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Ligand-specific differences in VEGFR-2 activation in response to VEGF-A and VEGF-E binding
No full textAngiogenesis is the process of generating new blood vessels from existing ones. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are the main proteins and receptors involved in this process. VEGFR-2 is the main receptor in the VEGFR family that contributes to angiogenesis, however, the activation of VEGFR-2 by human VEGF-A results in leaky and disorganised blood vessels which can promote tumour formation. VEGF-E is an Orf virus-derived VEGF that has been previously tested on mice and shown to form uniform and organised blood vessels without promoting tumour formation when activating VEGFR-2. Previous studies suggest that VEGF-A and VEGF-E generate a different rate of VEGFR-2 receptor internalization with differing amounts of VEGFR-2-Y951 and Src phosphorylation, a non-receptor protein tyrosine kinase.
This project aims to investigate whether VEGF-E-induced VEGFR-2 internalization is delayed relative to VEGF-A, and if this is associated with reduced Src and VEGFR-2- Y951 phosphorylation. HEK293 cells were transfected to express VEGFR-2-YFP (yellow fluorescence protein) with an haemagglutinin (HA) tag, the rate of receptor internalization is tested using an internalization assay and the phosphorylation of Src and VEGFR-2-Y951 is tested using western blot.
The study found that the internalization rate of VEGFR-2 when activated by VEGF-E, was significantly delayed compared to VEGF-A. The difference of Src and VEGFR-2- Y951 phosphorylation is unclear due to phosphorylated Src and VEGFR-2-Y951 are barely detected for both VEGF-E and VEGF-A.
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These findings suggest that VEGF-E induces a delayed internalization rate of VEGFR- 2 compared to VEGF-A. However, more studies need to be done on signalling molecules such as Src and other phosphorylation sites on VEGFR-2 to gain more understanding of VEGF-E. This investigation of the differences caused by VEGF-E and VEGF-A induced VEGFR-2 activation can develop potential treatments to normalise angiogenesis process for immune cells to target tumours
Explosive Submarine Volcanism at Lō`ihi Seamount, Hawai`i
Full text linkEven though the vast majority of volcanism on Earth occurs under water, very little is
known about submarine volcanoes and their eruptions. The hydrostatic pressure at submarine
vents was long thought to preclude submarine explosive eruptions, until recent exploration with
submersibles revealed that widespread volcaniclastic deposits bearing striking similarity to the
products of subaerial explosive eruptions are found to great depths in all the world’s oceans.
This has inspired the current investigation into the relative roles of magmatic degassing and
magma-water interaction that permit submarine basalt explosivity in the deep sea.
Lō`ihi Seamount is the youngest and southernmost active volcano in the Hawaiian-
Emperor Volcanic Chain. Its ~1 km deep summit plateau is home to many different volcaniclastic
and pyroclastic deposits. A sampling-focused submersible dive series to Lō`ihi in 2006 provided
the material for this study, which is divided into three parts, covering: Poseidic scoria cones,
primary pyroclastic deposit L8, and limu o Pele.
The “Poseidic” name is introduced for an end-member style of submarine basalt
explosivity identified by measurable features of pyroclasts from two scoria cones on Lō`ihi’s
summit plateau. Vesicle textures in lapilli, dissolved volatiles in matrix glasses and olivine
hosted glass inclusions, and fine ash morphology, are used to constrain this uniquely submarine,
cone-forming style of eruption. The Poseidic eruption style involves cooperative processes
of strongly volatile-coupled degassing and hydromagmatic fragmentation, that challenge
traditional assumptions about depth limitations to these processes.
A bedded, primary pyroclastic deposit (“L8”), exposed in a fault scarp on Lō`ihi’s
summit plateau allowed a series of samples to be collected upward through a volcaniclastic
sequence. The bedding characteristics, clast vesicularities, microtextures, and geochemistry
through the stratigraphy of this deposit indicate that the magma experienced variable ascent
rates, and complex cooling regimes in the conduit.
Deep-sea limu o Pele, shards of basaltic glass commonly described as “bubble walls,”
were found concentrated in ash lenses interbedded with thin lava sheets, and separated from an
overlying volcaniclastic sequence by a discontinuity. Different theories have been presented about
how these enigmatic particles form, either by hydrovolcanic volcanism, when submarine lava
flows entrap and vaporise seawater, or by Strombolian-like explosive eruptions. The geometry
and geochemistry of the Lō`ihi deposit provides compelling evidence for a hydrovolcanic,
sheet-flow related origin. Theoretical considerations are presented to demonstrate that this
process is viable even below the critical depth of seawater, where limu formation is driven by
supercritical water, rather than water vapour.
Submarine explosive eruptions are usually described by analogy to classical subaerial
eruption styles, and many key eruption style-determining processes have previously only been
treated theoretically. The robust samples collected for this study, and the detailed treatment of
them, shows: (1) that submarine explosive eruptions are different from subaerial ones in almost
all ways; (2) that many classical theories about what is and what is not possible at submarine
volcanoes need constant reevaluation as new data become available; and (3) that the textures
and chemistry of submarine pyroclasts can be used to rigorously determine eruption styles
Development of integrated distance sampling models
No full textDistance sampling methods are used to estimate abundance of biological populations. A set of randomly-placed lines or points are traversed and the distances to detected objects are recorded; these distances are used to estimate the probability of detection as a function of distance (the “detection function”) and hence infer how many objects were missed. In Chapter 1 we give the general context of the abundance estimation problem, the methods in use, and our motivating example. In Chapter 2 we revisit distance sampling and closed population capture-recapture methods in detail. We focus on the assumption of certain detection at distance zero, and endeavour to describe mark-recapture distance sampling (MRDS) methods and associated issues. In Chapter 3 we develop MRDS models to account for dependence between observers’ detections based on log-linear models for mark-recapture. With this simple parameterisation we are able to easily interpret the model parameters, extend the model to more than two observers, and understand what the implications of relaxing the independence assumptions are. In Chapter 4 we conducted an experiment using unmanned aerial vehicles (UAV) to sample availability considering the same group unit as the MRDS survey, where objects refer to groups. We model availability as a non-instantaneous process, where an object is subject to enter and leave the available state. Besides the standard exponential model for available and unavailable time intervals, we use Weibull and log-normal distributions. We also account for right censoring in the data and covariates using a hazard regression framework. We compare the UAV focal-follow approach to the time-depth data obtained using tagged animals. Finally, in Chapter 5, we integrate both the MRDS and availability models in order to estimate population size in absolute numbers. Throughout this thesis, our motivating example is a humpback whale breeding population off the Southwestern Atlantic ocean. For this, a double-observer aerial survey was carried out in 2015; time-depth data from tagged animals and focal-follow data collected from boat-based UAV surveys are used to estimate availability. The combined model allows us to estimate the most reliable abundance of humpback whales from aerial platform. We conclude that (i) there is lack of information to reliably estimate model parameters in various cases when we relax the independence assumption further than at distance zero; (ii) data collection to estimate availability using focal-follows from UAV platforms have advantages compared to time-depth recording data, and covariates describing the availability process may be important; (iii) detection and availability are not S-ancillary when availability depends on distance, which means that fitting the models separately produce biased estimates
“I guess that’s part of life”: The sexual victimisation of Aotearoa university students
Full text linkThere is mounting international evidence—and some limited national evidence—that university students are an at-risk group for experiencing sexual victimisation, compared to their peers and the general population. Establishing the scope of sexual victimisation, and how these experiences impact victimised students, is crucial both for prompting and for informing policy and intervention efforts to ensure the safety of university students. However, in Aotearoa there is little research that has examined the scope of sexual victimisation among university students or its impacts. What research there is has examined women’s experiences, omitting the impacts of sexual victimisation on university men in Aotearoa.
This thesis takes a gender-conscious approach to an empirical study of sexual victimisation at one of the eight universities in Aotearoa. It uses a mixed-methods approach of a survey (N = 2705) and interviews (N = 10), governed by a pragmatic paradigm. It is underpinned by an emotionally-engaged feminist framework.
Quantitative analysis was used to explore the scope of sexual victimisation and shows that more than one-in-three survey participants experienced sexual victimisation. Because the approach was gender-inclusive, the quantitative analysis included experiences that may be more typical for men—specifically being made to penetrate a perpetrator. The most common survey instrument used in this context was originally designed to capture women’s sexual victimisation experiences. The legacy of this focus has meant experiences that may be more typical for men have been excluded. Using a gender-inclusive approach established that women had disproportionately high reports of sexual victimisation, however, a substantial proportion of people identifying as another gender and men also reported experiencing sexual victimisation. The quantitative analysis also suggested that the scoring method of such victimisation surveys may function to underreport sexual victimisation.
The qualitative part of the study examines the way men and women describe the impacts of sexual victimisation experienced while attending an Aotearoa university. Again, the previous studies have focused on women’s experiences and while there have been calls for a more gender-inclusive approach, there has also been resistance to including men’s experiences in studies of sexual victimisation. This study provides a narrative analysis of ten students’ experiences of sexual victimisation, both male and female. The qualitative analysis found that while some impacts of sexual victimisation were experienced by both men and women, gender was salient in influencing the impacts of these experiences. I argue that any study of sexual victimisation must not only be gender-inclusive but also must be attuned to how gender shapes these experiences.
I argue that taken together, the quantitative and qualitative findings demonstrate that campus sexual victimisation as experienced by university students in Aotearoa is a gendered phenomenon and accordingly, responses to campus sexual victimisation must be gender-inclusive but also gender-responsive
Do sleep interventions change sleep duration in children aged 0-5 years? A systematic review and meta-analysis of randomised controlled trials
No full textTicking time bomb? Virome and microbiome characterisation of New Zealand tick species
No full textThe novel and emerging severe fever with thrombocytopenia syndrome virus (SFTSV) has spread throughout East Asia since discovery of the virus in 2009. This tick-borne negative-sense RNA virus has a human case fatality rate as high as 30% in endemic regions. Haemaphysalis longicornis, an Ixodid tick species, is considered a major vector of SFTSV. This tick was unintentionally introduced to New Zealand over a century ago, where it now thrives as an invasive species and can be found throughout the North and South Islands. The risk now lies with the fact that New Zealand has an effective vector for a deadly virus spreading in Southeast Asia. In this study, 454 ticks were collected from different animal species across New Zealand to characterise the associated virome and microbiome, while also searching for the potential introduction of SFTSV, or closely related tick-borne phleboviruses (TBPV). A series of molecular methods, including polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) as well as Sanger and deep sequencing methods were used to determine the species of ticks used in this study. Virus isolation was attempted by inoculating Vero cells with tick homogenate. A one-step qRT-PCR assay was established to detect SFTSV and/or TBPV from RNA extracted from the ticks. Deep sequencing (MiSeq, Illumina) was used to characterise the ticks virome and microbiome. Bioinformatics was performed using mostly IDseq, but also quantitative insights into microbial ecology (QIIME2) and Trinity. The ticks used in this study were found to be H. longicornis if they were collected from a land-based animal and Ixodes species if collected from penguins. Replication-competent viruses were not isolated from these ticks. Moreover, the phlebovirus specific qRT-PCR did not detect SFTSV and/or TBPV. Interestingly, both bioinformatics pipelines (IDseq and Trinity) identified sequences associated with three phleboviruses: Blacklegged phlebovirus 3, Norway phlebovirus and Beniji phlebovirus. More viral sequences were detected in ticks collected from penguins, compared to ticks collected from other animals. Finally, a difference in microbial community structure was detected between adult ticks and larvae, as well as fed and unfed ticks, with unfed larvae being the most rich group. In ticks collected from land-based animals, Proteobacteria was the most abundant phyla and Rickettsiella the most abundant bacterial genus. In summary, a comprehensive metagenomics analysis of the virome and microbiome of ticks circulating in New Zealand was conducted. Although SFTSV was not detected in this country, a series of phleboviruses were identified in ticks collected from the Otago Peninsula, highlighting the need to continue surveillance for potential emergent viruses in New Zealand. This work suggests directions for future work in terms of both analytical approach and directions of enquiry, specifically the role of New Zealand visiting seabirds in introducing and exporting SFTSV
The geology of the Green Valley, Morrisons area, North Otago
No full text“The area described comprises 40 square miles from Shag Valley Station to Pigroot Creek along Main Highway 85 (commonly known as the Pigroot). It lies within parts of the National One-mile Series Maps S135, S136 (Oamaru), S145, S146 (Moeraki), and in all or part of the following survey districts in the Otago Land District: Waihemo, Highlay, and Swinburn (…) The area mapped is in the fault angle depression paralleling the Kakanui Ranges and drained by the Shag or Waihemo River.” [Extract from Introduction
Effect of wholegrain particle size on breath metabolites in type 2 diabetes and normoglycaemia
No full textBackground:
Type 2 diabetes affects around 8.5% of adults globally and if untreated, hyperglycaemia can lead to nerve damage, blindness, kidney failure and increase the risk of cardiovascular disease. Therefore, for people with diabetes, reducing postprandial glycaemia is a priority to optimise health and reduce metabolic complications. Consumption of wholegrains such as oats, rice and wheat are associated with reduced risk of diabetes, cancer and heart disease and a lower glycaemic response compared to consumption of refined wholegrains. However, commercially available wholegrain foods vary from minimally to highly processed, and it is unclear whether processing of the grains (degree of intactness) influences the apparent health benefits. Short chain fatty acids (SCFA) are produced by microbial fermentation in the colon following wholegrain consumption and absorbed into the bloodstream with positive effects on appetite, body composition and insulin sensitivity. However, the effects of wholegrain particle size on SCFA production are currently unknown. Analysis of volatile metabolites and SCFA in exhaled breath provides a novel approach in understanding how foods are digested and metabolised in real time. As a non-invasive method, this may assist in understanding how differences in the degree of processing affects digestion and metabolism of wholegrains and SCFA production.
Design:
People with normal glucose tolerance (NGT; n=11 to 12) and type 2 diabetes (T2DM; n=11 to 12) participated in two randomised crossover studies examining glycaemic response and volatile metabolites in end tidal breath over 3-6 hours using proton transfer reaction mass spectrometry (PTR-MS) following consumption of three test foods. Each participant consumed all three test foods providing 50 g of available carbohydrate, on three separate occasions. These included: a glucose drink and two types of wholegrain breads differing only in wheat grain particle size one made with finely milled wholegrain wheat, the other with a mixture of intact, kibbled and finely milled wheat.
The aim of Study 1 was to measure the change in 17 volatile metabolites in exhaled breath and blood glucose over 3 hours following food consumption in two groups of participants, those with NGT and T2DM conducted with NGT and T2DM groups to measure the change in 17 volatile metabolites in exhaled breath and blood glucose over 3 hours following food consumption. The aim of Study 2 was to measure 17 volatiles metabolites and blood SCFA in three test foods over six hours (as similar to that described in Study 1). In addition, included matched NGT and T2DM participants for age, sex and BMI and was conducted in a more stable testing environment. Thus, improving upon limitations identified from the first study. Breaths collected in Tedlar bags were analysed with gas chromatography mass spectrometry (GC-MS) for identification of compounds in breath. Blood and breath SCFA were measured over 6 hours to examine the response to each food, which was hypothesised to rise between 4-6 hours following consumption of the bread products, but not for the glucose drink.
Outcomes:
Following consumption of the three test foods, breath VOCs followed three main trends; namely increasing over time, decreasing over time or a peaked response (initial increase then subsequent decrease back to baseline). Participants with diabetes had higher breath VOC concentrations at baseline and larger changes in VOC concentrations post-consumption.
The results of the first study (as measured by AUC) showed several breath VOCs (2-butanol, propanol, acetate and butyrate) were influenced by the digestibility of the carbohydrate, related to the intactness of the grain structure. In the T2DM group, the AUC of 2-butanol, propanol/acetate, butyrate and propionate (m/z 57, 61, 71 and 75, respectively) was the largest following consumption of the glucose drink and lowest following the bread with the largest particle size (more intact grain structure) (p=<0.05). However, in the NGT group, the lowest VOC response of propanol/acetate, propionate and butyrate (m/z 61, 75 and 89) was observed following consumption of the bread with the smallest particle size (most refined) (p<0.05).
In the second study, incremental area under the curve (iAUC) was used to measure relative change in breath VOCs following consumption of each test food. In the T2DM group, the glucose drink led to the largest iAUC of 2-butanol, propanol, acetate, butyrate and propionate (m/z 57, 61, 71 and 75, respectively) compared to either of the bread products (p0.05). This was possibly linked to tighter glycaemic control for normoglycaemic participants. No increase of SCFA in blood or breath was detected between baseline and 5 h for any test food in either the NGT or T2DM group. This was likely due to delayed gastric emptying and slow transit time for the bread formulations investigated.
Conclusions:
PTR-MS distinguished different patterns in the volatile metabolites in exhaled breath post-consumption between test foods and between subjects with and without type 2 diabetes, demonstrating significant differences in metabolism following consumption of wholegrain foods of differing intactness. This research extends the current published literature by showing that wholegrain foods with a larger particle size led to a reduced response in four exhaled metabolites during digestion and metabolism in participants with T2DM (m/z 57, 61, 71 and 75). Findings from Study 2 were unable to determine the potential for breath gas analysis for the determination of blood SCFA, possibly due to insufficient testing time post-consumption, which will need to be addressed in future research. This thesis has demonstrated the potential of breath gas analysis to facilitate greater understanding of metabolism in response to food consumption and that in future it could lead to a non-invasive tool for physicians and dietitians to monitor dietary intake in patients
Weight loss intentions and methods in New Zealand adolescents
Full text linkBackground: Weight control behaviours, particularly weight loss, are prevalent amongst adolescents of all body sizes. Methods of weight control encompass a broad range of actions, from exercising and eating more healthy foods to vomiting or starvation. There is limited research on weight-loss intentions and methods amongst adolescents in New Zealand and the relation to weight perception and body mass index (BMI).
Objective: This study aims to investigate weight control intentions and behaviours amongst a sample of male and female adolescents in New Zealand by (a) determining the prevalence of weight loss methods, body image perception, and weight loss intentions of a sample of adolescents in New Zealand; (b) identifying the association between weight perception and weight loss intentions; and (c) establishing the association between BMI with weight perception, weight loss intentions and methods in New Zealand adolescents.
Design: This is an observational cross-sectional study amongst 15-18-year-old New Zealand adolescents for the SuNDiAL (Survey of Nutrition, Dietary Assessment, and Lifestyles) project. Data collection occurred in two phases; February - November 2019 and February - May 2020. This study assessed methods of weight control through an online, self-administered questionnaire. Trained researchers collected anthropometric measures.
Results: In a sample of 246 females and 124 males, nearly half of the females (48%) and 28% of the males were currently attempting to lose weight; 34% of these females were of a healthy weight. Conversely, 2% of females were trying to gain weight, compared with 27% of males. More females than males reported using unhealthy weight loss methods in the past year; skipping meals (40% vs 22% ), vomiting (3% vs 2%), eating very little food (39% vs 15%), or smoking cigarettes (8% vs 1%). Among the participants, females were more likely to perceive themselves as heavier than males.
Conclusion: Intention to lose weight remains prevalent, and unhealthy weight loss methods are
not uncommon among New Zealand adolescents, particularly females. Further efforts and
discussion is required to resolve this double burden of body weight concerns and the potential development of disordered eating patterns
NZDep2018 analysis of census 2018 variables - DHB01: Northland
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/