Otago University Research Archive
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Mining reality to explore the 21st century student experience
No full textUnderstanding student experience is a key aspect of higher education research. To date, the dominant methods for advancing this area have been the use of surveys and interviews, methods that typically rely on post-event recollections or perceptions, which can be incomplete and unreliable. Advances in mobile sensor technologies afford the opportunity to capture continuous, naturally-occurring student activity. In this thesis, I propose a new research approach for higher education that redefines student experience in terms of objective activity observation, rather than a construct of perception. I argue that novel, technologically driven research practices such as ‘Reality Mining’—continuous capture of digital data from wearable devices and the use of multi-modal datasets captured over prolonged periods, offer a deeper, more accurate representation of students’ lived experience.
To explore the potential of these new methods, I implemented and evaluated three approaches to gathering student activity and behaviour data. I collected data from 21 undergraduate health science students at the University of Otago, over the period of a single semester (approximately four months). The data captured included GPS trace data from a smartphone app to explore student spaces and movements; photo data from a wearable auto-camera (that takes a photo from the wearer’s point-of-view, every 30 seconds) to investigate student activities; and computer usage data captured via the RescueTime software to gain insight into students’ digital practices. I explored the findings of these three datasets, visualising the student experience in different ways to demonstrate different perspectives on student activity, and utilised a number of new analytical approaches (such as Computer Vision algorithms for automatically categorising photostream data) to make sense of the voluminous data generated. To help future researchers wanting to utilise similar techniques, I also outlined the limitations and challenges encountered in using these new methods/devices for research.
The findings of the three method explorations offer some insights into various aspects of the student experience, but serve mostly to highlight the idiographic nature of student life. The principal finding of this research is that these types of ‘student analytics’ are most readily useful to the students themselves, for highlighting their practices and informing self-improvement. I look at this aspect through the lens of a movement called the ‘Quantified Self’, which promotes the use of self-tracking technologies for personal development.
To conclude my thesis, I discuss broadly how these methods could feature in higher education research, for researchers, for the institution, and, most importantly, for the students themselves. To this end, I develop a conceptual framework derived from Tschumi’s (1976) Space-Event-Movement framework. At the same time, I also take a critical perspective about the role of these types of personal analytics in the future of higher education, and question how involved the institution should be in the capture and utilisation of these data. Ultimately, there is value in exploring these data capture methods further, but always keeping the ‘student’ placed squarely at the centre of the ‘student experience’
Paleoseismology of the NW Cardrona Fault, Central Otago
No full textThis thesis documents a paleoseismic study of the Northwest (NW) Cardrona Fault at the Branch Creek Road site in the Cardrona Valley, Central Otago. The northeast-striking NW Cardrona Fault is a major range-bounding reverse fault with as much as c. 1 km of late Cenozoic, west-side-up, throw. It forms the northwestern component of a significant geological structure, the Nevis-Cardrona Fault System, and defines the western margin of the Otago ‘Range and Basin’ reverse fault province. A pre-existing knowledge of the NW Cardrona Fault was based mostly on mapping, trenching, and dating led by the late Sarah Beanland in the 1980s, as part of seismic hazard investigations for hydroelectric development (Beanland and Barrow-Hurlbert 1988). The Branch Creek Road trench was excavated in 1984 by Sarah Beanland across a scarp of the NW Cardrona Fault that shows east-side-up displacement; the opposite sense to that of the rest of the fault. Beanland’s early interpretations suggested the occurrence of three rupture events at the site; however, age control on the timing of these events was limited by the dating techniques available at the time. This thesis documents a re-excavation of the Branch Creek Road trench and interpretation of fault rupture chronologies via Optically Stimulated Luminescence (OSL) dating. With the aid of nine OSL samples, the timing of these events has been constrained to the following: an antepenultimate event between 37,800 ± 4,000 and 39,300 ± 4,400 years; a penultimate event between 27,200 ± 2,800 and 28,200 ± 2,600 years; and, the most recent event most prudently placed between 3,300 ± 600 and 14,300 ± 1,400 years. The 3.5 m of cumulative dip-slip displacement measured across these three surface rupture events equates to an average dip-slip single-event displacement of c. 1.2 m. Lastly, the opposite sense of fault slip at this site relative to other parts of the fault is interpreted as being a short-lived structural complexity, in that the fault is accommodating surface slip above the blind master NW Cardrona fault. Ruptures on the Branch Creek trace are therefore considered to be directly linked to ruptures on the master NW Cardrona Fault
The response of estuarine bivalve Austrovenus stutchburyi to hypoxic multiple-stressor environments
No full textEutrophication-induced hypoxia is amongst the most widespread anthropogenically deleterious environmental issue occurring globally in coastal marine environments. Along with habitat loss, overfishing and harmful algal blooms, hypoxia contributes to a suite of major stressors on marine organisms. These cause stress to aerobic organisms, changes to biogeochemical processes and loss of biodiversity and ecosystem function, particularly in estuaries.
The response of a species to a single stressor is often very different when compared to exposure in an environment with multiple stressors. The focus of the current thesis is on the sublethal and lethal effects of hypoxia, warming and nutrient enrichment on the estuarine bivalve Austrovenus stutchburyi. Hypoxia and warming rarely occur in isolation as stressors that shape a species or community response. Midday low tides have been identified as a driver of mortality events for bivalves globally as a combined result of thermal stress and desiccation. Laboratory experiments were used to test the effects of simulated midday low tides and chronic NH3 exposure on activity, respiration and survival of A. stutchburyi experiencing oxygen depletion.
A long-term decline in oxygen solubility associated with warming was identified for Coastal Otago. Monitoring of bottom-water dissolved oxygen (DO) in a shallow microtidal estuary on the South East Coast of New Zealand was undertaken to bridge observational and experimental work. This monitoring revealed diel- and seasonal DO cycling. Modelling indicated spatial variability within Waitati Inlet. Land-based influence from freshwater and tidal forcing was driving low DO in Waitati channel, while PAR and wind speed were key drivers of biological respiration and wind-induced mixing in Warrington channel which has Ulva spp., present in it. Daily DO minima occurred primarily early morning at low tide as a likely consequence of respiration by primary producers and the tidal ebb carrying water depleted of oxygen.
Siphon activity and respiration rates were enhanced under hypoxia (20% saturation) compared to normoxia in 22 °C and 25 °C water conditions, while survivorship decreased with exposure to increasingly stressful environments. Experimental findings indicated the likely existence of a positive feedback loop whereby A. stutchburyi, stressed by low oxygen, produce more ammonia waste, increasing risk of mortality and subsequent NH3 concentrations. A lethal emersion thermal threshold was surpassed at 33 °C in 20% and 100% DO, suggesting extreme thermal events such as heatwaves could have substantial detrimental implications for bivalve populations and subsequent ecosystem functions.
The findings of the present thesis are relevant to understanding the likely biological consequences of observed patterns of warming in the coastal marine environment and the decline in oxygen solubility observed in Otago. The increased biological oxygen demand due to warming may lead to more frequent hypoxic events and degradation of estuarine environments
Vitamin C as an Epigenetic Therapeutic for Acute Myeloid Leukaemia
No full textAcute myeloid leukaemia (AML) is a deadly disease characterised by the abnormal proliferation of immature blood cells in the bone marrow with a block in haematopoietic differentiation. The disease is heterogeneous, and genetic analysis has identified at least 11 different subgroups. Mutations in epigenetic enzymes occur commonly in AML and we now understand that epigenetic dysregulation is strongly implicated in the pathogenesis of the disease. For example, deletions and loss-of-function mutations in the epigenetic demethylase TET2 arise in approximately 10% of de novo AML cases.
The discovery of mutations in epigenetic enzymes as drivers of AML opens a window of opportunity for the identification of small molecule therapeutics to reverse epigenetic dysfunction. Recent evidence has cast a spotlight on vitamin C as one potential epigenetic therapeutic through its action as a co-factor for the TET and histone lysine demethylase enzymes.
I examined the epigenetic effects of vitamin C in AML, by using a SKM-1 myeloid leukaemia cell model characterised by a heterozygous loss-of-function mutation in TET2. Treatment with vitamin C decreased SKM-1 proliferation in vitro and promoted differentiation towards a more mature cell phenotype. Unexpectedly, vitamin C also inhibited the proliferation of NB4 and K562 cells, both leukaemia cell lines without TET2 mutations.
My research shows that vitamin C can act via at least two separate mechanisms to decrease the proliferation of leukaemia cells in vitro. One mechanism likely involves the generation of hydrogen peroxide causing cell death, and in the SKM-1 cells this mechanism was inhibited by catalase or by the substitution of ascorbate with phosphoascorbate, a redox stable alternative. The second mechanism was independent of hydrogen peroxide and caused decreased cellular proliferation. The increased activity of TET2 following vitamin C administration may play a role in the decrease in SKM-1 cell growth. This is because the changes in cellular surface antigen expression observed after treatment with vitamin C reflect the pattern observed in other studies following TET2 reactivation.
Combination treatments are the cornerstone for successful therapy in AML. Thus, vitamin C is likely to be most effective in AML as an adjunct therapy. For this reason, it is important to understand how vitamin C affects the activity of other therapeutics such as the anti-cancer drug Prima-1Met. Prima-1Met is a novel compound with the potential to reactivate mutant p53 and cause cancer cell death through oxidative stress mechanisms. The drug’s mechanisms of action are significant given that TP53 mutations are associated with a dismal prognosis in AML. I show that vitamin C does not appear to counteract the effects of Prima-1Met in the SKM-1 model. These results support the growing body of literature highlighting vitamin C’s potential as an epigenetic therapeutic in AML
Learning Gene Interactions and Networks from Perturbation Screens and Expression Data
No full textWe investigate a variety of methods to first discover and then understand genetic interactions. Beginning with pairwise interactions, we propose a method for inferring pairwise gene interactions en masse from short- interfering RNA screens. We use the siRNA off-target effects to form a matrix of knocked-down genes, and consider the observed fitness to be a linear combination of individual and pairwise effects in this matrix. These effects can then be inferred using a variety of statistical learning methods. We evaluate two such methods for this task, xyz and glinternet. Using either method, we are able to find interactions in small simulated data sets. Neither method scales to genome-scale data sets, however. In our larger simulations both methods suffer from scalability problems, either with their accuracy or running time. We overcome these limitations by developing our own lasso-based regression method, which takes into account the binary nature of our perturbation screens. Using a compressed sparse representation of the pairwise interaction matrix, and parallelising updates, we are able to run this method on exome-scale data. Generalising from pairwise interactions we then consider network models, in which pairwise gene interactions form edges of a graph. Such networks are often understood in terms of functional modules, groups of genes that act together to perform a task. We develop a method that combines pairwise interaction and gene expression data to effectively find functional modules in simulated data
One Flake at a Time: a study of adze production at Wairau Bar through debitage analysis
No full textThis thesis explores the adze industry of the early period of Māori history. The research focuses on the production of adzes at the site of Wairau Bar which dates to the earliest phase of New Zealand settlement. It aims to establish the role of this site in a wider system of adze production though the analysis of a debitage assemblage excavated from the site in the 2009 field season. The debitage assemblage consists of the waste material produced through adze manufacture and the analysis is structured to target what stages of manufacture the material represents, thereby determining the production practices being undertaken at the site. The results of the analysis are then tested against a proposed model of the adze industry, from raw material procurement to distribution, and conclusions are drawn about both the structure of the industry and the role Wairau Bar and its people would have played
Film Families and Friends: Creative Networks in a Precarious Industry
No full textFilms have been made in Aotearoa for more than a hundred years but the early 1970s saw significant growth in independent filmmaking. This thesis investigates the period of New Zealand film’s evolution from informal cottage industry to professional global industry, focusing on the changes and continuities in filmmaking culture between 1970 and 2020.
Drawing on the literature on filmmaking and creative industries, and using the theories of Actor-Network, and of habitus and capital developed by Pierre Bourdieu the thesis focuses on three distinctive characteristics of the New Zealand industry: project-based work, freelance networks, and the enculturation of second and third generations into filmwork. The place of families and friendships is central to the processes of enculturation and to all these networks. These three characteristics also shape the inclusion and exclusion of marginalised groups, especially women, LGBTQ, and Māori and Pasifika filmworkers.
Semi-structured interviews were conducted with twenty participants. I undertook a thematic analysis of the interviews, in the light of the secondary literature. The analysis showed strong connections between self-image and creative work, between habitus and family legacy occupation and between networks of the counterculture and the development of film in New Zealand. It also revealed changes in the industry as it becomes more open and diverse, and that the gendered participation of families has altered through successive generations
Tumour Necrosis Factor Signalling Heterogeneity in Inflammatory Bowel Diseases
No full textInflammatory bowel disease (IBD) is chronic, heterogeneous diseases characterised by excess inflammation in the gastrointestinal system and a dysfunctional mucosal immune response. Tumour necrosis factor (TNF) is a pleiotropic, pro-inflammatory cytokine upregulated in the serum and mucosa of IBD patients, compared to healthy controls (HCs). Anti-TNF treatment neutralises TNF, preventing the induction of downstream signalling pathways in immune cells. Cell death, pro-inflammatory and pro-survival responses can be mediated by TNF-induced ERK, p38 and NFĸBp65 proteins. The functions of these proteins are diverse and context dependent. Up to 40% of IBD patients do not initially respond to anti-TNF. It was hypothesised that the heterogeneity of TNF signalling in individuals may determine the anti-TNF response. TNF signalling pathways in peripheral blood mononuclear cells (PBMCs), derived from IBD patients and HCs, were activated using TNF stimulation or pan-stimulation by PMA/ionomycin. A phosphoflow cytometry protocol was optimised to allow visualisation of phosphorylated (activated) proteins in immune cells, in response to stimulation. Changes in phosphorylation were measured by normalised fold changes in mean fluorescence intensity (MFI). There was no difference in phosphorylated (P) p38, P-ERK or P-NFĸBp65 expression in CD3+ CD4+ T cells or CD14+ CD64+ monocytes between healthy (n=8) and IBD (n=5) groups (all p>0.05, Mann-Whitney U test). However, one IBD patient had comparatively higher P-p38 expression in CD3+ CD4+ T cells (MFI fold change = 3.8) and lower expression of P-NFĸBp65 in CD3+ CD4+ T cells (MFI fold change = 2), in response to PMA/ionomycin stimulation. A second patient had comparatively higher NFĸBp65 phosphorylation (MFI fold change = 6.21) in response to PMA/ionomycin stimulation, compared to IBD and HC individuals. Interestingly, the first patient was an anti-TNF non-responder. This study provides preliminary data showing the extent of individual heterogeneity in immune response. This study supports the individual analysis of IBD patients to inform the heterogeneity of IBD pathogenesis and how this may be implicated in treatment non-response
The role of SCN AVP neurons in modulating RP3V kisspeptin neuron activity in physiological and pathological reproductive states
No full textMammalian fertility is governed by a neural circuit that ultimately controls the activity of gonadotropin-releasing hormone (GnRH) neurons. Activation of GnRH neurons results in the pituitary release of luteinising hormone (LH) and follicle-stimulating hormone. Prior to ovulation, there is a surge in the release of LH, due to the increased activity of afferent kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V). These kisspeptin neurons are under the control of circadian inputs from the suprachiasmatic nucleus (SCN) and ovarian steroid hormone feedback. One key circadian input to kisspeptin neurons is the vasopressin (AVP) neurons from the SCN. Recent evidence has shown that AVP increases RP3V kisspeptin neuron activity, in relation to the level of ovarian steroids. As such, it is hypothesised that SCN AVP neurons are a key input onto RP3V kisspeptin neurons and their activation underpins the downstream activation of kisspeptin neurons and the resulting preovulatory LH surge.
Using genetically-mediated anterograde viral tract tracing, the projection from SCN AVP neurons was traced in the Avp-cre mouse model. Avp-cre projections to the RP3V were found in the RP3V and were in close appositions to kisspeptin neurons present. There was a significant correlation between the amount of viral-expression in Avp-cre neurons in the SCN to the density of projections seen in the RP3V; there was no correlation between other AVP- expressing regions and the RP3V. This indicates that the Avp-cre projection to the RP3V is specifically from the SCN, rather than from other areas if the brain.
To determine whether the Avp-cre projections to RP3V kisspeptin neurons were communicating by GABAergic fast-synaptic transmission, a viral vector expressing a channelrhodopsin (ChR2) variant was injected into the SCN of female Avp-cre:Kiss1-hrGFP mice. Using short pulses of blue light, the ChR2-expressing projections were optogenetically stimulated while whole-cell electrophysiological recordings were made from identified kisspeptin neurons in the RP3V. Despite the Avp-cre appositions to RP3V kisspeptin neurons, very few received inhibitory postsynaptic currents from ChR2-expressing Avp-cre projections in response to optogenetic stimulation. There were no differences to this input across the oestrous cycle.
To determine the contribution of AVPergic to RP3V kisspeptin neurons, high-frequency light stimulation (HFLS) of Avp-cre projections was carried out whilst on-cell loose-patch recordings were made from identified RP3V kisspeptin neurons. There was a significant increase in kisspeptin firing rate following HLFS solely in proestrus, which was not seen in other oestrous cycle stages. This response was able to be blocked by the V1R antagonist Manning Compound, indicating it was mediated by AVP release. Surprisingly, a second response was found, solely in oestrus. Rather than a delayed, AVP-mediated excitation of kisspeptin neurons, an immediate inhibition in kisspeptin firing was noted. This response was not seen in other oestrous cycle stages. To determine the potential mechanism of this inhibition, the GABAAR antagonist, gabazine, was applied throughout HFLS. This inhibited the HFLS- induced decrease during oestrus, suggesting it was mediated by GABA release. Both the excitatory and inhibitory responses seen across the oestrous cycle correlate to time points where the LH surge should and should not be initiated respectively. This points towards a mechanism by which SCN AVP neurons can either trigger or inhibit the onset of the LH surge.
This work was followed by an examination of the SCN-to-RP3V circuit in a mouse model of polycystic ovary syndrome (PCOS), which does not naturally mount an LH surge. In the prenatally androgen-treated (PNA) mouse model, the Avp-cre projection to the RP3V was reduced; as was the proportion of close appositions made with kisspeptin neurons. Despite this, kisspeptin neurons from the PNA mouse were able to respond to AVP application.
Overall, this work has confirmed a projection from SCN AVP neurons to RP3V kisspeptin neurons, that comprises an indirect pathway leading to GnRH neuron activation. Activation of this circuit shows oestrous cycle-dependent changes that are consistent with increases in neural activity at the time of the LH surge. Finally, as this circuitry is critical for the timing of the LH surge, its reduction in a clinically relevant mouse model, may be an underlying cause of ovulatory dysfunction seen in PCOS
Mucosal-associated invariant T cell regulation by bacterial signalling and immunometabolism
No full textMucosal-associated invariant T (MAIT) cells are a subset of antibacterial innate-like T cells that are localised to mucosal surfaces. MAIT cells are characterised by the expression of a semi-invariant T cell receptor, specific to a bacterial antigen presented on the MHC class I related protein, MR1. The bacterial ligand is derived from 5-amino-6-D-ribitylaminouracil (5-A-RU), produced as an intermediate in the bacterial riboflavin synthesis pathway. 5-A-RU undergoes non-enzymatic condensation with methylglyoxal (MG), a glycolysis by-product, to form the final ligand, 5 (2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). Presentation of 5 OP RU to MAIT cells stimulates a robust MAIT cell response. Given the abundance of MAIT cells at mucosal surfaces and the broad range of bacteria capable of activating them, it has been hypothesised that MAIT cell activation is tightly regulated to prevent hyperactivation and immunopathology. Understanding these regulatory mechanisms may enable modulation of MAIT cells to prevent or treat human disease. Here I show that both phagocytosis of bacteria by an antigen presenting cell (APC) and enhanced glycolysis regulate MAIT cell activation. To assess this, THP-1 cells, a monocytic cell line, served as APCs. THP-1 cells were incubated with glycolysis modulators, exogenous ligand, and non-ligand producing bacteria. Primary human MAIT cells were subsequently co-cultured with THP-1 cells and activation assessed by flow cytometry. Treatment with intact bacteria and 5-A-RU was found to activate MAIT cells to a greater extent than treatment with 5-A-RU alone or with lysed bacteria. Enhancement of THP 1 glycolysis augmented MAIT cell activation to 5-A-RU alone or 5-A-RU and lysed bacteria. In contrast, a reduction in activation was not observed when THP-1 cell glycolysis or PI3K, mTORC1, and mTORC2 signalling were inhibited. Furthermore, THP-1 cells did not exhibit increased glucose uptake upon stimulation with intact bacteria. These results suggest that phagocytosis of intact bacteria may enhance glycolysis, resulting in increased production of MG and formation of 5-OP-RU. However, further research is required to confirm this. The process described provides a potential regulatory mechanism by which MAIT cell activation is regulated in response to intact bacteria but not to soluble bacteria-derived 5-A-RU