429 results for Undergraduate

  • Inside New Zealand's little black box

    Turner, Jane (2003-10)

    Undergraduate thesis
    University of Otago

    The purpose of this study is to investigate the relative strengths of the channels through which monetary policy impacts upon the real sector in New Zealand. The three main channels that have been identified in the literature are the money channel, the exchange rate channel and the credit channel. A vector autoregresion (VAR) is employed and estimates the model over the period 1988 to 2002. The impulse response functions show that the movements in the exchange rate and money occur before the decline in output and prices. However the movements in credit are synchronised with the movements in output. Variance Decomposition reveals that in the short run the money channel and the credit channel is the most significant transmission vehicle. Moreover the money channel has a relatively stronger effect than the credit channel on the prices. However after one year the exchange rate channel is the dominant transmission channel to prices and output.

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  • Future auditors’ propensity to blow the whistle: an investigation of auditing students’ propensity to blow the whistle when faced with an ethical dilemma

    Newdick, Chris R E (2006)

    Undergraduate thesis
    University of Otago

    This dissertation examines the relationship between an individual’s level of moral reasoning, retaliation to whistle blowing, and their propensity to blow the whistle when faced with an ethical dilemma. To test this relationship 56 auditing students from Otago University were sampled using two versions of hypothetical whistle blowing scenarios and Welton, LaGrone and Davis (1994) moral reasoning instrument. The relationship between an individual’s level of moral reasoning and their propensity to blow the whistle was first examined. Retaliation was then implemented as a moderating variable. The result showed that a significant positive relationship existed between an individual’s moral reasoning level and propensity to blow. In addition to this, the results showed that retaliation was not acting as a moderating variable but as an independent variable. Furthermore, analysis showed that retaliation explained more of the variance in an individual’s propensity to blow the whistle than moral reasoning. Lastly, the results showed that regardless of an individual’s level of moral reasoning, if the strength of the retaliation was too strong then this prevented an individual from blowing the whistle. This finding is some what different to that of other studies as it showed that an individual level of moral reasoning may not play such as important role as the literature suggest. The implications for this finding are discussed in detail.

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  • Analysis of spatial distortions in a mental map using GPS and GIS

    Peake, Simon A J (2004-11-12)

    Undergraduate thesis
    University of Otago

    Mental maps are a cartographic illustration of a person's internal representation of the spatial environment in which they live. They are often used to provide an insight into how different ethnic or social groups perceive their environment. A new method of measuring the distortions present in mental maps is developed and tested in this present project. A subject's true spatial environment is generated through the use of a global positioning system and compared with the subject's mental representation of their environment. The distortions of the mental maps are calculated by minimising the mental maps to a finite set of nodes and the difference between the mental map and the true spatial environment is calculated. A geographic information system is used to process and analyse the data. Results suggest distortions are apparent the further away subjects travel from their familiar environment, such as the immediate vicinity of their home. The data also indicates that there is an inherent scale at which mental maps operate.

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  • Disaster recovery planning: A New Zealand perspective

    Fitzsimons, Matthew (2004-11-12)

    Undergraduate thesis
    University of Otago

    Disaster recovery planning is a cyclic process which has the goal of maintaining the availability of the information infrastructure, even in the event of a disaster. It is well documented that disaster recovery planning is important for organisations. It is, however, unclear if the business community is aware of this. As a result there is limited information on the acceptance of disaster recovery planning outside of the academic opinion, and even less within the New Zealand business community. This study attempts to remedy that, as it seeks to describe the state and opinions of disaster recovery planning within New Zealand. The study takes the form of a descriptive questionnaire which was delivered to 750 organisations, both privately owned companies and government departments were surveyed. The survey questioned organisations on three main categories pertaining to disaster recovery planning: cost of downtime, perceived importance of disaster recovery planning, and the state of disaster recovery planning within the organisation. It was found that New Zealand companies are better prepared than their American counterparts, with 75% of respondents having a disaster recovery plan. It was found that within New Zealand the perceived importance of disaster recovery planning is very high, this bodes well for the countries disaster preparedness.

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  • Reinstatement as a remedy for unjustified dismissal

    Mogensen, Patti-Jo (2000)

    Undergraduate thesis
    University of Otago

    This study sets out to determine the factors associated with the decision by those who have been dismissed unjustly, to seek or not to seek reinstatement as a remedy. This paper explores the factors that are said to influence a grievants decision that is the influence of the size of the workforce, length of time since dismissal, trust in the employer, the expected level of tension in the workplace, the anticipated reactions of fellow employees, the immediate and or other supervisors as factors, and there influence on the decision to seek reinstatement. This paper also looks at the legislation, case law and scholarly literature as explanations to this research question. The results show that while the variables above are considered as factors it seems that the overriding consideration is the desire for the employee seeking reinstatement to consider the factors above, but to remain in employment often regardless of the hostility or resentment felt by those within the organisation towards the grievant.

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  • The impact of the business case for sustainable development upon New Zealand organisations

    Simpson, Rebecca (2005-10-17)

    Undergraduate thesis
    University of Otago

    Corporate social disclosure is the provision of information regarding the impact of an organisation upon the natural environment and society. There is no consensus in the literature as to why some organisations voluntarily provide this information although one explanation for this may be the business case for sustainable development (BCSD). The impact of the BCSD upon New Zealand organisations was assessed by comparing their corporate social disclosure and profitability over a four year period with organisations that do not adopt the BCSD. The impact of legitimacy and stakeholder theories upon the BCSD and the disclosure of organisations was also considered. An assessment was also made regarding the compliance of those adopting the BCSD with social and environmental legislation. The findings suggest that there is no difference, with regard to corporate social disclosure and profitability, between organisations who adopt the BCSD and those who do not. The disclosures made by the sample were also found, in some instances, to be consistent with the explanations of corporate social disclosure put forward by legitimacy and stakeholder theories. Furthermore, some organisations who have adopted the BCSD were found to have acted inconsistently with its philosophy by breaching employee-related legislation and making no disclosure of this. It appears that the BCSD has not been fully integrated into the activities of those who profess to adopt it. It is believed that until organisations take this step, their behaviour and disclosure of social and environmental information is unlikely to be improved.

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  • The Balassa-Samuelson model in Asia

    Thomas, Alastair G A (2001-10)

    Undergraduate thesis
    University of Otago

    Two problems have occurred in the recent literature with regard to the empirical testing of the Balassa-Samuelson productivity based explanation of deviations from Purchasing Power Parity. First, empirical work has commonly focused only on the overall prediction of the model, instead of the underlying mechanisms. Second, the countries examined have, in almost all cases, been inappropriate given the underlying theory. This study focuses on two papers that combat these problems. Their approaches are combined and extended to construct a more logical and thorough procedure for testing the Balassa-Samuelson model. Cointegration analysis is used in a three-stage testing procedure examining eight Asian Countries relative to the United States. First, the validity of Purchasing Power Parity is tested, then the general prediction of the Balassa-Samuelson model, and finally the underlying mechanism of the model is tested. Support is found for the general prediction of the model, however in contrast to other recent studies no support is found for the underlying mechanism. This suggests two things: the theorised mechanism is not the true causative factor, and the general relationship tested here, and in several prior studies, is in fact misspecified. This relationship was consequently re-specified, the result being that less support was now found for the overall prediction.

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  • Which incentives deter crooks? An empirical investigation into the determinants of selected New Zealand crimes

    Trendle, Deborah (2003-10)

    Undergraduate thesis
    University of Otago

    This study investigates the possible determinants of selected reported crimes in New Zealand from 1962 to 2001. Using annual time series data, six offence groups are individually examined, namely homicide, drugs (cannabis), drugs (not cannabis), sex attacks, robbery and burglary. Previous literature indicates that several factors can influence the levels of crime in a nation. They are referred to generally as deterrence, economic, social and demographic factors. A stepwise backward elimination approach (using Multiple Regression Analysis) and General-to-Specific modelling approach (using PcGets) are applied to the general model, which includes a range of potential determinants. Additionally, models are estimated using two-stage least squares, to control for any simultaneity bias between crime and the explanatory variables. The results suggest that the four groups of factors referred to also provide the main determinants of crime in New Zealand. In particular, the previous year's crime rate, the conviction rate and severity of punishment, the proportion of total births that are ex-nuptial, and the proportion of youth in the population have a significant influence across a majority of the crimes investigated. However, wage, unemployment, divorce and social welfare payments also have a significant effect on some of the offence groups examined in this study.

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  • The relationship between perceived environmental uncertainty, organizational structure, leadership style and the balanced scorecard

    Zhao, Tianping Rose (2006)

    Undergraduate thesis
    University of Otago

    The primary intent of this dissertation is to provide some suggestions on what type of organizations suit better with the concept of balanced scorecards (BSC hereafter) than others in the New Zealand firm environment. To accomplish this attempt, a contingency approach, which takes into account the perceived environmental uncertainty, organizational structure, and leadership styles, is advocated. In this dissertation, several hypotheses are offered concerning the relationship between perceived environmental uncertainty, organizational structure and the BSC usage. Further, the relationship between leadership style and the BSC is also assessed. A questionnaire is distributed to a group of CFOs of selected New Zealand-owned companies in order to examine these proposed hypotheses. The results of this study suggest no significant relationship between perceived environmental uncertainty (PEU) and organizational structure. The statistics indicate that the BSC usages are not dependent on the internal corporate structure. Even though the last hypothesis is not supported due to the lack of clear presence of transformational and transactional leadership styles, the results of post hoc testing have captured a significant relationship between leadership and the BSC usages, suggesting that organizations with strong leaders tend to implement more advanced BSC. Despite several limitations, this study suggests practicing managers to consider their leadership before the BSC implementation. Further, future research is suggested to better understand the usage of the BSC in New Zealand companies.

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  • The audit expectation gap in New Zealand

    Robinson, Lisa A (2007)

    Undergraduate thesis
    University of Otago

    As a socially-embedded service provider, it is essential that the users of audit services, as well as the wider public, have confidence in the audit profession. The confidence appears to be eroding, with a gap appearing between user expectations and the services provided. This has been termed the ‘audit expectation gap’ (the ‘gap’). This study seeks to update the literature as to the gap’s existence in New Zealand, and explore the possibility of education of users helping to reduce the gap. Samples of auditors and directors throughout New Zealand were surveyed as to what duties they believe are currently included within the audit function, and what duties should be included in the audit function. The director sample were also surveyed as to whether they had any audit- or accounting-related education, or experience. Responses were analysed using non-parametric tests; specifically, chi-square cross tabulation tests. Results indicated that there are expectation gaps in the New Zealand environment, as per prior literature. Formal education of users also appears the be a potential tool for reducing the gap, as no significant differences were found between the responses of directors who have had some relevant education and those of auditors. Evidence was also found suggesting life education (or experience) may have potential as a tool for reducing the gap. This study provides a good starting point for further studies of the expectation gap in New Zealand, as well as the potential of both life and formal education as a tool to help mitigate the gap’s existence.

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  • Explaining relative labour market outcomes for Maori and non-Maori

    Sutherland, Hilary J (2001-10)

    Undergraduate thesis
    University of Otago

    This study investigates the level of discrimination between non-Maori and Maori in the New Zealand labour force. Multinomial logit techniques and wage regression analysis are combined so as to decompose the wage differential into components explained by differences in productivity characteristics, job discrimination and wage discrimination. Evidence of both job discrimination and wage discrimination is found. Small sample sizes meant that part-Maori data could not be utilised. The lack of data also impacted on the reliability of the results from the Maori wage regressions. Therefore, the major policy implication from this paper is that more extensive and detailed sampling of minority ethnic groups be carried out so that informative and accurate analysis of labour market disparities can be obtained,

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  • The Role of Dendritic Cell Subsets in the Early Immune Response to Mycobacterial Infection

    Manners, Kate Meredith (2014)

    Undergraduate thesis
    University of Otago

    The early immune response to tuberculosis (TB) is poorly understood. However, recent evidence has shown that dendritic cells (DC) are important for both control of bacterial growth and for activating adaptive immunity. DC are divided into functionally and phenotypically distinct subsets, but the role of each of these subsets in the early immune response to tuberculosis remains unknown. This study aimed to investigate the roles of DC subsets in a murine model of mycobacterial infection. Use of a fluorescent strain of the attenuated TB vaccine strain Mycobacterium bovis BCG, combined with multicolour flow cytometry, enabled detection of BCG associated DC subsets within the murine lung during the first 14 days of infection. The early immune response to mycobacterial infection was found to be highly dynamic, with significant variation in the proportion of BCG associated cells in each DC subset of the lung during infection. CD11b+ conventional DC (cDC) and plasmacytoid DC (pDC) were found to be associated with BCG during the first 14 days of infection, whereas CD103+ cDC were not. Differential expression of the cell surface markers GR-1, CD11b and CD11c detected within previously described DC subsets correlated with their propensity to associate with BCG. Conventional DC and pDC were found to respond differently to mycobacterial infection; cDC upregulated expression of CD86 during infection whereas pDC were found to do the opposite, suggesting that these subsets have distinct roles during early infection. Importantly, and contrary to current dogma, alveolar macrophages were not found to associate with BCG during early infection. This study highlights the distinct roles of different DC subsets during mycobacterial infection. This research may have implications for the development of a novel vaccine or therapy for tuberculosis, for which there is a significant need.

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  • Involvement of mitochondria and peroxiredoxin in TNF-mediated necroptosis

    Zawari, Masuma (2014)

    Undergraduate thesis
    University of Otago

    Necroptosis is a form of regulated necrosis considered to be involved in several pathophysiological conditions such as inflammation and ischaemia-reperfusion injury. The cellular events involved in the initiation of necroptosis are unclear, but recent studies indicate that the pseudokinase mixed lineage kinase domain like (MLKL) plays an important role. Understanding the molecular mechanisms regulating necroptosis is therefore an important priority that may lead to the development of new therapies. Mitochondria and reactive oxygen species generation has been reported in necroptosis, however it is not clear whether these play a direct role in the death process. These changes were investigated in a TNF-dependent model of necroptosis using mouse dermal fibroblasts (MDF) from wild-type and MLKL knock-out animals. Viability analysis by FACS and live cell imaging indicated early signs of cell death by 60 min and by three hours about half of the population were executed by necroptosis in an MLKL dependent manner. TMRE labelled cells showed a loss of mitochondrial membrane potential before cell death. Rapid increase in oxygen consumption 30 min after the injection of TNF indicated a direct link between the necrosome and downstream signalling to mitochondria for efficient necroptosis to occur. This is the first report of MLKL dependant effects on mitochondrial function. Western blot analysis indicated a rapid accumulation of oxidized mitochondrial peroxiredoxin in an MLKL dependent manner. Timing of mitochondrial changes and oxidation of peroxiredoxin suggest they may be early markers or even executors of cell death rather than a consequence of cellular damage. However further investigation is required to determine the importance of these changes in cell death.

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  • The effect of fetal exposure to androgen treatment on steroid receptors in the developing sheep ovary

    Vasilic, Mina (2013)

    Undergraduate thesis
    University of Otago

    Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility affecting more than 100 million women worldwide, yet its etiology remains unclear. Fetal exposure to elevated androgen levels has, however, become increasingly implicated in the development of the syndrome. It is hypothesized that increased exposure to androgens during fetal development affects the steroid receptors in the ovary. The aim of this study was to use a sheep model to determine the effect testosterone treatment to pregnant ewes has on the steroid receptors, ERα, ERβ and AR in the fetal ovary. Control and testosterone treated ovarian samples were collected at 90 days of gestation. Ovarian sections were examined histologically to determine the cell types and tissue organization at this stage of development and to observe if this was affected by testosterone treatment. Immunohistochemical staining was used for the protein localization of each steroid receptor. A radioactive in situ hybridisation (ISH) was undertaken to determine the localization of the mRNA transcripts. A quantitative analysis of the mRNA expression levels of each receptor was done using real-time quantitative PCT (qRT-PCR) (utilizing the fluorogenic dye, SYBR green). The histological organization of ovaries in this study was similar to previous descriptions that have investigated fetal ovarian histology in sheep. The day 90 ovary contained ovigerous cords with well-pronounced cell types both within and outside the cords. No differences in histology were observed between the control and testosterone treated ovaries. Immunohistochemistry (IHC) provided visualization of clear nuclear staining for each receptor. The staining was predominately observed in the ovarian cortex, specifically within the cells of the ovigerous cords. No observable were seen differences in the patterns of protein expression between control and testosterone treated ovaries, nor were differences in the intensities of staining apparent. This was consistent with all three steroid receptors (ERα, ERβ and AR). In situ hybridization provided evidence for the presence of mRNA transcripts of all three steroid receptors within the ovarian tissue but this method did not have the resolution to define specific cell expression. These findings were similar in both control and testosterone treated ovaries. High quality RNA was isolated from the ovaries and statistical analysis of the results obtained from the qRT-PCR provided evidence that there were no differences in mRNA expression levels of the receptors in control and testosterone treated ovaries. The results in the current study provided evidence that testosterone treatment does not effect the distribution or expression of the steroid receptors ER?, ER? and AR in fetal ovaries and thus does not support the hypothesis. This study provided further insight into the potential function of these steroid receptors in ovarian development. Specifically this highlighted their importance in the development of pre-granulosa cells from the ovarian surface epithelial cells, oogonia and their subsequent association to form primordial follicles.

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  • An in vivo investigation into the morphology of whole GnRH neurons

    Neill, Angus (2013)

    Undergraduate thesis
    University of Otago

    The ability to pass on genetic information through reproduction represents nature’s basic element of existence. Central to the control of reproduction is gonadotropin-releasing hormone (GnRH), a neuropeptide synthesized and released from GnRH neurons in the mammalian hypothalamus. Our understanding of these neurons has traditionally been limited to examination of the cell body and very proximal dendrite. However, recent technological advances have revealed that GnRH neurons possess extensive dendrites with numerous morphological features that aid in our understanding of their physiology. Despite this, current research has been limited to in vitro brain slice preparations that do not always encompass the entire extent of GnRH neurons and limit our ability to investigate specific in vivo physiological time points. In light of this, the first aim of the present study was to image the morphology of whole GnRH neurons in optically cleared, adenoviral injected mouse brains. We optimized a technical approach for studying GnRH neurons that combines in vivo cell-filling of GnRH neurons with optical tissue clearing and long working distance confocal microscopy. This novel approach utilized adenoviral vector-mediated expression of farnesylated enhanced green fluorescent protein (Ad-iZ/EGFPf) to “fill” whole GnRH neurons in vivo via a cranial injection. Following Ad-iZ/EGFPf injection, perfusion fixed mouse brains were made transparent by immersion in Scaleview-A2, a chemical solution that reduces the light absorbance of tissue, enabling imaging of deeper structures in thick tissue samples. Tissue absorbance was reduced from an average of 2.060 ± 0.09au in uncleared samples to 0.4914 ± 0.08au in Scaleview-A2 treated samples, at a wavelength of 490nm. In addition, we found injections of Ad-iZ/EGFPf to the rostral pre-optic area resulted in the expression of EGFPf along the entire cell membrane of a small population of GnRH neurons. After brains had been cleared for 14 days, long working distance confocal microscopy enabled visualisation of somal, dendritic and axonal compartments of GnRH neurons that could be traced on a millimetre scale, a feat that has challenged scientists in recent years. We were also able to identify microscopic features of GnRH neurons at a depth of >400μm through the brain tissue. The second objective of this study was to investigate the changes in GnRH neuron morphology associated with neuronal activation at the pre-ovulatory surge, a physiologically critical time point in females. The compatibility of chemical clearing with immunohistochemistry was confirmed with staining for c-Fos, a marker of neuronal activation. The LH plasma concentration from estradiol benzoate treated (n=5) and vehicle treated animals (n=5) was analysed to confirm the induction of the pre-ovulatory surge, before 1.5mm thick sagittal sections were immunostained for c-Fos. Tissue samples displayed c-Fos staining to an average depth of 130μm, however, some filled GnRH neurons were found at 400μm. Consequently no c-Fos positive GnRH neurons were identified meaning they could not be explicitly categorized as either activated or non-activated. Despite our inability to investigate changes in morphological features of GnRH neurons at this time point, unique features of the GnRH neurons identified with this novel technique were explored. Overall, the establishment of in vivo cell-filling in large volume tissue samples, and the subsequent ability to visualise and image entire GnRH neurons represents a great leap in GnRH research, taking us beyond the soma and proximal dendrite, and beyond in vitro brain slice preparations.

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  • The effect of riboceine on lipoprotein(a)

    Kader, Tanjina (2013)

    Undergraduate thesis
    University of Otago

    Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Atherosclerosis is characterized by the progressive formation of lipid plaques within blood vessel walls which eventually occlude the vessel lumen and block blood flow. Elevated concentrations of lipoprotein(a) [Lp(a)] are an independent risk factor for developing atherosclerosis and CVD. Lp(a) consists of a low-density lipoprotein like particle that is covalently linked to a unique glycoprotein apolipoprotein(a). Lp(a) possesses both atherogenic and thrombogenic properties. Lp(a) accumulates oxidised phospholipids (OxPL) from cell membranes of other lipoproteins and promotes lipid deposition and inflammation in the artery. Unfortunately, to date, there is no effective therapy available to lower Lp(a) or reduce these atherogenic properties of Lp(a). Riboceine is a cysteine analogue designed to increase synthesis of the antioxidant glutathione (GSH) by releasing L-cysteine, the precursor of GSH synthesis. This project aims to evaluate the potential of riboceine as a novel therapy to lower Lp(a) and increase GSH synthesis. As GSH is an essential cofactor for the reduction of OxPL, it may also reduce the OxPL content of Lp(a); thereby reduce atherogenicity of Lp(a). As OxPL are involved in the regulation of cholesterol levels, riboceine may also alter plasma cholesterol levels. This study showed that riboceine is not an ideal intervention for lowering Lp(a) levels as it reduces Lp(a) formation only by 15-20% and only at very high concentrations. Riboceine was shown to have no effect on already formed Lp(a). Riboceine showed a trend of increase in both plasma and liver GSH levels in vivo, indicating that riboceine may act as a promising therapeutic to increase GSH levels. Moreover, riboceine showed a trend of decrease in total plasma cholesterol levels in vivo. These results suggest that riboceine may increase GSH levels which could alter Lp(a) atherogenicity as well as reduce cholesterol levels, thus lowering the risk of atherosclerosis and heart disease. Future studies will require an increased sample size for both GSH and cholesterol studies in vivo. In addition, it will be required to measure cell membrane and Lp(a) OxPL content to confirm our hypothesis.

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  • CT Investigation of Thoracic Intervertebral Disc Morphometry

    Fletcher, Justin Geoffrey Revell (2013)

    Undergraduate thesis
    University of Otago

    Background: Despite being prone to degenerative disease and other pathology, relatively little is known of the morphology and morphometry of thoracic intervertebral discs in comparison to discs in the cervical and lumbar spines. The few studies of thoracic intervertebral disc morphometry that have been performed have included relatively small numbers of cadavers. No previous studies have attempted to investigate how thoracic intervertebral disc morphometry varies with sex and age. Aims: This study aimed to describe the normal morphometry of adult thoracic intervertebral discs in subjects with no known spinal disease and investigate potential associations with sex, disc level and age. Methods: Computed tomography (CT) scans on 128 recently deceased unembalmed cadavers (70 males, 58 females, aged 20-79 years, divided into 10-year age cohorts) with no known spinal pathology were obtained from the archives of the Victorian Institute of Forensic Medicine, Australia. Intervertebral disc height, anteroposterior and transverse disc dimensions, wedge-index and other morphometric parameters were measured at alternate intervertebral discs throughout the thoracic spine, beginning at T2-3. Data were analysed to determine associations between intervertebral disc parameters and sex, disc level and age (10-year age groups). Linear mixed models were fitted to anterior and posterior disc height and anteroposterior and transverse disc dimensions. Intra- and inter-rater variation were assessed by intraclass correlation coefficients (ICCs) performed on 25% and 18% of the whole sample, respectively. Measurement reliability was further assessed by investigating agreement between radiographic and equivalent measures performed directly on two cadaver thoracic spine specimens. Results: Intervertebral disc heights and axial dimensions were all significantly larger in males than females except middle disc height (anterior disc height 4.0 ± 1.4mm vs 3.6 ± 1.3mm; posterior disc height 3.6 ± 0.90 vs 3.4 ± 0.93, both p<0.05). Discs in the upper and lower thoracic spine were significantly more wedge-shaped and displayed greater convexity than those in the mid-thoracic spine (T6-7). Except at T2-3, anterior disc height decreased with advancing age while anteroposterior and transverse disc dimensions increased; posterior and middle disc heights and indices of disc shape showed no consistent statistically significant change. Most measured parameters showed substantial to almost perfect agreement for both intra-rater and inter-rater reliability while cadaver validation showed fair to almost perfect agreement between radiographic and anatomic measures. Conclusions: Thoracic intervertebral disc morphometry varies significantly and consistently with sex, disc level and age. This study provides unique data on normal thoracic intervertebral disc morphometry of adults, which should be useful in the detection of pathological changes and for informing biomechanical and functional studies.

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  • Regulation of voltage-gated calcium channels in PC12 cells by Leucine Rich Repeat Kinase 2

    Bedford, Cade Henry (2013)

    Undergraduate thesis
    University of Otago

    Leucine rich repeat kinase two (LRRK2) is a widely expressed protein belonging to the Roco family of proteins, mutations in which have recently been discovered as a cause of familial Parkinson’s disease (PD). Despite an array of interacting proteins having been identified across multiple cellular systems, LRRK2’s functional role remains to be determined. Manipulation of LRRK2 expression disrupts many Ca2+ dependent cellular processes. It, therefore, may act as an upstream regulator of initial Ca2+ signalling events, which could explain LRRK2’s widespread effects. The central aim of this study was to determine whether LRRK2 alters endogenous voltage-gated Ca2+ (CaV) channel function in PC12 cells using whole cell patch clamp electrophysiology. Additionally, transiently transfected PC12 cells underwent epifluorescence imaging to identify morphological changes and identify any effects of L-type Ca2+ blockers on morphology. Peak CaV channel currents in LRRK2 transfected cells showed a significantly (p=0.0025, n≥7, one way ANOVA with Tukeys post-hoc test) higher current density across a number of holding voltages relative to untransfected and EGFP transfected controls. These results indicate that LRRK2 up regulates endogenous CaV channel function. Morphological assessment, however showed no significant effect of LRRK2 transfection on morphological parameters relative to EGFP transfected and non-transfected controls (N≥63, Kruskal-Wallis test). Furthermore, addition of the L-type Ca2+ channel blocker nifedipine had no significant effect relative to untransfected and ethanol vehicle controls (N≥43,Kruskal-Wallis test). These results suggest that LRRK2 dependent modulation of CaV channel function does not affect neurite differentiation. Overall, this study has identified a novel effect of LRRK2 on CaV channels, which may explain how LRRK2 has such widespread cellular effects and advances our understanding of LRRK2s functional role. If the effect of LRRK2 on CaV channels is responsible for pathology, CaV channel blockers currently being investigated for Parkinson’s therapy may be particularly effective in Parkinson’s patients harbouring LRRK2 mutations.

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  • Isolation and characterization of human dental pulp derived stem cells

    Kang, Isaac (Jinho) (2013)

    Undergraduate thesis
    University of Otago

    Background: Dental caries remains a major public health concern. Dental endodontics (root canal) therapy involves extirpating the dental pulp and replacing with inert materials. For severe tooth decay, it is the only available treatment; however, it fails to restore the biological functions and vitality of the dental tissues and may ultimately leads to tooth loss. To overcome these shortcomings, dental pulp stem cells (DPSCs) are being investigated as a novel prospective approach to regenerate the dental tissue. In this study, we isolated and purified DPSCs and characterized the purified cells. Objectives: The aims of this study were as follows: (i) to rapidly extirpate dental pulp tissues from human third molar teeth under sterile conditions; (ii) to isolate, characterize, and purify a heterogeneous population of DPSCs using mesenchymal stem cell markers; (iii) to determine the ability of DPSCs to differentiate down an odontoblastic lineage. Design: DPSCs were mechanically and chemically isolated from human impacted third molar teeth. Cells were expanded, passaged, and a heterogeneous population of DPSCs isolated using a cloning cylinder. DPSCs were characterized and purified by flow cytometry using the mesenchymal stem cell markers, STRO-1, CD44, and CD146. DPSCs were induced under two different odontogenic conditions comprising different concentrations of beta-glycerophosphate, and dexamethasone. DPSCs were analysed for morphology, proliferation potential, collagen formation, mineralization characteristics, and expression of the dentin-specific markers dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1), using immunohistochemistry. Results: DPSCs were positive for the mesenchymal stem cell markers STRO-1, CD44, and CD146, although two populations of cells showed different levels of STRO-1 expression. Differentiated DPSCs (dDPSCs) demonstrated a significant increase in alkaline phosphatase concentration between days 14 and 21, while a similar increase in collagen deposition, mineralization, and calcification was also observed on day 28. The proliferation rate of dDPSCs decreased with time. Odontoblast characteristics of dDPSCs were observed, with increased expression of the dentin-specific markers DSPP and DMP-1. Conclusions: This investigation demonstrated successful isolation of DPSCs and differentiation of DPSCs down an odontoblastic lineage, indicating that DPSCs represent a promising approval for the regeneration of lost dental tissues.

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  • Effect of Delayed Treatment with Mesenchymal Stem Cells on Neonatal Hypoxic/Ischemic Brain Injury: A Behavioral and Stereological Study

    Alwakeel, Amr J. (2011)

    Undergraduate thesis
    University of Otago

    Hypoxia/ischemia is a major cause of acute neonatal brain injury and may lead to the development of neurological disabilities, mainly cerebral palsy. Hypoxic/ischemic (H/I) injury occurs as a result of decreased oxygen level in the brain and/or blood and reduced perfusion of the brain tissue. One of the main sites involved in neonatal H/I brain injury is the striatum. In children, injury to the striatum results in the muscular abnormalities of cerebral palsy. Medium-spiny neurons constitute the major neuronal population of the striatum in both primates and rodents. Hence, the rescue or restoration of the medium-spiny neuron population is a viable aim in treating neonatal H/I injury. Current evidence has shown hypothermia, a neuroprotective strategy, to be effective in treating H/I injury. However, hypothermia and other neuroprotective strategies can only be administered within 2 – 6 hours post-injury. The aim of this study was to investigate the therapeutic potential of a seven-day delay in treatment with mesenchymal stem cells (MSCs), a neurorestorative strategy, following hypoxia/ischemia in the neonatal rat. Furthermore, the effect of a subcutaneous injection of a high-dose (HD, 7.5 x 10^5 – 1 x 10^6) and of a low-dose (LD, 8.5 x 10^4 – 1.2 x 10^5) of MSCs was investigated. This was the first study to assess the efficacy of the subcutaneous route of delivery in mesenchymal stem cell (MSC) therapy following neonatal H/I injury. On postnatal day (PN) 7, male pups were exposed to H/I injury. After a seven-day delay (i.e. PN 14), pups were weight-matched in pairs or triplets and randomly assigned to either a diluent injection of Dulbecco's phosphate-buffered saline (DPBS) or a MSC injection. In the LD MSC experiment, five pups were administered the diluent while six pups received a LD MSC injection. In the HD MSC experiment, seven pups were administered the diluent while nine pups received a HD MSC injection. The therapeutic effect was assessed using behavioral testing, and stereological analysis of the absolute total number of striatal medium-spiny neurons. On PN 20, the functional outcome was assessed using the negative geotaxis, cylinder, elevated body swing and foot-fault tests. Each pup was sacrificed on PN 21 and their brain was dissected from the cranium. Injured hemispheres were subsequently embedded in Technovit, serially sectioned and stained. Sections were stereologically analyzed using the Cavalieri method and optical disector method to estimate the absolute number of striatal medium-spiny neurons between diluent- and MSC-receiving pups. To our knowledge, this was the first study that used unbiased modern stereological methods to quantify the absolute number of medium-spiny neurons in the striatum following MSC therapy in neonatal hypoxia/ischemia. A sub-aim of this study was to determine the efficacy of the negative geotaxis test in the study of neonatal H/I injury before the administration of any treatments. As such, pups were tested on the negative geotaxis apparatus on PN 12 and PN 14, prior to MSC and diluent injections on the afternoon of PN 14. The findings of this study showed that a seven-day delay in MSC treatment did not have a statistically significant improvement on the functional outcome following H/I injury. However, a positive trend was observed in the cylinder test in pups receiving MSCs. MSC administration resulted in a higher preference of using the contralateral injured limb over the ipsilateral uninjured limb when compared to the diluent-administered pups. This positive trend was more profound in the HD MSC group compared to the LD MSC pups. The stereological findings showed that delayed MSC therapy was effective in attenuating the loss in striatal medium-spiny neurons compared to diluent-receiving pups. This difference was found to be statistically significant. The HD MSCs were more effective than the LD MSCs and restored the number of striatal medium-spiny neurons to normal levels. The subcutaneous route was also shown to be an effective route in delivering MSCs. Finally, results from the negative geotaxis test showed that this test may not be an effective assessment in evaluating the functional outcome following neonatal H/I brain injury. In conclusion, the findings of this study suggest that delayed MSC therapy can be an effective tool in treating neonatal H/I brain injury. These findings may offer hope to children who have missed the critical period of 2 – 6 hours post-injury, which is limited to neuroprotective interventions.

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