Identification of hypothalamic genes implicated in the development of obesity in Psammomys obesus using differential display PCR

The hypothalamus is a key central controller of energy homeostasis and is the source and/or site of action of many neuropeptides involved in this process. The aim of this study was to isolate hypothalamic genes differentially expressed between lean and obese Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes. Differential display PCR was used to compare hypothalamic gene expression profiles of lean and healthy, obese and hyperinsulinemic, and obese, diabetic P. obesus in both the fed and fasted states. We conducted differential display with 180 separate primer combinations to amplify approximately 9000 expressed transcripts. Sixty differentially expressed bands were excised. Taqman PCR was performed on 36 of these transcripts to confirm differential gene expression in a larger sample population. Of these 36 transcripts, 9 showed homology to known genes, and 27 were considered to be novel sequences. Gene expression profiles for two of these genes are presented here. In conclusion, differential display PCR was successfully used to isolate several transcripts that may be involved in the central regulation of energy balance. We are currently conducting numerous studies to further investigate the role of these genes in the development of obesity in P. obesus.

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.

The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

Aims/hypothesis This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes.
Methods We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions.
Results We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic–euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, accounting for 5% of the variation in plasma insulin in elderly subjects.
Conclusions/interpretation Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

Social innovators or lagging behind: factors that influence managers' time use

Purpose – The broad aim of this paper is to investigate whether managers in Australia allocate their time differently than other occupational groups, and the impact gender and life situation (using marital status and presence or absence of dependent children as a proxy) has on time allocation.
Design/methodology/approach – To address these broad aims, data are drawn from the 1997 Australian Time Use Survey. This is a nationally representative survey that examines how people in different circumstances allocate time to different activities. Findings – The results of this study highlight three important issues. The first is that male and female managers display different patterns of time use. Male managers' time is dominated by paid employment activities, whereas female managers' time is spent predominantly on employment and domestic activities. The second is that life situation impacts on the time use of female managers, but not male managers. The third important find of this study is that managers' time use is different to other occupational groups. Practical implications – These findings have policy implications relating to work-life balance, career progression and changes in patterns of work. In terms of work-life issues, it reveals that male and female managers face a “time squeeze”, with some evidence of a “second-shift” for female managers. In addition, the findings provide insight into the work-life issues faced by male and female managers. Originality/value – The results of this inquiry provide insight into how different individuals spend their time – insight into “lifestyles”. However, in-depth qualitative studies are required to reveal why individuals allocate their time in this way and to understand the opportunities and constraints individuals face in time allocation.

Changes in attitudes to mothers working: evidence from Australian surveys

The aim of this article is to contribute to the development of our  understanding of two aspects of attitude change in Australia. First, both cohort and individual explanations for attitude change are tested empirically. Second, empirical evidence is provided about the nature and scope of change in gender role attitudes amongst males and females, and of different birth cohorts in Australia, as reported in two survey periods: 1994 and 2002. In particular, the question of whether there is empirical evidence of cohort differences in attitudes to gender roles in Australia is investigated. TheThe aim of this article is to contribute to the development of our understanding of two aspects of attitude change in Australia. First, both cohort and individual explanations for attitude change are tested empirically. Second, empirical evidence is provided about the nature and scope of change in gender role attitudes amongst males and females, and of different birth cohorts in Australia, as reported in two survey periods: 1994 and 2002. In particular, the question of whether there is empirical evidence of cohort differences in attitudes to gender roles in Australia is investigated. The findings show that birth cohorts display progressively more modern attitudes, but people tend not to change their attitudes as they get older. In addition, men and women have different attitudes to gender roles, with men displaying more traditional beliefs than women. Having more than one child makes women less inclined to express the belief that women should work.

Introduction: perspectives on work-life balance

Work-life balance has emerged as a major concern for researchers trying to map the dimensions and causes of the issue, for policy makers searching for uncontroversial solutions to the problem and for individuals trying to construct satisfying and productive lives. There is some agreement over the main contributors to the work-life balance 'problem': the increase in female participation in the workforce since the 1960s; changes to work from the mid-1970s, in particular greater work intensification, an increase in alternative work schedules away from the standard working week and the growth of casual jobs (particularly in Australia); and a de-differentiation of roles, which has contributed to greater spill-over between work and other roles.

These factors are embedded in economic, social and cultural changes that characterise the post-World War II development of late capitalism in the more developed economies. Each is itself the result of a set of complex processes of change. We do not attempt here to detail these changes in all their complexity but draw out those elements that are most important in attempting to understand the work-life issue in terms of causal forces, mediating support systems and the effects of work-life balance or 'imbalance' on individuals, households, communities and societies.

This issue of Labour and Industry brings together three papers that focus on different work-life balance issues as a result of differing causal forces, different configurations of work/life activities, varying outcomes and variations in terms of support available. In particular, the problem of work-life balance is examined through an analysis of change in attitudes to mothers working in Australia, a study of agency or labour hire, and a study of young professionals. These papers were first presented at the WorkTimes/LifeTimes Colloquium held in Geelong, Victoria in December 2004. The aim of this colloquium was to explore issues around working time and the impact that this has on other aspects of people's lives. Specialists in the area of working time, time use, employee relations, and work-family came together to share the results of their respective research areas and to debate the theoretical and policy implications of their findings.

Older Australians : involvement in civil society in the 1990s

As Australia’s population continues to age, questions about how older individuals use their time holds increasing interest and significance for scholars and policy makers. As individuals near the end of their paid working life, and family roles and responsibilities diminish, the type of activities that will fill this time void have important implications for the health and wellbeing of older Australians and for the strength of civil society. In Australia, there have been sustained moves at all levels of government to encourage the more active engagement in community services of this group of citizens, given the size and significant amount of human capital of this cohort. However, international research suggests that this enthusiasm has not translated into increased volunteer activity for seniors, and that older citizens tend to spend their expanding discretionary time pursuing leisure activities, such as watching television or listening to the radio (Robinson & Godbey 1997; Wilson & Musick 1997; Thoits & Hewitt 2001). This study builds on a broader interest in how people choose to utilise time across the life course and how the experience of ageing shapes such decisions. This aim of this paper is twofold – first, to investigate how older Australians allocated their time in the 1990s, and how these time use patterns changed over a 5-year period, using nationally representative, longitudinal data from two waves of the Australian Time Use Survey. Second, the time use characteristics of those individuals who devote more time to social participation activities are examined, to investigate trends in volunteering across age cohorts, with a focus on those above the age of fifty.

Identification of novel genes expressed during rhabdomyosarcoma differentiation using cDNA microarrays

Rhabdomyosarcomas (RMS) are highly aggressive tumors that are thought to arise as a consequence of the regulatory disruption of the growth and differentiation of skeletal muscle progenitor cells. Normal myogenesis is characterized by the expression of the myogenic regulatory factor gene family but, despite their expression in RMS, these tumor cells fail to complete the latter stages of myogenesis. The RMS cell line RD-A was treated with 12-O-tetradecanoylphorbol-13-acetate to induce differentiation and cultured for 10 days. RNA was extracted on days 1, 3, 6, 8 and 10. A human skeletal muscle cDNA microarray was developed and used to analyze the global gene expression of RMS tumors over the time-course of differentiation. As a comparison, the genes identified were subsequently examined during the differentiated primary human skeletal muscle cultures. Prothymosin alpha (PTMA), and translocase of inner mitochondrial membrane 10 (Tim10), two genes not previously implicated in RMS, showed reduced expression during differentiation. Marked differences in the expression of PTMA and Tim10 were observed during the differentiation of human primary skeletal muscle cells. These results identify several new genes with potential roles in the myogenic arrest present in rhabdomyosarcoma. PTMA expression in RMS biopsy samples might prove to be an effective diagnostic marker for this disease.

Good governance and market-based reforms : a study of Bangladesh

‘Good governance’ is increasingly regarded as pivotal to development in developing countries. The six indicators recognized as the most effective measurement tools of ‘good governance’ across the world are: voice and accountability; political stability and absence of violence; government effectiveness; regulatory quality; rule of law and control of corruption (Kaufmann, Kraay and Lobaton, 2003: 8–9). This paper investigates how lack of ‘good governance’ affects the success and sustainability of the market-based reforms undertaken in the agriculture sector of Bangladesh. The reforms have been associated with increased food grain production, improved food security conditions and easy access by farmers to agricultural inputs. However, a significant problem has arisen recently: the sale of low quality and underweight agricultural inputs sometimes at higher prices has become common. Not only is this problem undermining the positive impact of the reforms, it is also threatening their sustainability. The paper argues that the problems with regulatory quality, rule of law and control of corruption – indicators of good governance – are the underlying reasons for this problem. In the context of increasing pressures from donors to pursue market-based reforms, this paper stresses the need for integrated governance linking government, business and civil society as paramount for promoting good governance for the success and sustainability of the reforms.

Governance gone bad

The problems of the Bangladesh agriculture input sector are an example of good governance gone bad. The solution is a functional governance model bringing together state, the private sector and civil society, write Fara Azmat, Ken Coghill and Quamrul Alam.

Activation of the selenopritein SEPS1 gene expression by pro-inflammatory cytokines in Hep G2 cells

SEPS1 (also called selenoprotein S, SelS) plays an important role in the production of inflammatory cytokines and its expression is activated by endoplasmic reticulum (ER) stress. In this report, we have identified two binding sites for the nuclear factor kappa B in the human SEPS1 promoter. SEPS1 gene expression, protein levels and promoter activity were all increased 2–3-fold by TNF-α and IL-1β in HepG2 cells. We have also confirmed that the previously proposed ER stress response element GGATTTCTCCCCCGCCACG in the SEPS1 proximate promoter is fully functional and responsive to ER stress. However, concurrent treatment of HepG2 cells with IL-1β and ER stress produced no additive effect on SEPS1 gene expression. We conclude that SEPS1 is a new target gene of NF-κB. Together with our previous findings that SEPS1 may regulate cytokine production in macrophage cells, we propose a regulatory loop between cytokines and SEPS1 that plays a key role in control of the inflammatory response.

Association of genetic vatiation within UBL5 with phenotypes of metabolic syndrome

The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat, and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON, UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs), one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.