11319 research outputs found
Sort by
Island people rely on strengths
No full textPacific Island countries and territories are internationally portrayed as particularly vulnerable to Covid-19. However, in times of crisis, it is important not to forget their strengths
Calcium sensitivity and phosphorylation status of myofilament proteins in trained and untrained diabetic rats
No full textIn the 1970’s, data indicated that the diabetic heart exhibits dysfunction and increases the risk of developing heart failure 2- to 5 fold independent of other common risk factors. We now know that diabetic heart dysfunction is multifactorial including dysregulation or dysfunction of several different mechanisms, such as the sympathetic nervous system, fibrosis, filling volumes and pressures, accumulation of oxidative stress, apoptosis, calcium handling and more. Unfortunately, there is still no treatment specific to diabetic heart dysfunction.
In other aetiologies of heart failure, myofilament protein structure and function are altered and may prove to be an adequate target for normalizing the dysfunctional contraction and relaxation parameters seen in the diabetic heart. The calcium sensitivity of myofilaments can be either increased or reduced in the failing heart and often corresponds with altered post-translational modifications (PTM) of an important regulatory myofilament protein, cardiac troponin I (cTnI). Although there are a few studies testing the calcium sensitivity of diabetic myofilaments, none have investigated both calcium sensitivity and PTM within the same model of diabetes. Lastly, it is well-established that regular exercise benefits individuals with diabetes and increases cardiac reserve, but more work is necessary to establish how exercise may target the diabetic heart at the cellular level, potentially identifying aspects of the diabetic heart that are reversible and feasible to target with novel therapies. Exercise has been shown to alter the calcium sensitivity of healthy myofilaments, but has yet to be tested in a trained, diabetic model.
The Zucker Diabetic Fatty (ZDF) rat was used in this thesis based upon its ability to model the type 2 diabetic phenotype: hyperglycaemia, hyperinsulinemia and hyperlipidaemia. Twelve- and 20-week-old ZDF rats were used in Chapter 4 to test the time course of hyperglycaemia on myofilament function. Calcium sensitivity (pCa50), or the calcium concentration necessary to generate 50% of relative tension, was measured by attaching a permeated cell to a torque motor and force transducer. Total phosphorylation of key myofilament proteins was determined using the phospho-staining technique of ProQ Diamond gel stain followed by Sypro Ruby gel stain to normalize to the total protein present. Site-specific cTnI phosphorylation and total O-GlcNAcylation was determined using immunoblots. pCa50 was increased in diabetic ZDF rat hearts compared to non-diabetic ZDF rats, both at 12 and 20 weeks of age. Total cTnI and phospho-sites Serine (Ser)23/24 on cTnI were reduced in the diabetic ZDF heart. There was no difference in protein O GlcNAcylation.
In Chapter 5, I tested the effects of endurance training on calcium sensitivity and functionally relevant PTM on diabetic myofilaments. ZDF rats were obtained at 11 weeks of age and randomized to either a sedentary (SED) or training (TR) intervention. The TR group underwent an 8-week treadmill running protocol that was progressive, increasing in time and speed. pCa50 was measured with permeated cells as mentioned previously. The plantaris muscle citrate synthase activity was increased in both TR groups, indicating a significant effect of the treadmill protocol. pCa50 was increased in TR groups and, as seen above, pCa50 was also increased in diabetic ZDF hearts. The total and site specific phosphorylation of key myofilament proteins were affected by the diabetic phenotype, but not by the intervention. Training greatly reduced fasted blood glucose levels, but there was no difference in the amount of O GlcNAcylation occurring in the TR myocardium compared to the SED myocardium. In conclusion, the diabetic cardiomyocytes were capable of increasing pCa50 in response to training, as previously shown in the non-diabetic heart, but PTM that commonly affect the diabetic heart, such as phosphorylation and O-GlcNAcylation, were not altered by training
The natural history of lung function - A longitudinal analysis based on the Dunedin Multidisciplinary Health and Development Study
No full textLung function is related to health and mortality throughout the lifetime. Lung function impairment has been associated with earlier onset of respiratory, cardiovascular, and metabolic conditions and higher all-cause mortality. Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease affecting more than 251 million people worldwide and is the third leading cause of mortality. In New Zealand, it is estimated to affect 15% of adults aged over 45 years and is the fourth leading cause of mortality. Longitudinal evidence suggests that COPD can develop by mid-late adult life as a result of failure to attain the normal peak lung function in early adulthood and/or from, usually smoking-related, accelerated adult lung function decline. Investigating the longitudinal development of lung function in the general population would make important contributions to the epidemiology of COPD and potentially help to identify targets for prevention and early intervention.
Normally, the maximal spirometric lung volumes are attained between ages 20 and 25 years in men and several years earlier in women, then stay stable for several years in the plateau phase, before starting to gradually decline with age due to physiological lung ageing. There is heterogeneity in the patterns of lung function growth and decline, mainly because lung function development is a very complex process which may be affected by numerous genetic and environmental factors across the lifespan. Previous studies have attempted to identify the risk factors associated with impaired lung function growth or accelerated lung function decline, and the distinct trajectories of lung function. However, to date, few studies have sufficient high-quality data to examine the development of lung function from early life to mid-late adulthood in the general population.
In this thesis, the longitudinal development of lung function was investigated using unique data from the Dunedin Multidisciplinary Health and Development Study (Dunedin Study) – a prospective population-based birth cohort (n=1,037) with repeated assessments of lung function from age 9 to 45 years. Generalised estimating equations (GEE) and multiple linear regression were used to examine longitudinal associations between potential risk factors and development of lung function. Latent profile analysis (LPA) was conducted to identify distinct trajectories of lung function from age 9 to 45 years. Finally, multinomial logistic regression and penalised logistic regression were employed to relate early life factors and mid-adulthood COPD outcomes to identified trajectories.
The findings suggest that to attain the normal plateau lung function in early adulthood or prevent accelerated lung function decline during early-mid adulthood, targeted interventions could be focused on the better management of persistent asthma and airway hyperresponsiveness (AHR), prevention/reduction of cigarette smoking, and maintenance of a healthy body weight. A number of distinct trajectories of lung function (10 for FEV1, 9 for FVC, and 10 for FEV1/FVC) were identified in the cohort. For most Study members (79% in the FEV1 trajectories, 80% in the FVC trajectories, and 72% in the FEV1/FVC trajectories), their adult lung function trajectory appeared to be already established before age 9 years, with two exceptions: a smoking-related accelerated decline trajectory and a childhood AHR/asthma-associated persistently low trajectory, which started low and diverged from the other trajectories as age increased. Importantly, the three most adverse FEV1 trajectories (19% of the Study population) contributed more than half (55%) of the COPD outcomes at age 45 years.
This thesis provides novel insights into the natural history of lung function from childhood to the fifth decade of life in the general population. It highlights the longitudinal adverse effects of asthma and AHR, cigarette smoking, and obesity on lung function development. It also confirms the existence of distinct trajectories of lung function from childhood to mid-adult life in the general population. Most importantly, it delivers an important respiratory and public health message: for most people, their adult lung function trajectory may be already established before adolescence, therefore it is critical to maximise lung function growth in early life. To promote healthy lifetime lung function development and reduce COPD risk in mid-late adult life, intervention strategies could be developed and investigated with goals of maximising lung function growth in early childhood, better managing asthma and AHR, and avoiding cigarette smoking in adult life
"The Most Vital Change": Feminist Activism and the Criminalisation of Marital Rape in 1980s New Zealand
Get PDFSpousal immunity, a husband’s exemption to the legal consequences of rape, was an English legal import that was comprehensively protected in the patriarchal colonial context of New Zealand. Until 1985 New Zealand’s legal system played a crucial role in legitimising marital rape. Spousal immunity was ended in New Zealand through the Rape Law Reform Bill No.2 (1985). Repeal of spousal immunity was supported by research on sexual violence and a wide spectrum of the New Zealand public. After decades of legitimation for marital rape, parliamentary consensus shifted to agree that the principle was both illogical and wrong. By reforming rape laws politicians were not leading change, they were responding to change. This thesis argues that the criminalisation of marital rape in New Zealand was the result of feminist activism. Feminist initiatives included a critique of the existing marital structure, widening the definition of rape, and the establishment of feminist service organisations. The re-examination of spousal immunity which led to its repeal should be understood within the wider feminist concern for sexual violence rather than as an isolated campaign in its own right. Excerpts from public submissions to the Rape Law Reform process, feminist and government archives support this argument. To date, the limited research on marital rape in New Zealand has allowed the repeal of spousal immunity to be misunderstood as the inevitable modernisation of rape law from within the legal system. This thesis identifies social change, led by feminists, as preceding and prompting legal change. By centring the crucial role of feminist activists in the criminalisation of marital rape the relationship between feminism and the legal system can be more clearly understood
Structure-Activity Analysis of Peptidic Chlamydia HtrA Inhibitors
Get PDFChlamydia trachomatis high temperature requirement A (CtHtrA) is a serine protease that performs proteolytic and chaperone functions in pathogenic Chlamydiae; and is seen as a prospective drug target. This study details the strategies employed in optimizing the irreversible CtHtrA inhibitor JO146 [Boc-Val-Pro-ValP(OPh)2] for potency and selectivity. A series of adaptations both at the warhead and specificity residues P1 and P3 yielded 23 analogues, which were tested in human neutrophil elastase (HNE) and CtHtrA enzyme assays as well as Chlamydia cell culture assays. Trypsin and chymotrypsin inhibition assays were also conducted to measure off-target selectivity. Replacing the phosphonate moiety with α-ketobenzothiazole produced a reversible analogue with considerable CtHtrA inhibition and cell culture activity. Tertiary leucine at P3 (8a) yielded approximately 33-fold increase in CtHtrA inhibitory activity, with an IC50 = 0.68 ± 0.02 µM against HNE, while valine at P1 retained the best anti-chlamydial activity. This study provides a pathway for obtaining clinically relevant inhibitors.Peer Reviewe
Anatomy of intraplate monogenetic alkaline basaltic magmatism: clues from magma, crystals and glass
Get PDFIntraplate basaltic systems, often occurring as fields of small monogenetic volcanoes, are dominated by eruption of alkaline basaltic rocks, ranging from nephelinite/basanite to transitional/subalkaline. Their generally primitive erupted compositions imply limited crustal modification, and hence they provide an important probe into deep, lithospheric mantle and partial melting processes. Partial melting and magmatic ascent processes can be investigated using the composition of crystals, glass and wholerock, although a combination of these is preferable. The whole-rock chemical variability within single eruptions or over the temporal and spatial extent of a volcanic field is controlled by the characteristics
of the primary melting source, as well as near source percolative/reaction processes. Coupled crystaland-whole-rock detailed investigations are most promising to constrain the processes that modify primary melts into the primitive magmas that accumulate before ascent. Complex crystal textures and chemistry have so far demonstrated that basaltic magmas are principally processed and modified within the lithospheric mantle with minor modification en-route through the crust. Fractional crystallization and magma mixing modify melts throughout ascent, and can imprint secondary chemical intra-eruptive variability. Quantifiable temperature and pressure parameters based on crystalmelt compositions constrain the depth of formation, and hence provide information about the role of different mineral phases in deep versus shallow chemical evolution. Volatile components in the melt (e.g. H2O and CO2) can be quantified on glass and melt inclusions. These analyses, coupled with solubility models, may help to reconstruct initial dissolved volatile content to further constrain the source characteristics and magmatic ascent dynamics. Integrated studies of crystals and melt paint a picture of extended lithospheric mantle to minor crustal processing resulting from the complex deep
plumbing of monogenetic basaltic systems. This highlights the need for improved resolution to characterize true primary signatures and hence elucidate the formation of intraplate alkaline basalts.Peer Reviewe
Using Domestic Hot Water Cylinders as an Energy Storage System in Solar PV Microgrids
No full textDue to the need for energy security, increasing demand for renewable electricity, and mitigation of the effects of natural disasters, microgrids are being deployed for a decarbonized and decentralized electricity grid. The variability of both renewable energy sources and electricity demand creates a significant supply-demand mismatch in microgrids. This is normally dealt with battery storage systems coupled with microgrids to reduce intermittency by storing surplus generated energy for later use. However, batteries are expensive and have a limited lifecycle. It becomes pertinent to explore other affordable options with an extended lifespan. This thesis aims to assess the storage potential of domestic hot water cylinders as part of a residential microgrid comprised of a cluster of 19 households with solar photovoltaic (PV) supply.
To carry out an analysis of this potential, this thesis develops a physical model of a hot water cylinder that simulates the hot water electricity demand of the households under different control conditions. This simulation is based on a novel approach that determines hot water flow based on reverse engineering measured electricity data. The electricity demand data and PV supply data were based on data collected previously in the GREEN Grid project in New Zealand. Four performance metrics including system efficiency, self-sufficiency, solar PV self-consumption, and percentage reduction in battery capacity were used to compare two systems with and without domestic hot water cylinder storage under 10 scenarios.
The results showed that the system that includes domestic hot water cylinder storage required from 37-78% less battery capacity for the same percentage of self-sufficiency. Results of the systems also indicated that scenarios that meet 100% of the demand with solar PV are less efficient than scenarios that import a fraction of their supply from the utility grid to meet demand. We thus conclude that domestic hot water cylinders are useful for storing energy to reduce the size of batteries and increase PV self-consumption in the microgrid. We also found that microgrid systems connected to the utility grid are more efficient than stand-alone microgrids
Anatomy and physiology of the injection site – implications for extended release parenteral systems
No full textEnhancing students’ experimental knowledge with active learning in a pharmaceutical science laboratory
No full textThis study aimed to examine if an active learning approach used in a pharmaceutical science laboratory setting would enhance pharmacy students’ learning about foundation science knowledge about conducting an experiment. A pre-post-test study design was used to collect data from third-year undergraduate pharmacy students with two approaches to performing an experiment (active learning, traditional). Assessment data from 95 students (74% response rate) were analysed quantitatively and qualitatively, Results of a two-way analysis of variance showed significant differences found with large effects when the active learning and traditional approaches to performing an experiment were compared for knowledge about the variables to be measured and measurement method. A thematic analysis identified planning as unique to the post-test responses for the active learning session. The results of this study were cautiously interpreted to suggest that the laboratory session featuring active learning had a greater impact on student learning than the traditional experiment method.Peer Reviewe
Government Spending Multipliers in Times of Tight and Loose Monetary Policy: Evidence for New Zealand
Get PDFWe investigate the cumulative government spending multiplier in times of tight and loose monetary policy for New Zealand. Using local projections with instrumental variables, we find the spending multiplier peaks at 0.54 under loose monetary policy, while remaining statistically insignificant when monetary policy is tight. Splitting government spending into two components leads to different results. The government consumption multiplier does not depend on the stance of monetary policy and peaks at a value of 1.57. On the other hand, the government investment multiplier peaks at 1.10 when monetary policy is loose, but is not statistically significant when it is tight