Genetic variation and obesity in Australian women: A prospective study.

Objective: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the ß-3 adrenergic receptor, tumor necrosis factor-α, leptin, and leptin receptor (Lepr) in a cohort of Australian women.

Research Methods and Procedures: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double-energy X-ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2-year follow-up. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of all polymorphisms.

Results: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2-year period were not associated with genetic variation in the ß-3 adrenergic receptor (Trp64Arg), tumor necrosis factor-α promoter, or leptin genes in non-obese or obese women.

Discussion: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.

Tanis: a link between type 2 diabetes and inflammation?

Here we describe a novel protein, which we have named Tanis, that is implicated in type 2 diabetes and inflammation. In Psammomys obesus, a unique polygenic animal model of type 2 diabetes and the metabolic syndrome, Tanis is expressed in the liver in inverse proportion to circulating glucose (P = 0.010) and insulin levels (P = 0.004) and in direct proportion with plasma triglyceride concentrations (P = 0.007). Hepatic Tanis gene expression was markedly increased (3.1-fold) after a 24-h fast in diabetic but not in nondiabetic P. obesus. In addition, glucose inhibited Tanis gene expression in cultured hepatocytes (P = 0.006) as well as in several other cell types (P = 0.001–0.011). Thus, Tanis seems to be regulated by glucose and is dysregulated in the diabetic state. Yeast-2 hybrid screening identified serum amyloid A (SAA), an acute-phase inflammatory response protein, as an interacting protein of Tanis, and this was confirmed by Biacore experiments. SAA and other acute-phase proteins have been the focus of recent attention as risk factors for cardiovascular disease, and we contend that Tanis and its interaction with SAA may provide a mechanistic link among type 2 diabetes, inflammation, and cardiovascular disease.

New approaches to gene discovery with animal models of obesity and diabetes

DNA-based approaches to the discovery of genes contributing to the development of type 2 diabetes have not been very successful despite substantial investments of time and money. The multiple gene-gene and gene-environment interactions that influence the development of type 2 diabetes mean that DNA approaches are not the ideal tool for defining the etiology of this complex disease. Gene expression-based technologies may prove to be a more rewarding strategy to identify diabetes candidate genes. There are a number of RNA-based technologies available to identify genes that are differentially expressed in various tissues in type 2 diabetes. These include differential display polymerase chain reaction (ddPCR), suppression subtractive hybridization (SSH), and cDNA microarrays. The power of new technologies to detect differential gene expression is ideally suited to studies utilizing appropriate animal models of human disease. We have shown that the gene expression approach, in combination with an excellent animal model such as the Israeli sand rat (Psammomys obesus), can provide novel genes and pathways that may be important in the disease process and provide novel therapeutic approaches. This paper will describe a new gene discovery, beacon, a novel gene linked with energy intake. As the functional characterization of novel genes discovered in our laboratory using this approach continues, it is anticipated that we will soon be able to compile a definitive list of genes that are important in the development of obesity and type 2 diabetes.

A partnership model of corporate ethics

The stock market crash of 1987 had a profound effect on corporate Australia and the Australian community in general. The fall-out revealed that some of our most respected business figures had not been as ethical, or even as lawful, as we would have hoped. This impropriety produced in Australia an awakening to business ethics. Whilst many companies endeavoured to introduce ethical practices into their corporations, they perceived ethics as a way of minimising damage to the corporation and in some cases as a means of competitive advantage. What was lost was the reason that one should embark on business ethics; and that is to make the society and corporate Australia a more ethical place in which to exist.This paper proposes a model based on 2 factors: commitment and partnerships, as a means of enabling corporate Australia to refocus attention on the main purpose of being inherently ethical in all that we do. This ethical model requires a commitment to partnerships with all stakeholders both internal and external in an attempt to enhance the level of ethical business practices that are contemplated and pursued within corporate Australia. Whilst the research agenda and the information collected is Australian-based, it is hoped that the ideas contained within this paper will have a wider appeal to corporations in similar cultural settings.

Exercise training increases lipid metabolism gene expression in human skeletal muscle

The effects of a single bout of exercise and exercise training on the expression of genes necessary for the transport and beta -oxidation of fatty acids (FA), together with the gene expression of transcription factors implicated in the regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4 female, 28.9 ± 3.1 yr of age, range 20-42 yr, body mass index 22.6 kg/m², range 17-26 kg/m²) underwent a 9-day exercise training program of 60 min cycling per day at 63% peak oxygen uptake (V_{O2 peak}; 104 ± 14 W). On days 1 and 9 of the program, muscle biopsies were sampled from the vastus lateralis muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene expression of key components of FA transport [FA translocase (FAT/CD36), plasma membrane-associated FA-binding protein], beta -oxidation [carntine palmitoyltransferase(CPT) I, beta -hydroxyacyl-CoA dehydrogenase] and transcriptional control [peroxisome proliferator-activated receptor (PPAR)alpha , PPARgamma , PPARgamma coactivator 1, sterol regulatory element-binding protein-1c] were unaltered by exercise when measured at the completion and at 3 h postexercise. Training increased total lipid oxidation by 24% (P < 0.05) for the 1-h cycling bout. This increased capacity for lipid oxidation was accompanied by an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein abundance was also upregulated by exercise training. We conclude that enhanced fat oxidation after exercise training is most closely associated with the genes involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across the mitochondrial membrane (CPT I).

Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety and fatigue

Objective: This study was designed to investigate the role of depression, anxiety, and fatigue in Chronic Fatigue Syndrome (CFS) sufferers' objective and subjective cognitive performance. Methods: Twenty-three CFS sufferers and 23 healthy control participants were compared on objective and subjective assessments of cognitive performance. Depression, anxiety, and fatigue were also evaluated. Results: CFS sufferers did not demonstrate any impairment in objective cognitive functioning compared to the control group, and objective performance was not related to their higher levels of depression or their level of fatigue. Depression scores only accounted for a small amount of the variance in CFS sufferers' lower subjective assessment of their cognitive performance compared to control participants. There were no differences between the groups on anxiety scores. Conclusion: The results are discussed in terms of the heterogeneity of the CFS population and the complex interaction of symptomatological factors that characterise CFS.

Effect of alcohol intake on muscle glycogen storage after prolonged exercise

We studied the effects of alcohol intake on postexercise muscle glycogen restoration with samples from vastus lateralis being collected immediately after glycogen-depleting cycling and after a set recovery period. Six well-trained cyclists undertook a study of 8-h recovery (2 meals), and another nine cyclists undertook a separate 24-h protocol (4 meals). In each study, subjects completed three trials in crossover order: control (C) diet [meals providing carbohydrate (CHO) of 1.75 g/kg]; alcohol-displacement (A) diet (1.5 g/kg alcohol displacing CHO energy from C) and alcohol + CHO (AC) diet (C + 1.5 g/kg alcohol). Alcohol intake reduced postmeal glycemia especially in A trial and 24-h study, although insulin responses were maintained. Alcohol intake increased serum triglycerides, particularly in the 24-h study and AC trial. Glycogen storage was decreased in A diets compared with C at 8 h (24.4 ± 7 vs. 44.6 ± 6 mmol/kg wet wt, means ± SE, P < 0.05) and 24 h (68 ± 5 vs. 82 ± 5 mmol/kg wet wt, P < 0.05). There was a trend to reduced glycogen storage with AC in 8 h (36.2 ± 8 mmol/kg wet wt, P = 0.1) but no difference in 24 h (85 ± 9 mmol/kg wet wt). We conclude that 1) the direct effect of alcohol on postexercise glycogen synthesis is unclear, and 2) the main effect of alcohol intake is indirect, by displacing CHO intake from optimal recovery nutrition practices.

Communicating the ethos of codes of ethics in corporate Australia, 1995-2001: whose rights, whose responsibilities?

This paper considers the commitment to business ethics of the top 500 companies operating in the Australian private sector and communicates the results of a longitudinal study conducted from 1995 to 2001. Primary data was obtained (in 1995 and again in 2001) via a self-administered mail  questionnaire distributed to a census of these top 500 Australian  companies. This commitment of each company to their code of ethics was indicated and measured via a range of methods used by organizations to communicate the ethos of their codes to employees. Just as they were in  1995, it would appear that companies in 2001 still are good at ensuring that their rights are protected, but at the same time they do not seem to take on the responsibility to ensure that employees'' rights are just as well protected. This double standard leads to cynicism towards the current business ethics processes inherent in Australian companies.

Codes of ethics: what are they really and what should they be?

Codes of ethics are prevalent in major corporations around the world. They are seen as the first tangible commitment to being ethical. This paper examines codes of ethics and tries to establish what they are, how they are developed and their net utility. We then proffer the idea of codes as the first part of a five-stage process that leads to an overall corporate commitment to being ethical in one's business dealings.

Ethical behaviour: the means for creating and maintaining better reputations in arts organisations

Arts organisations, unsure of the level of continued government funding available and confronted with the need ever to improve, are seeking new ideas upon which they can focus. At a time when leadership and governance in arts organisations have changed in line with cultural expectations, how is their ethical stance assessed? How does their ethical stance impact on reputation? The challenge to build a good reputation starts at the top of the organisation; however, traditionally, one type of arts organisation, art museums, has focused on the activities level. In an age of globalisation, economic restructuring and technological change, museums therefore may be seen as a contradiction. Traditionally seen as temples for the muses, today’s museums are being challenged to be ethical for society and to build their reputation. As a solution, proposes a cooperative model of cultural organisational ethics that attempts to provide a framework by which arts organisations can put in place ethical artefacts that enhance organisational reputation, rather than detract from it.

Moby-Dick and the philosopher of pessimism

Herman Melville discovered the philosophy of Arthur Schopenhauer late in life, and must have been surprised to discover how close this writer's philosophy was to his own beliefs. Despite this late revelation, the influence on Melville's work was strong, and there are good arguments to show that Melville was inspired by his ideas in the creation of 'Bartleby , the Scrivener' and Billy Budd. Melville may well have been aware of Schopenhauer's philosophy earlier, however, regardless of his lack of proven or direct exposure to the work of the German writer at the time of its composition, Moby-Dick exhibits many affinities with Schopenhauer's thought and it is possible to examine the book through such a reading.

Regulation of selenoprotein SelS by glucose deprivation and endoplasmic reticulum stress - SelS is a novel glucose-regulated protein

SelS is a newly identified selenoprotein and its gene expression is up-regulated in the liver of Psammomys obesus after fasting. We have examined whether SelS is regulated by glucose deprivation and endoplasmic reticulum (ER) stress in HepG2 cells. Glucose deprivation and the ER stress inducers tunicamycin and thapsigargin increased SelS gene expression and protein content several-fold in parallel with glucose-regulated protein 78. The overexpression of SelS increased Min6 cell resistance to oxidative stress-induced toxicity. These results indicate that SelS is a novel member of the glucose-regulated protein family and its function is related to the regulation of cellular redox balance.