VictorJuiz/thesis huggingface dataset:
Innate Immunity Phenotypes in the Setting of Health and Tissue Inflammation

Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune response and are recruited to both healthy and inflamed tissues within the oral cavity. While PMNs were once considered a homogenous and terminally differentiated component of the innate immune system, contemporary literature indicates that circulating and tissue PMNs can exhibit substantial phenotypic heterogeneity. Moreover, exaggerated PMN responses in the presence of pre-existing oral inflammatory diseases has been theorized, but not fully elucidated. To probe these concepts, we first designed a robust murine model of oral inflammation through ligature-induced periodontal disease (PD) together with a novel oral rinse assay to interrogate oral PMNs. Utilizing multicolor flow cytometry to assess PMNs from multiple tissue compartments of healthy mice and those with various local inflammatory insults, we defined a hierarchy of tissue PMN immunophenotypes determined by varying surface expression of activation markers associated with sterile, healthy commensal biofilm-associated, and inflamed tissues. The generation of a concurrent inflammatory insult on the background of our murine model of PD demonstrated significantly increased PMN counts and ex vivo activation revealing a synergistic effect of multiple inflammatory events on PMN activity. After defining the contribution of PMNs in health and PD, this knowledge was applied to a second disease model associated with significant oral inflammation by utilizing a carcinogen-induced murine model of oral carcinogenesis to analyze the role of inflammatory mediators and PMNs in cancer progression. Our results demonstrated upregulated tumor necrosis factor α expression in murine cancer specimens which, upon neutralization, resulted in decreased serum cytokine expression, inhibited the development of invasive lesions and reduced tumour-associated neutrophils in vivo. While inflammation plays a critical role in preserving physiological homeostasis, the results generated utilizing multiple disease models of oral inflammation suggest a critical role for PMNs in influencing both local and systemic innate immune responses. These concepts may be leveraged to identify potential targeted immunotherapeutic approaches for treating both oral and systemic inflammatory diseases.

Advisor: Glogauer, Michael
Microbial Regulators of Immunoglobulin A and their Impact on Host-Microbiota Crosstalk

The microbiota plays an integral role in the regulation of host immunoglobulin A (IgA) responses. How viral and protozoan exposures alter the microbiota-IgA axis remains unclear. In this thesis, I explore how two microbes influence IgA production and reactivity including: (1) Tritrichomonas musculis (T.mu), a murine commensal protist that colonizes the intestinal tract, and (2) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), an opportunistic human pathogen that initiates infection through the upper respiratory tract. I tested the hypothesis that T.mu colonization elevated IgA levels in a T-dependent (Td) manner as well as altered IgA reactivity against fecal bacteria and the neo-antigen - Ovalbumin (OVA). In addition, I tested the hypothesis that acute SARS-CoV-2 infection impacted anti-microbial IgA levels in the oral cavity.

Keywords: B cells
Immunoglobulin A
Mucosal Immunology
SARS-CoV-2
Tritrichomonas musculis
Advisor: Gommerman, Jennifer JG
Mortha, Arthur AM
Playing Queer and Performing Gender at the Turn of the Eighteenth Century: The Unconventional Life, Voice, and Body of Julie D’Aubigny Maupin

The late seventeenth century in Western Europe is an intriguing period for queer historians: the imagined boundaries between genders, sexual orientations, and even biological sexes were considered far more permeable than we might expect of such a patriarchal society. In this study, I look to this era not to find a perfect reflection of my own queer non-binary identity, but to explore the culturally-contingent nature of all understandings of gender. At the centre of my research is seventeenth-century opera singer Julie d’Aubigny Maupin. Maupin was gender- non-conforming in her outward appearance, openly involved with lovers of all genders, and was an expert fencer and duellist. Simultaneously an outstanding exception to the conventions of gender in her day, and an example of the fluid possibilities of gender at the turn of the eighteenth century, Maupin serves as the case study through which I explore the ever-shifting perceptions of queer and gender-non-conforming people in this era. Through careful review of the few available sources, I reconstruct, as far as possible, an outline of Maupin’s life—and, due to the variable reliability of these sources, I note the many vagaries, contradictions, and impossibilities along the way. As I navigate this “speculative biography,” I rely on Valerie Traub’s concept of the unknowability of history, and am therefore careful to hold space for ambiguity, uncertainty, and all too often, an unsatisfiable curiosity. In subsequent chapters, I bring several aspects of Maupin’s life story, including her gender expression, sexuality, and status as a performer, into conversation with the surrounding social context of late seventeenth-century France, allowing me to offer insight into how Maupin’s contemporaries might have viewed her, as well as how her life relates to twenty-first century perspectives on gender. I then explore the many links between identity, character, and voice through an analysis of Maupin as a singer and performer, choosing four of Maupin’s most iconic roles and investigating them using interrelated lenses of historical context, performance practice, and my own embodied experience of singing excerpts from these operas. Lastly, I reflect on my personal connection with Maupin, and explore the philosophical implications of trying to retell a story as strange and unknowable as hers. Drawing on the Brechtian-inspired tradition of feminist theatre criticism set out by Elaine Aston, Sue-Ellen Case, and Gay Gibson Cima, I discuss the process of developing and writing the text for La Maupin, a solo cantata about Maupin’s life which I commissioned and premiered as a way to share her story with a wider audience. Throughout the dissertation, I also bring my research into dialogue with current views on gender-non-conforming people, including the latest research on the voice as a gendered phenomenon.

Keywords: Baroque
Early modern
Gender
Opera
Queer
Sexuality
Advisor: Gutsche-Miller, Sarah
Impacts of Domestication History on Trait Variation in Wheat

Crop domestication has resulted in a suite of crop trait trade-offs termed ‘domestication syndromes’. The often singular focus of domestication on increasing yield in high-input environments has led crops to express extreme aboveground traits, while less focus has historically been placed on understanding root trait expression. The use of such modern crop varieties may not be well suited to diverse and organic agroecosystems, as the ability of crops to express trait plasticity and intraspecific variation may be hindered due to breeding efforts focused on uniformity and growth environments devoid of stress. Using a functional trait-based approach, my PhD thesis aims to establish a link between the degree of crop domestication and intraspecific trait variation and plasticity in response to environmental resource gradients. Specifically, I seek to assess whether crop domestication constrains the expression of functional traits for beneficial resource acquisition in organic agriculture. As a model species, I used spring bread wheat (Triticum aestivum), one of the most important crops for caloric intake globally, grown in common garden, greenhouse, and organically managed large-scale agricultural settings. I found that a great degree of inter-variety variation present for both leaf and root trait expression, and that root trait plasticity is well maintained, and even increased, as a result of domestication. Furthermore, the overall phenotypic integration of traits increased when grown with organic amendments, presumably due to increased resource heterogeneity. However, rhizospheric conditions, notably microbial communities and enzymatic activity, were highly different among varieties and deeply impacted by the history of domestication. From a theoretical perspective, this research enhances our understanding of crop nutrient acquisition strategies across growth environments, providing new insights into functional trait expression from an eco-evolutionary perspective. From an applied perspective, this research demonstrates how the integration of varieties from diverse original growth conditions into current agricultural environments could provide increased resilience within organic and diversified environments. I provide novel information to better inform organic cropping decisions and management, as well as further promote the use of diverse crop varieties.

Advisor: Isaac, Marney
The Role of Child and Parental Factors on Parents' Feeding Practices in a Clinical Population of Children with Poor Growth

Failure to thrive (FTT) is a symptom of inadequate nutrition and growth. Parental feeding practices are important determinants in shaping weight and eating behaviors in children during a sensitive period of physical and cognitive development. The feeding interaction is a bidirectional relationship between the caregiver and the child and informed by different contextual factors such as family, parental and/or child characteristics. Responsive feeding has been found to promote children’s interest in feeding, as well as their awareness of hunger and satiety cues. This dissertation aims to explore parental beliefs and feeding practices in a clinical population of children with poor growth, as well as the contextual factors that influence parental feeding practices in this population. First, a systematic review and meta-analysis was conducted in order to synthesize the current literature examining association between parents’ stress and their feeding practices and/or styles, among parents of children ≤ 5 years old. Second, a clinical study with cross-sectional design was conducted among a clinical population of children with poor growth to examine the correlation between maternal concern about child weight or perceived feeding difficulties and feeding practices, and to investigate the role of child temperament and maternal mental health in a clinical population of children with poor growth. The findings from the two projects, showed that both general and parenting stress were associated with non-responsive feeding styles. Furthermore, higher maternal concern about child weight and perceived feeding difficulties were associated with less responsive feeding practices. Both child temperament and maternal mental health influenced the use of pressure feeding. Therefore, a review into current policies regarding parents’ mental health screening in a pediatric setting was conducted. The review suggests a lack of clear guidelines and recourse in order to support parents’ mental health screening in a pediatric setting. These findings provide a novel insight into the role of both the child and parents factors on parents’ beliefs and feeding practices. A better understanding of this relationship may provide pathways that could support and improve the clinical management of children with poor growth.

Keywords: child temperament
feeding beliefs
feeding practices
meant health
poor growth
public health policy
Advisor: Bandsma, Robert
Van Den Heuvel, Mathilda
Stereoselective Difunctionalization of Alkenes and Alkynes: Synthesis of Heterocyclic Scaffolds

Transition-metal catalyzed difunctionalization of alkenes and alkynes is utilized for the rapid construction of complex molecules by simultaneous addition of two functional groups across the unsaturation in one synthetic step. Within the various strategies that have been developed to functionalize π-systems, methods aimed at the synthesis of heterocyclic molecules continue to be explored as important targets in synthetic chemistry. The Lautens group has developed various transition-metal catalyzed domino cyclization methods for the synthesis of valuable carbo- and heterocyclic scaffolds. This thesis focuses on the development of base-metal catalyzed alkene/alkyne cyclization cascades to build different N-heterocyclic molecules.Chapter 1 describes two copper-catalyzed borylative cyclization strategies to synthesize γ-lactam scaffolds in a diastereoselective and enantioselective fashion. Using 1,1- or 1,2- disubstituted olefins, the reaction undergoes a boryl-cupration, and subsequent cyclization into a carbamoyl chloride motif to generate two different borylated lactam products. This strategy enables the stereoselective synthesis of these sp3 rich heterocycles, which are ubiquitous in nature, while serving as a complementary strategy to palladium-catalyzed domino reactions. Chapter 2 describes an asymmetric copper-catalyzed Kinugasa/Aldol cyclization reaction to form spirocyclic β-lactam scaffolds. Using alkyne-tethered ketones and nitrones, a highly diastero- and enantioselective β-lactam formation precedes a cyclization event to access products with three contiguous stereocenters. This methodology joins the few examples of Kinugasa/electrophilic addition reactions and serves as a facile route to valuable sp3 rich heterocyclic scaffolds. Chapter 3 describes an enantioselective cobalt-catalyzed enyne cyclization/indole C–H functionalization reaction. Methylene tethered pyrrolidine scaffolds are accessed by using 1,6-enynes, via a C–H functionalization at the C2 position of an indole. The reaction displays high atom-economy while generating products in a regio-, diastereo- and enantioselective fashion. This work highlights the potential of low-valent cobalt catalysis in C–H bond functionalization and enantioselective domino reactivity.

Keywords: Borylation
C-H functionalization
catalysis
cobalt
copper
heterocycles
Advisor: Lautens, Mark
The Role of Stakeholders in Outreach Policy: A Case Study of Private and Public Universities in São Paulo, Brazil

Universities often develop community outreach practices to establish deep links with different sectors of society and to contribute to economic and social development. In Brazil, the development of federal extension policy was the direct result of national debates around the role of extension in the development of a democratic society after a military dictatorship. However, the lack of government evaluation, low and even diminishing funding, as well as difficulties to operationalize an extension definition resulted in inconsistent implementation of emerging policies. In this context, this thesis investigates how institutions develop their extension approach and how they manage different stakeholders. This study used a case study approach and qualitative methods to construct institutional cases representing the four categories of Brazilian universities: for-profit, confessional, public federal, and public state. Participant observation included institutional visits to three universities in São Paulo, a visit to a private higher education sector union, and virtual participation in extension events. Forty-six interviews were conducted with leaders of national extension forums and universities, administration, professors, and students. Document analysis included the collection and analysis of national and institutional extension policies, extension reports, and other documents collected through fieldwork. The data was analyzed using a combined stakeholder and multi-level governance framework. The stakeholder analysis framework was used to identify relevant stakeholders, provide a description of their roles and interests, and analyze how they interact with university and non-university actors. The multi-level governance framework was used to describe the different contexts that stakeholders operate in, organize the findings, and analyze stakeholder behaviour in relation to governance processes and structures. The findings contribute to the understanding of institutional and individual decision-making processes, practices, and behaviours that can affect change in policy and practice. Extension stakeholders navigate a complex system to exert influence on extension policy and the institutional approach by employing a diverse set of strategies, such as policy lobbying and implementing new institutional practices for the management of extension. Institutions respond to national policies and societal demands for a more engaged university, while asserting their values and traditions influenced by their institutional type, affiliation, and history.

Keywords: Brazil
Case Study
Extension
Public and Private Universities
Stakeholder Analysis
University Governance
Advisor: Sá, Creso
Aging Alone, Together: Older Adult ICT Use, Health, and Place during the COVID-19 Pandemic

As adults progress into later life, they are likely to experience age-related mobility decline and social isolation. Social isolation has deleterious effects on mental and physical health, including increased anxiety, mortality rates, and cognitive aging. During the COVID-19 pandemic, older adults faced new obstacles to socializing: the closure of third places (e.g., libraries, coffee shops) and increased risk of serious illness. Information and communication technology (ICT) was widely adopted during this time to facilitate daily activities and social connection, but the extent to which it was able to replace the emotional satisfaction of in-person socializing (e.g., reducing feelings of loneliness) and support health is unclear. In this dissertation, I employ multiple methods, including qualitative interviews, structural equation modeling, and time-use cluster analysis, to investigate the relationship between ICT, mobility, and health. Ultimately, the aim of this dissertation is to explore how older adults socialized during the pandemic and the relationship between different modes of socializing (i.e., online or in-person) and health. In Chapter 2, I present qualitative evidence that older adults adopted ICT in a variety of ways to preserve their pre-pandemic routine and modify their homes into activity places. In Chapter 3, I provide details about data collection with an older Chinese migrant community during the pandemic. In Chapter 4, I test a theoretical framework using a sample of older Chinese migrants during the extended COVID-19 lockdown. This social isolation framework breaks the concept into two levels: spatial and technological isolation (conceptualized as community mobility and ICT use). Using a structural equation model, I find that higher community mobility is related to decreased feelings of loneliness, while higher ICT use is associated with better physical health. In Chapter 5, I use older Chinese migrants’ single-day activity diaries to explore socializing behavior, finding that a majority of older migrants were socializing online while relatively few were socializing in person during the extended lockdown. I also find that better physical health is associated with socializing in person. Taken together, the results of this work demonstrate the importance of considering ICT in tandem with spatial measures of social isolation. Findings also suggest that in-person socializing has a greater impact on mental and emotional health while ICT use has the potential to support physical health.

Keywords: COVID
ICT
Mental health
Migrants
Older adults
Social isolation
Advisor: Widener, Michael J.
Prejudice Reduction through Intergroup Contact on Social Media

Reducing prejudice has long been a central pillar of efforts to improve intergroup relations. Intergroup contact (i.e., fostering positive interactions between members of different groups) is arguably the most reliably effective tool for prejudice reduction known to social scientists. Yet, major challenges inherent to studying and applying intergroup contact hold it back from readiness for practical application at scale and in the real world. Because it is so widely used and allows for low- or no-cost, scalable intervention, I propose that using social media to study intergroup contact may help us push contact research forward to applied readiness. I therefore present a set of studies developing, validating, and testing an approach to using intergroup contact in the context of social media to intervene to reduce prejudice. In Study 1, I find that intergroup contact on social media is associated with less prejudice and more positive intergroup outcomes in a similar way as intergroup contact that takes place in-person. In Study 2, I find that the associations can be observed longitudinally and using behavioral variables collected in the field (i.e., on participants’ real Twitter accounts). In the Study 3 Pilot, I find that manipulating the racial demographics of accounts posting to participants’ real Twitter feeds impacts how much intergroup contact they subjectively experience on Twitter. Finally, in Study 3, I find that manipulating the racial demographics of accounts posting to participants’ real Twitter feeds may have a causal effect on their racial prejudice, but only when participants were interested in the content that was posted. These results suggest that a no-cost, scalable intervention strategy for reducing prejudice and improving intergroup relations through intergroup contact on social media may be effective. They also speak to the need for interventionists to attend to participants’ interests and motivations, particularly in field settings. Open materials and data for all studies and pre-registrations for Studies 2 and 3 can be found on the Open Science Framework: https://osf.io/jz8hm?view_only=64ac338f0a49482194df29149157180e.

Advisor: Page-Gould, Elizabeth
Chasteen, Alison