EMT and MET in carcinoma : clinical observations, regulatory pathways and new models

The articles collected here in this special edition Epithelial-Mesenchymal (EMT) and Mesenchymal-Epithelial Transitions (MET) in Cancer provide a snapshot of the very rapidly progressing cinemascope of the involvement of these transitions in carcinoma progression. Pubmed analysis of EMT and cancer shows an exponential increase in the last few years in the number of papers and reviews published under these terms (Fig. 1). The last few years have seen these articles appearing in high calibre journals including Nature, Nature Cell Biology, Cancer Cell, PNAS, JNCI, JCI, and Cell, signaling the acceptance and quality of work in this field.

Co-regulatory potential of vascular endothelial growth factor–A and vascular endothelial growth factor–C in thyroid carcinoma

Vascular endothelial growth factor (VEGF) promotes growth of blood or lymphatic vessels. The aim of the current study is to identify relationships between VEGF-A and VEGF-C, and their impact in angiogenesis and metastases in thyroid cancers. VEGF-A and VEGF-C mRNA and protein expression was investigated in 136 thyroid cancers (123 papillary thyroid carcinomas and 13 undifferentiated thyroid carcinomas) and 40 matched lymph node metastases with papillary thyroid carcinoma using reverse transcription polymerase chain reaction and immunohistochemistry. VEGF-A and VEGF-C mRNA expression was significantly different between conventional papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma, and undifferentiated thyroid carcinomas (P = 1 x 10(-6) and 1 x 10(-5), respectively). In undifferentiated carcinoma, VEGF-A and VEGF-C protein overexpression was noted in all cases. VEGF-A and VEGF-C mRNA overexpression was noted in 51% (n = 62) and 27% (n = 33) of the papillary thyroid carcinomas, whereas VEGF-A and VEGF-C protein overexpression was also identified in 70% (n = 86) and 62% (n = 76) of the carcinomas. VEGF-A mRNA was significantly higher in cancers with lymph node metastases compared with nonmetastatic cancers (P = .001), whereas most metastatic cancers underexpressed VEGF-C (P = .0002), with a similar trend for protein. The expression of VEGF-A and VEGF-C correlated with each other at both mRNA and protein levels (P = .00004 and .003, respectively). In summary, VEGF-A and -C expressions correlate with the pathological parameters and metastatic status of thyroid carcinomas. The significant correlations between the expressions of these genes add weight to hypotheses concerning VEGF-A and -C interaction in cancer progression.

Health and safety regulatory reform in Australia : challenges and issues for smaller ethnic firms

In recent times significant change has occurred to the Australian health and safety regulatory context. In this paper we consider the potential response of smaller firms in general, and ethnic owned and/or operated smaller firms in particular. We draw on literature examining smaller firms' responses to regulation and apply this to what little we know about smaller ethnic firms in Australia in the context of the regulatory change. We highlight the challenges to owner managers and what could be done to engage and support smaller ethnic firms to realise the opportunities resulting from this regulatory change.

Small firms and health and safety harmonisation : potential regulatory effects of a dominant narrative

Small firms are popularly viewed as resistant to complying with regulation. Harmonisation of Australia’s state-based work health and safety regimes is a significant regulatory change. In this article, we consider the likely responses of small firms to work health and safety harmonisation and argue that a range of choices are open to small firm owner-managers. These choices are shaped by individuals’ world views and are influenced by elements in the firms’ context. A significant element is the public narrative of work health and safety harmonisation, which can be understood by using discourse and sense-making concepts. Our analysis of small firm owner-manager choices takes into account small firms’ embeddedness in their regulatory context and the influence on organisational decision-making of the narrative of work health and safety harmonisation. The dominant narrative is arguably silent on the benefits of the work health and safety regulatory change and therefore the response of small firms is likely to be avoidance or minimalism. Non-compliance could be the result due to poor awareness of opportunities arising from this regulatory change.

Regulatory reforms and productivity : an empirical analysis of the Japanese electricity industry

The Japanese electricity industry has experienced regulatory reforms since the mid-1990s. This article measures productivity in Japan's steam power-generation sector and examines the effect of reforms on the productivity of this industry over the period 1978-2003. We estimate the Luenberger productivity indicator, which is a generalization of the commonly used Malmquist productivity index, using a data envelopment analysis approach. Factors associated with productivity change are investigated through dynamic generalized method of moments (GMM) estimation of panel data. Our empirical analysis shows that the regulatory reforms have contributed to productivity growth in the steam power-generation sector in Japan.

Regulatory interplay between pap operons in uropathogenic Escherichia coli

Pathogenic bacteria have a large repertoire of surface organelles involved in adherence, motility and protein export, but how individual bacteria co-ordinate surface organelle expression to prevent interference and excessive immune stimulation is unclear. Phase variation is a mechanism by which expression of surface factors is limited to a fraction of the bacterial population; however, the presence of multiple homologous surface structures controlled by related mechanisms and regulators antagonizes the independent expression achieved by phase variation. To investigate whether other mechanisms have evolved to sort out the bacterial cell surface, we examined regulatory cross-talk between multiple phase-variable pyelonephritis-associated pili (pap) operons in Escherichia coli isolates associated with urinary tract infections. Allelic variation identified in the regulatory regions and regulators acts synergistically to limit coexpression of homologous fimbrial operons. In particular, there is evidence that papI is under positive selection and PapI variants displayed differences in their capacity to activate related pap operons. Alleles of the high-affinity binding site for PapB were shown to contain a variable number of (T/A)3 repeats occurring every 9 bp that altered the sensitivity of pap operon activation. Taken together with other examples of surface organelle cross-talk, we illustrate how this regulation could promote sequential expression.

Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli

The majority of Escherichia coli strains isolated from urinary tract infections have the potential to express multiple fimbriae. Two of the most common fimbrial adhesins are type 1 fimbriae and pyelonephritis-associated pili (Pap). Previous research has shown that induced, plasmid-based expression of a Pap regulator, papB, and its close homologues can prevent inversion of the fim switch controlling the expression of type 1 fimbriae. The aim of the present study was to determine if this cross-regulation occurs when PapB is expressed from its native promoter in the chromosome of E. coli K-12 and clinical isolates. The regulation was examined in three ways: (1) mutated alleles of the pap regulatory region, including papB and papI, that maintain the pap promoter in either the off or the on phase were exchanged into the chromosome of both E. coli K-12 and the clinical isolate E. coli CFT073, and the effect on type 1 fimbrial expression was measured; (2) type 1 fimbrial expression was determined using a novel fimS : : gfp+ reporter system in mutants of the clinical isolate E. coli 536 in which combinations of complete fimbrial clusters had been deleted; (3) type 1 fimbrial expression was determined in a range of clinical isolates and compared with both the number of P clusters and their expression. All three approaches demonstrated that P expression represses type 1 fimbrial expression. Using a number of novel genetic approaches, this work extends the initial finding that PapB inhibits FimB recombination to the impact of this regulation in clinical isolates.

Glutathione transferase Ti and M1 genotype polymorphism in the normal population of Shanghai

Glutathione transferases are known to be important enzymes in the metabolism of xenobiotics. In humans genetic polymorphisms have been reported for the hGSTM1 and hGSTT1 genes leading to individual differences in susceptibility towards toxic effects, such as cancer. This study describes the distribution of the two polymorphisms of hGSTT1 and hGSTM1 in the normal Chinese population of Shanghai. Out of 219 healthy individuals having been genotyped for GSTTI and GSTMI, 108 (49%) were identified to be homozygously deficient for the GSTT1 gene and 107 (49%) for the GSTM1 gene.

The OHS regulatory challenges posed by agency workers: evidence from Australia

The purpose of this research is to analyse the problems for occupational health and safety (OHS)regulators posed by agency work/leased labour (also known as labour hire in Australasia), using Australian evidence. The analysis is based on an examination of prosecutions involving labour hire firms along with other documentary records (union, industry and government reports and guidance material). The study also draws on interviews with approximately 200 regulatory officials, employers and union representatives since 2001 and workplace visits with 40 OHS inspectors in 2004‐2005.The triangular relationship entailed in labour leasing, in combination with the temporary nature of most placements, poses serious problems for government agencies in terms of enforcing OHS standards notwithstanding a growing number of successful prosecutions for breaches of legislative duties by host and labour leasing firms. Research to investigate these issues in other countries and compare findings with those for Australia is required, along with assessing the effectiveness of new enforcement initiatives. The paper assesses existing regulatory responses and highlights the need for new regulatory strategies to combat the problems posed by labour. The OHS problems posed by agency work have received comparatively little attention. The paper provides insights into the specific problems posed for OHS regulators and how inspectorates are trying to address them.

Development of a new regulatory model for occupational health and safety in the New South Wales coal industry: an issues paper for the New South Wales Department of Mineral Resources

This paper addresses the regulatory issues arising in developing a new regulatory model for the New South Wales Coal Industry. As such, it identifies the relevant literature on this subject, the options available for reform, and the experience of Australian and key international bodies responsible for the development of regulatory standards in this area. In particular it: Identifies the main shortcomings in the existing regulatory approach; Identifies the potential roles/main strengths and weaknesses of different types of standards (eg specification, performance, process and systems-based rules) and potential “best practice’ combinations of standards; Examines the appropriateness of the current regulatory regime whereby the general OHS legislation (including the general duty provisions) applies to mining in addition to the large body of regulation which is specific to mining; Identifies the importance of, and possible means of addressing, issues of worker participation within the coal mining industry; Draws on the literature on what motivates companies and individuals for the purpose of recommending key provisions for inclusion in new legislation to provide appropriate personal and organisational incentives; Draws on the literature on major hazards facilities to suggest the appropriate roles for OHS management systems and safety reports or comparable approaches (eg mine safety management plans); Draws on the United Kingdom (UK) and United States of America (USA) experience of coal mine safety and its regulation for comparative purposes, and for insights as to what sort of regulation most effectively reduces work related injury and disease in coal mining; Examines the relevant roles of International Labour Organisation (ILO) Conventions; Examines the extent to which different regulatory regimes would be appropriate to open cut and underground coal mining; and Examines options for reform. This paper is focussed specifically on the issues identified above.

Regulatory focus moderates the relationship between task control and physiological and psychological markers of stress : a work simulation study

This experiment examined whether trait regulatory focus moderates the effects of task control on stress reactions during a demanding work simulation. Regulatory focus describes two ways in which individuals self-regulate toward desired goals: promotion and prevention. As highly promotion-focused individuals are oriented toward growth and challenge, it was expected that they would show better adaptation to demanding work under high task control. In contrast, as highly prevention-focused individuals are oriented toward safety and responsibility they were expected to show better adaptation under low task control. Participants (N = 110) completed a measure of trait regulatory focus and then three trials of a demanding inbox activity under either low, neutral, or high task control. Heart rate variability (HRV), affective reactions (anxiety & task dissatisfaction), and task performance were measured at each trial. As predicted, highly promotion-focused individuals found high (compared to neutral) task control stress-buffering for performance. Moreover, highly prevention-focused individuals found high (compared to low) task control stress-exacerbating for dissatisfaction. In addition, highly prevention-focused individuals found low task control stress-buffering for dissatisfaction, performance, and HRV. However, these effects of low task control for highly prevention-focused individuals depended on their promotion focus.

Competitive advantage through safety compliance : smaller firm responses to changes in the Australian occupational health and safety regulatory context

Smaller firms are often viewed as resistant to regulation due to cost burdens. However, evidence indicates that for some compliance is beneficial under certain conditions. Drawing on data on attitudes and responses of smaller firm owner-managers to changes in Australia’s harmonising work health and safety context we report on smaller firms’ responses to these changes. Despite uncertainty due to incomplete harmonisation, many owner-managers viewed safety compliance as important and necessary to do business. Those with negative views still linked positive safety performance to business outcomes. We categorise smaller firms’ responses and in this sample most are Positive Responders. We suggest ways forward for policy-makers to support smaller firms in complying with occupational health and safety regulation.

The applicability of the Precaution Adoption Process Model for understanding self-regulatory driving behaviour among older drivers

1. Introduction The success of self-regulation, in terms of enhancing older drivers’ safety and maintaining their mobility, depends largely upon older drivers’ awareness of the declines in their driving abilities. Therefore, interventions targeted at increasing older drivers’ safety should aim to enhance their awareness of their physical, sensory and cognitive limitations. Moreover, previous research suggests that driving behaviour change may occur through stages and that interventions and feedback may be perceived differently at each stage. 2. Study aims To further understand the process of driving self-regulation among older adults by exploring their perceptions and experiences of self-regulation, using the PAPM as a framework. To investigate the possible impact of feedback on their driving on their decision making process. 3. Methodology Research tool: Qualitative focus groups (n=5 sessions) Recruitment: Posters, media, newspaper advertisement and emails Inclusion criteria: Aged 70 or more, English-speaking, current drivers Participants: Convenience sample of 27 men and women aged 74 to 90 in the Sunshine Coast and Brisbane city, Queensland, Australia. 4. Analysis Thematic analysis was conducted following the process outlined by Braun and Clarke (2006) to identify, analyse and report themes within the data. Four main themes were identified.

Cytokine expression and secretion by skeletal muscle cells : regulatory mechanisms and exercise effects

Cytokines are important mediators of various aspects of health and disease, including appetite, glucose and lipid metabolism, insulin sensitivity, skeletal muscle hypertrophy and atrophy. Over the past decade or so, considerable attention has focused on the potential for regular exercise to counteract a range of disease states by modulating cytokine production. Exercise stimulates moderate to large increases in the circulating concentrations of interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist, granulocyte-colony stimulating factor, and smaller increases in tumor necrosis factor-α, monocyte chemotactic protein-1, IL-1β, brain-derived neurotrophic factor, IL-12p35/p40 and IL-15. Although many of these cytokines are also expressed in skeletal muscle, not all are released from skeletal muscle into the circulation during exercise. Conversely, some cytokines that are present in the circulation are not expressed in skeletal muscle after exercise. The reasons for these discrepant cytokine responses to exercise are unclear. In this review, we address these uncertainties by summarizing the capacity of skeletal muscle cells to produce cytokines, analyzing other potential cellular sources of circulating cytokines during exercise, and discussing the soluble factors and intracellular signaling pathways that regulate cytokine synthesis (e.g., RNA-binding proteins, microRNAs, suppressor of cytokine signaling proteins, soluble receptors).

Different correlation of Sphingosine-1-Phosphate receptor 1 with receptor activator of nuclear factor kappa B ligand and regulatory T cells in rat periapical lesions

Introduction Sphingosine-1-phosphate receptor 1 (S1P1) is crucial for regulation of immunity and bone metabolism. This study aimed to investigate the expression of S1P1 in rat periapical lesions and its relationship with receptor activator of nuclear factor kappa B ligand (RANKL) and regulatory T (Treg) cells. Methods Periapical lesions were induced by pulp exposure in the first lower molars of 55 Wistar rats. Thirty rats were killed on days 0, 7, 14, 21, 28, and 35, and their mandibles were harvested for x-ray imaging, micro–computed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. The remaining 25 rats were killed on days 0, 14, 21, 28, and 35, and mandibles were harvested for flow cytometry. Results The volume and area of the periapical lesions increased from day 0 to day 21 and then remained comparably stable after day 28. S1P1-positive cells were observed in the inflammatory periapical regions; the number of S1P1-positive cells peaked at day 14 and then decreased from day 21 to day 35. The distribution of S1P1-positive cells was positively correlated with the dynamics of RANKL-positive cells but was negatively correlated with that of Treg cells. Conclusions S1P1 expression was differentially correlated with RANKL and Treg cell infiltration in the periapical lesions and is therefore a contributing factor to the pathogenesis of such lesions.