VictorJuiz/thesis huggingface dataset:
Social Environment Influences Interaction Dynamics and Group Structure in Drosophila melanogaster

Drosophila melanogaster engage in a variety of social behaviours and interactions including complex courtship and mating rituals, aggregation in both lab and wild environments, and aggressive fights. Using social network analysis, I explore the effects of group composition and group size on individuals’ behaviours and group network cohesion. I first show that a strain of hyperaggressive flies differs from wildtype flies in both their individual behaviors and group level network properties. When combined in different ratios, mixed groups behave differently than either all hyperaggressive or all wildtype groups, and the shift in their individual and network properties is towards and past the hyperaggressive flies regardless of the ratio. Remarkably, a single hyperaggressive fly in a group of wildtype flies is enough to define the entire groups’ structure. In my second data chapter I show that flies are capable of discerning group size changes of a single individual. As group size increases, interaction rate and Betweenness Centrality, a network parameter that captures the importance of individuals for information flow, both increase. Disrupting different sensory modalities of flies does not eliminate their ability to discern group size; however, subtle changes in variation and in trends across all group sizes suggest that vision, olfaction, hearing, and mechanosensation are all at least partially involved sensing social group size. Analyses of Coefficients of Variation suggest that flies use the Approximate Number System to assess the size of their social groups, and that there is something biologically important about group sizes 9 and 10. The size and composition of flies’ social environments affects both individual behaviours and group level phenotypes.

Keywords: Behaviour
Genetics
Network
Advisor: Levine, Joel
A Multimodal Investigation of Age Differences in Inhibitory Control

Cognitive control – a set of mental processes that allow us to perform goal-directed actions and flexibly adapt our behavior under changing circumstances – is reduced in aging. Older age is also accompanied by changes in the structure and functioning of the frontoparietal network that supports cognitive control processes. This thesis examines the relationship between the white matter properties and functional recruitment of the frontoparietal network and their association with performance on cognitive control tasks in healthy aging. In a large, cross-sectional lifespan sample of adults, the first chapter explores the microstructural and macrostructural properties of frontoparietal white matter and its association with performance in three domains of cognitive control: working memory, inhibitory control, and updating ability. White matter microstructure (i.e., fractional anisotropy, FA) was associated with age-related reductions in response inhibition, as assessed by the go/no-go task. Based on the notion that brain function is constrained by the underlying anatomy, the second chapter investigates whether FA influences task-related activation (i.e., BOLD activity) of the frontoparietal network during inhibitory processing, as well as the joint contribution of frontoparietal FA and its functional recruitment to age-related differences in response inhibition. Frontoparietal FA was not related to BOLD activity, but it mediated age-related differences in go/no-go response times that in turn influenced age-related differences in accuracy. Thus, it appears that the microstructure of the frontoparietal network bears greater relevance than functional recruitment for explaining age-related differences in response inhibition. Lastly, the third chapter examines whether age differences in inhibitory control influence other aspects of cognition, namely, recognition memory. Inhibitory control was measured in two ways: through the ability to fixate (i.e., oculomotor control) and the ability to inhibit visual distraction (i.e., distractor suppression). Older adults were just as efficient as younger adults at inhibiting distraction, resulting in similar levels of subsequent distractor recognition between the two groups. Nonetheless, older adults still showed poor oculomotor control compared to younger adults. Altogether, this thesis demonstrates the heterogeneity in cognitive control processes as well as the neural correlates supporting one domain of control, namely, response inhibition, across the adult lifespan.

Keywords: aging
cognitive control
eye-tracking
fMRI
inhibitory control
tractography
Advisor: Olsen, Rosanna K
Grady, Cheryl
Designing for the Affective Resilience of Diasporic Population through Cultural Heritage

Affective resilience refers to the ability of individuals, families, and communities to adapt, cope, and recover feelingly from adverse events, challenges, or stressors. For migrants facing diaspora, their cultural heritage can be a critical aspect of affective resilience, as it provides a sense of belonging and purpose. Previous research in Human-Computer Interaction (HCI) regarding the affective resilience of migrants explored migrants’ relations with the larger social circle and the altered family dynamics within diasporic families. However, research in this realm often overlooked the significance of cultural heritage. To address this gap, this dissertation explores different design concepts to building technologies that can support migrants in acquiring, maintaining, and transmitting their cultural heritage, with the overarching goal of fostering their affective resilience. Specifically, the dissertation presents three design concepts targeting individual, family, and community levels respectively. At the individual scale, the user-led design concept was employed, resulting in the creation of “My Home Sketcher,” an augmented paper-based tool that enables novice users to design their homes, reflect their values, and express their space, light, and privacy preferences through sketches that are then transformed into 3D models by a computer algorithm. At the family scale, the community-based gamification concept was used to develop two applications, “Bornomala” and “KnowLink Exchange,” which aim to teach migrants’ children about their heritage language. At the community scale, the reenactment concept was employed, resulting in the creation of “Be Our Guest”, an augmented reality (AR) application where a user is virtually invited to the homes of people from different cultures and is asked to help with one of their cultural rituals through simple everyday objects. This dissertation contributes to our understanding of the intricate interplay between migration, cultural heritage, and resilience. The dissertation shows the significance of cultural heritage in shaping migrants’ sense of self and presents insights and recommendations on how to design with this aspect in mind, emphasizing the critical need for intentional integration of cultural heritage in HCI research. Finally, the dissertation highlights the multifaceted challenges encompassing cultural, linguistic, social, ethical, and academic dimensions encountered when working with migrants and offers methodological approaches that could be incorporated to navigate these complexities.

Keywords: cultural heritage
design
Human-Computer Interaction (HCI)
immigrant
resilience
Advisor: Ahmed, Syed Ishtiaque
Monoterpenoid Volatile Biosynthesis in Rose-Scented Geranium (Pelargonium graveolens)

Rose-scented geraniums (Pelargonium graveolens) are rich in monoterpene containing essential oil that is stored in glandular trichomes. This essential oil has substantial variation in its composition with its value directly correlated to the ratio of geraniol to p-menthane monoterpenes. Based on whole plant 13CO2 labeling experiments, at least two biosynthetic pathways contribute to the monoterpenes that are stored in glandular trichomes. Distinct chemotypic groups favor either the accumulation of cyclic p-menthanes such as isomenthone or acyclic monoterpene alcohols such as geraniol and citronellol. This metabolic split between ‘mint-like’ p-menthanes and ‘rose-like’ acyclic monoterpene alcohols reflects the relative contributions of two compartmentally separated monoterpenoid biosynthetic pathways, a scenario which departs from the classical view of plastids as the sole source of monoterpenoid backbones. In this species, p-menthane skeletons are produced in the plastid from geranyl diphosphate (GDP) derived from the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway in a pathway resembling monoterpene biosynthesis in most plant species. However, the acyclic monoterpene alcohols in P. graveolens are produced in the cytosol without the participation of a conventional monoterpene synthase. Instead, a cytosolic Nudix hydrolase acting on an atypical cytosolic pool of GDP forms geranyl monophosphate as a substrate for a phosphatase to produce geraniol directly in the cytosol. Biochemical characterization showed that a cytosolic, farnesyl diphosphate synthase-like cDNA encodes a multi-product enzyme that produces GDP which supplies substrate to this cytosolic geraniol pathway. The identification of distinct monoterpene pathways in the cytosol and plastid of these geraniums offers insight into essential oil biosynthesis in glandular trichome bearing plants.

Keywords: Essential oil
Glandular trichomes
Monoterpenes
Pelargonium
Terpenoids
Advisor: Phillips, Michael A
Sensorimotor integration in Parkinson’s disease during lower limb movements

External sensory information can be applied to facilitate balance in Parkinson’s disease (PD); however, in some instances, it can also disrupt movement (e.g., doorways and fast auditory cues). We examined visual-vestibular sensory integration during gait (Study 1) and neural oscillatory activity in response to doorways (Study 2) and auditory cues (Study 3) during foot pedaling. In Study 1, we tested 13 people with PD, 13 older adults (OA), and 15 young adults (YA). While walking in a virtual environment, visual and vestibular perturbations were applied to cause deviations in gait trajectories. We found that people with PD and OA integrated perturbed sensory information and showed more gait deviations than YA. In Study 2, we tested 19 people with PD while seated with electroencephalography. They were required to bilaterally pedal their feet to navigate through a virtual series of doors. Doorway-provoked lower limb motor blocks (LLMB) correlated with freezing severity and were associated with decreased beta and theta oscillations in the left temporal pole. Dopaminergic medications increased beta and theta power in the left fusiform gyrus and reduced LLMB percent durations. In Study 3, we tested 25 people with PD undergoing deep brain stimulation surgery. We recorded in the globus pallidus internus (GPi) or subthalamic nucleus (STN) while they pedaled their feet in a supine position in synchrony with auditory cues. We found that the GPi responded to the sensory aspect of the task, showing tonic beta desynchronization with fast cue frequencies. The STN responded to motor aspects of the task with beta rebounds following motor onset. Overall, we show that i) visual-vestibular sensory integration may be preserved in PD, and ii) motor block triggers, such as doorways and fast auditory cues, are related to decreased oscillatory activity in the ventral visual pathway and increased beta modulations in the basal ganglia. Understanding the role of these neurophysiological changes can open avenues to improve treatment in PD.

Keywords: balance
beta
lower limbs
motor blocks
Parkinson disease
sensorimotor integration
Advisor: Chen, Robert
Certain Cases of Hikita-Nakajima conjecture

Let $\mathfrak{M}_0$ be an affine Nakajima quiver variety, and $\mathcal{M}$ is the corresponding BFN Coulomb branch. Assume that $\mathfrak{M}_0$ can be resolved by the (smooth) Nakajima quiver variety $\mathfrak{M}$. The Hikita-Nakajima conjecture claims that there should be an isomorphism of (graded) algebras $H^*_{S}(\mathfrak{M},\mathbb{C}) \simeq \mathbb{C}[\mathcal{M}_{\mathfrak{s}}^{\mathbb{C}^\times}]$, where $S \curvearrowright \mathfrak{M}_0$ is a torus acting on $\mathfrak{M}_0$ preserving the Poisson structure, $\mathcal{M}_{\mathfrak{s}}$ is the (Poisson) deformation of $\mathcal{M}$ over $\mathfrak{s}=\on{Lie}S$, $\mathbb{C}^\times$ is a generic one-dimensional torus acting on $\mathcal{M}$, and $\mathbb{C}[\mathcal{M}_{\mathfrak{s}}^{\mathbb{C}^\times}]$ is the algebra of schematic $\mathbb{C}^\times$-fixed points of $\mathcal{M}_{\mathfrak{s}}$. In this thesis we prove the Hikita-Nakajima conjecture for $\mathfrak{M}= \widetilde{\C^2/ \Gamma}$ (Kleinian singularities) and $\mathfrak{M}=\mathfrak{M}(n,r)$ Gieseker variety ($ADHM$ space). In the latter case we produce the isomorphism explicitly on generators. We also describe the Hikita-Nakajima isomorphism above using the realization of $\mathcal{M}_{\mathfrak{s}}$ as the spectrum of the center of the rational Cherednik algebra corresponding to $S_n \ltimes (\mathbb{Z}/r\mathbb{Z})^n$ and identify all the algebras that appear in the isomorphism with the center of the degenerate cyclotomic Hecke algebra.

Keywords: Algebraic geometry
Representation theory
Symplectic duality
Advisor: Braverman, Alexander
An Examination of Maternal Sensitive Responsiveness and Children’s Cognitive and Socioemotional Development in the Context of Biopsychosocial Risk

This dissertation investigated the influence of distal and proximal factors on children's cognitive and socioemotional development, focusing on the mediating and moderating role of maternal sensitive responsiveness within the context of biopsychosocial risk. Utilizing a novel statistical technique, meta-analytic structural equation modeling (MASEM), Studies One and Two demonstrated that maternal sensitive responsiveness partially mediates the transmission of risk factors to children's language outcomes and psychopathology. Study Three examined the moderating effects of maternal sensitive responsiveness on neurocognitive outcomes in children where the maternal placenta was found to be non-optimal during the pregnancy. The findings revealed that placental pathology negatively effects aspects of children's executive functioning, and maternal sensitive responsiveness showed a borderline significant effect in moderating the development of executive functioning. Collectively, this dissertation provides valuable insights into the interplay between risk factors, maternal sensitive responsiveness, and children's cognitive and socioemotional development.

Advisor: Jenkins, Jennifer JJ
A Self-Determination Theory Perspective on Motivational Interviewing for Emerging Adults Who Use Cannabis

Emerging adults (EAs) between the ages of 20-to-24-years-old have the highest prevalence of past year cannabis use in Canada. It can be challenging to engage EAs in interventions to reduce their cannabis use and brief interventions have an important function as an initial step in the continuum of care. The current study involved a pilot of a single session of motivational interviewing delivered virtually. We also tested whether changes in basic psychological needs were associated with treatment, given recent theoretical models highlighting the link between motivational interviewing (MI) and Self Determination Theory (SDT). Participants were 40 EAs (ages 19-25), who engaged in high frequency cannabis use and were randomized to either a virtual MI intervention (n=20) or a control group (n=20). At a 90-day follow up, there was a significant increase in perceived competence to change cannabis use for the total sample, along with changes in basic psychological needs (autonomy satisfaction) (p = 0.00), there were no group differences in cannabis use consequences, autonomy satisfaction/frustration, competence satisfaction/frustration or relatedness satisfaction/frustration, autonomous and controlled treatment motivation, perceived competence to change one’s cannabis use, or participants’ willingness to initiate contact with follow-up treatment resources. The findings are discussed in the context of future directions for brief interventions and some of the limitations of the study, including delivery online during COVID-19, where sense of control and autonomy may have been more limited and changes to cannabis use more challenging.

Keywords: Brief Intervention
Cannabis
Emerging Adulthood
Motivational Interviewing
Self-Determination Theory
Advisor: Goldstein, Abby L
Dissecting The Differential Functions of the Two Isoforms of the Essential Argonaute CSR-1 Throughout Caenorhabditis elegans Development

Endogenous small RNA pathways play vital roles in regulating gene expression to ensure germline integrity across animal species. The key effectors of these pathways are Argonaute proteins (AGOs), which utilize small RNA partners to identify target transcripts in a sequence-specific manner. The Caenorhabditis elegans genome encodes nineteen functional AGOs that use 22G-RNAs, 26G-RNAs, miRNAs or piRNAs to regulate target transcripts. Only one Argonaute is essential under normal laboratory conditions: CSR-1. Although AGOs predominantly downregulate their targets, the essential C. elegans AGO CSR-1 has been shown to promote and fine-tune germline gene expression. While CSR-1 has been studied widely, nearly all studies have overlooked the fact that the csr-1locus encodes two isoforms. These isoforms differ by an additional 163 amino acids present in the N-terminus of CSR1a. Using a series of transgenes (MosSCI), endogenously GFP::3xFLAG-tagged strains (CRISPR/Cas9), and two different antisera that recognize 1) both isoforms of CSR-1 or 2) CSR-1a only, I have identified key differences between the CSR-1 isoforms. I found that CSR-1a is expressed during spermatogenesis and in several somatic tissues, including the intestine. CSR-1b is expressed constitutively in the germline. Phenotypic analyses reveal that the essential functions of csr-1 described in the literature coincide with CSR-1b, while CSR1a plays tissue-specific functions. Although my data also suggest CSR-1a can compensate for CSR-1b’s absence if expressed throughout the germline. small RNA sequencing of CSR-1 complexes shows that they interact with partly overlapping sets of 22G-RNAs. CSR-1a integrates into an sRNA regulatory network with spermatogenic AGOs ALG-3, ALG-4 and WAGO-10 that is necessary for fertility at 25˚C. Meanwhile CSR-1b functions alongside the spermatogenic AGOs, but also targets oogenic genes along with WAGO-4. In the intestine, CSR-1a silences immunity and pathogen-responsive genes, and its loss results in improved survival from the pathogen Pseudomonas aeruginosa. My findings functionally distinguish the CSR-1 isoforms and highlight the importance of studying each AGO isoform independently.

Keywords: Argonautes
C. elegans
CSR-1
sRNA
Advisor: Claycomb, Julie M
Investigating the Mechanisms that Regulate Rod Photoreceptor Positioning and Connectivity in the Developing Murine Retina

Correct positioning and connectivity of rod photoreceptors (PR) are essential for proper development and function of the retina. Cell replacement therapy involving the transplantation of immature donor PRs into the adult recipient retina is a promising therapeutic strategy for restoring vision in patients. Nonetheless, this approach faces challenges in terms of inefficient migration and synaptic integration of donor PRs. In this regard, understanding the mechanisms governing the positioning and connectivity of rod PRs during retinal development can shed light on the underlying causes of retinal diseases and enhance the effectiveness of cell replacement therapy. Thus, the primary objective of this thesis is to investigate the mechanisms that regulate rod PR positioning and connectivity in the developing murine retina. To investigate these mechanisms, a lentiviral labelling approach was developed to track a cohort of rod photoreceptors during development and identify the non-cell and cell autonomous mechanisms that mediate rod PR positioning. Direct evidence for a passive displacement model is presented, where the basal displacement of post-mitotic rod photoreceptors is caused by retinal progenitor cell proliferation, in a non-cell autonomous manner. Moreover, cell differentiation factors such as Crx, and synaptic function cell autonomously mediate rod basal soma translocation as loss of Crx or blocking neurosecretion results in mispositioned rod PR somas and synaptic defects. Using existing RNA sequencing datasets, several candidate genes were identified to be potentially involved in PR axon outgrowth, guidance, or synapse formation. Specifically, potential isoform specific roles for Ncam1 were identified in mediating early retinal development and lamination. Lastly, an optimized tissue clearing approach was developed to facilitate whole-eye fluorescent marker tissue imaging. Validation of this technique was conducted on various retinal model systems, and it was subsequently employed to investigate the role of the recipient retinal environment on donor positioning and connectivity in transplanted retinas. Overall, the findings of this thesis provide further insight into the complex mechanisms that regulate the development of rod PR positioning and connectivity in the murine retina. This work has important implications towards retinal disease, and in improving the efficacy of photoreceptor cell replacement therapy.

Advisor: Wallace, Valerie A
Mitochondrial Damage and Dysfunction in Severe Malnutrition

Background: Globally, undernutrition contributes to over 45% of deaths in children under five years of age. Hospital mortality rates for children with severe malnutrition remain high. Progress to improve mortality is hindered by a lack of understanding of the organ dysfunctions that underly severe malnutrition. Children with severe malnutrition suffer from metabolic disturbances and an enteropathy that contribute to a heightened mortality risk. Interestingly, children with complicated severe malnutrition have altered protein metabolism and reduced serum tryptophan levels. Disturbances in the tryptophan pathway and consequent mitochondrial dysfunction have been implicated in other intestinal disorders and malnutrition induced hepatic stress, however this pathway has never been studied in a model of severe malnutrition.Objective: The first objective was to determine if, and how, tryptophan pathway disturbances and downstream alterations in mitochondrial homeostasis were associated with malnutrition enteropathy. The second objective was to validate the existence and degree of mitochondrial alterations in severely malnourished patient samples. Methods: In the first study, mice were randomized into two dietary groups: control diet, low protein diet (LPD). Subsets of mice were treated with modulators of downstream tryptophan pathway components. In the second study, an intestinal organoid model of malnutrition enteropathy was generated. Intestinal permeability, mitochondrial parameters, and downstream targets of the tryptophan-NAD+ pathway were assessed. In the last study, post-mortem tissue biopsy samples were used to examine the degree of mitochondrial damage through histological techniques. Results: In the first study, feeding a LPD resulted in intestinal barrier dysfunction that was associated with disturbances in mitochondrial biogenesis, clearance, and function. This was improved through treatment with an NAD+ precursor, nicotinamide. In the second study, mitochondrial reactive oxygen species were elevated in organoids deprived of amino acids, causing impaired paracellular barrier function. In the last study, mitochondrial morphology was altered in the liver of children with severe malnutrition and was most severely perturbed in patients with edematous severe malnutrition. Significance: This study improves the current understanding of severe malnutrition induced enteropathy and points to the mitochondria as an important mediator of severe malnutrition organ dysfunction, potentially leading to the development of novel targeted treatments to reduce mortality.

Keywords: INTESTINAL BARRIER
MALNUTRITION
MITOCHONDRIA
ORGANOID
SEVERE WASTING
TIGHT JUNCTION
Advisor: Bandsma, Robert
Kim, Peter