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Driving away rats: candidate fertility targets for mammalian gene drives
No full textThe dispersal and subsequent proliferation of mammalian invasive species in new environments has significant impacts on food security, disease, and conservation worldwide, particularly in island nations where they have disproportionately large consequences in these unique insular ecosystems. Traditional control techniques such as kill trapping, and poison control strategies have served well in the past for controlling problem species. However, concerns for animal welfare, off-target effects and limits to long-term efficiency have fuelled a search for novel, highly effective control techniques. Harnessing the power of “super Mendelian inheritance”, gene drive technology can propagate a particular gene through a population, even if it is deleterious to the organism. By targeting key genes associated with reproductive processes, gene drives can be used to control a species by inducing infertility in one sex, while the other sex continues to propagate the impaired fertility phenotype through the population. Despite established theory and empirical experiments using gene drives in insects, there is, as yet, no gene drive fertility control system established for mammals. A major current limitation is the lack of validated candidate genes for mammalian gene drive systems.
My research establishes the first systematic review framework for identifying candidate genes for a range of invasive species. Using this framework, I have subsequently identified a list of 17 genes that could be targeted in a rodent gene drive system. Remarkably, results are significantly biased towards genes with male-specific fertility phenotypes, as those with female fertility phenotypes demonstrate additional pleiotropic attributes. I also provide a foundational bioinformatics pipeline to characterise these loci across populations of target invasive species, applying this to whole genome sequences from 42 ship rat (Rattus rattus) samples representative of the Aotearoa New Zealand (NZ) population. Subsequently, highly conserved sequences were used to inform potential gRNA design and parameters in a computational model exploring the dynamics of a CRISPR-Cas9 homing gene drive in the NZ ship rat population. Results from the model are consistent with previous findings that suggest targeting female fertility more reliably results in successful eradication, compared with targeting male fertility. However, the evident disparity between optimal theoretical parameters (i.e., targeting female fertility), and biological feasibility (i.e., candidate gene bias towards the male reproductive system) presents an important technical challenge for the design and development of mammalian gene drives.
To investigate the feasibility of utilising the same gene drive targets across a cohort of species, I further employed comparative genomics to evaluate sequence conservation of my candidate genes across nine invasive species in NZ - house mouse (Mus musculus), Norway rat (Rattus norvegicus), ship rat (Rattus rattus), European rabbit (Oryctolagus cuniculus), European hedgehog (Erinaceus europaeus), domestic cat (Felis catus), domestic ferret (Mustela putorius furo), stoat (Mustela erminea), and brushtail possum (Trichosurus vulpecula). Although no target loci that met my criteria were conserved across my evaluated list of invasive species, it is evident that several candidate genes have highly conserved sequences between distantly related groups of invasive species, implying that the molecular co-design of mammalian gene drives across several invasive species may be feasible.
Gene drive technology is still in its infancy, and many questions regarding the risks and benefits of its applications are yet to be resolved. However, in an era of global biodiversity crisis, it is necessary to thoroughly assess promising new avenues for the control of invasive species. My research contributes a list of strong candidate genes that could be targeted in a rodent gene drive for population suppression, and I further refined that list by identifying genes that may have strong multi-species utility. Such results progress research in a highly economically, socially, and environmentally significant area for international conservation
NZDep2018 analysis of census 2018 variables - TA21: Taupo District
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
The challenges we face: A professional identity analysis of learning technology implementation
No full textInstitutionally implemented learning technologies are often not adopted or are underused by academic staff. We aimed to better understand this problem by drawing on the notion of professional identity to explore the challenges academic staff experienced when they were to adopt a replacement learning management system (LMS). We describe a single case study approach in which focus group discussions, workshop evaluation data and documents are analysed. We found that challenges academic staff faced lay in the technology being a threat to professional identity, in the sense-making process, and in the diverse and individually distinct nature of teachers’ professional identities. Institutional support offered to facilitate staff adoption appeared not to fully address these challenges. The implications for academic development and technology implementation are explored.Peer Reviewe
Learning by Watching Others Learn: Vicarious Learning from Videoed Tutorials
No full textResearch attests to the efficacy of small group and individual tutoring in a range of educational contexts, but such tutoring requires resources that are beyond the means of many higher education institutions. In response, researchers have applied the notion of vicarious learning to explore the potential of having university students observe videos of tutorial discussions. The evidence from laboratory studies is very positive; students can and do learn from watching videos of tutorials, but the literature is somewhat confused, and a practical methodology has not been offered. This chapter reviews over two decades of research on observing others learn in tutorials. Additionally, the chapter shares the practice-based wisdom developed by the authors as they have sought to apply and test the approaches described in the research literature within a university business school. The chapter includes a series of recommendations with the aim of ensuring that learning vicariously from videoed tutoring is a pedagogy that can be successfully implemented by others.Peer Reviewe
Sustainable Domestic Food Waste Practices in Dunedin’s Tertiary Precinct
Get PDFFood waste is a ‘wicked’ problem that has environmental, economic, ethical, socio-cultural and resource management implications. It is becoming increasingly important within environmental policy planning around the world.
In New Zealand, young adults and large households have been identified as significant contributors to domestic food waste levels. Limited research has been done on the types of barriers to sustainable domestic food waste practices that these demographic groups experience. Dunedin’s tertiary precinct was selected as an ideal area for exploring such barriers due to its demographic trends.
The methods for data collection included an online survey open to residents of the tertiary precinct, complemented by interviews with key informants from a diverse range of positions within local institutions, local government, and student bodies. The research provided valuable insight into how several aspects of the local socio-cultural conditions, infrastructure, and the built environment hinder residents from minimizing domestic food waste and make it difficult for them to divert food waste from the landfill. Most of the barriers and issues that surfaced during this research are layered and inter-related to a high degree.
The timing of the research may be significant as several initiatives are in motion at both local government and tertiary institution level that have the potential to positively influence domestic food waste practices in the precinct. Recommendations were presented for how collaborative planning between actors can help address barriers to sustainable domestic food waste practices in the tertiary precinct and beyond
Constructive Arrows: An Introduction to Categories, Toposes and Logic
Get PDFCategory theory, especially topos theory, admits a new perspective on the study of logic and mathematical foundations. In this dissertation, we provide an introduction to the development of logic in a topos, and show why this logic does not validate the law of excluded middle. Assuming no prior knowledge of category theory, we motivate and introduce some main concepts of categories that allow for defining a topos. We briefly provide an introduction to order theory, giving the tools needed for analysis of the subobject algebras in a topos. We introduce the domain of formal logic and define propositional logical valuations on the subobject algebras and on a topos. We end with showing how the topos logic is intuitionistic, by virtue of the subobject algebras being Heyting algebras
Musical activity in older adulthood reverses age-related emotion recognition decline
No full textEmotion recognition is key to social functioning, though it declines across the adult lifespan. Why decline occurs and how it should be addressed is yet to be understood. In this thesis I investigated potential causes of emotion recognition decline, as well as the efficacy of a novel music training intervention with older adults to improve emotion recognition. I put forth in the Introduction the argument that age-related declines in emotion recognition are primarily caused by neurodegeneration, and that because music training is a uniquely powerful stimulus for facilitating neuroplasticity, musical engagement in older adulthood should improve neuropsychological functioning by attenuating neurodegeneration, particularly in the frontal lobes.
In Study 1, young (aged 18 to 30 years) and older adults (aged 59 years and older) completed laboratory tasks assessing facial and musical emotion recognition, facial age estimation, fluid intelligence, and musical competence. During all but the musical competence task, surface-level activity in the medial and lateral prefrontal cortex (PFC) was monitored using functional near-infrared spectroscopy. Older adults performed more poorly on the musical emotion task relative to young adults, and this was not due to having worse musical competence or cognitive ability. Face processing decline also did not appear to cause emotion recognition difficulties among older adults, as performance on the two face tasks were not correlated. Older adults also showed greater left and right lateral PFC activation during the two emotion tasks compared to young adults, and a contrast between the two emotion tasks within the older group revealed greater music-related than face-related activation in the lateral regions. Neurodegeneration was the most compelling explanation of the findings. Older adults appeared to require greater activation in cognitive control areas to compensate for neurodegeneration, proportionate to task difficulty.
In Study 2, the older adults who participated in Study 1 were randomly assigned either to a four-month, group-based music appreciation or guitar learning intervention designed specifically for this research. After the intervention, participants completed the same tasks as outlined above, again, while cortical PFC activity monitored. Facial and musical emotion recognition improved between pre- and post-intervention, collapsing across both groups, but I did not find evidence for a relative benefit of one intervention over the other on the behavioural or neuroimaging measures. However, older adults’ age moderated the effect of intervention group on changes in behavioural musical emotion recognition and PFC activation during facial emotion recognition. For guitar learners but not music appreciators, advancing age was associated with greater improvements in musical emotion recognition and increases in facial emotion-related PFC activation. Guitar learning, thus, promoted emotion recognition for those at ages where neurodegeneration has had its greatest impact.
The implications of Study 1 and Study 2 and their relation to previous research are examined in the General Discussion. Overall, the take-home message is this: we should look to brain health to both understand and improve older adults’ emotion recognition, and music training is a suitable vehicle to do so
Systemic, but not local, treatment with Epothilone D improves motor skills and axonal regrowth after focal stroke in adult male mice
Get PDFA stroke or cerebrovascular accident is one of the leading causes of death worldwide. Ischemic stroke, the most common form, is caused by a blockage in blood supply to the brain. It triggers a cascade of pathological events including inflammation, excitotoxicity and release of free radicals that lead to cell death. To date, drug therapies have attempted to target the loss of nerve cells. These therapies are collectively known as neuroprotectants. However, these therapies have failed to translate into the clinic. The only FDA-approved treatments for acute stroke are either thrombolytic agents such as alteplase and tenecteplase that have a therapeutic window of 4.5-6 h, or endovascular stent clot retrieval devices that can be used within 24 h. While these work well, they are only useful in approximately 15% of all stroke cases, which is why there is a compelling need to find new stroke treatments.
Recently, tumour suppression drugs have proven their ability in promoting microtubule (MT) equilibrium and growth cone development. In preclinical studies, the cancer treatment medications taxol and epothilones showed a capacity to stabilise microtubules (MTs). Epothilones have more advantages than taxol, such as the ability to cross the blood-brain barrier and induce less tissue toxicity. Epothilones represent a potential pharmacological treatment to modulate functional recovery outcomes after a stroke. Although the pharmacokinetics and pharmacodynamics of epothilone and taxol are available, more data needs to be collected to clarify their therapeutic potential. It is important to accurately test whether isotypes of these drug families can reduce drug-related side-effects, and to find the most appropriate pharmaceutical preparation for axonal growth and synaptic rewiring for functional recovery. To date, there has not been any trial to use a MT stabilizing agent in an animal stroke model. This project’s general aim is to test the effect of systemic and local administration of epothilone D on functional recovery and axonal growth in a mouse stroke model. The D isotype was investigated because it is a more potent microtubule stabilizer than other epothilone isotypes.
In this project adult male mice were randomly distributed among 6 groups (n=7 per group). Stroke was induced by photothrombosis in the treatment groups, while sham animals received the same procedure without a photothrombosis reaction. Epothilone D or vehicle was administered either as weekly 1.5 mg/kg intraperitoneal injections for 3 weeks or locally into the stroke cavity in the form of a hyaluronan/ heparin gel (5 nM). Animals were tested on grid walking and cylinder tasks for 7 weeks before euthanasia. Brains were collected for histological assessment. It was evident that epothilone D administered systemically significantly reduced the number of forelimb foot faults contralateral to the stroke injury side from 6 weeks post-stroke in a gridwalking task compared to mice receiving vehicle instead of epothilone D (P<0.05). Furthermore, axonal sprouting in the motor and premotor cortexes (assessed using neuroanatomical labelling following injection of the tract tracing dye biotinylated dextran amine, BDA) was improved in systemic epothilone D-treated stroke-affected mice in comparison to vehicle-treated stroke-affected animals (P=0.001). However, animals which received local infusion of epothilone D in the stroke cavity failed to show signs of improved behavioural outcomes or a significant change at the level of axonal sprouting. These results are promising regarding the potential use of epothilone D and other MT stabilizing drugs in stroke recovery, and they warrant further optimization to refine the delivery method and improve the outcomes
'Water we do about the river?' An Integrated Approach to Understanding Water Quality in the Waikaka Stream, Southland, New Zealand
Get PDFWater quality causes are a highly contested issue in New Zealand, with rivers and streams struggling with the effects of intensive pastoral agriculture. The Waikaka Stream in Southland is an example of a catchment that currently does not meet local water quality standards, due to ‘very poor’ water quality. Management of freshwater has changed significantly over time in New Zealand, but has typically been the responsibility of regional authorities, carried out with a reliance on technical and scientific information, often with a disregard for the socio-political dimensions of freshwater management. Consequently, in recent years communities in Southland have mobilised to form catchment management groups, offering an alternate bottom-up management regime. It is unknown how these community management groups fit into the wider environmental management structure in New Zealand, or how they can be best directed to contribute to the improvement of New Zealand waterways, including the Waikaka Stream. The aim of this study was to evaluate the water quality of the Waikaka Stream and analyse community responses to their perceived water quality problem. A socio-hydrology lens was employed to elucidate how the measured data compared to water quality perceptions. A mixed methodological approach used a 12-month data set with a monthly water sampling frequency, and semi-structured interviews with farmers in the Waikaka Catchment. Quantitative and qualitative results were integrated in the interpretation phase, to understand the disconnect between physical water quality parameters and community perceptions of the Waikaka Stream. The Waikaka Stream water quality was highly variable across the catchment, indicating that the current single monitoring site is not appropriate to be fully representative. Suspended sediment concentrations exceeded national guidelines across the entire catchment, with site averages ranging from 4.0 mg L-1 to 10.8 mg L-1. E. coli thresholds were exceeded at six sites, ranging from 126 CFU/100ml to a maximum of 1414 CFU/100ml. Total nitrogen ranged from 0.3 ppm to 3.0 ppm, while total phosphorus measured between 11.9 ppb and 242.6 ppb. The water quality results showing exceedance of national guidelines, which contradicted farmer perspectives of ‘good’ water quality, highlighting the hidden risk of water quality. This discord creates issues for freshwater management, as it introduces distrust between farmers and the regulating regional government. The power dynamics between stakeholders can further complicate the collaborative management process and limit the implementation of improved management strategies. The formation of the Waikaka Stream Catchment Group indicates that farmers and local community members are seeking collaborative action to improve freshwater health. This study demonstrates that catchment groups deliver an opportunity for social learning, and a format by which local knowledge can be better included in management, to work towards the principles of Integrated Catchment Management (ICM). Catchment groups provide a link between individual farmers and regional government, therefore building trust for future collaborative management
Wild self-care: Rethinking 'risky' health-related practices among members of the gay community
Get PDFGay and queer men tend to experience higher rates of mental health issues, STIs/HIV, suicide, substance dependency, and poor well-being than other demographics. Despite sustained public health efforts internationally, many of these issues continue to disproportionately affect members of the gay community. This thesis presents a new approach to the health issues gay and queer men face. It examines how ‘risky’ health-related practices including condomless sex and the use of illicit drugs might be legitimate ways of performing self-care and pursuing well-being.
In order to address this aim, I conducted 16 interviews over a 12-month period in New Zealand and Australia using a constructionist grounded theory approach and a theoretical framework that draws upon the work of Judith Butler, Elizabeth Grosz, Michel Foucault, Homi Bhabha, Kane Race, Nikolas Rose, and Pierre Bourdieu. My participants and I explore a wide range of topics including the performative nature of sex and the notion of ‘play’, how pleasure and the emotional significance of sex might be related to self-care, the ways in which space might influence sexual practices and experiences, and to what extent having sex outside the home might be a form of self-care. I also cover safer sex practices and the experience of disease, how PrEP has radically changed the way gay men approach sex, the way drugs are bound up in self-care practices, and the relationships between self-care and community.
The concept of ‘wild self-care’ emerged from these interviews and describes how practices or behaviours which appear risky, dangerous, or unhealthy can also be seen as legitimate ways of caring for the body and the self. I demonstrate how my participants used creative, unexpected, and alternative methods of caring for themselves using substances or ‘risky’ forms of sex and describe the way self-care is communal nature rather than a solitary practice. I also present the notion of health-as-process. This concept allows researchers to approach health as an ongoing process rather than a state of being that might be achieved. This speaks to the emotional and personal way that risk is constructed and experienced. All these facets come together to articulate the deeply complicated ways that people care for themselves