Molecular markers of obesity and diabetes

Recently it has been shown that the consumption of a diet high in saturated fat is associated with impaired insulin sensitivity and increased incidence of type 2 diabetes. In contrast, diets that are high in monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs), especially very long chain n-3 fatty acids (FAs), are protective against disease. However, the molecular mechanisms by which saturated FAs induce the insulin resistance and hyperglycaemia associated with metabolic syndrome and type 2 diabetes are not clearly defined. It is possible that saturated FAs may act through alternative mechanisms compared to MUFA and PUFA to regulate of hepatic gene expression and metabolism. It is proposed that, like MUFA and PUFA, saturated FAs regulate the transcription of target genes. To test this hypothesis, hepatic gene expression analysis was undertaken in a human hepatoma cell line, Huh-7, after exposure to the saturated FA, palmitate. These experiments showed that palmitate is an effective regulator of gene expression for a wide variety of genes. A total of 162 genes were differentially expressed in response to palmitate. These changes not only affected the expression of genes related to nutrient transport and metabolism, they also extend to other cellular functions including, cytoskeletal architecture, cell growth, protein synthesis and oxidative stress response. In addition, this thesis has shown that palmitate exposure altered the expression patterns of several genes that have previously been identified in the literature as markers of risk of disease development, including CVD, hypertension, obesity and type 2 diabetes. The altered gene expression patterns associated with an increased risk of disease include apolipoprotein-B100 (apo-B100), apo-CIII, plasminogen activator inhibitor 1, insulin-like growth factor-I and insulin-like growth factor binding protein 3. This thesis reports the first observation that palmitate directly signals in cultured human hepatocytes to regulate expression of genes involved in energy metabolism as well as other important genes. Prolonged exposure to long-chain saturated FAs reduces glucose phosphorylation and glycogen synthesis in the liver. Decreased glucose metabolism leads to elevated rates of lipolysis, resulting in increased release of free FAs. Free FAs have a negative effect on insulin action on the liver, which in turn results in increased gluconeogenesis and systemic dyslipidaemia. It has been postulated that disruption of glucose transport and insulin secretion by prolonged excessive FA availability might be a non-genetic factor that has contributed to the staggering rise in prevalence of type 2 diabetes. As glucokinase (GK) is a key regulatory enzyme of hepatic glucose metabolism, changes in its activity may alter flux through the glycolytic and de novo lipogenic pathways and result in hyperglycaemia and ultimately insulin resistance. This thesis investigated the effects of saturated FA on the promoter activity of the glycolytic enzyme, GK, and various transcription factors that may influence the regulation of GK gene expression. These experiments have shown that the saturated FA, palmitate, is capable of decreasing GK promoter activity. In addition, quantitative real-time PCR has shown that palmitate incubation may also regulate GK gene expression through a known FA sensitive transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), which upregulates GK transcription. To parallel the investigations into the mechanisms of FA molecular signalling, further studies of the effect of FAs on metabolic pathway flux were performed. Although certain FAs reduce SREBP-1c transcription in vitro, it is unclear whether this will result in decreased GK activity in vivo where positive effectors of SREBP-1c such as insulin are also present. Under these conditions, it is uncertain if the inhibitory effects of FAs would be overcome by insulin. The effects of a combination of FAs, insulin and glucose on glucose phosphorylation and metabolism in cultured primary rat hepatocytes at concentrations that mimic those in the portal circulation after a meal was examined. It was found that total GK activity was unaffected by an increased concentration of insulin, but palmitate and eicosapentaenoic acid significantly lowered total GK activity in the presence of insulin. Despite the fact that total GK enzyme activity was reduced in response to FA incubation, GK enzyme translocation from the inactive, nuclear bound, to active, cytoplasmic state was unaffected. Interestingly, none of the FAs tested inhibited glucose phosphorylation or the rate of glycolysis when insulin is present. These results suggest that in the presence of insulin the levels of the active, unbound cytoplasmic GK are sufficient to buffer a slight decrease in GK enzyme activity and decreased promoter activity caused by FA exposure. Although a high fat diet has been associated with impaired hepatic glucose metabolism, there is no evidence from this thesis that FAs themselves directly modulate flux through the glycolytic pathway in isolated primary hepatocytes when insulin is also present. Therefore, although FA affected expression of a wide range of genes, including GK, this did not affect glycolytic flux in the presence of insulin. However, it may be possible that a saturated FA-induced decrease in GK enzyme activity when combined with the onset of insulin resistance may promote the dys-regulation of glucose homeostasis and the subsequent development of hyperglycaemia, metabolic syndrome and type 2 diabetes.

Effect of rain on travel demand and traffic accidents

This paper studies the effect of rain on travel demand measured on the Tokyo Metropolitan Expressway (MEX). Rainfall data monitored by the Japan Meteorological Agency's meso-scale network of weather stations are used. This study found that travel demand decreases during rainy days and, in particular, larger reductions occur over the weekend. The effect of rainfall on the number of accidents recorded on 10 routes on the MEX is also analysed. Statistical testing shows that the average frequency of accidents, during periods of rainfall, is significantly different from the average frequency at other times.

Acid hydrolysis of easily dispersed and microaggregate-derived silt- and clay-sized fractions to isolate resistant soil organic matter

The current paradigm in soil organic matter (SOM) dynamics is that the proportion of biologically resistant SOM will increase when total SOM decreases. Recently, several studies have focused on identifying functional pools of resistant SOM consistent with expected behaviours. Our objective was to combine physical and chemical approaches to isolate and quantify biologically resistant SOM by applying acid hydrolysis treatments to physically isolated silt- and clay-sized soil fractions. Microaggegrate-derived and easily dispersed silt- and clay-sized fractions were isolated from surface soil samples collected from six long-term agricultural experiment sites across North America. These fractions were hydrolysed to quantify the non-hydrolysable fraction, which was hypothesized to represent a functional pool of resistant SOM. Organic C and total N concentrations in the four isolated fractions decreased in the order: native > no-till > conventional-till at all sites. Concentrations of non-hydrolysable C (NHC) and N (NHN) were strongly correlated with initial concentrations, and C hydrolysability was found to be invariant with management treatment. Organic C was less hydrolysable than N, and overall, resistance to acid hydrolysis was greater in the silt-sized fractions compared with the clay-sized fractions. The acid hydrolysis results are inconsistent with the current behaviour of increasing recalcitrance with decreasing SOM content: while %NHN was greater in cultivated soils compared with their native analogues, %NHC did not increase with decreasing total organic C concentrations. The analyses revealed an interaction between biochemical and physical protection mechanisms that acts to preserve SOM in fine mineral fractions, but the inconsistency of the pool size with expected behaviour remains to be fully explained.

Does the acid hydrolysis-incubation method measure meaningful soil organic carbon pools?

The literature was reviewed and analyzed to determine the feasibility of using a combination of acid hydrolysis and CO2-C release during long-term incubation to determine soil organic carbon (SOC) pool sizes and mean residence times (MRTs). Analysis of 1100 data points showed the SOC remaining after hydrolysis with 6 M HCI ranged from 30 to 80% of the total SOC depending on soil type, depth, texture, and management. Nonhydrolyzable carbon (NHC) in conventional till soils represented 48% of SOC; no-till averaged 56%, forest 55%, and grassland 56%. Carbon dates showed an average of 1200 yr greater MRT for the NHC fraction than total SOC. Longterm incubation, involving measurement of CO2 evolution and curve fitting, measured active and slow pools. Active-pool C comprised 2 to 8% of the SOC with MRTs of days to months; the slow pool comprised 45 to 65% of the SOC and had MRTs of 10 to 80 yr. Comparison of field C-14 and (13) C data with hydrolysis-incubation data showed a high correlation between independent techniques across soil types and experiments. There were large differences in MRTs depending on the length of the experiment. Insertion of hydrolysis-incubation derived estimates of active (C-a), slow (C-s), and resistant Pools (C-r) into the DAYCENT model provided estimates of daily field CO2 evolution rates. These were well correlated with field CO2 measurements. Although not without some interpretation problems, acid hydrolysis-laboratory incubation is useful for determining SOC pools and fluxes especially when used in combination with associated measurements.

Vulnerability factors for disaster-induced child post-traumatic stress disorder : the case for low family resilience and previous mental illness

Objective: The aim of the present study was to investigate whether parent report of family resilience predicted children’s disaster-induced post-traumatic stress disorder (PTSD) and general emotional symptoms, independent of a broad range of variables including event-related factors, previous child mental illness and social connectedness. ---------- Methods: A total of 568 children (mean age = 10.2 years, SD = 1.3) who attended public primary schools, were screened 3 months after Cyclone Larry devastated the Innisfail region of North Queensland. Measures included parent report on the Family Resilience Measure and Strengths and Difficulties Questionnaire (SDQ)–emotional subscale and child report on the PTSD Reaction Index, measures of event exposure and social connectedness. ---------- Results: Sixty-four students (11.3%) were in the severe–very severe PTSD category and 53 families (28.6%) scored in the poor family resilience range. A lower family resilience score was associated with child emotional problems on the SDQ and longer duration of previous child mental health difficulties, but not disaster-induced child PTSD or child threat perception on either bivariate analysis, or as a main or moderator variable on multivariate analysis (main effect: adjusted odds ratio (ORadj) = 0.57, 95% confidence interval (CI) = 0.13–2.44). Similarly, previous mental illness was not a significant predictor of child PTSD in the multivariate model (ORadj = 0.75, 95%CI = 0.16–3.61). ---------- Conclusion: In this post-disaster sample children with existing mental health problems and those of low-resilience families were not at elevated risk of PTSD. The possibility that the aetiological model of disaster-induced child PTSD may differ from usual child and adolescent conceptualizations is discussed.

Zoledronic acid once-yearly : what role in the prevention of non-vertebral osteoporotic fractures?

Osteoporosis is the most common bone disease. Low levels of oestrogens or testosterone are risk factors for primary osteoporosis. The most common cause of secondary osteoporosis is glucocorticoid treatment, but there are many other secondary causes of osteoporosis. Osteoporosis can be secondary to anti-oestrogen treatment for hormone-sensitive breast cancer and to androgen-deprivation therapy for prostate cancer. Zoledronic is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least a year after a single intravenous administration. The efficacy and safety of extended release (once-yearly) zoledronic acid in the treatment of osteoporosis is reviewed.

Stress and coping among migrant labourers in urban Vietnam : an adaptation cycle and health vulnerabilities

Rural-urban migration continues to grow in many developing countries including Vietnam. The experience of stress and coping associated with this process may vary for people from different circumstances. However, there has been little research on migrants to date. This study adopts a qualitative approach to research on unregistered, male, migrant freelance labourers in urban Vietnam and to explore factors contributing to stress and coping among this population. The study revealed an array of stressors related to migrants' life experiences in urban space, including physical, financial and social factors. Coping was diverse, including problem-focused coping (PFC) and emotion-focused coping (EFC), pro-social and anti-social, active and passive. Less active and anti-social coping appeared common. Together, weak social network and lack of support from formal systems placed coping and adaptation in a cyclic relationship. The results highlight a multi-disciplinary approach to help cope and adapt effectively for these men.

Cultural determinants of stress in the construction industry

The need to better understand and deal with workplace stress has major implications for the construction industry, especially on a project level, because of its potential to directly impact on site productivity and safety, and ultimately, the achievement of project objectives. While there has been some understanding of the effect of workplace stress within the construction industry, the majority of these studies have explored individual determinants of workplace stress among construction professionals such as architects, engineers, quantity surveyors etc. To date, very little research has focused on workplace stress as encountered by construction site operatives. This is an important research deficiency as construction site operatives typically make up a significant percentage of on-site workforce and contribute most directly to project success. To address this imbalance in research, this paper proposes a theoretical framework to better understand site operatives’ experience of stress from a cultural perspective on three levels: individual, project and organizational which has been largely neglected in previous studies.

A 3D visualisation model applied to a thick, multi-layered alluvial groundwater system under stress : Condamine Valley, QLD

The upper Condamine River in southern Queensland has formed extensive alluvial deposits which have been used for irrigation of cotton crops for over 40 years. Due to excessive use and long term drought conditions these groundwater resources are under substantial threat. This condition is now recognised by all stakeholders, and Qld Department of Environment and Resource Management (DERM) are currently undertaking a water planning process for the Central Condamine Alluvium with water users and other stakeholders. DERM aims to effectively demonstrate the character of the groundwater system and its current status, and notably the continued long-term drawdown of the watertable. It was agreed that 3D visualisation was an ideal tool to achieve this. The Groundwater Visualisation System (GVS) developed at QUT was utilised and the visualisation model developed in conjunction with DERM to achieve a planning-management tool for this particular application

Fumaric acid monoethyl ester-functionalized poly(D,L-Lactide)/N-vinyl-2- pyrrolidone Resins for the preparation of tissue engineering scaffolds by stereolithography

Polymer networks were prepared by photocross-linking fumaric acid monoethyl ester (FAME) functionalized, three-armed poly(D,L-lactide) oligomers using Af-vinyl-2-pyrrolidone (NVP) as diluent and comonomer. The use of NVP together with FAME-functionalized oligomers resulted in copolymerization at high rates, and networks with gel contents in excess of 90 were obtained. The hydrophilicity of the poly(D,L-lactide) networks increases with increasing amounts of NVP, networks containing 50 wt of NVP absorbed 40 of water. As the amount of NVP was increased from 30 to 50 wt , the Young's modulus after equilibration in water decreased from 0.8 to 0.2 GPa, as opposed to an increase from 1.5 to 2.1 GPa in the dry state. Mouse preosteoblasts readily adhered and spread onto all prepared networks. Using stereolithography, porous structures with a well-defined gyroid architecture were prepared from these novel materials. This allows the preparation of tissue engineering scaffolds with optimized pore architecture and tunable material properties.