Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation

Introduction During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes. Methods In this study, we investigated the differential expression of 84 stem cell–related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation. Results Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Wnt, transforming growth factor β (TGF-β)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration. Conclusions This study has generated an overview of stem cell–related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-β/BMP, and cadherin signalling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration

A comparative study : regulatory requirements on subdivisions for increasing passive cooling

A major project in the Sustainable Built Assets core area is the Sustainable Sub-divisions – Ventilation Project that is the second stage of a planned series of research projects focusing on sustainable sub-divisions. The initial project, Sustainable Sub-divisions: Energy focused on energy efficiency and examined the link between dwelling energy efficiency and sub-divisional layout. In addition, the potential for on site electricity generation, especially in medium and high-density developments, was also examined. That project recommended that an existing lot-rating methodology be adapted for use in SEQ through the inclusion of sub divisional appropriate ventilation data. Acquiring that data is the object of this project. The Sustainable Sub-divisions; Ventilation Project will produce a series of reports. The first report (Report 2002-077-B-01) summarised the results from an industry workshop and interviews that were conducted to ascertain the current attitudes and methodologies used in contemporary sub-division design in South East Queensland. The second report (Report 2002-077-B-02) described how the project is being delivered as outlined in the Project Agreement. It included the selection of the case study dwellings and monitoring equipment and data management process. This third report (Report 2002-077-B-03) provides an analysis and review of the approaches recommended by leading experts, government bodies and professional organizations throughout Australia that aim to increase the potential for passive cooling and heating at the subdivision stage. This data will inform issues discussed on the development of the enhanced lot-rating methodology in other reports of this series. The final report, due in June 2007, will detail the analysis of data for winter 2006 and summer 2007, leading to the development and delivery of the enhanced lot-rating methodology.

A re-examination of the Ghrelin and Ghrelin receptor genes

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

Establishment of a mouse model of colitis and its use to evaluate the anti-inflammatory effects of two ghrelin peptides

Ghrelin is a gut-brain peptide hormone that induces appetite, stimulates the release of growth hormone, and has recently been shown to ameliorate inflammation. Recent studies have suggested that ghrelin may play a potential role in inflammation-related diseases such as inflammatory bowel diseases (IBD). A previous study with ghrelin in the TNBS mouse model of colitis demonstrated that ghrelin treatment decreased the clinical severity of colitis and inflammation and prevented the recurrence of disease. Ghrelin may be acting at the immunological and epithelial level as the ghrelin receptor (GHSR) is expressed by immune cells and intestinal epithelial cells. The current project investigated the effect of ghrelin in a different mouse model of colitis using dextran sodium sulphate (DSS) – a luminal toxin. Two molecular weight forms of DSS were used as they give differing effects (5kDa and 40kDa). Ghrelin treatment significantly improved clinical colitis scores (p=0.012) in the C57BL/6 mouse strain with colitis induced by 2% DSS (5kDa). Treatment with ghrelin suppressed colitis in the proximal colon as indicated by reduced accumulative histopathology scores (p=0.03). Whilst there was a trend toward reduced scores in the mid and distal colon in these mice this did not reach significance. Ghrelin did not affect histopathology scores in the 40kDa model. There was no significant effect on the number of regulatory T cells or TNF-α secretion from cultured lymph node cells from these mice. The discovery of C-terminal ghrelin peptides, for example, obestatin and the peptide derived from exon 4 deleted proghrelin (Δ4 preproghrelin peptide) have raised questions regarding their potential role in biological functions. The current project investigated the effect of Δ4 peptide in the DSS model of colitis however no significant suppression of colitis was observed. In vitro epithelial wound healing assays were also undertaken to determine the effect of ghrelin on intestinal epithelial cell migration. Ghrelin did not significantly improve wound healing in these assays. In conclusion, ghrelin treatment displays a mild anti-inflammatory effect in the 5kDa DSS model. The potential mechanisms behind this effect and the disparity between these results and those published previously will be discussed.

A regulatory analysis of international climate change regulation

The political challenges impeding the negotiation of a comprehensive multilateral agreement on international climate change have received a great deal of attention. A question that has gone somewhat overlooked is what essential components an effective regulatory scheme to reduce greenhouse gas emissions should contain. The objective of this article is to examine the regulatory architecture of current international arrangements relating to global climate change regulation. A systematic analysis of the structure, substantive composition, and administrative characteristics of the UNFCCC and Kyoto Protocol is undertaken. The analytical standard against which the agreements are examined is whether current international regulatory arrangements satisfy the basic requirements of regulatory coherence. The analysis identifies how the present scheme consists of a complex institutional structure that lacks a substantive regulatory core. The implications of the absence of functional and effective mechanisms to govern greenhouse gas emission reductions are considered in relation to the principles of good regulatory design. This, in turn, provides useful insights into how a better regulatory scheme might be designed.

Regulatory approaches to genetic testing in insurance

Rapid advancements in the field of genetic science have engendered considerable debate, speculation, misinformation and legislative action worldwide. While programs such as the Human Genome Project bring the prospect of seemingly miraculous medical advancements within imminent reach, they also create the potential for significant invasions of traditional areas of privacy and human dignity through laying the potential foundation for new forms of discrimination in insurance, employment and immigration regulation. The insurance industry, which has of course, traditionally been premised on discrimination as part of its underwriting process, is proving to be the frontline of this regulatory battle with extensive legislation, guidelines and debate marking its progress.

Competition laws and policies in China and Hong Kong : a tale of two regulatory journeys

Reviews the background to China's enactment of the Anti-Monopoly Law in 2007 and compares the debate surrounding the proposed introduction of similar legislation in Hong Kong. Examines the main issues arising during the Law's 13 year drafting stage, its key provisions and the remaining areas of uncertainty concerning its enforcement. Discusses ongoing efforts to introduce competition law regulations in Hong Kong, the main features of the draft General Competition Law and the shortcomings of its approach to penalties and exemptions.

Narrative on the "Compliance and Regulatory Journal" : past, present and future

A conversation over a cup of coffee in late 2005 between Australasian Compliance Institute members Bill Dee and Dr Len Gainsford quickly turned to previously unsuccessful attempts to start a professional journal about compliance. There were two main issue - the difficultly in getting a professional journal off the ground and then sustaining a continuous flow of quality contributions. As practitioners, Bill and Len knew there was a considerable amount of 'thought and practice leadership' compliance material out there but they also knew that such material had not been presented in a relevant and interesting way. A foolish thought arose - could we start a professional journal that practitioners might actually read and use?

Regulatory multiplicities in telecommunications reforms in Indonesia and China

Telecommunications is a key component in any country's economic infrastructure, requiring a vast amount of capital injection and ongoing technical support and innovation. Many developing countries experience handicaps in accessing capital and sustaining the required technical capability in their industralisation process. Therefore, attracting both capital investments and expertise by attuning the developing country's economic policies and legal environment to meet investors' expectations is a priority. Privatisation has been seen as a triumph by international institutions such as the World Bank, and a major requirement for developing economies to industrialise. However from a regulatory perspective, this process is far from straightforward. Implementing economic policies requires a number of regulations and regulatory instruments to be in place. Apart from the need for an independent regulator, regulatory outcomes are often dependent on the willingness of various stakeholders to comply with the course of actions undertaken by authorities. This article examines the factors steering the processes and changes in the telecommunication reforms of Indonesia and China.

Ramifications of development projects deemed “state significant”

Purpose, Design/methodology / approach The acknowledgement of state significance in relation to development projects can result in special treatment by regulatory authorities, particularly in terms of environmental compliance and certain economic and other government support measures. However, defining just what constitutes a “significant project”, or a project of “state significance”, varies considerably between Australian states. In terms of establishing threshold levels, in Queensland there is even less clarity. Despite this lack of definition, the implications of “state significance” can nevertheless be considerable. For example, in Queensland if the Coordinator-General declares a project to be a “significant project” under the State Development and Public Works Organisation Act 1971, the environmental impact assessment process may become more streamlined – potentially circumventing certain provisions under The Integrated Planning Act 1997. If the project is not large enough to be so deemed, an extractive resource under the State Planning Policy 2/07 - Protection of Extractive Resources 2007 may be considered to be of State or regional significance and subsequently designated as a “Key Resource Area”. As a consequence, such a project is afforded some measure of resource protection but remains subject to the normal assessment process under the Integrated Development Assessment System, as well as the usual requirements of the vegetation management codes, and other regulations. Findings (Originality/value) & Research limitations / implications This paper explores the various meanings of “state significance” in Queensland and the ramifications for development projects in that state. It argues for a streamlining of the assessment process in order to avoid or minimise constraints acting on the state’s development. In so doing, it questions the existence of a strategic threat to the delivery of an already over-stretched infrastructure program.

The aftermath of the Lehman Brothers collapse in Hong Kong : the saga, regulatory deficiencies and government responses

The paper examines the fallout of the Lehman Brothers collapse in Hong Kong. As an international financial hub in Asia, Hong Kong was profoundly affected by the collapse of this company. As a result, it impacted negatively on the public’s confidence in the Hong Kong’s banking sector. Furthermore, this event has exposed a number of regulatory deficiencies in Hong Kong. In response to this financial crisis, the Hong Kong government had made an unprecedented move to negotiate with local banks to refund the investors. In addition, the government has also sought public consultation on proposal to enhance the regulation of the sale of financial products. This paper argues that there needs to be amendments to the prevailing laws and the inclusions of legal rules to back up those proposed measures so that the disclosed information from the financial institution will not mislead the investors or misrepresent the products offered.

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.