The genetic basis of human height : the role of estrogen

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

Frontiers in Materials Science and Technology

This special issue aims to provide up-to-date knowledge and the latest scientific concepts and technological developments in the processing, characterization, testing, mechanics, modeling and applications of a broad range of advanced materials. The many contributors, from Denmark, Germany, UK, Iran, Saudi Arabia, Malaysia, Japan, the People’s Republic of China, Singapore, Taiwan, USA, New Zealand and Australia, present a wide range of topics including: nanomaterials, thin films and coatings, metals and alloys, composite materials, materials processing and characterization, biomaterials and biomechanics, and computational materials science and simulation. The work will therefore be of great interest to a broad spectrum of researchers and technologists.

In-vehicle driver distractions : characteristics underlying drivers' risk perceptions

Driver distraction continues to receive considerable research interest but the drivers‟ perspective is less well documented. The current research focussed on identifying features that are salient to drivers in their risk perception judgements for 19 in-vehicle distractions. Both technological (e.g. mobile phones) and non technological (e.g. eating) distractions were considered. Analysis identified that males and females were rating 7 of the 19 distractions differently. The current paper presents the data for the female participants (n = 84). Multidimensional scaling analysis identified three main dimensions contributing to female drivers‟ risk perception judgements. Qualitative characteristics such as the level of exposure to a distraction were identified as significant contributors to drivers‟ risk perception as well as features inherent in the distractions such as distractions being related to communication. This exploratory work contributes to better understanding female drivers‟ perceptions of risk associated with in-vehicle distractions. Understanding the drivers‟ perspective can help guide the development of road safety messages and ultimately improve the impact of such messages.

Beyond the intercultural to the accented body : an Australian perspective

'Beyond the intercultural to the Accented Body’ foregrounds contemporary choreography as a multi-modal practice which is increasingly interdisciplinary and engages with interactive technologies. These concepts are explored in the context of intercultural dance and performance practices particularly in relation to issues of identity, hybridity, the diaspora and transformation. Four models of intercultural choreography are proposed: in-country immersion; collaborative international exchanges through sharing of culturally diverse practices; hybrid practices of diasporic artists; and implicit intercultural connections. The latter model is investigated via a case study of an interactive, multi-site and interdisciplinary collaboration Accented Body.

Predication, propagation, and mediation SFL, CDA, and the inculcation of evaluative meaning systems

In this chapter I propose a theoretical framework for understanding the role of mediation processes in the inculcation, maintenance, and change of evaluative meaning systems, or axiologies, and how such a perspective can provide a useful and complementary dimension to analysis for SFL and CDA. I argue that an understanding of mediation—the movement of meaning across time and space—is essential for the analysis of meaning. Using two related texts as examples, I show how an understanding of mediation can aid SFL and CDA practitioners in the analysis of social change.

No borders : virtual communities in online learning

It can be argued that technological advances and increasing familiarity with technology in the general population has created a huge potential for expansion of online learning (OL) across the educational spectrum. The growth of OL at the university level over the last few years has brought with it an increasing need to understand the learning processes and social processes involved in the ‘cyber’ or ‘virtual’ lecture hall and seminar room by asking questions such as: What are ‘virtual universities’? How – or more critically whether – virtual learning environments are different from face-to-face (F2F) ones? In other words, there is a critical need to explore how students relate to each other and their lecturer(s) in a literal ‘school without walls’? This paper explores the development of a virtual community within a wholly online MA in Applied Linguistics program within the framework of online community development proposed by Haythornthwaite et al (2000).

Rethinking the notion of culture in the national history curriculum

Major global changes are placing new demands on the Australian education system. Recent statements by the Prime Minister, together with current education policy and national curriculum documents available in the public domain, look to education’s role in promoting economic prosperity and social cohesion. Collectively, they emphasise the need to equip young Australians with the knowledge, understandings and skills required to compete in the global economy and participate as engaged citizens in a culturally diverse world. However, the decision to prioritise discipline-based learning in the forthcoming Australian history curriculum without specifically encompassing culture as a referent, raises the following question. How will students acquire the cultural knowledge, understandings and skills necessary for this process? This paper addresses this question by situating the current push for a national history curriculum, with specific reference to the study of Indigenous history and the study of Asia in Australia.

Theater 38.3 : Censorship and Performance

Censorship and Performance, edited by Tom Sellar, examines the politics of censorship, and continuing contests over the ‘right’ to claim theatrical and cultural stages for controversial forms of social and self representation, at the start of the twenty-first century. In bringing this collection together, Sellar has taken a broad-based approach to the concept of censorship in theatrical performance—and, indeed, to the concept of theatrical performance itself. Sellar and his contributors clearly accept that surveillance, suppression and restriction of specific forms of representation is a complex, culturally specific phenomenon. In this sense, Censorship and Performance addresses direct political control over content, as well as thornier arguments about media controversy, moral panic, and the politics of self-censorship amongst artists and arts organisations.

Analysing policy values in a knowledge economy

This fascinating handbook defines how knowledge contributes to social and economic life, and vice versa. It considers the five areas critical to acquiring a comprehensive understanding of the knowledge economy: the nature of the knowledge economy; social, cooperative, cultural, creative, ethical and intellectual capital; knowledge and innovation systems; policy analysis for knowledge-based economies; and knowledge management. In presenting the outcomes of an important body of research, the handbook enables knowledge policy and management practitioners to be more systematically guided in their thinking and actions. The contributors cover a wide disciplinary spectrum in an accessible way, presenting concise, to-the-point discussions of critical concepts and practices that will enable practitioners to make effective research, managerial and policy decisions. They also highlight important new areas of concern to knowledge economies such as wisdom, ethics, language and creative economies that are largely overlooked.

Creative Economies, Creative Cities: Asian-European Perspectives

Thirteen papers examine Asian and European experiences with developing national and city policy agendas around cultural and creative industries. Papers discuss policy transfer and the field of the cultural and creative industries--what can be learned from Europe; creative industries across cultural borders--the case of video games in Asia; spaces of culture and economy--mapping the cultural-creative cluster landscape; beyond networks and relations--toward rethinking creative cluster theory; the capital complex--Beijing's new creative clusters; the European creative class and regional development--how relevant Richard Florida's theory is for Europe; getting out of place--the mobile creative class taking on the local--a U.K. perspective on the creative class; Asian cities and limits to creative capital theory; the creative industries, governance, and economic development--a U.K. perspective; Shanghai's emergence into the global creative economy; Shanghai moderne--creative economy in a creative city?; urbanity as a political project--toward post-national European cities; and alternative policies in urban innovation. Contributors include economists. Kong is with the Department of Geography at the National University of Singapore. O'Connor is at Queensland University of Technology. Index.

Development of a particle number and particle mass emissions inventory for an urban fleet : a study in South-East Queensland

Motor vehicles are a major source of gaseous and particulate matter pollution in urban areas, particularly of ultrafine sized particles (diameters < 0.1 µm). Exposure to particulate matter has been found to be associated with serious health effects, including respiratory and cardiovascular disease, and mortality. Particle emissions generated by motor vehicles span a very broad size range (from around 0.003-10 µm) and are measured as different subsets of particle mass concentrations or particle number count. However, there exist scientific challenges in analysing and interpreting the large data sets on motor vehicle emission factors, and no understanding is available of the application of different particle metrics as a basis for air quality regulation. To date a comprehensive inventory covering the broad size range of particles emitted by motor vehicles, and which includes particle number, does not exist anywhere in the world. This thesis covers research related to four important and interrelated aspects pertaining to particulate matter generated by motor vehicle fleets. These include the derivation of suitable particle emission factors for use in transport modelling and health impact assessments; quantification of motor vehicle particle emission inventories; investigation of the particle characteristic modality within particle size distributions as a potential for developing air quality regulation; and review and synthesis of current knowledge on ultrafine particles as it relates to motor vehicles; and the application of these aspects to the quantification, control and management of motor vehicle particle emissions. In order to quantify emissions in terms of a comprehensive inventory, which covers the full size range of particles emitted by motor vehicle fleets, it was necessary to derive a suitable set of particle emission factors for different vehicle and road type combinations for particle number, particle volume, PM1, PM2.5 and PM1 (mass concentration of particles with aerodynamic diameters < 1 µm, < 2.5 µm and < 10 µm respectively). The very large data set of emission factors analysed in this study were sourced from measurement studies conducted in developed countries, and hence the derived set of emission factors are suitable for preparing inventories in other urban regions of the developed world. These emission factors are particularly useful for regions with a lack of measurement data to derive emission factors, or where experimental data are available but are of insufficient scope. The comprehensive particle emissions inventory presented in this thesis is the first published inventory of tailpipe particle emissions prepared for a motor vehicle fleet, and included the quantification of particle emissions covering the full size range of particles emitted by vehicles, based on measurement data. The inventory quantified particle emissions measured in terms of particle number and different particle mass size fractions. It was developed for the urban South-East Queensland fleet in Australia, and included testing the particle emission implications of future scenarios for different passenger and freight travel demand. The thesis also presents evidence of the usefulness of examining modality within particle size distributions as a basis for developing air quality regulations; and finds evidence to support the relevance of introducing a new PM1 mass ambient air quality standard for the majority of environments worldwide. The study found that a combination of PM1 and PM10 standards are likely to be a more discerning and suitable set of ambient air quality standards for controlling particles emitted from combustion and mechanically-generated sources, such as motor vehicles, than the current mass standards of PM2.5 and PM10. The study also reviewed and synthesized existing knowledge on ultrafine particles, with a specific focus on those originating from motor vehicles. It found that motor vehicles are significant contributors to both air pollution and ultrafine particles in urban areas, and that a standardized measurement procedure is not currently available for ultrafine particles. The review found discrepancies exist between outcomes of instrumentation used to measure ultrafine particles; that few data is available on ultrafine particle chemistry and composition, long term monitoring; characterization of their spatial and temporal distribution in urban areas; and that no inventories for particle number are available for motor vehicle fleets. This knowledge is critical for epidemiological studies and exposure-response assessment. Conclusions from this review included the recommendation that ultrafine particles in populated urban areas be considered a likely target for future air quality regulation based on particle number, due to their potential impacts on the environment. The research in this PhD thesis successfully integrated the elements needed to quantify and manage motor vehicle fleet emissions, and its novelty relates to the combining of expertise from two distinctly separate disciplines - from aerosol science and transport modelling. The new knowledge and concepts developed in this PhD research provide never before available data and methods which can be used to develop comprehensive, size-resolved inventories of motor vehicle particle emissions, and air quality regulations to control particle emissions to protect the health and well-being of current and future generations.

Long-term exposure to gaseous air pollutants and cardio-respiratory mortality in Brisbane, Australia

Air pollution is ranked by the World Health Organisation as one of the top ten contributors to the global burden of disease and injury. Exposure to gaseous air pollutants, even at a low level, has been associated with cardiorespiratory diseases (Vedal, Brauer et al. 2003). Most recent epidemiological studies of air pollution have used time-series analyses to explore the relationship between daily mortality or morbidity and daily ambient air pollution concentrations based on the same day or previous days (Hajat, Armstrong et al. 2007). However, most of the previous studies have examined the association between air pollution and health outcomes using air pollution data from a single monitoring site or average values from a few monitoring sites to represent the whole population of the study area. In fact, for a metropolitan city, ambient air pollution levels may differ significantly among the different areas. There is increasing concern that the relationships between air pollution and mortality may vary with geographical area (Chen, Mengersen et al. 2007). Additionally, some studies have indicated that socio-economic status can act as a confounder when investigating the relation between geographical location and health (Scoggins, Kjellstrom et al. 2004). This study examined the spatial variation in the relationship between long-term exposure to gaseous air pollutants (including nitrogen dioxide (NO2), ozone (O3) and sulphur dioxide (SO2)), and cardiorespiratory mortality in Brisbane, Australia, during the period 1996 - 2004.

Participatory Learning in the Early Years : Research and Pedagogy

The early years are an important period for learning, but the questions surrounding participatory learning amongst toddlers remain under-examined. This book presents the latest theoretical and research perspectives about how ECEC (Early Childhood Education and Care) contexts promote democracy and citizenship through participatory learning approaches. The contributors provide insight into national policies, provisions, and practices and advance our understandings of theory and research on toddlers’ experiences for democratic participation across a number of countries, including the UK, Australia, New Zealand, the United States, Canada, Sweden, and Norway.

How to tell the difference between production and consumption : a case study in Doctor Who fandom

A television series is tagged with the label "cult" by the media, advertisers, and network executives when it is considered edgy or offbeat, when it appeals to nostalgia, or when it is considered emblematic of a particular subculture. By these criteria, almost any series could be described as cult. Yet certain programs exert an uncanny power over their fans, encouraging them to immerse themselves within a fictional world.In Cult Television leading scholars examine such shows as The X-Files; The Avengers; Doctor Who, Babylon Five; Star Trek; Xena, Warrior Princess; and Buffy the Vampire Slayer to determine the defining characteristics of cult television and map the contours of this phenomenon within the larger scope of popular culture.Contributors: Karen Backstein; David A. Black, Seton Hall U; Mary Hammond, Open U; Nathan Hunt, U of Nottingham; Mark Jancovich; Petra Kuppers, Bryant College; Philippe Le Guern, U of Angers, France; Alan McKee; Toby Miller, New York U; Jeffrey Sconce, Northwestern U; Eva ViethSara Gwenllian-Jones is a lecturer in television and digital media at Cardiff University and co-editor of Intensities: The Journal of Cult Media.Roberta E. Pearson is a reader in media and cultural studies at Cardiff University. She is the author of the forthcoming book Small Screen, Big Universe: Star Trek and Television.

Modelling sustainable and optimal solutions for building services integration in early architectural design : confronting the software and professional interoperability deficit

Decisions made in the earliest stage of architectural design have the greatest impact on the construction, lifecycle cost and environmental footprint of buildings. Yet the building services, one of the largest contributors to cost, complexity, and environmental impact, are rarely considered as an influence on the design at this crucial stage. In order for efficient and environmentally sensitive built environment outcomes to be achieved, a closer collaboration between architects and services engineers is required at the outset of projects. However, in practice, there are a variety of obstacles impeding this transition towards an integrated design approach. This paper firstly presents a critical review of the existing barriers to multidisciplinary design. It then examines current examples of best practice in the building industry to highlight the collaborative strategies being employed and their benefits to the design process. Finally, it discusses a case study project to identify directions for further research.