Expression and regulation of microsomal prostaglandin E synthase-1 in human osteoarthritic cartilage and chondrocytes

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

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.

Expression and regulation of microsomal prostaglandin E synthase-1 in human osteoarthritic cartilage and chondrocytes

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

DIGITAL HISTORY: DESIGNING VIRTUAL ENVIRONMENTS THAT SUPPORT CRITICAL THINKING AND IDEA EXCHANGE, MOTIVATE AND ENGAGE USERS

In my thesis I argue for the use of system designs that: a) open access to a variety of users and allow for collaboration and idea exchange, while at the same time, b) are designed to motivate and engage users. To exemplify my proposed systems design, I created an interactive and open digital history project focused on Romanian culture and identity during Communism, from 1947, when the Communist Party took power by forcing the King to abdicate, until the revolution in 1989, which marked the end of Communism in Romania (Gilberg, 1990, Boia, 2014). In my project, I present the possibility to recreate Habermas’ notion of public sphere and “the unforced force of the better argument” (Habermas, 1989) and Dewey’s (2004) understanding of democracy as a mode of associated living imbued of the spirit of inquiry within contemporary digital history projects. Second, I outline system designs that motivate and engage users, by satisfying the basic psychological needs outlined in Ryan and Deci’s (2000) self-determination theory: autonomy, competence, and relatedness. Two more concepts are included to complete the proposed digital history project design: presence (Ryan, Rigby, & Przybylski, 2006) and learner hero (Rigby & Przybylski, 2009).

From Customer-Oriented Strategy to Organizational Financial Performance: The Role of Human Resource Management and Customer-Linking Capability

Drawing on the organizational capabilities literature, the authors developed and tested a model of how supportive human resource management (HRM) improved firms’ financial performance perceived by marketing managers through fostering the implementation of a customer-oriented strategy. Customer-linking capability, which is the capability in managing close customer relationships, indicated the implementation of the customer-oriented strategy. Data collected from two emerging economies – China and Hungary –established that supportive HRM partially mediated the relationship between customer-oriented strategy and customer-linking capability. Customer-linking capability further explained how supportive HRM contributed to perceived financial performance. This study explicates the implication of customer-oriented strategy for HRM and reveals the
importance of HRM in strategy implementation. It also sheds some light on the ‘black box’ between HRM and performance. While making important contributions to the field of strategy, HRM and marketing, this study also offers useful practical implications.

Knowledge and acceptance of Human Papillomavirus (HPV) and HPV vaccination in adolescent boys worldwide: a systematic review

Aim

To determine HPV and HPV vaccine awareness, knowledge and acceptance in male adolescents worldwide.

Methods

A mixed methods systematic review was conducted. In accordance with PRISMA guidelines, relevant literature was identified through an electronic database search using specified keywords from inception to September 2015. Non-interventional studies presented in English that assessed HPV knowledge and provided data on male adolescents were included. If available, data on HPV and HPV vaccine perceptions, attitudes and/or HPV vaccine acceptance were also extracted. All studies were critically appraised to provide an indication of methodological quality. Results were compiled using a convergent synthesis.

Results

22 papers were included. The majority of studies were cross-sectional and conducted in the US and Europe. Across continents, regardless of a country’s HPV vaccination programme status, boys’ knowledge of HPV and/or HPV vaccination was generally low to moderate and significantly lower than female knowledge or awareness. There was a disagreement in the association of knowledge and vaccine acceptance, with higher knowledge not always being predictive of acceptance.

Conclusions

Comparison and synthesis of research concerning HPV knowledge and attitudes was made difficult due to the lack of universal definition of vaccine acceptance, and no universally accepted tool for its measurement or for the measurement of HPV knowledge. It is imperative that future research utilises consistent measures of HPV knowledge and attitudes to facilitate interpretation and comparison across studies internationally. Prospective longitudinal studies would be more informative providing data on factors that influenced the move from vaccine intention to uptake.

Learning from Text: Examining Teacher Thinking and Practice in AP Environmental Science

Thesis (Ph.D.)--University of Washington, 2016-08

Jatropha cultivation in Malawi and Mozambique: impact on ecosystem services, local human well-being, and poverty alleviation

Jatropha-based biofuels have undergone a rapid boom-and-bust cycle in southern Africa. Despite strong initial support by governments, donors, and the private sector, there is a lack of empirical studies that compare the environmental and socioeconomic impacts of Jatropha’s two dominant modes of production: large plantations and smallholder-based projects. We apply a rapid ecosystem services assessment approach to understand the impact of two Jatropha projects that are still operational despite widespread project collapse across southern Africa: a smallholder-based project (BERL, Malawi) and a large plantation (Niqel, Mozambique). Our study focuses on changes in provisioning ecosystem services such as biofuel feedstock, food, and woodland products that can have important effects on human well-being locally. Qualitative information is provided for other regulating and cultural ecosystem services. Although at this stage no impact is tremendously positive or negative, both projects show some signs of viability and local poverty alleviation potential. However, their long-term sustainability is not guaranteed given low yields, uncertain markets, and some prevailing management practices.

Societal human resources management and development

Based on a broad conceptualization of Human Resources Management and Development (HRMD) as a technical, political, and strategic field concerned to managing and developing people within and towards work context(s), this research aims to explore a potential societal role of Human Resources (HR) profession. Framed on a larger project on “New Human Resources roles”, this particular study approaches HR profession by analysing its macro-societal challenges and intervention spaces.

Individual human resource management and development: career management

Framed on a wider project on Individual Human Resource Management and Development (HRMD), this project aims to explore Individual Career Management and Development (CMD) as an emergent professional field of HRMD.

Human Rights Protection and Terrorism – Reflections in the Context of Strasburg Jurisprudence

The phenomenon of terrorism is one of the most asymmetrical, amorphous and hybrid threats to international security. At the beginning of the 21st century, terrorism grew to a pandemic. Ensuring freedom and security of individuals and nations has become one of the priority postulates. Terrorism steps out of all legal and analytic-descriptive standards. An immanent feature of terrorism, e.g. is constant conversion into malicious forms of violence. One of the most alarming changes is a tendency for debasement of essence of law, a state and human rights Assurance of safety in widely accessible public places and in private life forces creation of various institutions, methods and forms of people control. However, one cannot in an arbitrary way limit civil freedom. Presented article stresses the fact that rational and informed approach to human rights should serve as a reference point for legislative and executive bodies. Selected individual applications to the European Court of Human Rights are presented, focusing on those based on which standards regarding protection of human rights in the face of pathological social phenomena, terrorism in particular, could be reconstructed and refined. Strasbourg standards may prove helpful in selecting and constructing new legal and legislative solutions, unifying and correlating prophylactic and preventive actions.