Investigation of molecular mechanisms regulating biomineralization of pearl oyster Pinctada maxima

Biomineralization is a process encompassing all mineral containing tissues produced within an organism. The most dynamic example of this process is the formation of the mollusk shell, comprising a variety of crystal phases and microstructures. The organic component incorporated within the shell is said to dictate this remarkable architecture. Subsequently, for the past decade considerable research have been undertaken to identify and characterize the protein components involved in biomineralization. Despite these efforts the general understanding of the process remains ambiguous. This study employs a novel molecular approach to further the elucidation of the shell biomineralization. A microarray platform has been custom generated (PmaxArray 1.0) from the pearl oyster Pinctada maxima. PmaxArray 1.0 consists of 4992 expressed sequence tags (ESTs) originating from the mantle, an organ involved in shell formation. This microarray has been used as the primary tool for three separate investigations in an effort to associate transcriptional gene expression from P. maxima to the process of shell biomineralization. The first investigation analyzes the spatial expression of ESTs throughout the mantle organ. The mantle was dissected into five discrete regions and each analyzed for gene expression with PmaxArray 1.0. Over 2000 ESTs were differentially expressed among the tissue sections, identifying five major expression regions. Three of these regions have been proposed to have shell formation functions belonging to nacre, prismatic calcite and periostracum. The spatial gene expression map was confirmed by in situ hybridization, localizing a subset of ESTs from each expression region to the same mantle area. Comparative sequence analysis of ESTs expressed in the proposed shell formation regions with the BLAST tool, revealed a number of the transcripts were novel while others showed significant sequence similarities to previously characterized shell formation genes. The second investigation correlates temporal EST expression during P. maxima larval ontogeny with transitions in shell mineralization during the same period. A timeline documenting the morphologicat microstructural and mineralogical shell characteristics of P. maxima throughout larval ontogeny has been established. Three different shell types were noted based on the physical characters and termed, prodissoconch I, prodissoconch 11 and dissoconch. PmaxArray 1.0 analyzed ESTs expression of animals throughout the larval development of P. maxima, noting up-regulation of 359 ESTs in association with the shell transitions from prodissoconch 1 to prodissoconch 11 to dissoconch. Comparative sequence analysis of these ESTs indicates a number of the transcripts are novel as well as showing significant sequence similarities between ESTs and known shell matrix associated genes and proteins. These ESTs are discussed in relation to the shell characters associated with their temporal expression. The third investigation uses PmaxArray 1.0 to analyze gene expression in the mantle tissue of P. maxima specimens exposed to sub-lethal concentrations of a shell-deforming toxin, tributyltin (TBT). The shell specific effects of TBT are used in this investigation to interpret differential expression of ESTs with respect to shell formation functions. A lethal and sublethal TBT concentration range was established for P. maxima, noting a concentration of 50 ng L- 1 TBT as sub-lethal over a 21 day period. Mantle tissue from P. maxima animals treated with 50 ng L- 1 TBT was assessed for differential EST expression with untreated control animals. A total of 102 ESTs were identified as differentially expressed in association with TBT exposure, comparative sequence identities included an up-regulation of immunity and detoxification related genes and down-regulation of several shell matrix genes. A number of transcripts encoding novel peptides were additionally identified. The potential actions of these genes are discussed with reference to TBT toxicity and shell biomineralization. This thesis has used a microarray platform to analyze gene expression in spatial, temporal and toxicity investigations, revealing the involvement of numerous gene transcripts in specific shell formation functions. Investigation of thousands of transcripts simultaneously has provided a holistic interpretation of the organic components regulating shell biomineralization.

Mathematical modelling of muscle recruitment and function in the lumbar spine

Low back pain is an increasing problem in industrialised countries and although it is a major socio-economic problem in terms of medical costs and lost productivity, relatively little is known about the processes underlying the development of the condition. This is in part due to the complex interactions between bone, muscle, nerves and other soft tissues of the spine, and the fact that direct observation and/or measurement of the human spine is not possible using non-invasive techniques. Biomechanical models have been used extensively to estimate the forces and moments experienced by the spine. These models provide a means of estimating the internal parameters which can not be measured directly. However, application of most of the models currently available is restricted to tasks resembling those for which the model was designed due to the simplified representation of the anatomy. The aim of this research was to develop a biomechanical model to investigate the changes in forces and moments which are induced by muscle injury. In order to accurately simulate muscle injuries a detailed quasi-static three dimensional model representing the anatomy of the lumbar spine was developed. This model includes the nine major force generating muscles of the region (erector spinae, comprising the longissimus thoracis and iliocostalis lumborum; multifidus; quadratus lumborum; latissimus dorsi; transverse abdominis; internal oblique and external oblique), as well as the thoracolumbar fascia through which the transverse abdominis and parts of the internal oblique and latissimus dorsi muscles attach to the spine. The muscles included in the model have been represented using 170 muscle fascicles each having their own force generating characteristics and lines of action. Particular attention has been paid to ensuring the muscle lines of action are anatomically realistic, particularly for muscles which have broad attachments (e.g. internal and external obliques), muscles which attach to the spine via the thoracolumbar fascia (e.g. transverse abdominis), and muscles whose paths are altered by bony constraints such as the rib cage (e.g. iliocostalis lumborum pars thoracis and parts of the longissimus thoracis pars thoracis). In this endeavour, a separate sub-model which accounts for the shape of the torso by modelling it as a series of ellipses has been developed to model the lines of action of the oblique muscles. Likewise, a separate sub-model of the thoracolumbar fascia has also been developed which accounts for the middle and posterior layers of the fascia, and ensures that the line of action of the posterior layer is related to the size and shape of the erector spinae muscle. Published muscle activation data are used to enable the model to predict the maximum forces and moments that may be generated by the muscles. These predictions are validated against published experimental studies reporting maximum isometric moments for a variety of exertions. The model performs well for fiexion, extension and lateral bend exertions, but underpredicts the axial twist moments that may be developed. This discrepancy is most likely the result of differences between the experimental methodology and the modelled task. The application of the model is illustrated using examples of muscle injuries created by surgical procedures. The three examples used represent a posterior surgical approach to the spine, an anterior approach to the spine and uni-lateral total hip replacement surgery. Although the three examples simulate different muscle injuries, all demonstrate the production of significant asymmetrical moments and/or reduced joint compression following surgical intervention. This result has implications for patient rehabilitation and the potential for further injury to the spine. The development and application of the model has highlighted a number of areas where current knowledge is deficient. These include muscle activation levels for tasks in postures other than upright standing, changes in spinal kinematics following surgical procedures such as spinal fusion or fixation, and a general lack of understanding of how the body adjusts to muscle injuries with respect to muscle activation patterns and levels, rate of recovery from temporary injuries and compensatory actions by other muscles. Thus the comprehensive and innovative anatomical model which has been developed not only provides a tool to predict the forces and moments experienced by the intervertebral joints of the spine, but also highlights areas where further clinical research is required.

A comparison of executive function in very preterm and term infants at 8 months corrected age

Executive function (EF) emerges in infancy and continues to develop throughout childhood. Executive dysfunction is believed to contribute to learning and attention problems in children at school age. Children born very preterm are more prone to these problems than their full-term peers.

Regulating corporate governance in China and Hong Kong : do Chinese values and ethics have a place in the age of globalization?

Much has been said about the convergence of corporate governance and regulations. The underlying assumptions of this phenomenon are driven by globalisation and the dominance of the Anglo-US model of corporate governance. Since the Asian crisis in 1997, Hong Kong and perhaps to a less extend Mainland China, had amended both Company laws and Stock Exchange Listing Rules obligations, arguably, mirroring provisions and rules in the UK and US. However, there has been a small amount of literature in law drawing from cross cultural management asking the question - is Western governance and regulation appropriate for the East? This paper will approach this issue from a different mindset, instead of drawing distinctions about East and West, a meta-regulatory framework will attempt to incorporate Western ‗hard‘ and ‗soft‘ laws with Asian ethical values. The aim is to combine laws and ethics thereby enhancing corporate governance and, improve compliance of those rules by adapting Chinese ethical values like Confucianism into the regulatory system. The overarching goal of this exercise is to adapt the wisdom of Chinese ethics into regulatory guidelines to suit the modern global market.

Regulating non-executive directors in Australia : a socio-legal approach

Discusses the role of legislation and codes of conduct in influencing the behaviour of non-executive directors. Outlines the functions of a board of directors and considers the role on non-executive directors in particular. Traces the development of standards of skill required on non-executive directors both under the Australian Corporations Act 2001 and under common law. Questions whether these have brought about a real change in behaviour. Considers whether professionalisation of directorship could be more effective.

Does Chinese traditional values matter in regulating China's company directors? Preliminary findings from surveys in Hong Kong

Much has been said about Chinese corporate governance and the new laws on companies. While most literature focuses on either the political or the legal doctrinal issues, this paper argues that Chinese traditional values do matter in Chinese corporate governance. The object of this paper is to report on the preliminary findings of a project supported by the General Research Fund in Hong Kong (HK). Thus far the survey results from HK respondents support our hypothesis. As such, traditional Chinese values should be on the agenda of the next round of company law reforms in China.

Re-conceptualising IS function's support performance : a preliminary model

While IS function has gained widespread attention for over two decades, there is little consensus among information systems (IS) researchers and practitioners on how best to evaluate IS function's support performance. This paper reports on preliminary findings of a larger research effort proceeds from a central interest in the importance of evaluating IS function's support in organisations. This study is the first that attempts to re-conceptualise and conceive evaluate IS function's support as a multi- dimensional formative construct. We argue that a holistic measure for evaluating evaluate IS function's support should consist of dimensions that together assess the variety of the support functions and the quality of the support services provided to end-users. Thus, the proposed model consists of two halves, "Variety" and "Quality" within which resides seven dimensions. The Variety half includes five dimensions: Training; Documentation; Data- related Support, Software-related Support; and Hardware-related Support. The Quality half includes two dimensions: IS Support Staff and Support Services Performance. The proposed model is derived using a directed content analysis of 83 studies; from top IS outlets, employing the characteristics of the analytic theory and consistent with formative construct development procedures.

The legal framework of the Australian health system

This chapter is about the role of law in the creation and operation of Australian health systems. Accordingly, this chapter discusses how law regulates the way in which health services in Australia are funded, organised, regulated, managed, operated and governed. (The question of how health professionals are regulated is discussed in Chapter 15.) Although the focus of much of health law is on legal mechanisms for the resolution of disputes or disagreements between the state, health providers, professionals, patients and families and friends, and through dispute resolutions processes setting standards for practice, these are only some of the “jobs” that health law performs. In health systems where the state undertakes a significant role in regulating, funding, managing and providing health services, health law also performs an important constitutive function. Health law declares the values upon which the health system is based, shapes social processes to achieve public ends and provides a structure for the complex interactions that occur within a modern health system. Health law regulates decision-makers in health systems by establishing who has the power to participate in decisions and in what circumstances, establishing processes through which decisions are made and creating mechanisms for decision-makers to be held publicly accountable. It is this broader constitutive function of health law that is a primary focus of much of this chapter — how and why governments use their legislative powers to structure and shape the health system.

Regulating IVF and pre-implantation tissue-typing for the creation of "saviour siblings" : a harm analysis

Scientific discoveries, developments in medicine and health issues are the constant focus of media attention and the principles surrounding the creation of so called ‘saviour siblings’ are of no exception. The development in the field of reproductive techniques has provided the ability to genetically analyse embryos created in the laboratory to enable parents to implant selected embryos to create a tissue-matched child who may be able to cure an existing sick child. The research undertaken in this thesis examines the regulatory frameworks overseeing the delivery of assisted reproductive technologies (ART) in Australia and the United Kingdom and considers how those frameworks impact on the accessibility of in vitro fertilisation (IVF) procedures for the creation of ‘saviour siblings’. In some jurisdictions, the accessibility of such techniques is limited by statutory requirements. The limitations and restrictions imposed by the state in relation to the technology are analysed in order to establish whether such restrictions are justified. The analysis is conducted on the basis of a harm framework. The framework seeks to establish whether those affected by the use of the technology (including the child who will be created) are harmed. In order to undertake such evaluation, the concept of harm is considered under the scope of John Stuart Mill’s liberal theory and the Harm Principle is used as a normative tool to judge whether the level of harm that may result, justifies state intervention or restriction with the reproductive decision-making of parents in this context. The harm analysis conducted in this thesis seeks to determine an appropriate regulatory response in relation to the use of pre-implantation tissue-typing for the creation of ‘saviour siblings’. The proposals outlined in the last part of this thesis seek to address the concern that harm may result from the practice of pre-implantation tissue-typing. The current regulatory frameworks in place are also analysed on the basis of the harm framework established in this thesis. The material referred to in this thesis reflects the law and policy in place in Australia and the UK at the time the thesis was submitted for examination (December 2009).