407 results for Undergraduate

  • Understanding demand for wood products in New Zealand’s major log markets.

    Drummond, Ryan C.M. (2015)

    Undergraduate thesis
    University of Canterbury Library

    New Zealand’s forestry sector is largely reliant on the presence of a strong export market with 57% of the volume harvested being exported of which 99% goes to Japan, the Republic of Korea, China and India. This identifies the need to analyse demand in these countries to better understand their needs in the future. Consumption of wood products per capita is a commonly used metric for estimating demand and was used in this research. Volumes of imports, exports and production were collected from the Food and Agricultural Organisation of the United Nations (FAO) and data for a range of explanatory variables was collected from a variety of official sources. Historical trends in consumption identified that as countries develop socially and economically their consumption shifts from largely solid wood products such as sawn timber to more processed products such as wood-based panels and paper and paperboard. Consumption was modelled using linear regression techniques to develop models which could be used to forecast consumption in the future. A wide variety of potential explanatory variables were considered and the models presented represent the most effective of these. GDP per capita was found to be the single most effective explanatory variable being highly significant (p<0.01) in all models. Price was also found to be a strong determinant of consumption, understandable as price is a major component of supply and demand dynamics. Measures of construction activity were found to be related to consumption of sawn timber in all studied countries and for wood-based panels in Japan. Forecasts produced for consumption in Japan should be used as only an example of the capability of the models presented herein. More work is required to develop these equations into a form where they can be used to more accurately estimate future consumption.

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  • Comparing performance of seedlot types in the Kaingaroa Forest using ground pilots and aerial LIDAR : comparing the performance of open-pollinated, control pollinated and clonal seedlots in a plantation trial in the Kaingaroa forest utilising airborne LIDAR.

    Henderson, Theo J. A. (2016)

    Undergraduate thesis
    University of Canterbury Library

    Problem: As more improved planting stock such as clones and genetically improved seedlings are introduced to the market it is important to properly understand the benefits of each production type. Various breeding programmes make claims around performance of their seedlots but there is a shortage of literature around the performance of these production types in a plantation setting for most production species. Approach: One seedling, two cuttings, and 7 clonal varieties were compared in a plantation setting on a single site. The stand was measured via five permanent sample plots (PSPs) per seedlot. The seedlots were categorised by material production type and compared using pair-wise analysis to find statistically significant differences. The seedlots were then compared individually to find any intramaterial differences. Available aerial LIDAR was then used to estimate tree height for the total seedlot area and establish whether this was an accurate estimate. Average LIDAR height was then used to estimate tree height for each of the five PSPs to establish whether this would improve the prediction of heights and permit its use for large-scale evaluation of genetic material. Results: Categorising seedlots by material type there was no statistical difference for height performance but there was for DBH and basal area. Clones and open-pollinated seedlots showed superior performance over controlled-pollinated material, but not different from each other. Clones showed reduced height variability over non-clones. DBH and basal area variability was also reduced but the difference was only statistically significant versus open-pollinated seedlots. Comparing seedlots individually there was large variation in performance and variability within material types, with clones showing some superiority and non-clones inconsistent improvements. The LIDAR tree height model for whole seedlot area showed to be a significant predictor average PSP height but poorly predicted CV. Predicting PSP area provided with LIDAR improved correlations over whole stand predictions for both values. Implications: The performance superiority for clones over other production types in this trial is not as pronounced as previously suspected. Clones do, however, provide a more uniform crop. The LIDAR tree height model could be used for further analysis but not for height variability without further improvement. Result validity was, however, reduced by the lack of trial replication and randomisation. This is the key limitation and makes guaranteeing improvements are due to improved genetics (not environment) problematic.

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  • Factors which influence corewood stiffness in radiata pine.

    Jones, Grace (2016)

    Undergraduate thesis
    University of Canterbury Library

    Increasing stocking and competition with weeds significantly increased Hitman estimates of stiffness at the significance level α=0.05. Accuracy of models predicting Hitman from TreeTap measurements can be improved by customizing them for particular silvicultural regimes and diameter at 1.4m (DBH). Controlled factors: genetics, wind sway and fertilizer use, did not significantly influence Hitman estimates of stiffness. Tree height did not significantly influence stiffness estimates, but including DBH in prediction models improved models of stiffness estimates. Stiffness in 10 year old Pinus radiata stems was studied in an experiment with the following factors: genetics, herbicide/fertilizer use, stocking and wind sway. Acoustic velocity was used as an estimate of modulus of elasticity (MOE) and was estimated using 2 different tools: Hitman, a resonance based tool used on 2m log sections, and TreeTap, a time-of-flight based tool used on 1.2m outer-wood sections of standing trees. DBH and tree height were also recorded for each tree. Green density was measured using submersion in order to use the formula: MOE = green density∗ acoustic velocity² Stiffness estimates from TreeTap were strongly correlated with Hitman estimates, but were about 30% higher on average. The relationship between stiffness estimates from these tools changed with weed competition and with stocking. No significant difference in stiffness was found between the northwest and the southeast sides of the stems when using the TreeTap tool, and an average value for each tree was used for subsequent analyses. These findings are similar to those from other studies carried out on different sites, and to a previous destructive sample at the same site. There were a few major outliers, but despite these the final model relating TreeTap and Hitman estimates was significant (P<0.0001). Weed competition and stocking significantly affected the intercept (P=5.71e-05 and P=1.08e 05 respectively) of a model predicting Hitman values from TreeTap estimates of stiffness.

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  • Men’s experience of virtual simulation to aid patient education for radiation treatment to the prostate

    Flockton, Alannah - Jayne (2017)

    Undergraduate thesis
    University of Otago

    Prostate cancer affects more than 3000 New Zealand men each year. Many of these men receive a complex type of radiation treatment which requires patients to have a full bladder and empty rectum to aid in the accuracy of treatment delivery and minimise side effects. These concepts can be difficult to explain and current patient education involves verbal and written materials. A 3D immersive teaching tool Virtual Environment Radiotherapy Training system (VERT) can visually simulate and demonstrate how radiation treatment is delivered to the prostate. There is sufficient evidence to support VERT as a useful teaching tool in the academic environment however; using VERT for one-on-one patient education is a novel approach. This qualitative, pilot study set out to explore men’s experience of VERT when it was incorporated into education sessions for prostate radiation treatment. More specifically, how VERT shaped the men’s understanding of how radiation treatment is delivered; why a full bladder and empty rectum is required; and their initial treatment experience. Data collection involved semi-structured interviews one week after the participants had experienced the VERT education and received their first week of radiation treatment. Interpretative phenomenological analysis (IPA) was used to offer insight into the men’s experience of the VERT education session. The findings strongly suggest VERT education enhances patient understanding of radiation treatment through visual learning. There is a preference to have the VERT education delivered sometime near the first treatment appointment and VERT has the potential to support men through engagement, information sharing and encouraging peer support. There is a role for visual tools such as VERT to be included as part of patient education sessions for radiation treatment to the prostate.

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  • Novel Organic Carbon Monoxide Releasing Molecules as a Potential Treatment for Triple Negative Breast Cancer

    Gunatunga, Kishan (2011)

    Undergraduate thesis
    University of Otago

    Carbon monoxide (CO) plays a role in many physiological and pathophysiological processes as a second messenger. Emerging evidence reveals the potential CO has as a therapeutic agent as it has been implicated in the modulation in a range of intracellular functions including apoptosis and proliferation. In the case of cancer, specifically triple negative breast cancer (TNBC), there is very little information regarding the effects of this molecule. Here we hypothesize that the targeted delivery of CO to a tumour will result in an anti-cancer effect in TNBC. The current study examines a novel class of compounds termed organic CO releasing molecules (CORMs) (CO-1 – CO-8) and previously published metal containing CORMs (CORM-2), as potential treatments for TNBC. Firstly a wide range of synthesised novel organic CORMs were screened for toxicity in MDA-MB-231 cells, a model for TNBC, and the lead compound CO-1 was identified from a range of 8 potential candidates (CO-1 – CO-8). Analysis of cell viability data revealed that CO-1 (1 – 200 μM) resulted in significant reductions in cell viability with an IC75 value of around 5 μM in the MDA-MB-231 TNBC cell line, while the by-product of CO-1, BP-1, demonstrated no residual cytotoxic effects. Time course and gas chromatograph-mass spectrometry (GC-MS) studies revealed that the compound released CO at a slow rate with a half-life in vitro between 9 and 24 hours. The ability of CO-1 and CORM-2 to modulate cell death via the induction of apoptosis was demonstrated using Annexin V conjugated to fluorescein (FITC) and propidium iodide (PI) staining followed by FACS analysis. CO-1 was able to induce apoptosis in MDA-MB-231 cells at both low (10 μM) and high (200 μM) concentrations (6% and 6% respectively) with no apoptotic or necrotic effects being observed when cells were treated with the by-product of CO-1, BP-1. The transition metal containing CORM-2 (200 μM) did not increase apoptotic markers compared to control, however treatment of cells with its “inactive” counterpart iCORM-2 (200 μM) resulted in a significant increase (7%) in apoptosis. In addition high (200 μM) but not low (5 and 10 μM) concentrations of CO-1 and CORM-2 produced a significant increase in the percentage of cells with a damaged mitochondrial membrane (3% and 5% for CO-1 and CORM-2 respectively), indicating that CO may have some concentration specific effects in vitro. High (200 μM) concentrations of both CO-1 and CORM-2 were also shown to induce mitochondrial damage in the MDA-MB-231 cell line and further to the potential anti-cancer effects of the novel compound CO-1, we have shown that low (10 μM) concentrations of the molecule causes a 1.2-fold and 1.4-fold increase in caspase 3 and p53 expression and a 1.2-fold increase in caspase 3 activation. The safety of both organic and transition metal CORMs were also assessed in the renal epithelial MDCK cell line. In MDCK cells treated with CO-1 (10 and 200 μM), COM-2 and iCORM-2 (20 and 100 μM) showed histopathological changes indicative of cell death were observed. These changes were not present in cells treated with the by-product of CO-1, BP-1. Interestingly the changes in histological architecture in MDCK cells treated with iCORM-2 appeared more extensive and severe that in cells treated with the active form of the compound CORM-2. Furthermore treatment of MDCK cells with low (10 μM) concentrations of CO-1, 20 and 200 μM CORM-2 and 200 μM iCORM-2 resulted in G2/M cell cycle arrest in the MDCK cell line. The current study proved CO-1, to be a safe and efficacious pharmacological agent with the ability to induce a cytotoxic and cytostatic effect in the MDA-MB-231 and MDCK cell line with no residual toxic effects resulting from treatment of cell with the by-product of CO-1 (BP-1). Our findings cast doubt over the notion that existing transition metal CORMs in their “inactive” form are not without biological effects. Therefore the current study has shown that novel organic CORMs have a combination of properties that translate into a desirable and potential treatment for TNBC.

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  • Predictors of Referral Delay and Treatment Response to Intravitreal Bevacizumab for Wet Age-Related Macular Degeneration

    Ang, Wee Choen (Sebastian) (2017)

    Undergraduate thesis
    University of Otago

    Background: Recent years have seen anti-vascular endothelial growth factor (VEGF) agents revolutionize the treatment of wet age-related macular degeneration (AMD). To ensure optimal outcomes for this time-sensitive disease, current guidelines recommend that patients should be seen in clinic within two weeks of referral and treated with a loading phase of three injections, followed by a follow-up visit for reassessment. However, meeting these guidelines is challenging due to the increasing global prevalence of wet AMD and the accumulating cohort of patients requiring treatment. In addition, services with inefficient referral pathways and limited treatment capacities have been shown to threaten patient access to prompt treatment and increase adverse patient outcomes. Aims and Methods: This project is a two-year retrospective audit conducted at the Eye Department in Dunedin Public Hospital with the aims to (1) assess the efficiency of the current wet AMD referral pathway against contemporary guidelines and (2) identify any risk factors that are predictive of referral delay and treatment outcome. Relevant patient, referrer, referral and clinical characteristics were retrieved from retrospective analysis of clinical records and OCT scans of 113 patients. The outcome measures were referral delay (i.e. duration from point of referral to first assessment clinic); and treatment response measured by changes in visual acuity, changes in central macular thickness (CMT) and clearance of macular fluid. All potential predictors of these outcome measures were analysed via multivariable binomial logistic regression. Results: Only 49% of patients at Dunedin Public Hospital met referral guidelines, but 85% met treatment guidelines. Overall median time from point of referral to first treatment was 10 days. A loading phase of three bevacizumab injections significantly improved mean visual acuity by 5 ± 24 letters (p=0.03) and reduced mean central macular thickness (CMT) by 55μm (p85 years) were associated with an increased likelihood of CMT reduction (OR 9.157; 95% CI 2.6, 31.747; p<0.001 and OR 4.79; 95% CI 1.11, 20.7; p=0.036 respectively), whereas patients with longer duration of symptoms (1 to 3 months) were significantly associated with a decreased likelihood of CMT reduction compared to patients with symptoms of less than one month (OR 1.65; 95% CI 0.044, 0.616, p value = 0.007). Thicker baseline CMT was also found to be significantly associated with a greater reduction of macular fluid (OR 1.475; 95% CI 0.75, 4.578; p=0.017) after treatment, and so were females compared to males (OR 3.9; 95% CI 1.2, 12.58; p=0.02). Conclusion: This study identified that the current wet AMD referral pathway at Dunedin Public Hospital can and should be more efficient, and quality improvement work is warranted to improve compliance to contemporary guidelines.

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  • Nanopore Sequencing of RNA from Breast Cancer Genes

    de Jong, Lucy Clair (2016)

    Undergraduate thesis
    University of Otago

    Abnormal mRNA splicing can disrupt gene function and influence the course of disease. Analysis of abnormal splicing is an important part of determining whether a particular genetic variant found in the population is pathogenic or not. However, to correctly identify abnormal splicing, we must first understand what is normal. This project assessed the isoforms of the genes BRCA1 and BARD1, which are particularly relevant to the onset of breast cancer. BRCA1 is a tumour suppressor gene implicated in breast cancer onset. BARD1 codes for a protein that interacts with BRCA1 and produces a smaller mRNA transcript. Normal exon skipping events have been identified for both BRCA1 and BARD1, however, current methods are unable to reliably identify full transcripts. This has resulted in knowledge of individual exon skipping events but often does not tell us whether multiple events occur in the same transcript. The MinION nanopore sequencer (Oxford Nanopore Technologies), uses a nanopore to produce long-read, single molecule sequences. This has great potential for identifying multiple long isoforms, which is not practical using current technologies. The aim of this project was to examine the ability of the MinION to identify mRNA splicing patterns of transcripts derived from BRCA1 and BARD1. All mRNA from a normal lymphoblastoid cell line was converted to cDNA and targeted genes of interest were amplified by polymerase chain reaction (PCR). All potential isoforms generated from BRCA1 and BARD1 were then pooled and analysed using the MinION sequencer. After trialling many different analysis methods, the read data was analysed using the BLAST-like Alignment Tool (BLAT) with two outputs, a tabular and a graphical format. The tabular format grouped reads into potential isoforms, while the graphical format allowed visualisation of these isoforms and identified the exon/intron boundaries. Using both these formats 34 BRCA1 isoforms and 39 BARD1 isoforms were identified, 24 and 17 of which were potential novel isoforms respectively. Two of these novel isoforms from the BRCA1 dataset (Δ10-17 and Δ11q21) were further verified using Sanger sequencing. This was a proof of principle research project that demonstrated the potential use of the MinION nanopore sequencer for successful characterisation of multiple mRNA isoforms. This research has successfully identified a number of novel isoforms from the BRCA1 and BARD1 genes using the MinION sequencing device.

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  • The effect of Mepitel Film on skin reaction severity in patients undergoing radiation therapy for head and neck cancer: a feasibility study

    Wooding, Hayley (2017)

    Undergraduate thesis
    University of Otago

    Radiation skin reactions are a common side effect of radiation therapy and can be distressing and painful for patients. Head and neck cancer patients receive a high dose of radiation to the skin and are therefore at high risk of acute skin toxicity. There have been many clinical trials investigating topical agents to reduce or prevent these reactions but the evidence to date is lacking and many centres still base their practice on anecdotal evidence. Recently clinical trials in breast cancer patients have shown that using Mepitel Film® (Mölnlycke Health Care AB, Gothenburg, Sweden) reduced skin reaction severity and stopped the development of moist desquamation when used prophylactically (from the first day of radiation therapy). Mepitel Film and other soft silicone dressings that adhere very closely to the folds of the skin, have been hypothesized to decrease skin reaction severity by stopping friction by clothing and allow the radiation damaged skin to repair itself. The aim of this randomised controlled feasibility study in this thesis was to investigate whether Mepitel Film dressings were superior to Sorbolene cream in reducing or managing radiation-induced skin reactions in patients with head and neck cancer Head and neck cancer patients are prescribed a higher dose than breast cancer patients, have an uneven surface for the Mepitel Film to adhere to and have complex non-homogenous dose distributions, This means that testing the effect of Mepitel Film in this cohort would be challenging. Despite this, it was hypothesised that Mepitel Film was superior to standard Sorbolene cream in decreasing the severity of acute radiation-induced skin reaction in patients receiving radiation therapy for head and neck cancer. In order to test this hypothesis a randomised, controlled, multi-centre, international, open label intra-patient feasibility study was conducted in New Zealand and China. This thesis analyses a subset of 12 patients recruited at the Canterbury Regional Cancer and Haematology Service (CRCHS) at Christchurch Public Hospital. For the first six patients, the study area was chosen as the area of first erythema which was divided into equal halves. Each half was randomised to either Mepitel Film or Sorbolene cream. Mepitel Film was applied as soon as erythema was visible (management protocol). For the next six patients, the study area was chosen at the planning stage to include an area of relatively uniform high dose (>40Gy). This area was divided into two equal halves; one half was randomised to Mepitel Film the other half to Sorbolene cream. Mepitel Film was applied from day one of radiation therapy treatment (prophylactic protocol). Sorbolene cream was applied twice a day by the patient. The Modified Radiation-induced Skin Reaction Assessment Scale (RISRAS) and the Modified Radiation Therapy Oncology Group (RTOG) skin toxicity score were used to assess skin reaction severity three times a week. Patients also filled out the New Zealand validated Distress screening tool once a week and completed exit questionnaires at the end of the follow-up period. Thermoluminescent dosimeters (TLDs) were used to measure the actual dose to the skin underneath Mepitel Film and the control cream for all patients. When results of all 12 patients were combined, there was a statistically significant decrease in skin reaction severity in favour of Mepitel Film of 29% for combined scores, of 15% for researcher scores and of 49% for patients’ scores (p= 0.001, 0.002 and 0.004 respectively). The difference in peak RISRAS score between skin covered with Mepitel Film and control skin covered in cream was also significantly lower (p=0.02). The results were disappointing compared to those reported by the breast cancer trial where skin reaction severity was reduced by more than 90% when Mepitel Film was used prophylactically. Several factors may explain the lack of effectiveness of the Mepitel Film in this patient cohort. Dose to the skin was significantly higher in head and neck cancer patients and Mepitel Film did not adhere well to skin with heavy beard stubble, which meant Mepitel Film needed to be replaced almost daily for the first few weeks of radiation therapy. The latter may also explain why there was no difference in the Mepitel Film effect between the skin of patients on the management protocol and those on the prophylactic protocol which should have had the strongest skin protective effect. In addition, compared with skin covering the breast area, skin in the neck area may be “tougher” and less likely to benefit from “friction protection”. The results suggest that Mepitel Film does reduce skin reaction severity in head and neck cancer patients but the increase in skin folds, beard growth and high skin dose mean that the protective effects of Mepitel Film are limited, particularly in men with heavy beard growth. Mepitel Film appeared to be more effective in women but there were too few women in this trial to perform a statistically meaningful analysis. Future research should include clinical studies in different cohorts of head and neck patients, such as in women and men with less beard growth.

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  • Development of Novel Triadin-Based Biosensor for the Quantification of H2O2 in the Cardiac Dyad Microdomain

    McLachlan, Julia Jocelyn (2016)

    Undergraduate thesis
    University of Otago

    Release of Ca2+ from the sarcoplasmic reticulum (SR), mediated by the activation of the ryanodine receptor (RyR2), initiates myocardial contraction. This process of Ca2+-induced Ca2+ release is confined within a 20 nm region termed the dyad, located between the transverse tubule and the SR. Architectural properties of the dyad restrict diffusion of Ca2+ and other intracellular messengers to create a unique, subcellular microdomain. Previous research has shown that endogenous producers of reactive oxygen species (ROS) are abundant within the dyad, and have attributed alterations in Ca2+ release with the oxidation of RyR2. However, the spatiotemporal dynamics of ROS within this microdomain remain unquantified due to an absence of tools that enable subcompartmental ROS resolution. Therefore, this research aimed to utilise the recent development of genetically encoded redox biosensors, capable of ROS detection, to create a biosensor tethered to the N-terminus of the dyadic protein, triadin. A Human Embryonic Kidney (HEK) 293 cell model was used to characterise two ROS (H2O2) sensors, HyPer3 and roGFP2-Orp1, in vitro to determine the biosensor more suitable for the triadin-based construct. Using single-cell imaging, HEK 293 cells transiently transfected with HyPer3 or roGFP2-Orp1 were superfused with a range of oxidising and reducing agents. Based on these data, roGFP2-Orp1 exhibits a greater dynamic range, increased sensitivity, and faster oxidation-reduction kinetics than HyPer3, and thus was selected for the triadin-based construct. In parallel, single-cell Ca2+ imaging was used to confirm that co-expression of triadin has a neutral effect on RyR2 function. HEK 293 cells expressing RyR2 WT or RyR2 WT + triadin were loaded with the cytosolic Ca2+ indicator, Fluo-4 AM and superfused with 0.1–1 mM Ca2+ to activate RyR2 WT. These data found a non-significant (p = 0.9) difference in Ca2+ release in RyR2 WT (61.9 ± 3.1%) and RyR2 WT + triadin (60.3 ± 3.5%) cells exposed to 1 mM Ca2+. To create roGFP2-Orp1-triadin, overlap extension PCR was used to generate an SfaAI restriction site that enabled roGFP2-Orp1 to be subcloned into the triadin plasmid. However, the development of roGFP2-Orp1-triadin was unsuccessful. This research highlights a novel method for H2O2 quantification within the dyadic microdomain. Characterisation of HyPer3 and roGFP2-Orp1 revealed that roGFP2-Orp1 exhibits the sensitivity and reversibility required for an in vivo biosensor. In addition, co-expression of triadin has a neutral effect on the properties of RyR2-mediated Ca2+ release, which indicates that triadin is an appropriate tether for the dyadic localisation of roGFP2-Orp1. Future directions include the generation of an animal model to further understand the spatiotemporal dynamics of ROS in relation to alterations in Ca2+ release in vivo.

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  • The University of Otago's Home Science Extension Service, 1929-1954

    Clarke, Katherine Mary (2003)

    Undergraduate thesis
    University of Otago

    The Home Science Extension Service (HSES) of the Otago University was established in 1929. The Service intended to remedy a lack in the educational facilities available for rural women. The HSES developed from the example of the rural educational work in the United States. The founders hoped that home science instruction could reduce many of the hardships and problems of rural domestic life. They wanted to improve health standards through dietary advice and educating women about cleanliness. They believed instruction about efficient homemaking techniques could reduce the toil of rural women. They also wanted to provide a source of enjoyment, by offering leisure activities and mental stimulation. The extension of home science teaching into the community needs to be seen in the wider context of two international movements, adult education and home science. New Zealand adult education largely developed from the British adult education system, while the American model of home economics inspired New Zealand's tradition of home science. The HSES fused these international themes in a New Zealand experiment into the possibilities for rural adult education. […] This investigation covers the founding of the HSES and its first twenty-five years of operation, from 1929 to 1954. The period ends in 1954 partly because this confines the study to the time before feminist movements began to openly challenge the belief that a woman's proper role was to be a homemaker. It is appropriate to study an organisation which helped women with homemaking during a period when many believed that this was to be their destiny. The twenty-five year period also encompasses three phases in the HSES's development: the 'Carnegie period'; the 'war years'; and the 'adult education era'. The changes within the HSES during these years provide insights into wider developments in New Zealand society. [extract from Introduction]

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  • The proportion of fast and slow neuromuscular junctions in young and old mice

    Lloyd, Jordan (2017)

    Undergraduate thesis
    University of Otago

    Human skeletal mass and strength increase from birth until ~35 years of age, thereafter a decline in mass and strength occurs in a process called sarcopenia. Beyond 60 years of age muscular weakness falls to a point where it imposes physical disability and individuals lose the ability to live independently. The loss of muscle mass and strength can be attributed, at least in part, to a fast to slow muscle fibre type transition (increased proportion of slow type muscle fibres. An age associated change in the innervation of skeletal muscle with ageing is a probable underlying cause of this fibre type transition. Muscle fibre types are determined by their innervating axon; fast muscle fibres are innervated by fast axons forming fast neuromuscular junctions (NMJs) and slow muscle fibres are innervated by slow axons forming slow NMJs. If a muscle fibre is innervated by a motor axon of the wrong type e.g. a fast muscle fibre is innervated by a slow axon, that axon converts the muscle fibre type to slow. The present study hypothesised that the reduction in the proportion of fast muscle fibres seen in ageing may be caused by a selective loss of innervation of fast muscle fibres with a subsequent reinnervation by slow axons resulting in the conversion of the fast muscle fibres to slow muscle fibres. This fast to slow muscle fibre type change would therefore be coupled with an increased proportion of slow NMJs with a reduction of fast NMJs (a fast to slow NMJ transition). To determine this, a comparison of the proportion of fast and slow NMJs present in the soleus (containing both fast and slow muscle fibres), and extensor digitorum longus, (containing almost entirely fast muscle fibres) of young (2-2.4 months old) and old (20-24 months old) C57BL/6 mice was made. Immunohistochemistry was used to selectively label slow NMJs by targeting SV2a, a synaptic vesicle protein present only in the nerve terminals of slow axons. Nicotinic acetylcholine receptors (nAChRs) and Synaptophysin, present in all nerve terminals, were used as a general marker for NMJs. The proportion of SV2a positive (slow) NMJs was compared to the proportion of SV2a negative (fast) NMJs in young and old mice to determine whether there was a difference in the proportion of slow and fast NMJs with ageing. Sectioned muscles were viewed by widefield fluorescence microscopy. An average of 180 NMJs were counted in each soleus muscle and 162 in each EDL. A reduction in the proportion of fast nerve terminals with an increase in slow was found in the soleus muscle, 40.41 ± 3.3% of young NMJs were fast and 59.59 ± 3.3% were slow, of old NMJs 10.80 ± 4.1% were fast and 90.20 ± 4.1% were slow. No change was found in the EDL, 89.66 ± 6.3% of young NMJs were fast and 10.44 ± 6.3% were slow. Of old NMJs 90.06 ± 2.5% were fast and 9.94 ± 2.5% were slow. There was an insufficient number of EDL muscles used (n=2) meaning no valid statistical analysis could be drawn from the EDL results. These observations suggest that in the soleus there may be a deinnervation of fast muscle fibres with a reinnervation by slow axons occurring which promotes an increase in the proportion of slow NMJs with ageing and reduces the proportion of fast NMJs. This deinnervation-reinnervation process may underlie the increase in slow muscle fibres with a reduction in fast muscle fibres seen in the ageing soleus.

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  • The performance of blocks of clones in a radiata pine production forest.

    Farmery, Acacia (2015)

    Undergraduate thesis
    University of Canterbury Library

    Problem: Genetically identical clones of Pinus radiata are being planted in New Zealand plantation forests. There have been many clonal trials carried out; however there is a weakness in published literature surrounding the performance of clones in production blocks. Method: Five comparisons in four of Pan Pac Forests Products production forests were measured. Three comparisons were measured at age 4.5 years old and two were measured at 7.5 years old. There were six Forest Genetics clones and three different control-pollinated seedlots measured in these comparisons. Each comparison had a different number and selection of seedlots. There were six different traits measured for the trees; diameter at breast height over bark, height, acoustic velocity, straightness, branching habit, and malformation. The different traits were compared between the seedlots within each comparison. The differences in variation for diameter at breast height and modulus of elasticity were compared between clones and control-pollinated seedlots. Finally, the results by clone for the traits, excluding height, were compared to the expected performance supplied by Forest Genetics. Results: There were differences in performance between seedlots. Four clones performed well across a range of traits. One clone performed well in the 7.5 year old blocks but not in the 4.5 year old blocks. One clone did not perform well in size and stiffness. Clones were significantly less variable than control-pollinated seedlots for diameter at breast height but not for modulus of elasticity. The performance of each clone in Pan Pac Forest Products forests was very similar to the expected performance provided by Forest Genetics. Implications: There are clones that can produce desired yield, stiffness and form. Clones will provide a more uniform crop in diameter than control-pollinated seedlots. Pan Pac Forest Products can rely on Forest Genetics prediction of clonal performance as a guide to performance in their forests.

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  • Anatomical Characterisation of Prolactin Receptor Expression in the Developing Mouse Brain

    Boyes, Kendra Michelle (2016)

    Undergraduate thesis
    University of Otago

    Prolactin signalling through the prolactin receptor plays a significant role in many physiological processes. The diverse biological functions attributed to prolactin are largely dependent on the distribution of its receptor. In particular, the distribution of the prolactin receptor has been well characterised in the adult brain of rodents, but has yet to be fully documented in the developing brain of neonates. To determine the role of the prolactin receptor in the developing brain of neonates, we have developed a transgenic mouse in which cre-recombinase is expressed under the control of an internal ribosomal entry site (IRES) in the long form of the prolactin receptor gene (PrlrL-IRES-Cre). The PrlrL-IRES-Cre mouse has been crossed with a cre-dependent tau-GFP reporter line. In this study tau-GFP is expressed wherever the prolactin receptor gene has been transcribed. The tau-GFP associates with microtubules in neuronal processes, which is important, because in addition to identifying neuronal cell bodies expressing the prolactin receptor, we were able to study the projections of prolactin-responsive neurons for the first time. Post natal day (PND) 1 (n = 8), PND 14 (n = 8) and PND 28 (n = 6) male and female mouse brains were perfused using 4% paraformaldahyde, cut in 20 micron serial sections and thaw mounted onto slides. To visualise PrlrL expressing cells, immunohistochemistry was performed. Sections were incubated with rabbit polyclonal anti-GFP (green fluorescent protein) (A-6455, Life Technologies), for 48 hours at 4℃, followed by an incubation with goat anti-rabbit biotinylated secondary antibody (BA-1000, Vector) for 3 hours. Labelled cells were visualised using nickle enhanced 3,3'-diaminobenzidine (DAB), and identified using an Olympus AX70 light microscope. Staining showed minimal expression in any part of the brain of PND 1 mice, whereas staining could be identified in the choroid plexus, anterior ventral periventricular nucleus and arcuate nucleus of PND 14 and 28 mice. Interestingly, minimal staining was observed in the amygdala and no staining was observed in the paraventricular nucleus in any of the ages examined. These are areas that exhibit high levels of PrlrL expression in adult mice. The increase in PrlrL expression may indicate an age dependent upregulation of the prolactin receptor through the availability of the PrlrL gene, likely driven by hormonal changes associated with puberty. The age-associated increase in PrlrL expression in the anteroventral periventricular nucleus and arcuate nucleus in prepubertal animals suggests a developmental role for prolactin in these regions.

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  • Effects of maternal immune activation on brain arginine metabolism and microglia during neonatal neurodevelopment

    Zhang, Jiaxian (2016)

    Undergraduate thesis
    University of Otago

    Schizophrenia is a debilitating chronic mental disorder with prominent frontal and hippocampal dysfunction. While the exact cause of schizophrenia is poorly understood, a number of factors, including neurodevelopmental disruption, have been linked to the aetiology of the disease. Maternal immune activation (MIA) is a neurodevelopmental model of schizophrenia based on epidemiological evidence that prenatal exposure to infections increases the risk of schizophrenia in adulthood. This model often uses a single systemic administration of the synthetic cytokine inducer polyinosinic:polycytidilic acid (polyI:C) during mid-gestation (e.g., gestation day 15) to induce MIA in pregnant rats. A number of anatomical, neurochemical and behavioral features of schizophrenia are evident in the adult MIA rat offspring. Accumulating evidence implicates altered metabolism of L-arginine, an amino acid with a number of bioactive metabolites, and microglial dysfunction in the pathogenesis of schizophrenia. Recent research has shown altered brain arginine metabolic profile and microglial dysfunction in the adult, as well as adolescent, MIA rat offspring. However, does a single MIA insult during the early stage of neurodevelopment affect brain arginine metabolism and microglia has not been addressed previously. We hypothesized that MIA during neonatal neurodevelopment might alter brain arginine metabolism and affect microglial maturation. To test these hypotheses, we designed the following three experiments to investigate how polyI:C-induced MIA affected brain arginine metabolism and microglia in rats at the age of postnatal day (PD) 2. Twenty-four pregnant Sprague-Dawley rats were given a single tail vein injection of polyI:C (4.0 mg/kg; MIA) or saline (control) on gestation day 15 (n = 12/group). Experiment 1 quantified the tissue concentrations of L-arginine and its nine downstream metabolites (L-citrulline, L-ornithine, glutamate, glutamine, GABA, agmatine, putrescine, spermidine and spermine) in the forebrain of male and female control and MIA offspring (n=12/sex/group) at PD2 using high performance liquid chromatographic (HPLC) and liquid chromatography/mass spectrometric (LC/MS) assays. There were no significant differences between the control and MIA groups in both sexes for the ten neurochemical variables measured, suggesting that MIA did not have a global effect on brain arginine metabolism at this age. Since schizophrenia is associated with prominent frontal and hippocampal dysfunction, Experiment 2 measured tissue concentrations of L-arginine and its nine downstream metabolites in the frontal cortex and hippocampus of male and female control and MIA offspring (n=8/sex/group) at PD2. There were increased levels of L-arginine, glutamate, putrescine, spermidine and spermine and glutamate/GABA ratio, but decreased glutamine/glutamate ratio, in both male and female MIA offspring relative to the controls in a region-specific manner. These results provide the first evidence that a single MIA insult during early neurodevelopment altered arginine metabolism in the frontal cortex and hippocampus at the neonatal stage. Human genetic studies have identified schizophrenia risk genes encoding neuronal nitric oxide synthase (nNOS), one of the key arginine metabolising enzymes. Experiment 3 compared nNOS immunoreactive profiles and microglial migration and maturation in the brains of control and MIA offspring in both sexes (n = 4/sex/group) at PD 2. Immunohistochemistry revealed markedly increased number of nNOS-positive cells in the somatosensory cortex, striatum and the CA3 and dentate gyrus sub-regions of the hippocampus, but not frontal cortex, in the MIA offspring relative to the controls in both sexes. Moreover, there were delayed microglial migration and maturation in both male and female MIA offspring when compared with the controls. This study, for the first time, demonstrates that a single MIA insult alters the brain arginine metabolism and leads to the up-regulation of nNOS and abnormal development of microglia at the age of PD 2. These findings further support the involvement of L-arginine metabolism and microglia in the pathogenesis of schizophrenia. The changes during early neonatal neurodevelopment may contribute to neuronal and behavioral dysfunctions observed in the juvenile and adult MIA rat offspring.

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  • Does prolactin act directly on AgRP neurons in the arcuate nucleus?

    MacLeod, Morgan Anna (2016)

    Undergraduate thesis
    University of Otago

    The development of a positive energy balance occurs during pregnancy to support the growth of fetal and maternal tissues, and to increase energy stores in preparation for the metabolic demands of lactation. Leptin levels increase as pregnancy advances, along with appetite and fat deposition. This is unusual, as in the non-pregnant state, leptin decreases food intake and increases energy mobilization. Therefore, leptin is not being recognized during pregnancy. Leptin-responsive neurons, such as Agouti-related peptide (AgRP) and Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, do not respond normally to leptin during pregnancy. It is likely that changes in gestational hormonal profile have a role in mediating leptin resistance. Increased plasma prolactin is observed during pregnancy and, in addition, there are prolactin receptors in the same regions of the brain that control food intake. Prolactin is also known to have an orexigenic effect. We hypothesise that prolactin is a mediator of this increased appetite and resistance to leptin during pregnancy. The aim of this study was to examine whether prolactin directly targets leptin-responsive neurons in the arcuate nucleus. We examined the AgRP neurons, known to be involved in stimulating food intake. Transgenic mouse models and double-label immunohistochemistry were used to look at whether prolactin action is observed in neurons that express AgRP. In separate experiments, AgRP-Cre-tdTomato mice and AgRP-Cre-tauGFP mice were injected with prolactin and perfused. The brains were used to detect prolactin-induced phosphorylation of STAT5, an indicator of prolactin action. The sections were then double-labelled to identify AgRP neurons with labeling of either the tdTomato transgene or GFP respectively. AgRP neurons were readily detected in the arcuate nucleus. Many pSTAT5-stained nuclei were also detected in the arcuate nucleus of prolactin-treated animals, however, none of the AgRP neurons showed pSTAT5-positive nuclei. To confirm these results, we looked at conditional deletion of the prolactin receptor in AgRP neurons using AgRP-PRLR flox/flox mice. We looked at differences in food intake and body weight between these knockout mice and wildtype littermates, no significant differences were observed. We also used immunohistochemistry to look at GFP expression. These mice would be expected to show Cre-induced expression of GFP if the prolactin receptor was normally expressed in the AgRP neurons. vGAT-Cre-Prlr flox/flox transgenic mice were used as a positive control as previous work suggests that GABA neurons express the prolactin receptor. While GFP was readily detected in the positive controls, no staining of any neurons was visible in the non-pregnant, pregnant or lactating brains from AgRP-PRLR flox/flox mice, indicating that the prolactin receptor gene is not normally expressed in AgRP neurons. From these experiments we were able to conclude that prolactin-induced pSTAT5 does not colocalise with AgRP neurons, and that the prolactin receptor gene is not expressed in AgRP neurons. Therefore, the results obtained did not support our hypothesis that prolactin-induced increases in food intake are mediated by direct actions of prolactin by AgRP cells, and showed that prolactin does not directly act upon AgRP neurons to mediate leptin resistance during pregnancy.

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  • Creating a New Code: Artificial Creation & Erasure of Epigenetic Memory in Mammalian Cells

    Wang, Andrew Hue-Yen (2016)

    Undergraduate thesis
    University of Otago

    ABSTRACT Cytosine methylation is perhaps the most dynamic and best-studied form of epigenetic modification. Occurring predominantly in the CG dinucleotide context within mammalian genomes, it is essential for normal embryonic development, X chromosome inactivation, genomic imprinting and transposon silencing. The uniqueness of CG methylation lies in its ability to be maintained following cell division in the absence of the signal which created it. Together, the global distribution of CG methylation forms an “epigenetic memory” that contributes to the differentiation and maintenance of distinctive somatic cell fates. Artificial manipulation of cytosine methylation (known as “synthetic epigenetics”) could potentially improve the creation and differentiation of developmentally potent cells, which will be instrumental in the advancement of regenerative medicine. I have undertaken two experimental projects investigating the potential of synthetic epigenetics, whereby epigenetic modifiers of non-mammalian provenance were overexpressed in mouse embryonic stem cells (ESCs). In plant genomes, methylation occurs at CHG nucleotides (where H is any base other than G) in an analogous manner to mammalian CG methylation, due to the action of the CMT3 methyltransferase. Thus, in the first project, I created transgenic cell-lines with inducible overexpression of Arabidopsis CMT3, with the aim of creating methylation at CHG nucleotides. Overexpression of CMT3 was performed in three mouse embryonic stem cells (mESC) lines; two wild-type lines (E14 and V6.5) and a DNA methylation depleted line known as (DNMT-TKO). My experimental results to date suggest that CMT3 alone is inadequate for CHG methylation establishment in mammalian genomes, however, increased levels of methylation in the CG context were detected, suggesting it may have previously unappreciated maintenance capacity in this context. The second experimental project explored the nature of DNA methylation removal. Cytosine methylation can be actively removed from DNA by the Ten eleven translocation (TET) enzymes, which oxidise 5-methylcytosine (5mC) to 5 hydroxymethylcytosine (5hmC), and further oxidised derivatives 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Exactly how these analogues are returned to unmodified cytosine is unknown, partly because there are currently few molecular tools to control the transition between 5hmC, 5fC and 5caC. Unpublished in vitro observations suggest that Ten eleven translocation (TET) enzymes from the amœba Naegleria gruberi are far more effective at iteratively producing 5fC and 5caC, compared to mammalian homologues which produces 5hmC predominantly (T.P. Jurkowski, personal communication). I created mouse embryonic stem cells with inducible expression of Naegleria TET and mutated Naegleria TET variants, and used bisulphite sequencing to assess their relative ability to demethylate DNA. I found that the amœba TET variants were ineffective at demethylating DNA compared to mammalian TET controls. Unexpectedly, some constructs even showed significant increased methylation. I hypothesise that the Naegleria TET variants I created act as non-functional competitors of endogenous TET when overexpressed in mammalian cells. While this likely precludes their widespread use in the field of synthetic epigenetics, they still may provide a useful experimental tool for further study of TET enzyme biology.

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  • Functional Role of Uric Acid in Cardiac Stem Cell Homeostasis

    Cheakhun, Cindy (2016)

    Undergraduate thesis
    University of Otago

    In New Zealand, cardiovascular disease (CVD) affects 1 in 20 adults and is the leading cause of mortality. Cardiac pathophysiology along with diabetes mellitus is historically associated with glucose metabolism, but recently it has been suggested that elevated serum uric acid (SUA) could be a major driver of these complications. Cardiac stem cells (CSCs) are a new therapy approach for CVD, however, the therapeutic effects are usually mixed. A major contributing factor could be the necrotic environment that the stem cells are being isolated from or transplanted back into. Elevated SUA could contribute significantly to the necrotic environment. Hence, our goal was to characterise the effects of elevated SUA, reflected by changes in extracellular uric acid (EUA) on cardiac progenitor cell (CPC) function in order to improve stem cell therapy, as CPCs are also investigated for use in stem cell therapy and are similar to CSC in terms of physiology and function. We characterised the uric acid (UA) transporter expression profile in human CPCs including known renal transporters: ABCG2, MRP4, GLUT9, URAT1, OAT1, OAT2, OAT4 and NPT4, using qPCR. Human CPCs as well as mRNA from human heart tissue express UA efflux transporters ABCG2 and MRP4 to a greater extent than UA influx transporter GLUT9, irrespective of diabetic status. The expression of GLUT9, ABCG2 and MRP4 were also confirmed at the protein level through western blot analyses of proteins extracted from CPCs. This transporter profile in human CPCs support our new concept of a ‘cellular uric acid homeostasis’ (CUAH), and the fact that a disturbance of CUAH, as in diabetes mellitus, may be detrimental to the function of CPCs and ultimately affect stem cell therapy. From functional assays, it appears that CPCs are sensitive to changes in EUA concentrations. By the end of UA treatment, 300μM UA treatment, which is considered normal SUA, had the most viable cells. The amount of viable cells decreased with 200μM UA and 500μM UA significantly (p<0.01). In sum, the results support the idea that CUAH is crucial for the functionality of CPCs, and therefore changes in CUAH, or the environment that stem cells and progenitor cells are transplanted into can impair their ability to integrate into the host tissue, and therefore decrease the efficacy of stem cell therapy.

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  • Sex-differential expression of microRNAs during mammalian neurodevelopment

    Szakats, Susanna Katharine (2016)

    Undergraduate thesis
    University of Otago

    Pervasive sex differences between male and female brain development have been implicated in neurodevelopmental disorders featuring a distinct sex bias, such as autism. To further our understanding of sex differences we hypothesised that sex-differential microRNA expression occurs in the developing brain. MicroRNAs are powerful regulators of gene expression whose function is essential for normal brain development, and are thought to mediate development of sex differences. Small RNA sequencing was performed with RNA isolated from E15.5 mouse brains (n=3 per sex), representing early brain differentiation. Comparison of microRNA expression identified 12 microRNAs that were differentially expressed between sexes (p<0.05). Differences in expression were validated using real time quantitative RT-qPCR for miR-10, and miR-205 and miR-5099. miR-10 is encoded within the Hox gene complex, a cluster of genes conferring positional identity to structures along the anterior-posterior axis of the developing embryo. As miR-10 is thought to be controlled in the same spatially co-linear manner as the Hox genes, we anticipated that it has a distinctive expression domain. Using in situ hybridisation with a locked nucleic acid (LNA)-probe targeting miR-10, strong staining for miR-10 expression was found in the hindbrain and anterior spinal cord of embryos at E15.5. Not only did we investigate known microRNAs, we also analysed novel microRNAs aligning to the mouse Anti-Müllerian Hormone AMH gene. Previous experiments identified a non-coding RNA (ncRNA) transcribed at this locus, bearing hallmarks of a primary microRNA. Subsequent preliminary small RNA sequencing at E12.5 (n=1 per sex) showed microRNA profiles at the AMH locus unique to each sex. Using RT-qPCR validation, female-specific expression of a novel microRNA aligning to exon 3 of AMH was determined. Interestingly, an increase in microRNA expression occurred in mouse lines where the exons 1 and 2 of the AMH gene were deleted. This observation lead to identification of a putative repressor element within exon 2, thought to negatively regulate expression of ncAMH. Our findings indicate that sex-differential expression of microRNAs occurs in the developing mouse brain during a key stage of brain patterning. The identified microRNAs are known to influence development and neurological functions, and therefore their expression in a sex-differential manner may contribute to sex differences established in the developing brain.

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  • Efficacy of Prototype Vaccines for Prevention of Tuberculosis

    Sandford, Sarah (2016)

    Undergraduate thesis
    University of Otago

    Tuberculosis (TB) is a pulmonary disease caused by Mycobacterium tuberculosis, which killed 1.5 million people in 2014. The current TB vaccine, live attenuated Mycobacterium bovis bacille Calmette Guérin (BCG), effectively protects against neonatal TB yet has variable efficacy against pulmonary TB in adults. Consequently, a more effective preventive vaccine is needed. This project aimed to characterise the ability of two innovative new vaccines to improve antigen delivery and induce protective mucosal immune responses against mycobacterial infection in mice. The first vaccine approach employed sustained release of protein antigen together with adjuvants to enhance immunogenicity. To that end, a vaccine comprising the mycobacterial antigen 85B (Ag85B) with poly lactic-co-glycolic acid nanoparticles in a thermoresponsive chitosan gel was developed. This vaccine was hypothesised to prolong antigen exposure, enhancing the development of an effective immune response, and reducing the need for booster vaccinations. The second approach was designed to activate mucosal immune responses, using non-pathogenic Lactococcus lactis as a vector. Genetically engineered to overexpress the model antigen Ovalbumin (Ova) on its surface via a Group A Streptococcus serotype M1 Pilus (L. lactis PilM1-Ova), this prototype vaccine was hypothesised to improve antigen delivery to the mucosal immune system. The chitosan gel vaccine containing Ag85B, and the L. lactis PilM1-Ova vaccine were administered separately to groups of mice. For both vaccines, the activation state and cytokine responses of antigen-specific T cell populations were detected using flow cytometry. Compared to BCG, the chitosan gel vaccine did not induce higher frequencies of activated, proliferating, cytokine-producing, or memory Ag85B-specific T cells, and failed to protect against an intranasal BCG challenge. By contrast, L. lactis PilM1-Ova induced more activated, proliferating, cytokine-producing and memory Ova-specific T cells than recombinant BCG expressing Ova (BCG-Ova). Although L. lactis PilM1-Ova was not protective against intranasal BCG-Ova challenge, this may have been due to slow in vivo growth of the recombinant BCG-Ova. This work suggests that the chitosan gel vaccine requires further development to improve immunogenicity, for example by selecting a different antigen or antigen dose. L. lactis PilM1 shows promise as a vaccine delivery system for TB and is worthy of further studies, ideally with expression of an endogenous mycobacterial antigen to measure vaccine-induced antigen-specific T cell responses and protection against TB.

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  • The Influence of Exercise and Hyperlipidaemia on Breast Cancer

    Buss, Linda (2016)

    Undergraduate thesis
    University of Otago

    Exercise reduces the risk of breast cancer development, and improves survival in breast cancer patients. However, the underlying mechanisms of this protective effect remain to be fully elucidated. It is unclear whether exercise can attenuate or modify the pro-tumour effects of obesity and related conditions, such as hyperlipidaemia, on breast cancer growth. The main aims of this study were (1) to develop a relevant, tumour-bearing mouse exercise model and (2) to determine the effect of exercise and hyperlipidaemia on the breast tumour microenvironment. We hypothesise that exercise attenuates the negative effect of hyperlipidaemia through ‘normalisation’ of the tumour microenvironment. Hyperlipidaemic ApoE-/- and wild-type (WT) C57BL/6 mice with orthotopic EO771 breast tumours were randomly assigned to intermittent or continuous voluntary wheel running or sedentary control. When tumours reached maximum size, mice were sacrificed and the serum, organs and tumours removed for analysis of tumour cell proliferation, immune infiltrate, circulating inflammatory factors, perfusion, microvessel density, hypoxia, HIF-1α protein level and GLUT-1 protein expression. This was done by immunohistochemistry, immunofluorescence, ELISA and Western blotting. Although exercise and hyperlipidaemia did not significantly impact tumour growth rate, exercising mice had significantly reduced body weights. Tumour-bearing mice showed a significant increase in serum monocyte chemoattractant protein 1 (MCP-1) compared to non-tumour-bearing mice (p<0.05), but perfusion was not significantly altered. Further studies are necessary to clarify and confirm these results, as this study was limited both by a short exercise and tumour-bearing time period. This study identifies a number of key considerations in the design of future preclinical exercise studies in tumour-bearing mice. In addition, our results provide evidence for the potential value of MCP-1 as an exercise-regulated, prognostic biomarker in mouse models, and indicate that hyperlipidaemia normalises the microenvironment of the tumour.

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