Memorial University of Newfoundland

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    Adaptations in physiological and neuronal function during diet-induced obesity

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    Obesity significantly increases the risk of developing chronic conditions including type II diabetes, cardiovascular disease, and some cancers. The rate of obesity has tripled globally since 1975, which is in part due to the sudden prevalence and overconsumption of palatable high-fat diets (HFDs). Obesity profoundly perturbs the neural control of energy balance, affecting diverse cell types within the hypothalamus. However, an incomplete understanding of how HFD impacts the regulation of energy balance hinders our ability to more effectively treat obesity. In this thesis, I describe the physiological and neuronal response to HFD feeding in rodents. We identified that HFD exposure elevates the body weight set point, which is initially driven by a transient hyperphagia. This hyperphagia coincides with increased excitatory transmission to lateral hypothalamic orexin (ORX) neurons, which regulate acute food intake. This suggests that ORX neurons may be involved in the initial hyperphagia, implicating them in the development of obesity. As HFD prolongs, body weight gain slows and reaches a new steady state regardless of age at the start, duration of feeding, or palatability of the diet. This sustained weight coincides with increased synaptic contacts to melanin-concentrating hormone (MCH) neurons, which promote weight gain and food intake, likely contributing to the maintenance of obesity. The molecular mechanism underlying the establishment of a new set point remains elusive. During HFD feeding, the presence of a chronic low-grade hypothalamic inflammation exacerbates weight gain, therefore we reasoned that inflammatory factors could modulate appetite-promoting neurons to maintain a new set point. We found that the inflammatory mediator prostaglandin E2 (PGE2) activate MCH neurons via its EP2 receptor (EP2R). Suppressing PGE2-EP2R on MCH neurons partially protects against excess weight gain and fat accumulation in the liver during HFD feeding. This mechanism could contribute to the maintenance of an elevated body weight set point in during diet-induced obesity. Without long-term treatment options in face of the increasing rates of obesity, we are in desperate need of novel interventions. In the future, we hope that targeting EP2R on MCH neurons can lower body weight set point and aid in combatting obesity

    Exposure-, infection, and vaccine-induced immune responses to SARS-COV-2

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    There is tremendous diversity in the way individuals experience severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. We analyzed immune responses to SARS-CoV-2 in the context of susceptibility to infection before and after vaccination. Within a cohort of subjects who were highly exposed to SARS-CoV-2 prior to vaccination and seronegative against the immunodominant spike (S) protein, there was evidence of cross-reactive immunoglobulin (Ig) G to nucleocapsid (N) from common -coronavirus exposure and specific cellular immune responses against SARS-CoV-2 envelope (E), membrane (Mem), N, and S proteins. There was no evidence of underlying innate protection or natural immunity against SARS-CoV-2. Considering that the strength of the cellular immune responses correlated with time since exposure, we speculated that either rapid cellular immune responses or abortive infection resulted in infection being contained below the threshold for direct viral detection or generation of a humoral immune response. We analyzed the characteristics and significance of circulating vaccine-induced IgA in a post-vaccination cohort with a relatively high incidence of breakthrough infection. Higher levels of vaccine-induced IgA were negatively associated with breakthrough infection. Breakthrough Omicron infection increased anti-ancestral S IgA responses more than booster vaccines. Longitudinal analysis of post-infection anti-S IgA decay showcased the durability of infection-induced responses. As reported for IgG responses, vaccination with ancestral SARS-CoV-2 S antigen-imposed imprinting on circulating IgA responses. This research addressees the variability in humoral and cellular immune responses to SARS-CoV-2 and illustrates how the timing and nature of exposure to viral antigens impact the responses generated

    Comprehensive screening of persistent organic pollutants in industrial wastewater using GC and LC cyclic ion mobility-high resolution mass spectrometry

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    Industrial chemicals play an important role in all facets of modern society; from flame retardants in electronics and furniture to non-stick coatings in cookware and food packaging. However, despite their extensive applications and many desired benefits, chemicals are sometimes released during their lifecycle resulting in deleterious ecological and human health effects. Industrial wastewater effluents are rich in chemical pollutants, both known and unknown as well as legacy and emerging. In this study, a combination of screening strategies was used to analyze industrial wastewater samples from over 10 sectors in Ontario for halogenated persistent organic pollutants (POPs). Samples were characterized with both gas chromatographic and liquid chromatographic cyclic ion mobility mass spectrometry (GC/LC-cIM-MS) methods. A novel non-target screening (NTS) technique utilizing GC-cIM-MS, capable of isolating unknown per- and polyfluoroalkyl substances (PFAS) and other halogenated compounds based on the ratio of their mass and collision cross section (CCS) values, was recently developed in our group. When the combined dataset from GC-cIM-MS analysis of the wastewater samples was subjected to this novel filtering strategy, 344 potentially brominated, chlorinated or fluorinated chemical species were identified from the ~27,000 initially present. Following the application of a previously developed script tool (R code) and manual investigation, 44% of these ions were confirmed to be halogenated. Five compounds belonging to frequently detected classes were identified by suspect screening (e.g., polybrominated diphenyl ethers; PBDEs, polychlorinated biphenyls; PCBs, organophosphate flame retardants; OPFRs and perfluorosulfonamides; PFSMs). Confirmed suspects represented a mere 14% of the halogenated ions (9% intensity) indicating that 86-91% of the halogenated content is truly “unknown”. A more in-depth look at these unknown ions revealed 19 suspected PFAS including 2 classes that were detected in the environment for the first time. Targeted analyses showed that legacy pollutants such as PBDEs, PCBs, polychlorinated naphthalenes (PCNs) and organochlorine pesticides (OCPs) were either not detected or present at low levels. For characterization via LC-cIM-MS, wastewater samples were extracted using a tandem solid phase extraction (SPE) technique with weak anion exchange (WAX) and weak cation exchange (WCX) cartridges. LC-cIM-MS experiments revealed the presence of ~50,000 chemical species across all samples and filtering based on CCS and m/z yielded 937 likely brominated, chlorinated or fluorinated compounds. Further data reduction and mass defect analysis led to the discovery of roughly 300 potential PFAS by NTS. Only half of them were matched to a suspect screening database implying that the chemical identities of several PFAS in the Ontario environment are unknown. Multiply charged ions formed during electrospray ionization were found to be non-problematic when filtering data using CCS and m/z. As such, this novel way of data prioritization is a promising approach for PFAS discovery in complex samples when analyzed by LC-ESI-IM-MS. GC-APCI-IM-MS was also found to be a complementary technique for PFAS discovery since comparable numbers were identified using the same workflow

    Collaborative water governance in Burgeo, Newfoundland and Labrador: challenges, successes, and opportunities

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    Water—a finite natural resource—is complex, thus greater stakeholder representation is encouraged in decision-making. Collaborative governance processes, through which diverse actors pool resources and share responsibilities to effectively solve problems that they could not solve independently, have gained popularity as tools for effective water governance. In 2015, Burgeo lifted a long-term boil water advisory, and this was a shared effort between the Town of Burgeo and its staff, the residents of Burgeo, the Government of Newfoundland and Labrador, the Government of Canada, and other actors. Despite achieving this milestone, Burgeo continues to face other water-related concerns, including water overuse and high concentrations of certain contaminants. These newer concerns indicate a need for further collaboration to achieve positive water-related outcomes for Burgeo’s water security. This study sought to explore collaborative water governance in Burgeo by examining the interactions, particularly communication and coordination, between the various actors who have been involved in attempting to provide clean, safe drinking water to the residents. An exploratory case study was developed, and data were collected from a range of sources including existing literature, secondary documents, and semi-structured interviews. A collaborative governance framework was developed to aid data collection and analysis. Drivers of collaborative governance in Burgeo included knowledge-power-resource asymmetries, prehistory of cooperation, and new water concerns. Knowledge-power-resource imbalances were also identified as challenges to successful collaboration, while facilitative leadership and conflict resolution strategies required improvement. The more resources and knowledge an actor/group possessed, the more power they had to influence decision-making in their favour. These power imbalances, in turn, impacted trust and the extent to which certain actors/groups felt that their contributions were valid and valued

    A comparison of behavioural procedures for measuring Vernier acuity and grating acuity

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    I evaluated a novel 4/4 vision testing procedure recently implemented by our laboratory in a larger study to estimate the maturation ages of three visual functions. This rigorous procedure requires participants to locate a stimulus on four consecutive presentations before progressing to more difficult stimuli. I determined the time-efficiency of the procedure and whether children are affected differently than adults by the procedure, which would suggest that maturation age estimates from the larger study are inaccurate. Fifty-five adults and 52 children were tested on grating acuity and vernier acuity using the Teller acuity cards (TAC) and vernier acuity cards, respectively. I hypothesized that the 4/4 procedure would agree with the widely-used staircase and TAC procedures for both visual functions and across age groups, and that the 4/4 procedure would be more time-efficient than the staircase procedure. The 4/4 procedure showed strong to acceptable agreement with the staircase and TAC procedures for grating acuity, while levels of agreement for vernier acuity were poorer due to the misalignment step sizes. For both visual functions, levels of agreement were stable across age indicating that the measurement of children’s acuity was not affected differently than the measurement of adults’ acuity when tested with the 4/4 procedure. Although for both visual functions, the 4/4 procedure had longer completion times than the TAC procedure, it was more time-efficient than the staircase procedure. Thus, this procedure is sufficiently accurate and practical to measure visual maturation

    Mapping areas of interest for coastal enhancement related to capelin spawning in Conception Bay, Newfoundland and Labrador

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    Capelin is a forage fish species that plays a key role in Newfoundland and Labrador (NL) marine ecosystems. The species tends to spawn on beaches possessing specific environmental characteristics, such as gentle slopes and granular sediment sizes. Many beaches on the island of Newfoundland have been modified by humans and are no longer suitable for capelin spawning. Coastal enhancement work, which could help increase the suitability of beaches for capelin spawning, requires an understanding of beach dynamics and geomorphology to identify suitable sites for enhancement and long-term effectiveness. Three beaches along Conception Bay, NL were examined to inform potential future coastal enhancement work: Lance Cove, Chapel’s Cove, and Harbour Main. Aerial photos and digital surface models (DSM) of the beaches were acquired at different times throughout 2019 using an uncrewed aerial vehicle, complemented by field observations. A multi-criteria decision analysis (MCDA) approach was then used to provide a systematic way to prioritize these beaches for enhancement suitability. The MCDA prioritization accounts for key components of capelin spawning, wind direction, beach protection, sediment grain size, slope, and anthropogenic footprint. Key components were addressed both in terms of capelin spawning suitability and coastal stability. DSM and geomorphological data indicate that beaches experience different changes throughout a season, although they present somewhat similar physical characteristics. Adjacent beaches can exhibit very different responses to the same weather event, indicated by the geomorphic dynamics of Lance Cove, Chapel’s Cove, and Harbour Main. Of the three sites, Chapel’s Cove is most suitable for coastal enhancements to make the beach more suitable for capelin spawning. Chapel’s Cove is more dynamically stable than Lance Cove, and is much less anthropogenically influenced than is Harbour Main. Findings demonstrate the key factors influencing beach geomorphology and how it pertains to planning species-specific enhancement projects, building on the idea that enhancement projects require a multi-dimensional approach

    The energy landscapes of metamorphic proteins

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    Most proteins fold into a unique three-dimensional structure called the native state. Recently some examples have been found of so-called metamorphic proteins that undergo reversible large-scale structural transformations between different native states. In this thesis, we develop simulation methods and models to study the thermodynamics of these transformations, both at the coarse-grained and all-atom levels. Because our understanding of the physics fold switching is incomplete, our models utilize in part so-called structure-based or Gō-like potentials, which provide energetic bias towards one, or more, native states. We employ these computational methods to two different fold switch systems: the bacterial protein RfaH and the engineered fold switch system GA/GB. Our models are developed and tested on experimental data for these systems. We study both equilibrium properties, such as stability properties and the characteristics of their energy landscapes, and kinetic properties, such as the mechanism that trigger fold switching and molecular details of the fold switch process. We also study, for the GA/GB system, what role macromolecular crowding effects play for controlling which of the native states is most stable

    The effect of attentional focus cues on corticospinal excitability and neuromuscular efficiency during a sustained task

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    Attentional focus has been studied in the context of physical activity and sports as a form of feedback or instruction that aims to improve performance by directing a person's focus either externally or internally. Adopting an external focus (i.e., focus on goals and environment) has been shown to be beneficial to performance relative to an internal focus (i.e., focus on self and body movements) for a range of tasks. However, little is understood about the mechanisms underlying improved performance associated with external focus. Emerging neuroimaging studies have shown changes in brain activity relative to the direction of attention, and data from electromyography shows changes at the muscular level. To bridge the gap in knowledge between what is seen in the brain and the muscle during external and internal focus, we explored corticospinal excitability, which is the connection between brain and muscle and reflects the ability of the motor cortex to generate movement. Understanding the relationship between attentional focus and corticospinal excitability is important for advancing our understanding of basic neural mechanisms and informing the development of interventions aimed at improving motor function and physical performance in individuals

    Reconstruction of volcanic and hydrothermal settings and mineralization of the ABM deposit, Finlayson Lake district, Yukon, Canada

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    The ABM deposit is a bimodal-felsic, replacement-style volcanogenic massive sulfi de (VMS) deposit located in the Finlayson Lake district, Yukon, Canada. In this dissertation, detailed core mapping, petrography, lithogeochemistry, and microanalytical methods are used to reconstruct the tectonostratigraphic framework for the deposit, the hydrothermal footprint, mineral chemical composition of the mineralization, and to integrate these to understand the genesis of the ABM deposit. The deposit is hosted by Late Devonian continental back-arc-related volcano-sedimentary rocks of the Kudz Ze Kayah formation. The distribution and character of coherent felsic and mafi c rocks suggest that the rocks were deposited in a back-arc basin proximal to a volcanic center, and the chemostratigraphy shows three sequences with distinct geochemical signatures. Reconstruction of the basin architecture has identified two sets of synvolcanic faults, and an argillite lens at the contact between the sequence hosting the mineralization and the hanging wall sequence that documents a period of volcanic inactivity during which the hydrothermal system was active. Hydrothermal alteration assemblages extend for 100s-1000s of meters laterally and into the footwall and hanging wall. The main alteration processes are feldspar destruction and formation of white mica and chlorite. The earliest and most extensive alteration assemblage is moderate white mica ± chlorite that formed at ~215±30 °C. It is overprinted by a pervasive white mica assemblage that formed at ~250±15 °C. A pervasive chlorite assemblage formed at ~320±10 °C (temperatures were determined by illite and chlorite thermometry) and overprints the white micarich assemblages. The massive sulfi de mineralization occurs as a series of stacked and stratabound lenses subparallel to the volcanic stratigraphy, overprinting the pervasive alteration assemblages. Three major mineralization assemblages occur: (1) a pyrite-sphalerite assemblage enriched in Zn- Pb-As-Sb-Ag-Au that formed at temperatures ~200-270 °C; (2) a pyrite-chalcopyrite-magnetitepyrrhotite assemblage enriched in Cu-Bi-Se-Co that formed at temperatures ~300-350 °C and occurs at the center of the mineralization lenses; and (3) a minor chalcopyrite-pyrrhotite-pyrite stringer assemblage that occurs at the margins of the lenses and formed at temperatures >300 °C. The mineralization formed by mixing of seawater infi ltrated in the subsurface with hot reduced acidic hydrothermal fl uids and consequent zone refi ning

    Placelessness through children’s literature

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    Where do you belong? This seemingly simple question can be answered very differently by individuals of different ages. What is the developmental age when we find the answer to this question? What factors can influence our answer to this question? Answering this question or just feeling we are being questioned about it can contribute to feelings of placelessness. This can be especially difficult for the immigrant population (Schwartz et al., 2011; Syed & Juang, 2014). Additionally, since the place we live can act as a significant marker of identity (Corcoran, 2002), determining how they are connected to the place can also have an effect on a child's sense of culture and belonging. This qualitative study addresses the lacuna of research focused on the pedagogical practices teachers can use to enhance the voices of immigrant children through new understandings of place attachment in school immigrant populations and shows how schools can be supportive of children’s expression of culture and community. The study will explore how arts-based pedagogical practices and children’s literature can help to enhance students' identities and voices through their shared place-based narratives. Furthermore, it will explore challenges and successes with the multimodal expressions of immigrant children's voices in a primary classroom in an Eastern Canadian school with a diverse population

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