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.

Identification et caractérisation de gènes impliqués dans la virulence de Salmonella typhi suite à une analyse globale par biopuces de l'infection de macrophages humains en culture

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Lost in Translation? Russian Media Portrayals and Laypersons’ Interpretations of Angelina Jolie’s Breast Cancer Discourse

In May 2013, Angelina Jolie revealed that because she had a family history of breast and ovarian cancer and carried a rare BRCA gene mutation, she had undergone a preventive double mastectomy. Media coverage has been extensive around the world, including in Russia, not an English-language country, where all global news is inevitably filtered by translation. After examining the reactions of Russian mass media and members of the public to Jolie’s disclosure, I consider what transformations have occurred with Jolie’s message in the process of cross-cultural transfer. I explore the mass media portrayal of Jolie’s announcement, laypersons’ immediate and prolonged reactions, and the reflections of patients involved directly in the field of hereditary breast cancer. To my knowledge, this multifaceted and bilingual project is the first conceptualization of Jolie’s story as it has been translated in a different sociocultural environment. I start with examination of offline and online publications that appeared in Russia within two months after Jolie’s announcement. In this part of my analysis, I conceptualize the representation of Jolie’s case in Russian mass media and grasp what sociocultural waves were generated by this case among general lay audiences. Another part of my study contains the results of qualitative in-depth interviews. Eight women with a family history of hereditary breast cancer were recruited to participate in the research. The findings represent Jolie’s case through the eyes of Russian women with the same gene mutation as Jolie. Consolidating my findings, I argue that Jolie’s announcement was misinterpreted and misrepresented by Russian mass media, as well as misunderstood by a considerable part of the media audience. Jolie’s perspective on hereditary breast cancer mostly remained unheard among members of the Russian public. I make suggestions about the reasons for such a phenomenon, and demonstrate how Jolie’s case is implicated in politics, economics, and the culture of contemporary Russia.

#DressCodePM & Re-Framing The Niqab: News Sources, Hashtag Activism, and Media Representation

This thesis originates from my interest in exploring how minorities are using social media to talk back to mainstream media. This study examines whether hashtags that trend on Twitter may impact how news stories related to minorities are covered in Canadian media. The Canadian Prime Minister Stephen Harper stated the niqab was “rooted in a culture that is anti-women” on 10 March 2015. The next day #DressCodePM trended in response to the PM’s niqab remarks. Using network gatekeeping theory, this study examines the types of sources quoted in the media stories published on 10 and 11 March 2015. The study’s goal is to explore whether using tweet quotes leads to the representation of a more diverse range of news sources. The study compares the types of sources quoted in stories that covered Harper’s comments without mentioning #DressCodePM versus stories that mention #DressCodePM. This study also uses Tuen A. van Dijk’s methodology of asking “who is speaking, how often and how prominently?” in order to examine whose voices have been privileged and whose voices have been marginalized in covering the niqab in Canadian media from the 1970s and until the days following the PM’s remarks. Network gatekeeping theory is applied in this study to assess whether the gated gained more power after #DressCodePM trended. The case study’s findings indicates that Caucasian male politicians were predominantly used as news sources in covering stories related to the niqab for the past 38 years in the Globe and Mail. The sourcing pattern of favouring politicians continued in Canadian print and online media on 10 March 2015 following Harper’s niqab comments. However, ordinary Canadian women, including Muslim women, were used more often than politicians as news sources in the stories about #DressCodePM that were published on 11 March 2015. The gated media users were able to gain power and attract Canadian Media’s attention by widely spreading #DressCodePM. This study draws attention to the lack of diversity of sources used in Canadian political news stories, yet this study also shows it is possible for the gated media users to amplify their voices through hashtag activism.

Active energy - London: capital / climate / culture

As negotiators and the media descended on Paris, the Festival explored how culture in London interacts with the climate crisis through bringing together artists, journalists, politicians and academics to debate London’s role as a city of fossil fuels, and the responsibility of culture to drive a rupture with business as usual. The Active Energy project provided an example of how older citizens are able to draw on their extensive life experience to help counter climate crisis, and the role of the arts in facilitating that process.

Understanding Media Production: A rejoinder to Murdock and Golding

This article is a rejoinder to Murdock and Golding’s response to my critique of the political economy of communications (PEC) analysis of media production (see Author 2015). This article sets this exchange in the context of a broader debate in recent editions of Media, Culture & Society (Garnham 2016, Fuchs, 2016) about the value of PEC. Much of this debate stems from Garnham’s (2011) critical review of 40 years of PEC research.

Learning Environments in Design Studio Culture

The paper reports on a study of design studio culture from a student perspective. Learning in design studio culture has been theorised variously as a signature pedagogy emulating professional practice models, as a community of practice and as a form of problem-based learning, all largely based on the study of teaching events in studio. The focus of this research has extended beyond formally recognized activities to encompass the student’s experience of their social and community networks, working places and study set-ups, to examine how these have contributed to studio culture and how there have been supported by studio teaching. Semi-structured interviews with final year undergraduate students of architecture formed the basis of the study using an interpretivist approach informed by Actor-network theory, with studio culture featured as the focal actor, enrolling students and engaging with other actors, together constituting an actor-network of studio culture. The other actors included social community patterns and activities; the numerous working spaces (including but not limited to the studio space itself); the equipment, tools of trade and material pre-requisites for working; the portfolio enrolling the other actors to produce work for it; and the various formal and informal events associated with the course itself. Studio culture is a highly charged social arena: The question is how, and in particular, which aspects of it support learning? Theoretical models of situated learning and communities of practice models have informed the analysis, with Bourdieu’s theory of practice, and his interrelated concepts of habitus, field and capital providing a means of relating individually acquired habits and modes of working to social contexts. Bourdieu’s model of habitus involves the externalisation through the social realm of habits and knowledge previously internalised. It is therefore a useful model for considering whole individual learning activities; shared repertoires and practices located in the social realm. The social milieu of the studio provides a scene for the exercise and display of ‘practicing’ and the accumulation of a form of ‘practicing-capital’. This capital is a property of the social milieu rather than the space, so working or practicing in the company of others (in space and through social media) becomes a more valued aspect of studio than space or facilities alone. This practicing-capital involves the acquisition of a habitus of studio culture, with the transformation of physical practices or habits into social dispositions, acquiring social capital (driving the social milieu) and cultural capital (practicing-knowledge) in the process. The research drew on students’ experiences, and their practicing ‘getting a feel for the game’ by exploring the limits or boundaries of the field of studio culture. The research demonstrated that a notional studio community was in effect a social context for supporting learning; a range of settings to explore and test out newly internalised knowledge, demonstrate or display ideas, modes of thinking and practicing. The study presents a nuanced interpretation of how students relate to a studio culture that involves a notional community, and a developing habitus within a field of practicing that extends beyond teaching scenarios.

Media web sites interactivity: Searching new ways to dialog with their users

Currently the media have made many new tools on their websites in order to broaden the dialogue with its users, a feature that has been called interactivity. The objective of this research is to describe the interactive resources of Chilean media websites. The analysis was conducted at 20 sites using a pattern of six dimensions with interactive forms which are today using identified. The findings indicate that digital media Chileans are expanding the possibilities of dialogue with users on social media, especially Twitter and Facebook, and the mediauser interaction is monological, that is to say, from the media to the user, but with very low feedback.

Narratives Around Iberian Culture at Valencia Museums and Archaeological Sites: From Official Discourses to Social Perceptions

Museums and archaeological sites are considered the most authoritative places for talking about the past and the heritage from a scientific perspective. In fact, visitors assume their discourses as reliable and indisputable. In spite of that, professionals of archaeology must critically analyse the production of narratives at heritage sites, since they often reflect social, political and identity issues related to the present-day realities. The aim of this paper is to study official and popular discourses about the Iberian culture (Iron Age) collected in museums and archaeological sites from Valencia region.

The activity of the feminist online publications: challenges for the transmission of the feminist culture in Spain

Traditionally, big media corporations have contributed to hiding the women’s movement itself, as well as its main claims and topics of discussion (Marx, Myra y Hess, 1995; Rhode, 1995; Mendes, 2011). This has led the feminist movement to develop its own media generally print publications, usually, with a very specialized character and reduced audience. This is similar to what has occurred with quality main stream media, asthese publications have had to adapt themselves to a new communicatiion context, because of the financial crisis and  technological evolution. Feminist media has found in the Internet an excellent opportunity to access citizens and communicate their messages. , In view of this scene of change and renovation,  this article offers the results of a qualitative analysis focused on the experiences of four feminist online media sites edited in Spain: Pikaramagazine.com, Proyecto-kahlo.com, Mujeresenred.net and Laindependent.cat. Besides exploring the characteristics and content of these sites, the article pays attention to the virality of their contents spread through Facebook and Twitter. The onclusion estimates their social impact, insofar as they symbolize the specialization, diversification and dialogue promoted by the Web.

Vaisseau sanguin reconstruit par génie tissulaire : Développement d'une nouvelle approche pour la reconstruction de la media et interaction avec les microparticules

La media vasculaire est au coeur des processus physiopathologiques qui entraînent le développement de l’athérosclérose. L’utilisation d’une media reconstruite par génie tissulaire permet d’étudier les cellules musculaires lisses (CML) humaines dans un environnement plus physiologique que les cellules en culture monocouche. Les travaux présentés dans cette thèse sont orientés autour de la media vasculaire reconstruite par génie tissulaire comme modèle d’étude pharmacologique et prothèse vasculaire autologue. La première partie des travaux porte sur l’étude des interactions de cette tunique avec les microparticules (MP) circulantes. D’abord, nous avons montré que la présence de l’adventice modifie la réponse de la media aux MP produites in vitro à partir des lymphocytes T. Ensuite, l’étude de l’effet des MP isolées du sérum de patients en choc septique sur la media humaine a démontré que ces MP sont en mesure d’augmenter la contraction de la media par un mécanisme impliquant une diminution du NO et une augmentation de l’expression de l’ARN messager de l’interleukine-10. L’incubation de la media reconstruite avec cette cytokine anti-inflammatoire bloque l’hyporéactivité induite par les lipopolysaccharides. Le même phénomène a été reproduit in vivo, chez le rongeur. Ces résultats suggèrent que les SMP auraient un effet protecteur sur la fonction vasculaire, en potentialisant la contraction de la media. Ensuite, nous avons optimisé l’approche de reconstruction de prothèses vasculaires par auto-assemblage proposée initialement pour l’adapter au contexte particulier des CML. L’objectif principal était de permettre l’étude physiopathologique de la media à partir de toutes les lignées de CML; indépendamment de leur capacité de synthèse de matrice extracellulaire. Pour ce faire, nous avons développé un échafaudage de matrice extracellulaire produit par auto-assemblage à partir de fibroblastes humains. L’utilisation de cet échafaudage génère une media plus résistante et plus contractile que la technique initiale. Enfin, une anisotropie a été créée dans cet échafaudage pour permettre une orientation physiologique des CML. La media reconstruite devient ainsi plus résistante et plus contractile. Ces améliorations permettent de reconstruire des media à partir des cellules de plus de patients et mèneront à des études pharmacologiques plus représentatives de la population. Cet échafaudage facilitera la translation clinique de ce modèle de media reconstruite par génie tissulaire.

You play your part – participatory media and older women.

This chapter will examine participatory and collaborative production strategies that create opportunities for older women to participate in media production. It draws on practice-led research in participatory and community-based media in the Govan area of Glasgow, Scotland. In particular, it examines the production process of a participatory documentary I produced and directed with senior citizens who are members of the Govan Seniors Film Club, based at the Portal Arts Centre in Govan.You Play Your Part is a 20-minute documentary about campaigning women in and around Govan.