compounds of potential pharmacological importance. In part I some compounds with heterocyclic rings (pyrazoles, isoxazoles, and furazans) fused to ring-A have been synthesized by chemical methods. These have been tested for cytotoxic properties against lymphoid leukemia L-1210. The equilibria and n.m.r. spectra of some formyl ketones have also been studied. In part II attempts have been made to oxidize some lanosterol derivatives with microbial cultures in pursuit of synthetically useful intermediates. 3β-Hydroxy-11-keto-4, 4, 14α-trimethyl-5α-chol-8-enic acid methyl ester (35e) has been synthesized from lanosterol and transformed by Trichotecium roseum to a dihydroxy-5α-cholenic acid derivative. Extensive chemical transformations have been carried out on lanosterol to prepare substrates for microbial transformation. In particular a new efficient method for the mild degradation of the lanosterol side chain to a 17β-acetyl group has been developed.
Status epilepticus: mechanisms of generation and associated neuropathology
(ResearchSpace@Auckland, 1996) Young, Deborah; Assoc. Prof. Mike Dragunow
Status epilepticus (SE) is a prolonged and dangerous epileptic condition that can cause brain damage and may be one of the predisposing factors for the subsequent development of temporal lobe epilepsy. In this thesis, I investigate causes of SE as well as the receptors maintaining seizures and the associated neuropathological changes (cell death, sprouting) that occur in SE brain. An unequivocal role for a defect in either excitatory and inhibitory systems in SE generation has not been established. An alternative approach to unravelling the causes of SE may be to investigate whether an impairment of endogenous seizure termination mechanisms, likely to be mediated by adenosine may lead to SE development. The findings that specific A1-adenosine receptor antagonists with a central site of action were able to transform brief electrically-induced seizures into SE, while co-administration of specific A1-adenosine receptor agonists blocked this effect supports this hypothesis. Pertussis toxin-treated animals also developed SE after elicitation of a seizure suggesting inactivation of Gi-protein linked receptors are involved in SE development. Although GABAB and 5HT1A receptors are also coupled to the same subset of anticonvulsant K+ channels as the A1-adenosine receptor, antagonists at these receptors could not transform brief seizures into SE following seizure elicitation, although a GABAB, agonist had anticonvulsant effects. While chemically-induced SE models suggest that glutamatergic and cholinergic mechanisms are involved in SE initiation and maintenance, whether similar receptor mechanisms operate to initiate and maintain electrically-induced SE are unclear. Using specific antagonists of muscarinic and glutamate receptors, I have shown that NMDA receptors and possibly AMPA/kainate receptors are involved in the initiation of electrically-induced SE. AMPA/kainate receptors may be predominantly involved in maintaining SE, although NMDA receptors may sustain seizures in neocortical regions. Muscarinic and metabotropic glutamate receptors do not appear to have a role in initiation and maintenance of electrically-induced SE. Distinct neuropathological features associated with SE including cell loss and morphological changes in the hippocampus were observed. As early as six days after SE, selective damage to hippocampal neurons in the hilus, CA1 and CA3 pyramidal regions and interneurons immunoreactive for parvalbumin and somatostatin were observed after SE in the absence and presence of the A1-adenosine receptor antagonist 8-cyclopentyl-l, 3-dimethylxanthine (8-CPT). Seizure severity generated in the presence of 8-CPT is likely to account for the increased neuronal damage found in this model. Other changes included increases in selected GABAA receptor subunit (α1, α2, β2/β3 and γ2) immunoreactivity in the dentate granule cell and molecular layer of the hippocampus suggesting the possible increased formation of GABAA receptors with the subunit configurations α1,β2,γ2 and α1,β3,γ2. Neuronal injury was also accompanied by reactive gliosis and microglial proliferation and astrocytic expression of the growth factors basic fibroblast growth factor (bFGF) and insulin-like growth factor 1 (IGF-1). Long-term sequelae of SE-induced hippocampal damage such as the appearance of spontaneous seizures in the animals and synaptic reorganisation in the supragranular layer of the dentate gyrus were found 1-2 months after SE. The sprouting response was associated with an increase in brain-derived neurotrophic factor (BDNF) immunoreactivity in dentate granule cells and mossy fibre axons 1 and 2 months after SE. A BDNF and clusterin-immunoreactive band was also present in the supragranular layer at 2 months, suggesting these molecules may be involved in mediating the sprouting response. BDNF immunoreactivity was also present in mossy fibre axons in normal and epileptic human hippocampi but was only present in the inner molecular layer in epileptic tissue. In conclusion, the results in this thesis provide some new insights into possible mechanisms of SE development and associated neuropathological changes, which may be applicable to that found in humans.
Neural progenitor cells in the partial progressive 6-OHDA lesion rat model and the post-mortem human brain in Parkinson’s disease
(ResearchSpace@Auckland, 2007) Aponso, Palingu M.; Faull, Richard; Connor, Bronwen
The demonstration of endogenous progenitor cells in the adult mammalian brain has raised the exciting possibility that progenitor cells could have potential use in cell replacement therapy for neurodegenerative diseases, such as Parkinson’s disease. Previous studies have shown that progenitor cells in the adult mammalian brain undergo proliferation and neurogenesis in response to neuronal cell loss. In this study, immunohistochemical techniques were used to demonstrate progenitor cell proliferation and differentiation in the subventricular zone (SVZ) adjacent to the striatum/caudate nucleus and in the midbrain regions, in response to dopamine (DA) cell death in the substantia nigra, using the partial progressive 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson’s disease and post-mortem human Parkinson’s disease brains. In the rat model, multiple intraperitoneal injections of the mitotic marker bromodeoxyuridine (BrdU) injected at various time points showed, a significant increase in BrdU positive cells in the SVZ, striatum and the midbrain regions of 6-OHDA-treated rats compared to SHAM controls. Further, the newborn cells were shown to produce glial cells in the striatum of 6-OHDA-treated rats. The normal and Parkinson's disease human brains were stained with a proliferative marker, proliferating cell nuclear antigen (PCNA), to label dividing cells. The results demonstrated a significant 2.1-fold increase of PCNA positive cells in the SVZ adjacent to the caudate nucleus when compared to normal brains. Close inspection of individual human brains demonstrated significant asymmetry between the left and the right hemisphere of one Parkinson’s disease brain treated with deep brain stimulation. Further, the presence of migrating neuroblasts and glial cells was also demonstrated in the Parkinson’s disease human brains. The results in this thesis demonstrate progenitor cell proliferation in response to DA cell loss in the experimental rodent brain and the human Parkinson’s disease brain and further, indicate the regenerative potential of the adult mammalian brain in Parkinson’s disease. The findings from this thesis suggest the potential for the development of novel therapeutic approaches in the treatment of neurodegenerative diseases.
Rarotongan society: the creation of tradition
(ResearchSpace@Auckland, 1978) Baddeley, Josephine Gail; Dr A.B. Hooper
This work examines aspects of contemporary Rarotongan society selected to illustrate how Rarotongans structure their reality. This is not a study of social change, but it does show how the vestiges of ideologies from the past have been reinterpreted and incorporated into the contemporary society. To demonstrate how the “traditional” ideologies have survived and co-exist with “modern” ideas, institutions of a pre-European origin, such as adoption practices, Māori medicine and the transmission of chiefly titles, are discussed. Rarotongans may view these and other customary practices according to several criteria from which they choose the one which is most appropriate to their purposes on any particular occasion. It is shown that Rarotongans are in the process of creating a cultural tradition which incorporates elements from their traditional past and European influences which are being transformed into something that is perceived as essentially Rarotongan.
Hubert Parry and Cyril Scott : two post-Victorian songwriters: with an introductory essay on the musical problems of Great Britain in the nineteenth century
(ResearchSpace@Auckland, 1975) Dart, William
The following study is an attempt to assess the state of song composition in England in the period between the nineteenth century and our own twentieth century. Generally speaking it was a time of increasing musical activity – the second English musical Renaissance, as Frank Howes has termed it. Although England failed to produce a vocal composer of a status equal to the giants of Continental Europe, nevertheless the most gifted indigenous composers were by no means insignificant musical talents. The failings of many were the failings of the period in general, for the Victorian mores tended to impose severe limitations on the work of both domestic and visiting composers. The nineteenth century was a highly productive period – the age of the three-volume novel and the oratorio – and this productivity extended likewise to the field of song composition. The purpose of this study, therefore, is to examine the manner in which composers responded to the limitations imposed by the Victorian Age and reacted against in the period immediately after it, and to this effect the solo songs of two composers will be examined in detail: namely, those of Charles Hubert Hastings Parry (1848-1918) and Cyril Meir Scott (1879-1970). In view of the importance of the musico-sociological background to this survey, the study will commence with an examination of-contemporary attitudes in Victorian Britain to art in general.
Daz sint noch ungelogeniu wort: a literary and linguistic commentary on the Gurnemanz episode in Book iii of Wolfram’s Parzival (161,9-179,12)
(ResearchSpace@Auckland, 1997) Gilmour, Simon Julian; Professor Kathryn Smits
The present work is a detailed study of the Gurnemanz Episode in Wolfram von Eschenbach’s Parzival. Its main body encompasses a commentary on the Gurnemanz episode of Wolfram’s work. The intention of the commentary is o provide exact and comprehensive information and discussion on aspects of the text that could cause the reader difficulty, or to enhance his/ her appreciation of the text and the context in which it had its genesis. The commentary follows the principle of analysing from large to small. The largest section encompasses a chapter of the thesis, the smallest an individual word. Each of the five chapters is introduced by a literary interpretation which encompasses, among other aspects such as themes, motifs, plot and character development, structure, and a comparison between Wolfram’s text and that of his source, Chrétien de Troyes’s Perceval. Then a closer examination of smaller units of the text takes place. This includes principally the analysis of Wolfram's use of language and his style. The commentary is introduced by a discussion of the commentary form and the theoretical basis which this work follows, and concluded by a short evaluation. All important secondary literature which appeared before 1997 and was available to the author has been considered for this work. Furthermore, this thesis is appended with an article in German that deals with the possibility of reading Parzival 652,10 and 173,3 with the less favoured MS G readings. This article bears the fruit of the discussion needed to comment on the MS G reading at 173,3, and is soon to be published in the periodical Euphorion. A fold-out copy of the Parzival text for each chapter is found inside the back cover.
GABAA receptors in the basal ganglia of the rat, baboon and the human brain
(ResearchSpace@Auckland, 2000) Waldvogel, Henry J.; Professor Richard Faull; Dr. Louise Nicholson
The regional, cellular and subcellular distribution of GABAA receptors was investigated in the striatum and globus pallidus of the rat, baboon and human brain using receptor autoradiography, and multiple immunohistochemical labelling techniques at the light, confocal and electron microscopic levels using antibodies to the α1, α2, α3, β2,3 and γ2-subunits of the GABAA receptor complex. The results demonstrated that GABAA receptors in the striatum showed considerable subunit heterogeneity in their regional (primate brain) and cellular distribution (rodent and primate brain). At the regional level in the baboon and human brain, GABAA receptors in the striosome compartment contained the α2, α3, β2,3 and γ2-subunits while receptors in the matrix compartment contained the α1, α2, α3, β2,3 and γ2-subunits In general terms in both the rodent and the primate brain, up to six different types of neurons were identified in the striatum. There was considerable species diversity in the cell types. Two main types of neurons (type 1 and type 2) immunoreactive for the subunits α1,β2,3,γ2 were identified in the striatum. They were GAD positive and were classified according to their cellular morphology and staining properties; rat type 1 neurons were GAD positive only, while human type 1 neurons were GAD and parvalbumin positive. Type 2 neurons were identified in both the rat (GAD positive only) and in human (GAD and calretinin positive). All three mammalian species showed the presence of type 3 neurons which were large neurons with few spines and immunoreactive for subunits α1,3,β2,3,γ2. Type 4 neurons were calbindin positive and immunoreactive for subunits α2,3,β2,3,γ2. The remaining neurons were immunoreactive for ChAT and the α3-subunit (type 5), or immunoreactive for neuropeptide Y with no GABAA receptor subunit immunoreactivity (type 6). The globus pallidus contained three types of neurons; type 1 neurons contained parvalbumin and type 2 contained parvalbumin and calretinin and both were immunoreactive for subunits α1,β2,3, γ2 while type 3 neurons were medium-sized calretinin neurons immunoreactive for the subunits α1,β2,3,γ2 At the ultrastructural level in the globus pallidus, α1 and β2,3-subunits were localised on large neurons (types 1 and 2) and were found at three types of synaptic terminals. These results show that the subunit composition of GABAA receptors displays considerable regional and cellular variation in the striatum, but is more homogeneous in the globus pallidus.
Candidate genes in rheumatoid arthritis
(ResearchSpace@Auckland, 2003) Pokorny, Ljubica Violetta; Dr Lachy Mclean; Associate Professor Fiona McQueen
Rheumatoid arthritis (RA) is a systemic inflammatory disease with autoimmune features and primarily manifests in the synovial joints. There is a prominent genetic component. We investigated candidate polymorphisms in the genes encoding several molecules implicated in RA: HLA-DRB1, CCR5, CTLA-4, IFN-γ, TNFα, MBL, TGFβ1, and TcRBV14SI. The Caucasian and Maori and Polynesian study populations were derived from 563 unrelated RA patients and 1022 healthy controls from New Zealand (NZ), providing good statistical power for association genetic analysis. 126 of the patients were from a prospective early RA (ERA) cohort with detailed assessment, and including 42 examined with magnetic resonance imaging of the dominant wrist. HLA-DRB1 typing by exon 2 DNA sequencing confirmed the relationship between the ‘shared epitope’ (codons 70 - 74 QKRAA, QRRAA, or RRRAA) and disease severity in Caucasians in the early RA cohort (OR for erosions at 2 years 6.41, 95% CI 2.96 - 13.84, p < 0.0001) but this was not seen in Maori and Polynesian ERA patients. A low-resolution study of the larger cohort (563 RA, 1022 healthy controls) confirmed the HLA-DR4 association (OR 4.3, 95% CI 3.34 - 5.40, p < 0.0001), validating the collections. We found a significant protective effect of the common non-functional CCR5 ∆32 variant on RA prevalence (RA heterozygotes 17%, healthy controls 11%, p = 0.007; no ∆32 homozygote patients detected), but with CCR5 (and the other non-HLA genes examined) there was no impact on RA severity. The HUMCTLA-4A position +49 G allele (associated with reduced CTLA-4 down-regulatory function on T-cells) was assessed by PCR-RFLP and was significantly higher in RA patients than in controls (p = 0.0003), consistent with a genetic contribution from impaired T-cell immunoregulation. An association between the VNDR microsatellite in intron A of the gene for pro-inflammatory IFN-γ (HUMIFNG) and RA was noted (124 bp (CA)12 allele frequencies RA 0.49 and healthy controls 0.40, p < 0.0001, p (corr.) < 0.0005; 126 bp 0.41 and 0.46, p = 0.009, p (corr.) = 0.04; 128bp 0.05 and 0.09, p = 0.0005, p (corr) = 0.002, although a reported strong effect of the 126 bp (CA)13 on RA severity could not be confirmed. Comparison of the TNFa variable number dinucleotide repeat (VNDR) microsatellite polymorphism allele length frequencies showed a strong negative association with TNFa7 (p < 0.0001, p corrected (corr.) < 0.001 and TNFa12 (p = 0.0007, p (corr.) = 0.009). An interaction between TNFa6 and DRB1*04 was noted, but this relationship is complicated by the strong linkage between the TNFA and DRB1 loci. A reported association between a non-conservative single nucleotide polymorphism (SNP) of the mannose binding lectin gene HSMBPCA1 (MBL 54B) and RA was examined by SSP-PCR, but this was not confirmed (RA allele frequency 11%, healthy controls 10%; p = 0.70). Similarly, an association between the TGFβ1 (HSTGFβ1) cytokine gene (T/C at +869; Leu→Pro substitution in codon 10) was not confirmed when the NZ samples were examined using PCR-RFLP. Based on previous reports of elevated T cell receptor BV14SI (Vβ14) transcript levels in RA, we undertook sequence-based mutation screening of the TcRBV14SI gene and found two novel SNP's in non-coding regions. Although one (G3’137A) was present in 6 of 17 RA but none of 12 healthy controls initially sequenced, by using PCR-RFLP on larger samples no difference was shown. In summary, we found genetic association evidence supporting a role in RA for HLA-DRB1, CCR5, CTLA-4, IFN-γ and TNFα. It is likely that other genes contribute, with individually weak effects that require study with large samples. The lack of association for the SNP’s in MBL, TGFβ1 and TcRBV14SI does not rule out their role in RA. The genetics of RA are as complex as the disease itself.

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