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Mechanisms of bactericidal action and β-lactam synergy by the zinc ionophore PBT2
Full text linkThe emergence and global spread of antimicrobial resistance (AMR) is an increasingly serious threat to human and veterinary medicine. Driven by the misuse and overuse of antibiotics, resistance to our antibiotic armoury is rapidly outpacing our current efforts to discover and develop novel agents. In light of this, there is restimulated interest in exploiting metals for novel antibacterial strategies. Zinc is an essential metal ion for various cellular pathways in bacterial physiology, yet excess amounts are toxic. The involvement of zinc in modulating antibiotic efficacy and resistance pathways is also becoming increasingly evident. Zinc ionophores, molecules that transport zinc into cells, offer a strategy to capitalize on the anti-infective potential of this metal. The zinc ionophore PBT2, an 8-hydroxyquinoline derivative, has recently been discovered to potentiate zinc toxicity and antibiotic efficacy against several AMR pathogens, suggesting possibilities for zinc ionophores as a novel class of standalone antibiotic or antibacterial adjuvant in either animal or human medicine. A molecular understanding of these actions, however, is currently lacking. This body of work examines the bactericidal action of PBT2 against the veterinary pathogen Streptococcus uberis, and the underlying mechanism of synergy between PBT2 and β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA).
A combination of bacterial physiology, biochemistry, genetics, and chemical biology approaches were utilised to investigate the mechanisms of zinc ionophores in both lines of this research. We revealed PBT2-mediated intracellular zinc accumulation disrupts zinc and manganese homeostasis and cellular redox balance in S. uberis, ultimately exerting its bactericidal action through intracellular zinc accumulation and manganese starvation, ROS accumulation, and the impairment of manganese-dependent antioxidant activity. We further demonstrated that β-lactam antibiotic resensitization in MRSA by PBT2 and related structural analogues is likewise associated with a destabilization of cellular zinc and manganese homeostasis. Mechanistic investigations revealed this zinc ionophoric activity perturbs multiple elements involved in β-lactam resistance in MRSA, including the expression of key resistance determinants, cell wall and membrane integrity, and the proton motive force (PMF). Further, PBT2 and β-lactam combination treatment significantly improved animal survival rates and pathogen clearance in a murine model of invasive MRSA infection. This study provides novel mechanisms of intracellular zinc toxicity and demonstrates a targetable overlap between metal homeostasis, cell wall and membrane metabolism and β-lactam resistance. Overall, this data contributes and adds to the field of bacterial metal homeostasis and exemplifies how it can be exploited for novel antibacterial strategies in veterinary and human medicine
Micropatterned Aluminium Surfaces for Anti-icing and Anti-frosting Applications
Full text linkDeveloping anti-icing and anti-frosting technology is vital for many different energy generation and consumption systems such as wind turbines, aircraft and heat exchangers, where ice and frost formation is a barrier for efficiency and can severely damage infrastructure and injure people.
This work investigates anti-icing and anti-frosting properties of aluminium hierarchical structures with varying geometric parameters. These structures consisted of micro-milled microstructures with nanoscale roughness due to the milling. Fixed-pitch and gradient-pitch structures were tested, the latter of which have not been tested for ice adhesion previously. The structures are characterised for their geometric and surface wetting properties using a scanning electron microscope and a goniometer respectively, then tested for anti-icing properties using a force probe and anti-frosting properties using a wind tunnel with Peltier cooling. Both systems were custom built for this purpose.
These aluminium surfaces rely only on topographic modifications - no lubricants, coatings or polymers, which tend to be prone to damage and impractical to reapply in many applications. It was found that these gradient-pitch microstructures had equivalent or better anti-icing/anti-frosting performance than the fixed-pitch structures for both ice adhesion and frosting delay
Identity construction in online dating
Full text linkOnline dating has emerged as one of the most widely used opportunities provided by the internet, yet only a small number of studies have focused on online daters who have met and developed successful relationships with partners from an internet dating website. In this environment, online daters must become their own marketing managers in terms of creating their own advertising campaign which ensures they are presenting a self which appears both attractive and desirable, yet at the same time is genuine and honest.
Using the concepts of Belk’s re-embodiment through online constructed identity (2013; 2016) and Gonzales and Hancock’s (2008) identity shift, this research investigates the relationship between the construction of an online identity, through the disclosure of personal information, in the form of a dating profile, and the successful formation of a relationship initiated through an online dating site. Using individual and dyadic in-depth interviews, twenty one individuals who met their current partners on a dating site were interviewed for this study.
The findings suggest the role of online dating could be considered two-fold. Not only is it an avenue for initiating a meeting with another individual, which may lead to a long-term romantic relationship. It may also be used for evaluating and modifying one’s self-identity, by reducing the discrepancy between one’s actual and ideal self. Evidence was found of this occurring, with respondents using online dating as an opportunity to portray themselves as being more confident and self-assured than they actually were in real life. For many of these respondents, online dating provided the opportunity to alter, and in some cases, reconstruct aspects of their identity during a period of ambiguity and role uncertainty in their lives. Many of the online daters in this study were in a period of liminality, and through feedback and reassurance from others, as well as learning from past dating experiences, they were able to evaluate, make adjustments and craft a newly constructed re-embodied self-identity by means of an identity shift, which was closer to a real sense of who they were.
This research extends existing theory on online identity formation, self-disclosure, liminality, identity shift and self-growth by contributing to the growing consumer behaviour literature surrounding online dating research
Teaching analytics and teacher dashboards to visualise SET data: Implication to theory and practice
Full text linkTeaching Analytics (TA) is an emergent theoretical approach that combines teaching expertise, visual analytics, and design-based research to support teachers' diagnostic pedagogical ability to use data as evidence to improve teaching quality. The thesis is focused on designing dashboards to help teachers visualise Student Evaluation of Teaching (SET) data as a form of TA for improving the quality of teaching. The research examined the role of TA by deploying customisable dashboards to support teachers in using data to design and facilitate learning. The researcher carried out an integrated literature review to explore the notion of TA and SET data. Moreover, a Data Science Life Cycle model was proposed to guide teachers and researchers using SET data to improve learning and teaching quality. The research comprised several phases. In phase I, a simulated data technique was used to generate SET scores that informed the development of a preliminary teacher dashboard. Phase II surveyed teachers' use of SET data. The survey results indicated that more than half of the participants used SET for improving teaching practice. The research also showed that participants valued the free-text qualitative comments in SET data. Hence, phase III collected real free-text qualitative comments in SET data on students' perceptions of a previously tutored course. The survey results further indicated that although teachers were unaware of a dashboard's value in presenting data, they wanted to visualise SET data using dashboards. Phase IV redesigned the preliminary dashboards to present the real SET data and the simulated SET scores. Finally, phase V carried out usability testing to evaluate teachers' perceptions of usability and usefulness of the teacher's dashboards. Overall, the result of the usability study indicated the perceived value of the teacher's dashboards
Associations Between Physical Activity and Fruit and Vegetable consumption in Female Adolescents in New Zealand
Full text linkBackground: Inadequate physical activity and low fruit and vegetable consumption are arguably the greatest modifiable risk factors for cardiometabolic diseases in adolescents. Physical activity (PA) and fruit and vegetable consumption have been reported previously in this age group, however, the associations between these two health behaviours together has not been heavily researched. Understanding the relationship between these two crucial risk factors is likely to support the development of future public health messages.
Objective: The purpose of this study was to investigate and describe the relationship between physical activity and fruit and vegetable consumption among adolescent females of the SuNDiAL project.
Design: Adolescent females aged 15-18 y were recruited from high schools in 8 regions around New Zealand (NZ). Hip-worn Actigraph GT3X+ accelerometers and self-report wear-time diaries were used for seven consecutive days to measure moderate-to-vigorous physical activity (MVPA). Fruit and Vegetable consumption was measured using a dietary habits questionnaire.
Results: Participants performed an average of 43 minutes/day in MVPA, and more than 75% of females failed to meet physical activity guidelines of ≥60 min of MVPA per day. Fruit and vegetable consumption were generally low, with only 27% of females consuming ≥5 serves per day. Physically active females were 4.7 (95%CI: 1.7 to 13.1, p=0.0024) and 2.7 (95%CI: 1.1 to 6.6, p=0.0302) times more likely to meet fruit and total fruit and vegetable intakes respectively, than inactive females.
Conclusion: Physical activity and fruit and vegetable intakes are both insufficient in adolescent females. Girls who were more physically active were also more likely to meet the fruit and vegetable guidelines. It is possible that the facilitators and inhibiting factors associated with meeting both the physical activity and fruit and vegetable guidelines are similar. Further research in this area is clearly needed before targeted public health interventions can be developed or implemented
The Cascade Rock Avalanche: Structure and deformation in a catastrophic rock avalanche
Full text linkCatastrophic rock avalanches involving large volumes of bedrock are primary drivers of surface erosion in mountainous landscapes and pose a considerable threat to both human life and infrastructure. These events typically involve > 106 m3 of material and show increased mobility and long runouts compared to relatively small landslide events. Investigations of these deep-seated, catastrophic events have previously been undertaken to explore the relationships between mobility, volume, and physical properties of the rock mass. Several processes are thought to play a significant role in the increased mobility, including mechanical grain fragmentation, acoustic grain fragmentation, frictional melting, and mixing between the rock avalanche and substrate. To further constrain the role of these processes, this thesis will investigate the structural and deformation aspects of a rock avalanche deposit located in South Westland, New Zealand.
The Cascade Rock Avalanche (CRA) was first identified as a large volume catastrophic rock avalanche by Barth (2013), having initially been interpreted as glacial moraine in previous studies. The CRA contains three main lithological groups: the Dun Mountain Ultramafic Group, the Greenland Group, and the Brook Street Volcanic Group. The deposit consists of c. 0.75 km3 of material and was likely triggered by a rupture on the Alpine Fault c.660 A.D.
Observations from fieldwork presented in this thesis reveal characteristic rock avalanche textures and facies that formed during transportation. These facies include a carapace, quasi-bedding defined by the alignment of blocky material. Typical textures that had formed include fine-grained material in shear bands, jigsaw-style fractured clasts, liquefied material, and survivor clasts. Shear bands within the Greenland Group are subvertical, while those in the Dun Mountain Ultramafic Group are shallowly dipping. The quasi-bedding planes in the Dun Mountain Ultramafic Group are broadly parallel to the shear bands. These results indicate that there may have been structural and lithological controls on the formation of the shear bands and bedding surfaces during transportation of the rock avalanche.
Three samples were selected for quantitative grain size and shape analysis to establish whether there were structural and lithological controls on grain fragmentation processes during transportation. Two samples represent shear band material and the other sample represents material from the body of the CRA. Results indicate that shear band material is texturally more mature than body material. Both of the shear band samples have a smaller mean grain size (5.39 µm and 6.13 µm) and higher fractal 3-dimensional (D), between 2.61 and 3.17) than the body material (mean grain size = 7.62 µm; D3D = 2.32 –3.27). The D values are comparable to those found in tectonic fault rocks. However, the D values established for both the shear band and body material are both above and below theoretical models of fragmentation which indicates that multiple fragmentation processes have taken place. Grain shape analysis provides evidence that grains within shear bands are more circular and have fewer grain-boundary asperities than grains within the bulk avalanche material. In conjunction with the field observations, the grain size and shape analyses indicate that grain fragmentation played a significant role in transportation and mobility of the CRA, likely contributing to the long runout of the material
Dietary intakes and major food sources of vitamin B12 among New Zealand adolescent males and females
Full text linkBackground: Adolescence is a period of rapid growth and thus, is an essential time for ensuring adequate intake of all nutrients. Vitamin B12 in particular, is an essential nutrient for DNA synthesis, red blood cell formation and neurological function. Based on data from the 2008/09 New Zealand Adult Nutrition Survey, vitamin B12 intake of New Zealand adolescents were shown to be largely adequate, however, changes in dietary patterns over the last 10 years may have negatively impacted the major dietary contributors of vitamin B12 intake. In particular, with global trends emphasizing plant- based diets and the subsequent decline in consumption of milk and animal source foods, it is currently unclear what New Zealand adolescents are eating. As vitamin B12 is naturally found in food of animal origin, young adults that choose to omit animal products are at increased risk of deficiency.
Objective: The aim of the present study was to evaluate dietary vitamin B12 intake, and its major food sources among female and male adolescents aged 15-18 years.
Methods: The present study was part of a larger nutrition assessment project; the Survey of Nutrition Dietary Assessment and Lifestyle (SuNDiAL). SuNDiAL was designed as a clustered, cross-sectional study of 401 female and male adolescents nationwide. Recruitment of participants and data collection took place in 19 secondary schools across ten different regions in New Zealand between February 2019 and April 2020. Eligible participants provided information of their demographic and health status; dietary habits and vegetarian status; and attitudes, motivations and beliefs regarding food choices via online self-administered questionnaires. Anthropometric measurements including height and weight were taken, and BMI (kg/m2) and BMI z- scores were determined. Dietary intake information was collected via two 24-hour recalls on non-consecutive days (the first face-to-face, the second by telephone or video link) within two weeks. Food recall data were entered into a nutrient analysis software programme, FoodWorks 9 to calculate energy and vitamin B12 intake. Energy and dietary vitamin B12 intakes were adjusted for within person variation using the Multiple Source Method to represent usual intakes. Nutrient adequacy was assessed using the EAR cut-point method.
Results: The sample population consisted of 266 females and 135 males self- identifying as New Zealand European or Other (71.2%), Māori (13.7%), Asian (12.7%) and Pacific (2.3%). Only 9% of the sample population reported adopting a vegetarian lifestyle, with a high proportion of vegetarians among female participants compared to males (11% vs 4%, respectively). Usual dietary vitamin B12 intakes were found to be higher in males at 3.8 μg/day compared to that of females at 2.5 μg/day. In addition, inadequate vitamin B12 intake (below <2.0 μg/day) was higher in females (22.6%) than males (10.8%). However, participants who reported following a vegan (n=6) or vegetarian dietary pattern (n=23) showed the highest prevalence of inadequate vitamin B12 intake at 83.3% and 34.8%, respectively. Lastly, the top three major food group contributors of vitamin B12 were foods of animal origin among both females and males; milk, beef and veal, poultry representing 28.3% and 40.5% of total dietary vitamin B12 intake, respectively.
Conclusion: Vitamin B12 intakes in adolescents are largely dependent on consumption of animal products. Majority of participants were achieving their daily recommended requirement (>2.0 μg/day) albeit inadequacy was higher among females and those reporting vegan and vegetarian lifestyles. Consumption of fortified alternatives or supplements may be recommended to attenuate the higher prevalence of inadequate intake among at risk groups
Intakes and food sources of dietary protein among New Zealand adolescents
Full text linkBackground: Adolescence is a nutritionally vulnerable period, characterised by rapid growth and development as an individual transitions from childhood to adulthood. Protein is necessary to support these rapid changes and is paramount to supporting immunity, bone health and hormone production. There is limited up-to-date data on the protein intakes among New Zealand (NZ) adolescents, as the last assessment was conducted over a decade ago.
Objective: To assess the protein intakes and main food sources of protein among New Zealand adolescents aged 15-18 years. Furthermore, the present study aimed to compare intakes, sources and the prevalence of inadequacy between males and females.
Design: The present thesis is part of a wider population-based cross-sectional study, the Survey of Nutrition, Dietary Assessment and Lifestyle, which was conducted over an 18-month period in NZ adolescents, aged 15-18 years. A convenience sample of adolescents, clustered by high schools were the study participants. Measurements were taken over three phases from February 2019 to April 2020. Two 24-hour diet recalls, taken on non-consecutive days, were undertaken to assess the protein intakes of adolescents using the ‘multiple pass method’. Participants also completed online questionnaires on demographics and dietary habits. Usual average protein intake was estimated using the multiple source method in absolute terms, as a percentage of total energy and per gram per kilogram of bodyweight. The Estimated Average Requirement (EAR) cut off method was used to determine the prevalence of inadequacy among adolescents. Body mass index (BMI) z-scores were calculated using standardised height and weight measurements.
Results: The population comprised 66% females (n=266) and 34% males (n=135). Mean usual dietary protein intakes were significantly higher among males compared with females (109.5 g/day (95% CI: 104.1, 114.9) and 1.63 g/kg (95% CI: 1.54, 1.73) vs 73.0 g/day (95% CI: 70.6, 75.3) and 1.14 g/kg (95% CI: 1.09, 1.18)). The prevalence of inadequacy among females was low (0.3%) in absolute terms (g/day), although increased to 6.3% when body weight is accounted for (g/kg). Females who were Māori, resided in areas of high deprivation or were obese had the highest rates of inadequacy, while no male had inadequate mean protein intake. Contribution of protein to total energy was statistically 18% higher among males compared with females (18.6% total energy (TE) (95% CI: 18.1, 19.2) vs 15.4% TE (95% CI: 15.1, 15.7). Notably, mean contributions to total energy sit towards the lower end of the Acceptable Macronutrient Distribution Range (AMDR). A concerning 47.7% of females had intakes below the AMDR (15- 25% TE) while only 13.7% of males were below this limit. Main food sources for adolescents were similar between sexes, with poultry (12.8%), grains and pasta (10.0%), and bread (9.4%) contributing the main sources of protein.
Conclusion: Protein intakes among the adolescent population in New Zealand are mostly sufficient to meet their physiological needs, and the prevalence of inadequacy appears to be low. Males consistently consume more dietary protein than females. In turn, females living in highly deprived areas or of Māori ethnicity are at higher risk of protein inadequacy. Increasing intakes to sit within the AMDR is an avenue in which adolescent health can be optimised on a population level by ensuring a balanced diet. Protein quality and the amino acid composition of foods should be assessed in future analyses to determine the contribution of protein-rich foods to overall diet quality. Larger, nationally representative studies are required to support the present findings
Indigenous peoples, consents and rights: Troubling subjects
No full textAnalysing how Indigenous Peoples come to be identifiable as bearers of human rights, this book considers how individuals and communities claim the right of free, prior and informed consent (FPIC) as Indigenous peoples.
The basic notion of FPIC is that states should seek Indigenous peoples’ consent before taking actions that will have an impact on them, their territories or their livelihoods. FPIC is an important development for Indigenous peoples, their advocates and supporters because one might assume that, where states recognize it, Indigenous peoples will have the ability to control how non-Indigenous laws and actions will affect them. But who exactly are the Indigenous peoples that are the subjects of this discourse? This book argues that the subject status of Indigenous peoples emerged out of international law in the late 1970s and early 1980s. Then, through a series of case studies, it considers how self-identifying Indigenous peoples, scholars, UN institutions and non-government organizations (NGOs) dispersed that subject-status and associated rights discourse through international and national legal contexts. It shows that those who claim international human rights as Indigenous peoples performatively become identifiable subjects of international law – but further demonstrates that this does not, however, provide them with control over, or emancipation from, a state-based legal system. Maintaining that the discourse on Indigenous peoples and international law itself needs to be theoretically and critically re-appraised, this book problematises the subject-status of those who claim Indigenous peoples’ rights and the role of scholars, institutions, NGOs and others in producing that subject-status. Squarely addressing the limitations of international human rights law, it nevertheless goes on to provide a conceptual framework for rethinking the promise and power of Indigenous peoples’ rights.
Original and sophisticated, the book will appeal to scholars, activists and lawyers involved with indigenous rights, as well as those with more general interests in the operation of international law.Peer Reviewe
The Application of Circulating Tumour DNA to the Management of Gastrointestinal Cancers.
Full text linkCirculating tumour DNA (ctDNA) are small fragments of DNA released by tumours
into the circulation. These fragments contain pathogenic mutations which can be
detected and quantified by various next generation sequencing approaches to monitor
tumour burden. Many ctDNA analyses rely on sequencing of tumour tissue using large
sequencing panels, querying hundreds of genes to find candidate ctDNA biomarkers for
follow-up. Whilst this approach has been successfully implemented to track changes in
tumour burden over time, it requires the sequencing of tumour tissue – which is
difficult to obtain and may not accurately represent the entire genomic landscape of
tumours. Hence, this study designed a targeted DNA sequencing panel to detect
pathogenic mutations directly from the plasma of gastric and colorectal cancer patients.
In addition, the criteria of selecting ctDNA biomarkers was investigated in colorectal
cancers by comparing the ability of mutations in tumour suppressor genes and
oncogenes to track changes in tumour burden throughout chemotherapy treatment.
The gastrointestinal cancer sequencing panel (GI cancer panel) designed in this study
successfully identified pathogenic mutations in the plasma of gastric and colorectal
cancer patients. By restricting the panel to only 21 genes, and designing specialised
oligonucleotide sequencing primers, a high analytical sensitivity was reached.
Mutations were successfully identified down to a frequency of 0.5%. This study also
identified technical challenges associated with ctDNA sequencing approaches –such as
distinguishing pathogenic mutations from sequencing errors and benign variants found
in the plasma. Finally, this study highlighted several factors that should be considered
when selecting ctDNA biomarkers – including the necessity to monitor multiple
mutations to better represent the total tumour burden. Overall, this study has generated
evidence supporting the implementation of ctDNA technologies into the healthcare
system to better manage gastrointestinal cancers