The environment always matters

Superficially, the high human populations of prosperous, well-fed city-states such as Singapore and Hong Kong might appear to support the view that high concentrations of human dynamism and enterprise can alone transcend environmental constraints. Indeed, extrapolations from such densely populated regions to the whole world form the historical basis for the most optimistic estimates of how many people the Earth might support. In fact, these affluent, densely populated regions require goods and services that are produced by areas far larger than the residential area of the state. For the foreseeable future, the whole world cannot live as densely and as well as Singapore. For example, some of the fish eaten in Hong Kong is captured in Pacific Island fisheries. Beef from the Northern Territory is exported to Japan. More generally, the supply of environmentally dependent goods - including sinks for wastes - is always limited, as are inputs such as fertile soil, clean fresh water and a benign climate.

Leptin and the development of obesity

The focus of this thesis was leptin and its role in the development of obesity and non-insulin-dependent diabetes mellitus (NIDDM). Studies in Psammomys obesus, a polygenic animal model of obesity and NIDDM, showed that ob gene expression and plasma leptin concentration correlated significantly with body weight, percentage body fat and plasma insulin concentration. In addition, plasma leptin concentrations were significantly elevated in insulin resistant Psammomys obesus independent of body weight. Dietary energy restriction from weaning in Psammomys obesus prevented excessive body weight gain, hyperleptinemia and hyperglycemia compared with ad libitum fed animals. Interestingly, 19% of the energy-restricted animals still developed hyperinsulinemia and tended to have increased plasma leplin compared with normoinsulinemic energy-restricted Psammomys obesus. Fasting for 24 hours significantly reduced plasma leptin concentration in lean, insulin-sensitive but not obese, insulin-resistant P. obesus, suggesting a dysregulation in the response of leptin to acute caloric deprivation in these animals. The effects of leptin administration to P. obesus were also investigated. Single daily intraperitoneal injection of 5 mg leptin/kg body weight for 14 days had no significant effect in lean or obese P. obesus. This dose had previously been shown to rapidly and significantly reduce food intake and body weight in ob/ob and wild-type mice, suggesting relative leptin resistance in P. obesus. Acute (8 hour) effects of administration of 5 mg leptin/kg body weight were also investigated. No significant effects on food intake or plasma insulin were detected, however blood glucose concentrations were significantly elevated in obese, glucose intolerant P. obexus, suggesting an exacerbation of insulin resistance in susceptible animals. Treatment of lean, healthy P. obesus with 45 mg leptin/kg body weight/day for 7 days resulted in significant decreases in food intake and percentage body fat, showing that the leptin resistance observed in this species could be overcome by the administration of very large doses of leptin. In another study, leplin was shown to significantly inhibit maximal insulin binding to isolated adipocytes, suggesting that leptin may respresent an important link between obesity and NIDDM. Links between aspects of obesity and NIDDM and polymorphisms in the ob and p3-adrencrgic receptor genes were also investigated in two human populations.

Liver fat metabolism, obesity and diabetes in Psammomys obesis

Defects in fat metabolism are central to the aetiology and pathogenesis of obesity and type II diabetes. The liver plays a central role in these disease states via its regulation of glucose and fat metabolism. In addition, accumulation of fat within the liver has been associated with changes in key pathways of carbohydrate and fat metabolism. However a number of questions remain. It is hypothesised that fat accumulation within the liver is a primary defect in the aetiology and pathogenesis of obesity and type II diabetes. Fat accumulating in the liver is the result of changes in the gene expression of key enzymes and proteins involved with fat uptake, fat transport, fat oxidation, fat re-esterification or storage and export of fat from the liver and these changes are regulated by key lipid responsive transcription factors. To study these questions Psammomys obesus was utilised. This polygenic rodent model of obesity and type II diabetes develops obesity and diabetes in a similar pattern to susceptible human populations. In addition dietary and environmental changes to Psammomys obesus were employed to create different states of energy balance, which allowed the regulation of liver fat gene expression to be examined. These investigations include: 1) Measurement of fat accumulation and fatty acid binding proteins in lean, obese and diabetic Psammomys obesus. 2) Characterisation of hepatic lipid enzymes, transport protein and lipid responsive transcription factor gene expression in lean, obese and diabetic Paammomys obesus. 3) The effect of acute and chronic energy restriction on hepatic lipid metabolism in Psammomys obesus. 4) The effect of sucrose feeding on the development of obesity and type II diabetes in Psammomys obesus. 5) The effect of nicotine treatment in lean and obese Psammomys obesus, 6) The effect of high dose leptin administration on hepatic fat metabolism in Psammomys obesus. The results of these studies demonstrated that fat accumulation within the liver was not a primary defect in the aetiology and pathogenesis of obesity and type II diabetes. Fat accumulating in the liver was not the result of changes in the gene expression of key enzymes and proteins involved in hepatic fat metabolism. However changes in the mRNA level of the transcription factors PPAR∝ and SREBP-1C was associated with the development of diabetes and the gene expression of these two transcription factors was associated with changes in diabetic status.

Role of leptin receptors in the development of obesity

The focus of this dissertation was leptin and the leptin receptor, and the role of these genes (OB and OB-R) in the development of obesity and type 2 diabetes in humans and Psammomys obesus, a polygenic rodent model of obesity and type 2 diabetes. Studies in humans showed that circulating leptin concentrations were positively associated with adiposity, and independently associated with circulating insulin and triglyceride concentrations. Analysis of two leptin receptor sequence polymorphisms in a Caucasian Australian population and a population of Nauruan males, with very high prevalence rates of obesity, showed no associations between sequence variation within the OB-R gene and obesity- or diabetes-related phenotypic measures. In addition, these two OB-R polymorphisms were not associated with longitudinal changes in body mass or composition in either of the populations examined. A unique analysis of the effects of multiple gene defects in the Nauruan population, demonstrated that the presence of sequence alterations in both the OB and OB-R genes were associated with insulin resistance. Psammomys obesus is regarded as an excellent rodent model in which to study the development of obesity and type 2 diabetes in humans. Examination of circulating leptin concentrations in Psammomys revealed that, as in humans, leptin concentrations were associated with adiposity, and independently associated with circulating insulin concentrations. This animal model was utilised to examine expression of OB-R, and the regulation of expression of this gene after dietary manipulation. OB-R is known to have several isoforms, and in particular, OB-RA and OB-RB gene expression were examined. OB-RB is the main signalling isoform of the leptin receptors. It has a long intracellular domain and has previously been shown to play an important role in energy balance and body weight regulation in rodents and humans. OB-RA is a much shorter isoform of OB-R, and although it lacks the long intracellular domain necessary to activate the JAK/STAT pathway, OB-RA is also capable of signalling, although to a lesser degree than OB-RB. OB-RA is found to be expressed almost ubiquitously throughout the body, and this isoform may be involved in transport of leptin into the cell, although its role remains unclear. OB-RA and OB-RB were both found to be expressed in a large number of tissues in Psammomys obesus. Interestingly, obese Psammomys were found to have lower levels of expression of OB-RA and OB-RB in the hypothalamus, compared to lean animals. This finding raises the possibility that decreased leptin signalling in the brain of obese, hyperleptinemic Psammomys obesus may contribute to the leptin resistance previously described in this animal model. However, the primary defect is unclear, as alternatively, increased circulating leptin concentrations may lead to down-regulation of leptin receptors. The effect of fasting on leptin concentrations and gene expression of OB-RA and OB-RB was also examined. A 24-hour fast resulted in no change in body weight, but a reduction in circulating leptin concentrations, and an increase in hypothalamic OB-RB gene expression in lean Psammomys. In obese animals, fasting again did not alter body weight, but resulted in an increase in both circulating leptin concentrations and hypothalamic OB-RB gene expression. In the liver, fasting resulted in a large increase in OB-RA gene expression in both lean and obese animals. These results highlighted the fact that regulation of leptin receptor gene expression in polygenic models of obesity and type 2 diabetes is complex, and not solely under the control of circulating leptin concentrations. Sucrose-feeding is an established method of inducing obesity and type 2 diabetes in rodents, and this experimental paradigm was utilised to examine the effects of longer term perturbations of energy balance on the leptin signalling pathway in Psammomys obesus. Addition of a 5% sucrose solution to the diet of lean and obese Psammomys resulted in increased body weight in both groups of animals, however only obese Psammomys showed increased fat mass and the development of type 2 diabetes. The changes in body mass and composition with sucrose-feeding were accompanied by decreased circulating leptin concentrations in both groups of animals, as well as a range of changes in leptin receptor gene expression. Sucrose-feeding increased hypothalamic OB-RB gene expression in obese Psammomys only, while in the liver there was evidence of a reduction in OB-RA and OB-RB gene expression in both lean and obese animals. The direct effects of sucrose on the leptin signalling pathway are unclear, however it is possible to speculate that the effect of sucrose to decrease leptin concentrations may have been involved in the exacerbation of obesity and the development of type 2 diabetes in obese Psammomys, From these studies, it appears that sequence variation in the OB and OB-R genes is unlikely to be a major factor in the etiology of obesity in human populations. The ability to examine regulation of expression of these genes in Psammomys obesus, however, has demonstrated that the effects of nutritional modifications on leptin receptor gene expression need closer attention. The role of the OB and OB-R genes in metabolism and the development of type 2 diabetes also warrants further examination, with particular attention on the differential effects of dietary modifications on leptin receptor gene expression across a range of tissues.

Ecological correlates of the threat of extinction in neotropical bird species

Predicting the threat of extinction aids efficient distribution of conservation resources. This paper utilises a comparative macroecological approach to investigate the threat of extinction in Neotropical birds. Data on ecological variables for 1708 species are analysed using stepwise regression to produce minimum adequate models, first using raw species values and then using independent contrasts (to control for phylogenetic effects). The models differ, suggesting phylogeny has significant effects. The raw species analysis reveals that number of zoogeographical regions occupied, elevational range and utilisation of specialised microhabitats were negatively associated with threat, while minimum elevation and body mass were positively associated, whereas the independent contrasts analysis only identifies zoogeographical regions as important. Confining the analysis to the 582 species restricted to a single zoogeographical region reveals elevational range and number of habitats occupied to be negatively correlated with threat whether the analysis is based on the raw data or on independent contrasts. Analysis of four contrasting zoogeographical regions highlights regional variation in the models. In two Andean regions the threat of extinction declines as the elevation range across which the species occurs increases. In the presence of substantial human populations on high Andean plateaus, a species with a greater elevational range may be more likely to persist at some (relatively) unsettled altitudes. In Central South America, the strongest predictor of threat is minimum elevation of occurrence: species with a lower minimum are less threatened. The minimum elevation result suggests that lowland species experiencing an ecological limit to their minimum elevation (min. elevation >0 m) may be more at risk than those not experiencing such a limit (min. elevation = 0 m). Finally, in southern Amazonia, where there is little altitudinal variation, the only weak predictors of threat are body size, larger species being more threatened, and number of habitats, species occupying more habitats being less threatened. These contrasting results emphasise the importance of undertaking extinction risk analyses at an appropriate geographical scale. Since the models explained only a low percentage of total variance in the data, the effects of human-mediated habitat disturbance across a wide range of habitats may be important.

Preserving the environment and traditional communities : a land use change modeling approach

Human populations can cause serious damage to the natural environment. This, however, depends on the type of society and its size. Many traditional communities have a balanced relation with the environment, using practices for managing the soil, water and natural resources in order to satisfy their needs that are compatible to the general goals of environmental preservation.

The most usual approach to environmental conservation in the world sees human beings as intruders, potentially destroyers of the nature and, as a consequence, generally requires local population to be expelled from the protected regions. This situation has generated social conflicts because many protected areas, particularly in developing countries, are inhabited by indigenous or other traditional communities.

The disagreement about expelling or maintaining traditional communities in environmental conservation areas is strengthened by the lack of diagnostics on which changes are produced or suffered by communities in the region where they live. This paper presents a methodology developed to analyse land use dynamics in region with environmental conservation and traditional communities. We seek a better understanding of the way traditional communities use their space, the spatial pattern of land uses, which factors drive land use change, which impacts can be seen in those regions and identify the effects of conservation policies on land use dynamics.

The application of the method to the National Park of Superagui, Brazil, has successfully performed characterisation, analysis and simulation of land use dynamics in a region of environmental importance. Testing different scenarios has suggested that the adoption of a less restrictive policy for environmental conservation would have resulted in less social conflict with the same environmental efficiency than the established current policy.

The role of lipogenesis in the development of obesity and diabetes in Israeli sand rats (Psammomys obesus)

Obesity and diabetes in Israeli sand rats, Psammomys obesus, occur with the sequential transition of animals from normal insulin sensitivity to impaired insulin sensitivity, accompanied by increased adiposity, prior to insulin resistance and obesity, in a manner similar to susceptible human populations. The current study was designed to examine the role of de novo lipid synthesis in the development of excessive weight gain in P. obesus. Sand rats were classified at 12 wk of age into three groups: A, normoglycemic normoinsulinemic; B, normoglycemic hyperinsulinemic; C, hyperglycemic hyperinsulinemic, based on glucose and insulin responses in fed sand rats. Body weight, liver weight, white adipose tissue (WAT) mass and food intake were significantly elevated in Group C compared to Group A (P < 0.05). Lipogenic rate was measured by the amount of 3H incorporated into subscapular brown adipose tissue (BAT), epidiymal WAT and liver per hour, from sand rats with and without access to food. No difference in lipogenic rate was found between the groups in BAT, indicating that this tissue is of minor importance in whole body lipogenesis in P. obesus. In the WAT there was a greater lipogenic rate with the development of obesity and hyperinsulinemia (Group B vs. Group A) but no difference in the liver. However, the onset of hyperglycemia (Group C) further stimulated WAT lipogenesis and initiated increased hepatic lipogenesis, both of which contributed to the pre-existing obesity. This study suggests that elevated lipogenesis is not the primary cause of obesity in P. obesus, as lipogenic rate only markedly increases after obesity is already present in hyperglycemic animals.

Resolving future fire management conflicts using multicriteria decision making

Management strategies to reduce the risks to human life and property from wildfire commonly involve burning native vegetation. However, planned burning can conflict with other societal objectives such as human health and biodiversity conservation. These conflicts are likely to intensify as fire regimes change under future climates and as growing human populations encroach farther into fire-prone ecosystems. Decisions about managing fire risks are therefore complex and warrant more sophisticated approaches than are typically used. We applied a multicriteria decision making approach (MCDA) with the potential to improve fire management outcomes to the case of a highly populated, biodiverse, and flammable wildland-urban interface. We considered the effects of 22 planned burning options on 8 objectives: house protection, maximizing water quality, minimizing carbon emissions and impacts on human health, and minimizing declines of 5 distinct species types. The MCDA identified a small number of management options (burning forest adjacent to houses) that performed well for most objectives, but not for one species type (arboreal mammal) or for water quality. Although MCDA made the conflict between objectives explicit, resolution of the problem depended on the weighting assigned to each objective. Additive weighting of criteria traded off the arboreal mammal and water quality objectives for other objectives. Multiplicative weighting identified scenarios that avoided poor outcomes for any objective, which is important for avoiding potentially irreversible biodiversity losses. To distinguish reliably among management options, future work should focus on reducing uncertainty in outcomes across a range of objectives. Considering management actions that have more predictable outcomes than landscape fuel management will be important. We found that, where data were adequate, an MCDA can support decision making in the complex and often conflicted area of fire management.

ORP-3, a human oxysterol-binding protein gene differentially expressed in hematopoietic cells

Using differential display polymerase chain reaction, a gene was identified in CD34+-enriched populations that had with low or absent expression in CD34- populations. The full coding sequence of this transcript was obtained, and the predicted protein has a high degree of homology to oxysterol-binding protein. This gene has been designated OSBP-related protein 3 (ORP-3). Expression of ORP-3 was found to be 3- to 4-fold higher in CD34+ cells than in CD34- cells. Additionally, expression of this gene was 2-fold higher in the more primitive subfraction of hematopoietic cells defined by the CD34+38- phenotype and was down-regulated with the proliferation and differentiation of CD34+ cells. The ORP-3 predicted protein contains an oxysterol-binding domain. Well-characterized proteins expressing this domain bind oxysterols in a dose-dependent fashion. Biologic activities of oxysterols include inhibition of cholesterol biosynthesis and cell proliferation in a variety of cell types, among them hematopoietic cells. Characterization and differential expression of ORP-3 implicates a possible role in the mediation of oxysterol effects on hematopoiesis.

Healthy nature healthy people: 'contact with nature' as an upstream health promotion intervention for populations

Whilst urban-dwelling individuals who seek out parks and gardens appear to intuitively understand the personal health and well-being benefits arising from `contact with nature', public health strategies are yet to maximize the untapped resource nature provides, including the benefits of nature contact as an upstream health promotion intervention for populations. This paper presents a summary of empirical, theoretical and anecdotal evidence drawn from a literature review of the human health benefits of contact with nature. Initial findings indicate that nature plays a vital role in human health and well-being, and that parks and nature reserves play a significant role by providing access to nature for individuals. Implications suggest contact with nature may provide an effective population-wide strategy in prevention of mental ill health, with potential application for sub-populations, communities and individuals at higher risk of ill health. Recommendations include further investigation of `contact with nature' in population health, and examination of the benefits of nature-based interventions. To maximize use of `contact with nature' in the health promotion of populations, collaborative strategies between researchers and primary health, social services, urban planning and environmental management sectors are required. This approach offers not only an augmentation of existing health promotion and prevention activities, but provides the basis for a socio-ecological approach to public health that incorporates environmental sustainability.

Health and well-being naturally: 'contact with nature' in health promotion for targeted individuals, communities and populations

Issue addressed: The increase in mental health disorders worldwide makes it important to recognise health promotion interventions that are effective, accessible and affordable. Although natural spaces are coming to be recognised as health-promoting settings for general populations, little is understood about the use of nature contact in treatment and care for individuals experiencing ill-health.

Methods: This paper provides a summary of key research findings and presents a case study examining the self reported health and well-being benefits of nature contact for a small clinical sample. The 'Spectrum of Interventions for Mental Health Problems and Mental Disorders' provides a conceptual framework for ordering current and future information relating to nature-based interventions.

Results: Evidence demonstrates that separately, physical activity, social connection, and contact with nature enhance human health and well-being. The case example illustrates how 'active', 'social' and 'adventurous' contact with nature may be combined within a treatment intervention to protect and enhance the health of individuals experiencing chronic mental, emotional and physical health difficulties.

Conclusions: 'Contact with nature' constitutes a health promotion strategy with potential application in prevention, early intervention, treatment and care. Recommendations include further research to investigate the benefits of nature contact within existing interventions, and the impacts of 'active' and 'social' nature contact within tailored interventions for targeted individuals and communities.

Ecological and human dimensions of management of feral horses in Australia: a review

In Australia, the management of feral horse populations is a contentious issue, owing to their pluralistic status as an introduced pest and a national icon. In this review, we synthesise current knowledge of the ecological effects of feral horses and the human dimensions of feral horse management, using case studies from around the world to illustrate contentious and successful management practices. We highlight gaps in the literature and suggest that more peer-reviewed research would be beneficial in reducing the current public controversy surrounding management of feral horses.

GAD2 on chromosome 10p12 is a candidate gene for human obesity

The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11–12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of γ-aminobutyric acid (GABA), which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C>A and +83897 T>A (OR = 0.81, 95% CI [0.681–0.972], p = 0.0049) and an at-risk SNP (−243 A>G) for morbid obesity (OR = 1.3, 95% CI [1.053–1.585], p = 0.014). Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C>A and +83897 T>A haplotype (χ2 = 7.637, p = 0.02). In the murine insulinoma cell line βTC3, the G at-risk allele of SNP −243 A>G increased six times GAD2 promoter activity (p < 0.0001) and induced a 6-fold higher affinity for nuclear extracts. The −243 A>G SNP was associated with higher hunger scores (p = 0.007) and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic β cells, we analyzed GAD65 antibody level as a marker of β-cell activity and of insulin secretion. In the control group, −243 A>G, +61450 C>A, and +83897 T>A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively). SNP +83897 T>A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of β-cell function (p = 0.009 and 0.01, respectively). These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.

Effects of human activities on rocky shores of the Surf Coast Shire: scientific basis for management at the regional level

The Surf Coast Shire in regional Victoria contains some of the most spectacular coastline in Australia, running from Point Impossible in the east to just west of the resort town of Lorne. The Surf Coast Shire council is committed to ecologically sustainable tourism based on its coastal assets, including the important intertidal environments. The challenge for the Shire is to protect and enhance the biodiversity of its intertidal areas whilst allowing for their sustainable use as a critical component of the local economy. In order to do this the Council needed to identify the conservation values of intertidal areas within the shire and assess the impacts that current human use has on these values. The impacts of shellfish collecting on rocky shores were identified as an issue of particular concern. We have conducted a research project with the Shire to provide a scientific basis for management decisions. The principal aims of this project were to: (1) determine the patterns of human use of intertidal habitats; (2) measure the impacts of human usage on biological communities and species populations; and (3) to identify intertidal sites of regional conservation significance for the Surf Coast Shire. Surveys of human usage identified reef walking, looking in rock pools and fossicking as major uses of rocky shores within the Surf Coast. This poster reports the effects of this usage on gastropod populations of rocky shores within the Surf Coast Shire. A small proportion of visitors collected intertidal organisms. Shores were categorized as high or low use based on total numbers of people observed at each shore over the first year of the project. Mean size and catch per unit effort were compared for several gastropod species between high use and low use shores. The results presented here show that the populations of some gastropod species are of smaller mean size and less abundant on high use shores than on low use shores. There was also a noticeable difference in degree of effect detected between sandstone and mudstone shores. The implications of these results are briefly discussed in terms of management options available to the Shire.

Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle

Diabetes is quickly reaching epidemic proportions, with 216 million people worldwide predicted to be diagnosed with the disease by 2010. While it appears that the expression of the insulin responsive glucose transporter isoform 4 (GLUT4) is not reduced in diabetic populations, overexpression of GLUT4 exclusively in muscle enhances insulin action and improves glucose homeostasis. Consequently, understanding the regulation of GLUT4 expression is considered important in identifying potential therapeutic targets for the treatment and management of insulin resistance and related disorders such as type 2 diabetes. Using transgenic mice, we have identified two conserved regions on the GLUT4 gene promoter that are required for normal skeletal muscle GLUT4 expression. The first region contains a binding site for the myocyte enhancer factor 2 (MEF2) transcription factor, between –464 and –473 bp, and it appears that a MEF2A/D heterodimer binds this sequence. However, this site is not sufficient to support full GLUT4 expression, and another region between –712 and –742 bp, termed Domain 1, is also required. A novel transcription factor, named the GLUT4 enhancer factor (GEF), was found to bind to this region. It appears that MEF2 and GEF physically interact in order to induce GLUT4 expression. A single bout of exercise is sufficient to increase both GLUT4 transcription and mRNA abundance. However, the molecular mechanisms underpinning this response remain largely unexplored, particularly in human skeletal muscle. Therefore, the aim of this study was to determine whether a single, acute bout of exercise increases the DNA-binding activity of both MEF2 and GEF in human skeletal muscle.