Human preadipocyte proliferation and differentiation

Obesity represents a major health, social and economic burden to many developing and Westernized communities, with the prevalence increasing at a rate exceeding almost all other medical conditions. Despite major recent advances in our understanding of adipose tissue metabolism and dynamics, we still have limited insight into the regulation of adipose tissue mass in humans. Any significant increase in adipose tissue mass requires proliferation and differentiation of precursor cells (preadipocytes) present in the stromo-vascular compartment of adipose tissue. These processes are very complex and an increasing number of growth factors and hormones have been shown to modulate the expression of genes involved in preadipocyte proliferation and differentiation. A number of transcription factors, including the C/EBP family and PP ARy, have been identified as integral to adipose tissue development and preadipocyte differentiation. Together PP ARy and C/EBPa regulate important events in the activation and maintenance of the terminally differentiated phenotype. The ability of PP ARy to increase transcription through its DNA recognition site is dependent on the binding of ligands. This suggests that an endogenous PP ARy ligand may be an important regulator of adipogenesis. Adipose tissue functions as both the major site of energy storage in the body and as an endocrine organ synthesizing and secreting a number of important molecules involved in regulation of energy balance. For optimum functioning therefore, adipose tissue requires extensive vascularization and previous studies have shown that growth of adipose tissue is preceded by development of a microvascular network. This suggests that paracrine interactions between constituent cells in adipose tissue may be involved in both new capillary formation and fat cell growth. To address this hypothesis the work in this project was aimed at (a) further development of a method for inducing preadipocyte differentiation in subcultured human cells; (b) establishing a method for simultaneous isolation and separate culture of both preadipocytes and microvascular endothelial cells from the same adipose tissue biopsies; (c) to determine, using conditioned medium and co-culture techniques, if endothelial cell-derived factors influence the proliferation and/or differentiation of human preadipocytes; and (d) commence characterization of factors that may be responsible for any observed paracrine effects on aspects of human adipogenesis. Major findings of these studies were as follows: (A) Inclusion of either linoleic acid (a long-chain fatty acid reported to be a naturally occurring ligand for PP ARy) or Rosiglitazone (a member of the thiazolidinedione class of insulin-sensitizing drugs and a synthetic PPARy ligand) in differentiation medium had markedly different effects on preadipocyte differentiation. These studies showed that human preadipocytes have the potential to accumulate triacylglycerol irrespective of their stage of biochemical differentiation, and that thiazolidinediones and fatty acids may exert their adipogenic and lipogenic effects via different biochemical pathways. It was concluded that Rosiglitazone is a more potent inducer of human preadipocyte differentiation than linoleic acid. (B) A method for isolation and culture of both endothelial cells and preadipocytes from the same adipose tissue biopsy was developed. Adipose-derived microvascular endothelial cells were found to produce factor/s, which enhance both proliferation and differentiation of human preadipocytes. (C) The adipogenic effects of microvascular endothelial cells can be mimicked by exposure of preadipocytes to members of the Fibroblast Growth Factor family, specifically ~-ECGF and FGF-1. (D) Co-culture of human preadipocytes with endothelial cells or exposure of preadipocytes to either ~-ECGF or FGF-1 were found to 'prime' human preadipocytes, during their proliferative phase of growth, for thiazolidinedione-induced differentiation. (E) FGF -1 was not found to be acting as a ligand for PP ARy in this system. Findings from this project represent a significant step forward in our understanding of factors involved in growth of human adipose tissue and may lead to the development of therapeutic strategies aimed at modifying the process. Such strategies would have potential clinical utility in the treatment of obesity and obesity related disorders such as Type II Diabetes.

Thinking spatially, acting collaboratively : a GIS-based health decision support system for improving the collaborative health-planning practice

The field of collaborative health planning faces significant challenges due to the lack of effective information, systems and the absence of a framework to make informed decisions. These challenges have been magnified by the rise of the healthy cities movement, consequently, there have been more frequent calls for localised, collaborative and evidence-driven decision-making. Some studies in the past have reported that the use of decision support systems (DSS) for planning healthy cities may lead to: increase collaboration between stakeholders and the general public, improve the accuracy and quality of the decision-making processes and improve the availability of data and information for health decision-makers. These links have not yet been fully tested and only a handful of studies have evaluated the impact of DSS on stakeholders, policy-makers and health planners. This study suggests a framework for developing healthy cities and introduces an online Geographic Information Systems (GIS)-based DSS for improving the collaborative health planning. It also presents preliminary findings of an ongoing case study conducted in the Logan-Beaudesert region of Queensland, Australia. These findings highlight the perceptions of decision-making prior to the implementation of the DSS intervention. Further, the findings help us to understand the potential role of the DSS to improve collaborative health planning practice.

An observational study of how objects support engineering design thinking and communication : implications for the design of tangible media

There has been an increasing interest in objects within the HCI field particularly with a view to designing tangible interfaces. However, little is known about how people make sense of objects and how objects support thinking. This paper presents a study of groups of engineers using physical objects to prototype designs, and articulates the roles that physical objects play in supporting their design thinking and communications. The study finds that design thinking is heavily dependent upon physical objects, that designers are active and opportunistic in seeking out physical props and that the interpretation and use of an object depends heavily on the activity. The paper discusses the trade-offs that designers make between speed and accuracy of models, and specificity and generality in choice of representations. Implications for design of tangible interfaces are discussed.

Human resource management and innovation: what are knowledge-intensive firms doing?

An undeniable shift in focus from traditional production companies to Knowledge-Intensive Firms (KIFs) poses challenges for academics and practioners alike. In particular, effective management of an organization's human resources has become a critical issue for ensuring sustained innovation capacity. The relationship between Human Resource Management (HRM) in KIFs is however still a largely unexplored arena. The objective of this paper is to explore this relationship in an effort to identify HRM practices that support innovation. To this end, the paper includes reviews of the literature relevant to HRM and innovation in KIFs and four case studies from companies in Denmark and Australia that have been recognized for excellence in innovation. On the basis of content analyses conducted on the case data, some preliminary conclusions are posited regarding the role of HRM in KIFs. More specifically, the findings from this study suggest that while there are commonalities between HRM practices in traditional manufacturing companies and KIFs, there are also important differences, especially in terms of staffing practices. The paper contributes by offering recommendations for management of HRM in innovative KIFs and potential avenues for research to further develop our understanding of how HRM can support innovation in KIFs.

Commercialisation of regenerative human tissue : Regulation and reform in Australia and England, Wales and Northern Ireland

The commercialisation of therapeutic products containing regenerative human tissue is regulated by the common law, statute and ethical guidelines in Australia and England, Wales and Northern Ireland. This article examines the regulatory regimes in these jurisdictions and considers whether reform is required to both support scientific research and ensure conformity with modern social views on medical research and the use of human tissue. The authors consider the crucial role of informed consent in striking the balance between the interests of researchers and the interests of the public.

Discrepancy between human resource research and practice : comparison of industrial/organisational psychologists and human resource practitioners' beliefs

There is a large and growing body of research to show that human resource (HR) practices affect individual performance, organisational productivity and organisational performance. Academic findings about effective HR practices, however, have not readily been adopted by practitioners. A variety of theoretical and practical explanations have been advanced about the research-practice gap. Research by Rynes, Colbert, and Brown (2002) suggested that the research-practice gap is due to a lack of knowledge, but the extent to which these findings apply to the Australian context is unknown. The sample consisted of 102 industrial/organisational (I/O) psychologists and 89 HR practitioners. The main aim of the present study was to replicate and extend the work of Rynes et al. by examining and comparing the knowledge of I/O psychologists and HR practitioners. It was found that overall I/O psychologists were better informed about HR research than HR practitioners; in particular, they were more knowledgeable about management practices and recruitment and selection. In both groups, of the five content areas examined (Management Practices; General Employment Practices; Training and Development; Recruitment and Selection; and Compensation and Benefits), the greatest gaps were in Recruitment and Selection.

Rethinking Prostitution : feminism, sex and the self

Prostitution is a difficult issue, particularly for feminists. Are prostitutes victims of exploitation or the most honest of women? Are clients perverts or just acting instinctively? Should prostitution be eliminated or supported? This book examines these contemporary questions and offers a way of thinking about the issues, which does not rely on these inappropriate and often ineffectual options. Repositioning the institution and its main players outside the confines of the prostitution debate offers new and exciting ways of thinking and acting for all those interested in moving this discussion into the twenty-first century.

P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions.

It is known that adenosine 5'-triphosphate (ATP) is a cotransmitter in the heart. Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X(1-7) and P2Y(1-14) receptors; however, the presence of P2X and P2Y receptor subtypes in strategic cardiac locations such as the sinoatrial node has not been determined. An understanding of P2X and P2Y receptor localization would facilitate investigation of purine receptor function in the heart. Therefore, we used quantitative PCR and in situ hybridization to measure the expression of mRNA of all known purine receptors in rat left ventricle, right atrium and sinoatrial node (SAN), and human right atrium and SAN. Expression of mRNA for all the cloned P2 receptors was observed in the ventricles, atria, and SAN of the rat. However, their abundance varied in different regions of the heart. P2X(5) was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y(1), P2Y(2), and P2Y(14) mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y(2) and P2Y(14) levels were highest, respectively. We extended these studies to investigate P2X(4) receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X(4) receptor mRNA was upregulated by 93% in SAN (P < 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X(4)-mediated effects might be modulated in heart failure. mRNA for P2X(4-7) and P2Y(1,2,4,6,12-14), but not P2X(2,3) and P2Y(11), was detected in human right atrium and SAN. In addition, mRNA for P2X(1) was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X(4) and P2X(7) mRNA was the highest for P2X receptors. P2Y(1) and P2Y(2) mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y(1), P2Y(2), and P2Y(14) were the most abundant P2Y receptor subtypes in human SAN. This study shows a widespread distribution of P2 receptor mRNA in rat heart tissues but a more restricted presence and distribution of P2 receptor mRNA in human atrium and SAN. This study provides further direction for the elucidation of P2 receptor modulation of heart rate and contractility.

Concentrations of polybrominated diphenyl ethers (PBDEs) in matched samples of human milk, dust and indoor air

Polybrominated diphenyl ethers (PBDEs) are lipophilic, persistent pollutants found worldwide in environmental and human samples. Exposure pathways for PBDEs remain unclear but may include food, air and dust. The aim of this study was to conduct an integrated assessment of PBDE exposure and human body burden using 10 matched samples of human milk, indoor air and dust collected in 2007–2008 in Brisbane, Australia. In addition, temporal analysis was investigated comparing the results of the current study with PBDE concentrations in human milk collected in 2002–2003 from the same region. PBDEs were detected in all matrices and the median concentrations of BDEs -47 and -209 in human milk, air and dust were: 4.2 and 0.3 ng/g lipid; 25 and 7.8 pg/m3; and 56 and 291 ng/g dust, respectively. Significant correlations were observed between the concentrations of BDE-99 in air and human milk (r = 0.661, p = 0.038) and BDE-153 in dust and BDE-183 in human milk (r = 0.697, p = 0.025). These correlations do not suggest causal relationships — there is no hypothesis that can be offered to explain why BDE-153 in dust and BDE-183 in milk are correlated. The fact that so few correlations were found in the data could be a function of the small sample size, or because additional factors, such as sources of exposure not considered or measured in the study, might be important in explaining exposure to PBDEs. There was a slight decrease in PBDE concentrations from 2002–2003 to 2007–2008 but this may be due to sampling and analytical differences. Overall, average PBDE concentrations from these individual samples were similar to results from pooled human milk collected in Brisbane in 2002–2003 indicating that pooling may be an efficient, cost-effective strategy of assessing PBDE concentrations on a population basis. The results of this study were used to estimate an infant's daily PBDE intake via inhalation, dust ingestion and human milk consumption. Differences in PBDE intake of individual congeners from the different matrices were observed. Specifically, as the level of bromination increased, the contribution of PBDE intake decreased via human milk and increased via dust. As the impacts of the ban of the lower brominated (penta- and octa-BDE) products become evident, an increased use of the higher brominated deca-BDE product may result in dust making a greater contribution to infant exposure than it does currently. To better understand human body burden, further research is required into the sources and exposure pathways of PBDEs and metabolic differences influencing an individual's response to exposure. In addition, temporal trend analysis is necessary with continued monitoring of PBDEs in the human population as well as in the suggested exposure matrices of food, dust and air.

Mechanisms of change in negative thinking and urinary monoamines in depressed patients during acute treatment with group cognitive behavior therapy and antidepressant medication

This naturalistic study investigated the mechanisms of change in measures of negative thinking and in 24-h urinary metabolites of noradrenaline (norepinephrine), dopamine and serotonin in a sample of 43 depressed hospital patients attending an eight-session group cognitive behavior therapy program. Most participants (91%) were taking antidepressant medication throughout the therapy period according to their treating Psychiatrists' prescriptions. The sample was divided into outcome categories (19 Responders and 24 Non-responders) on the basis of a clinically reliable change index [Jacobson, N.S., & Truax, P., 1991. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12–19.] applied to the Beck Depression Inventory scores at the end of the therapy. Results of repeated measures analysis of variance [ANOVA] analyses of variance indicated that all measures of negative thinking improved significantly during therapy, and significantly more so in the Responders as expected. The treatment had a significant impact on urinary adrenaline and metadrenaline excretion however, these changes occurred in both Responders and Non-responders. Acute treatment did not significantly influence the six other monoamine metabolites. In summary, changes in urinary monoamine levels during combined treatment for depression were not associated with self-reported changes in mood symptoms.

Liking vs. wanting food : importance for human appetite control and weight regulation

Current train of thought in appetite research is favouring an interest in non-homeostatic or hedonic (reward) mechanisms in relation to overconsumption and energy balance. This tendency is supported by advances in neurobiology that precede the emergence of a new conceptual approach to reward where affect and motivation (liking and wanting) can be seen as the major force in guiding human eating behaviour. In this review, current progress in applying processes of liking and wanting to the study of human appetite are examined by discussing the following issues: How can these concepts be operationalised for use in human research to reflect the neural mechanisms by which they may be influenced? Do liking and wanting operate independently to produce functionally significant changes in behaviour? Can liking and wanting be truly experimentally separated or will an expression of one inevitably contain elements of the other? The review contains a re-examination of selected human appetite research before exploring more recent methodological approaches to the study of liking and wanting in appetite control. In addition, some theoretical developments are described in four diverse models that may enhance current understanding of the role of these processes in guiding ingestive behaviour. Finally, the implications of a dual process modulation of food reward for weight gain and obesity are discussed. The review concludes that processes of liking and wanting are likely to have independent roles in characterising susceptibility to weight gain. Further research into the dissociation of liking and wanting through implicit and explicit levels of processing would help to disclose the relative importance of these components of reward for appetite control and weight regulation.

Critical thinking and organisation theory : embedding a process to encourage graduate capabilities

The need for the development of effective business curricula that meets the needs of the marketplace has created an increase in the adoption of core competencies lists identifying appropriate graduate skills. Many organisations and tertiary institutions have individual graduate capabilities lists including skills deemed essential for success. Skills recognised as ‘critical thinking’ are popular inclusions on core competencies and graduate capability lists. While there is literature outlining ‘critical thinking’ frameworks, methods of teaching it and calls for its integration into business curricula, few studies actually identify quantifiable improvements achieved in this area. This project sought to address the development of ‘critical thinking’ skills in a management degree program by embedding a process for critical thinking within a theory unit undertaken by students early in the program. Focus groups and a student survey were used to identify issues of both content and implementation and to develop a student perspective on their needs in thinking critically. A process utilising a framework of critical thinking was integrated through a workbook of weekly case studies for group analysis, discussions and experiential exercises. The experience included formative and summative assessment. Initial results indicate a greater valuation by students of their experience in the organisation theory unit; better marks for mid semester essay assignments and higher evaluations on the university administered survey of students’ satisfaction.