The Effects of Brominated Flame Retardants on Thyroid Hormone Homeostasis in Human Placenta Tissues and Cell Culture

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) that have been heavily used in consumer products such as furniture foams, plastics, and textiles since the mid-1970’s. BFRs are added to products in order to meet state flammability standards intended to increase indoor safety in the event of a fire. The three commercial PBDE mixtures, Penta-, Octa-, and DecaBDE, have all been banned in the United States, however, limited use of DecaBDE is still permitted. PBDEs were phased out of production and added to the Stockholm Convention due to concerns over their environmental persistence and toxicity. Human exposure to PBDEs occurs primarily through the inadvertent ingestion of contaminated house dust, as well as though dietary sources. Despite the phase-out and discontinued use of PBDEs, human exposure to this class of chemicals is likely to continue for decades due to the continued use of treated products and existing environmental reservoirs of PBDEs. Extensive research over the years has shown that PBDEs disrupt thyroid hormone (TH) levels and neurodevelopmental endpoints in rodent and fish models. Additionally, there is growing epidemiological evidence linking PBDE exposure in humans to altered TH homeostasis and neurodevelopmental impairments in children. Due to the importance of THs throughout gestation, there is a great need to understand the effects of BFRs on the developing fetus. Specifically, the placenta plays a critical role in the transport, metabolism, and delivery of THs to the fetal compartment during pregnancy and is a likely target for BFR bioaccumulation and endocrine disruption. The central hypothesis of this dissertation research is that BFRs disrupt the activity of TH sulfotransferase (SULT) enzymes, thereby altering TH concentrations in the placenta.

In the first aim of this dissertation research, the concentrations of PBDEs and 2,4,6-TBP were measured in a cohort of 102 placenta tissue samples from an ongoing pregnancy cohort in Durham, NC. Methods were developed for the extraction and analysis of the BFR analytes. It was found that 2,4,6-TBP was significantly correlated with all PBDE analytes, indicating that 2,4,6-TBP may share common product applications with PBDEs or that 2,4,6-TBP is a metabolite of PBDE compounds. Additionally, this was the first study to measure 2,4,6-TBP in human placenta tissues.

In the second aim of this dissertation research, the placenta tissue concentrations of THs, as well as the endogenous activity of deiodinase (DI) and TH SULT enzymes were quantified using the same cohort of 102 placenta tissue samples. Enzyme activity was detected in all samples and this was the first study to measure TH DI and SULT activity in human placenta tissues. Enzyme activities and TH concentrations were compared with BFR concentrations measured in Aim 1. There were few statistically significant associations observed for the combined data, however, upon stratifying the data set based on infant sex, additional significant associations were observed. For example, among males, those with the highest concentrations of BDE-99 in placenta had T3 levels 0.80 times those with the lowest concentration of BDE-99 (95% confidence interval (CI): 0.59, 1.07). Whereas females with the highest concentrations of BDE-99 in placenta had T3 levels 1.50 times those with the lowest concentration of BDE-99 (95% CI: 1.10, 2.04). Additionally, all BFR analyte concentrations were higher in the placenta of males versus females and they were significantly higher for 2,4,6-TBP and BDE-209. 3,3’-T2 SULT activity was significantly higher in female placenta tissues, while type 3 DI activity was significantly higher in male placenta tissues. This research is the first to show sex-specific differences in the bioaccumulation of BFRs in human placenta tissue, as well as differences in TH concentrations and endogenous DI and SULT activity. The underlying mechanisms of these observed sex differences warrant further investigation.

In the third aim of this dissertation research, the effects of BFRs were examined in a human choriocarcinoma placenta cell line, BeWo. Michaelis-Menten parameters and inhibition curves were calculated for 2,4,6-TBP, 3-OH BDE-47, and 6-OH BDE-47. 2,4,6-TBP was shown to be the most potent inhibitor of 3,3’-T2 SULT activity with a calculated IC50 value of 11.6 nM. It was also shown that 2,4,6-TBP and 3-OH BDE-47 exhibit mixed inhibition of 3,3’-T2 sulfation in BeWo cell homogenates. Next, a series of cell culture exposure experiments were performed using 1, 6, 12, and 24 hour exposure durations. Once again, 2,4,6-TBP was shown to be the most potent inhibitor of basal 3,3’-T2 SULT activity by significantly decreasing activity at the high and medium dose (1 M and 0.5 M, respectively) at all measured time points. Interestingly, BDE-99 was also shown to inhibit basal 3,3’-T2 SULT activity in BeWo cells following the 24 hour exposure, despite exhibiting no inhibitory effects in the BeWo cell homogenate experiments. This indicates that BDE-99 must act through a pathway other than direct enzyme inhibition. Following exposures, the TH concentrations in the cell culture growth media and mRNA expression of TH-related genes were also examined. There was no observed effect of BFR treatment on these endpoints. Future work should focus on determining the downstream biological effects of TH SULT disruption in placental cells, as well as the underlying mechanisms of action responsible for reductions in basal TH SULT activity following BFR exposure.

This was one of the first studies to measure BFRs in a cohort of placenta tissue samples from the United States and the first study to measure THs, DI activity, and SULT activity in human placenta tissues. This research provides a novel contribution to our growing understanding of the effects of BFRs on TH homeostasis within the human placenta, and provides further evidence for sex-specific differences within this important organ. Future research should continue to investigate the effects of environmental contaminants on TH homeostasis within the placenta, as this represents the most critical and vulnerable stage of human development.

Whither culture? Australian horror films and the limitations of cultural policy

Cultural policy that attempts to foster the Australian film industry’s growth and development in an era of globalisation is coming under increasing pressure. Throughout the 2000s, there has been a substantial boom in Australian horror films led by ‘runaway’ horror film Saw (2004), Wolf Creek (2005), and Undead (2003), achieving varying levels of popularity and commercial success worldwide. However, emerging within a national cinema driven by public subsidy and valuing ‘quality’ and ‘cultural content’ over ‘entertainment’ and ‘commercialism’, horror films have generally been antithetical to these objectives. Consequently, the recent boom in horror films has occurred largely outside the purview and subvention of cultural policy. This paper argues that global forces and emerging production and distribution models are challenging the ‘narrowness’ of cultural policy – a narrowness that mandates a particular film culture, circumscribes certain notions of value and limits the variety of films produced domestically. Despite their low-culture status, horror films have been well suited to the Australian film industry’s financial limitations, they are a growth strategy for producers, and a training ground for emerging filmmakers.

Independent television production, TV formats and media diversity in China

Beginning around 2003, television studies has seen the growth of interest in the genre of reality shows. However, concentrating on this genre has tended to sideline the even more significant emergence of the program format as a central mode of business and culture in the new television landscape. "Localizing Global TV" redresses this balance, and heralds the emergence of an important, exciting and challenging area of television studies. Topics explored include reality TV, makeover programs, sitcoms, talent shows and fiction serials, as well as broadcaster management policies, production decision chains and audience participation processes. This seminal work will be of considerable interest to media scholars internationally.

Teachers' attitudes towards the gifted : the importance of professional development and school culture

Given that teachers have one of the most significant influences on the educational development of gifted students, reports of negative attitudes and beliefs in popular myths about giftedness are cause for concern. It is important to understand teachers’ attitudes and beliefs to implement effective training and educational practices to improve education for gifted students. This study explored the attitudes of Australian primary school teachers (N = 126) towards intellectually gifted children and their education at eight schools. These schools could be categorised into four different classifications in regards to their involvement in gifted education. Key findings include significant associations between teachers’ attitudes and their school classifications (p < .001), and their participation in gifted and talented education inservice training (p < .001). Findings from this study suggest that further teacher training and school-wide involvement in gifted education may assist in improving attitudes towards intellectually gifted children and their education.

Aligning communication, cultural and media studies research and scholarship with industry and policy : Australian instances

This article reflects on aspects of what is claimed to be the distinctiveness of Australian communication, cultural and media studies, focusing on two cases – the cultural policy debate in the 1990s, and the concept of creative industries in the 2000s – and the relations between them, which highlight the alignment of research and scholarship with industry and policy and with which the author has been directly involved. Both ‘moments’ have been controversial; the three main lines of critique of such alignment of research and scholarship with industry and policy (its untoward proximity to tenets of the dominant neo-liberal ideology; the evacuation of cultural value by the economic; and the possible loss of critical vocation of the humanities scholar) are debated.

Re-imagining China's future : soft power, cultural presence and the East Asian media market

As various contributors to this volume suggest, the term soft power is multifaceted. In 2002 Joseph Nye, the political scientist who coined the term more than a decade previously, noted that the soft power of a country rests on three resources: a country’s culture, its political values, and its foreign policies (Nye 2002). However, several factors can be drawn together to explain China’s adoption of this concept. First, China’s economic influence has precipitated a groundswell of nationalism, which reached its apex at the Opening Ceremony of the 2008 Beijing Olympics. This global media event provided an international platform to demonstrate China’s new found self-confidence. Second, cultural diplomacy and foreign aid, particularly through Third World channels is seen by the Chinese Communist Party leadership as an appropriate way to extend Chinese influence globally (Kurlantzick 2007). Third, education in Chinese culture through globally dispersed Confucius Institutes is charged with improving international understanding of Chinese culture and values, and in the process renovating negative images of China. Fourth, the influence of Japanese and Korean popular culture on China’s youth cultures in recent years has caused acute discomfit to cultural nationalists. Many contend it is time to stem the tide. Fifth, the past few years have witnessed a series of lively debates about the importance of industries such as design, advertising, animation and fashion, resulting in the construction of hundreds of creative clusters, animation centres, film backlots, cultural precincts, design centres and artist lofts.

Analysing queer student media using a combined queer theoretical and media studies approach

Australian queer (GLBTIQ) university student media is an important site of cultural and political self-representation. These groups exist within university student unions and the unions provide them with space, financial support and resources. Community media is a significant site for the development of queer identity, community and a key part of queer politics. This paper reviews my research into queer community media which is grounded in a Queer Theoretical perspective of identity performativity. Cover argues that Queer Theoretical approaches that study media products fail to consider the material contexts which contribute to their construction. I use an ethnographic approach combined with discourse analysis in order to reveal queer student activists’ media representations of queer, and the production contexts which shape them. My research contributes to queer media scholarship by using a methodology to address the gap that Cover identifies.

The Scottish media and politics

This chapter will explore the performance of the Scottish media in post-devolution political life, before turning its attention to the specific coverage of the 2007 election.

Communication, Cultural and Media Studies : The Key Concepts (4th Edition)

This fourth edition of Communication, Cultural and Media Studies: The Key Concepts is an indispensible guide to the most important terms in the field. It offers clear explanations of the key concepts, exploring their origins, what they’re used for and why they provoke discussion. The author provides a multi-disciplinary explanation and assessment of the key concepts, from ‘authorship’ to ‘censorship’; ‘creative industries’ to ‘network theory’; ‘complexity’ to ‘visual culture’. The new edition of this classic text includes: * Over 200 entries including 50 new entries * All entries revised, rewritten and updated * Coverage of recent developments in the field * Insight into interactive media and the knowledge-based economy * A fully updated bibliography with 400 items and suggestions for further reading throughout the text

The younger audience : children and broadcasting in New Zealand

The role and influence of media in the lives of children are ongoing sources of public, political and academic debates. These debates move back and forth along a care-control continuum (Cohen, 1997), and reflect a commitment both to educate children and to regulate their media experiences. Rapid advancements in computer technologies have vastly expanded the range of media experiences available to children. The development of Internet information and the rapid expansion of channels as a result of digital television have created increasingly accessible and diverse sources of media for children. These media are instantaneous and, in some circumstances, constantly available. As a result, a substantial body of international research has emerged that examines the influence of media consumption on children. How much time do children spend interacting with media? What sorts of media do they access? Are media harmful or beneficial to children? If so, in which contexts? Do media influence children�s personal development? And what role should governments, broadcasters and independent producers play in the regulation of the media? These questions remain central to contemporary debates about children and the media.