Relationships between humans and the environment are messy and complex. This thesis makes sense of this complexity by using relational approaches to bridge social-ecological systems research with insights from the more-than-human social sciences and humanities. I focus on the case of environmental governance and conservation research in two of Ontario's National Historic Waterways: the Rideau Canal and the Trent-Severn Waterway. I analyze knowledge maps of factors that influence the environment of the waterways and the perception of relationships between humans and non-humans in the context of research. Through social-ecological network analysis, it was revealed different that groups conceptualize the Rideau Canal differently, but that all groups overemphasized social factors when identifying components that influence the environment. Knowledge maps, representing participants' mental models of the Rideau Canal, are used to generate narratives to inform policy and engagement strategies. Social-ecological network analysis was also used to make visible the different types of relationships between humans and non-humans in the context of conservation research. This unveiled a paradox of conservation. Attempts to produce evidence to conserve non-human populations and habitats are anchored in tense encounters, and sometimes procedures that are harmful for the individuals targeted by the research. I mobilize relational approaches and concepts from the social sciences to propose practical and theoretical insights and pathways for conservation research to become more-than-human. Such work necessitates the explicit recognition of the contributions of non-humans in research processes.

<p> Physical inactivity or deconditioning has been shown to be an independent risk factor for cardiovascular disease. Contrary to the previously demonstrated effects of exercise training on the cardiovascular system, the vascular adaptations that occur with a deconditioned state have not been adequately characterized within a young, healthy population. Thus, it was the interest of the present study to examine vascular adaptations to 12 days of unilateral lower limb immobilization (ULI) in young, healthy humans. Previous studies have used other models to mimic a deconditioned state such as paraplegia, simulated micro gravity and bed rest; however, such models are also associated with factors that are not physiologically applicable to normal deconditioning in the able-bodied population. Fifteen young, healthy participants [age: 20.6±0.51 (mean ± SEM)] participated in the 12-day knee-braced immobilization period that consisted of PRE and 12-DAY time point testing sessions. Measurements of supine common carotid, popliteal and common femoral artery cross sectional compliance as well as popliteal artery endothelial function (using flow mediated vasodilation (FMD)) were acquired prior to the 12-day immobilization (PRE) and on the 12th day of the immobilization (12-DAY). Arterial characteristics of the Immobilized legs (IMM) and NON-Immobilized (NIM) legs were assessed by echo Doppler ultrasound and applanation tonometry.</p> <p> Resting carotid artery cross sectional compliance and blood flow showed no change throughout the 12-day time period, (Compliance: PRE = 0.001209 ± 0.000067 mm^2/mmHg, 12-DAY= 0.001230 ± 0.00085 mm^2/mmHg; Blood Flow: PRE = 242.8±14.2 mL/min, 12-DAY = 226.0±14.27 mL/min). Popliteal artery cross sectional compliance decreased significantly over the 12 day time period in both legs (p<0.05) (IMM PRE = 5.7±0.4 10^-4mm^2/mmHg, IMM 12-DAY = 3.8±0.4 10^-4mm^2/mmHg; NIM PRE= 6.7±0.9 10^-4mm^2/mmHg, NIM 12-DAY = 5.5±0.6 10^-4mm^2/mmHg). Common femoral artery cross sectional compliance decreased in the immobilized leg but not in the non-immobilized leg (p<0.05) over 12 days of immobilization (PRE= 1.2±0.1 10^-4mm^2 /mmHg, 12-DA Y =: 0. 79±0.1 10^-4mm^2/mmHg). Neither popliteal nor common femoral artery mean blood flow changed throughout the 12 days of immobilization. Popliteal arterial mean diameter decreased significantly over time in both the IMM and NIM legs showing greater decreases in the IMM leg, while common femoral arterial mean diameter decreased in both the IMM and NIM legs through the 12 days (Popliteal: IMM PRE = 0.57±0.02 cm, IMM 12-DAY = 0.50±0.02 cm; NIM PRE = 0.59±0.02 cm, NIM 12-DAY = 0.55±0.02 cm; Common Femoral IMM PRE = 0.83±0.04 cm, IMM 12-DAY = 0.77±0.03 cm; NIM PRE = 0.81±0.03 cm, NIM 12-DAY = 0.77±0.03 cm). Popliteal artery endothelial function, calculated as both relative FMD and FMD normalized to shear stress, increased (p<0.05) throughout the 12 days in the immobilized leg while showing no change in the non-immobilized leg (Relative FMD: IMM PRE 6.0 ± 1.4%, IMM 12-DAY = 12.6 ± 2.7%; NIM PRE = 5.8 ± 1.4%, NIM 12-DAY = 8.3 ± 1.6 %; Normalized FMD: IMM PRE = 0.023 ± 0.007%/^sec-1, IMM 12-DAY = 0.037 ± 0.008%/^sec-1; NIM PRE = 0.016 ± 0.003%/^sec-1, NIM 12-DAY = 0.022 ± 0.004%/^sec-1).</p> <p> In conclusion, 12 days of deconditioning by ULI was able to cause structural and functional changes in the arteries of the immobilized leg, but not the central elastic artery in the neck in healthy young humans. Specifically in the legs, a decrease in arterial compliance, increases in mean blood velocity and increases in endothelial function were noted, with no change in volumetric blood flow. Surprisingly, our results suggest, with regards to endothelial function, that the vascular effects of deconditioning are not simply the inverse of exercise training which also shows increases in endothelial function. Thus the present study concludes that there exists a very short time course to arterial adaptations in healthy young humans with significant changes within the vasculature occurring within 12 days of deconditioning.</p> / Thesis / Master of Science (MSc)

<p> We aimed to examine the satellite cell response and the potential of HGF signaling in mediating satellite cell activation and proliferation. To achieve this, we determined the time course of satellite cell activation and expression of HGF, HGFA, HAI-l, HAI-2 and the MRFs in skeletal muscle, as well as HGF protein in the blood, before and over five days following an acute bout of eccentrically-biased exercise. Eight recreationally active participants (20.6 ± 2.1 y; 180.5 ± 5.2 cm; 81.4 ± 9.8 kg) were recruited for the study. Subjects were required to perform 300 eccentric contractions involving the quadriceps femoris muscles at 180 °/s, over a 60° range of motion with a randomly selected leg. A baseline biopsy (PRE) was taken from the opposite leg. Muscle and blood samples were taken before the exercise (PRE) and at 4 h (T4), 24 h (T24), 72 h (T72) and 120 h (T120) following the exercise. The exercise protocol resulted in an increase in the number of satellite cells (N-CAM labeled cells), expressed both relative to myofiber number and relative to total myonuclei, between PRE and T4 which was sustained over the time course (p<0.001). Further increases in N-CAM labeled cells, expressed relative to myofibre cross-section, were observed between T4 and T24 (p=0.01) and between T4 and T72 (p=0.002). Myf5 mRNA expression increased significantly from both PRE and T4 by T24 (p=0.04). MyoD mRNA increased significantly from PRE by T4 (p=0.02). Myogenin mRNA increased significantly at T24 versus PRE (p=0.02). No significant change was observed over time for MRF4. HGF protein increased significantly in serum from baseline (PRE) to T4 (p=0.04). Active HGF protein was detected in skeletal muscle at rest (14.4±1.3 avg IDV/actin avg IDV) and tended to increase from PRE to T24 (p=0.12). HGFA protein increased significantly from PRE to T24 (p=0.04). HAI-2 increased significantly from PRE at T72 (p=0.03) and T120 (p=0.04). HAI-1 protein increased significantly from PRE to T24 (p=0.02). HAI-2 (32 kDa) increased significantly from baseline (PRE) by T24 (p=0.03), and also by T72 and T120 (p=0.02). HAI-2 (28 kDa) protein showed no significant change over time HGF, HGFA, HAI-1, and HAI-2 transcripts were undetected over the time course. We conclude that a single bout of high-intensity exercise is sufficient to activate satellite cells, which may involve both a local and systemic response to exercise-induced injury. Furthermore, we propose that HGF signaling plays an important role in the regulation of satellite cells in the post exercise period.</p> / Thesis / Master of Science (MSc)

Background: Brown adipose tissue (BAT) preferentially oxidizes stored triglycerides (TAGs) to generate heat during acute exposure to cold. However, the time course of its activation is not well described as we are currently limited to BAT measurements before and after an acute stimulus. Magnetic resonance imaging (MRI) is a preferred modality to uncover such evidence, as it estimates TAG content via fat fraction (FF), and permits repeat scans in the same subject. As such, serial FF measurements in a defined BAT region of interest during a uniform whole-body temperature challenge is warranted. Objectives: The first objective of this study was to assess the pattern of change in supraclavicular (SCV) BAT and posterior neck subcutaneous adipose tissue (SAT; a region with an unestablished role in non-shivering thermogenesis) FF during a mild cold exposure in adult males. The second objective was to evaluate if indices of body composition were related to the pattern of cold-induced change in SCV BAT FF. The final objective was to assess the influence of warming immediately following cooling on these changes. Methods: Twelve males between the ages of 19 and 28 were recruited to this cross-sectional study. Users of tobacco, nicotine, and/or alcohol, those with contraindications for magnetic resonance imaging (MRI), and diseases, surgeries, and/or medications associated with thermogenesis were excluded. There were two study visits in total. During the initial visit, anthropometric measurements were carried out in triplicate (i.e. height and weight to determine body mass index (BMI), and body composition measurements (i.e. % body total fat and lean mass (kg)) were obtained using Dual Emission X-Ray Absorptiometry. Within 30 days of this initial visit, subjects attended a time course MRI session. At this visit, participants underwent standardized cold (3-hours at 18°C) and subsequent warm (30 minutes at 32°C) exposures using a water-perfused suit while lying in a 3 Tesla MRI scanner, and the temperature of the water entering and leaving the suit was recorded throughout. FF in the SCV region and posterior neck SAT was measured at defined intervals during both temperature challenges. Separate time course plots of the mean reduction in FF from baseline were constructed for the cooling and warming phases. For the first objective, the rate and magnitude of FF changes in SCV BAT and posterior neck SAT over defined time intervals were determined through calculations of slope and area under the curve (AUC), respectively. Identification of the earliest point of change from baseline, and the point at which changes were no longer different from those measured after 3 hours of cooling, were accomplished through paired comparisons using a random-slope linear mixed model with measures at 0 minutes and 180 minutes used as the reference values, respectively. A random-intercept multilevel regression model was used to define the cold-induced change in FF over time. For the second objective, a Spearman rank-order correlation assessed the association between indices of body composition (i.e. BMI and % total body fat) and indices of BAT activity (i.e. AUC and FF reduction) at time points of interest as identified by objective 1. Results: The mean±SD of BMI, LMI, and % total body fat were 24.7±2.8kg/m2, 17.6±1.6kg/m2 and 25.0±7.4%, respectively. Seven of the twelve subjects completed three hours of cold exposure (58.3%), and a further five endured at least one hour. A significant cold-induced reduction in SCV BAT FF was detected at 10 minutes following the onset of cold exposure (mean difference = -1.6%; p=0.005), and changes in FF beyond 30 minutes of cooling were similar to those measured after three hours (p<0.05). Meanwhile, the posterior neck SAT did not experience significant cold-induced changes in FF. A novel attempt at identifying a quadratic model to predict one’s BAT-specific response to a cold challenge was carried out, and the intercept, time, time2, and intraclass correlation coefficient (i.e. parameters which described the relationship between FF and time) were highly significant (p<0.001). Although every participant had a measurable decline in FF, those with a higher BMI and % body fat had a smaller magnitude of change throughout the time course. In particular, a strong negative correlation between BMI and AUC FF decline existed as soon as 10 minutes following the onset of cold (rho=-0.786), indicating that those with a lower BMI had a larger magnitude of change in SCV BAT FF at this point. Finally, warming did not visually influence the trajectory of SCV BAT FF. Limitations: Only seven of the twelve participants completed the full 180 minutes of cold exposure, which further limited the already low statistical power of this study. Moreover, complementary measures of BAT activity, such as energy expenditure, and objective measurements of shivering, such as electromyography, could not be evaluated. Conclusions: These findings suggest that significant cold-induced changes in BAT FF occur much sooner than three hours. Thus, a shorter duration of cold exposure may be considered in future studies using MRI to detect BAT activity, as this could increase the feasibility of gathering larger and younger sample populations. / Thesis / Master of Science (MSc)

No / The right temporoparietal cortex plays a critical role in body representation. Here, we applied repetitive transcranial magnetic stimulation (rTMS) over right extrastriate body area (EBA) and temporoparietal junction (TPJ) to investigate their causative roles in perceptual representations of one's own and others' body. Healthy women adjusted size-distorted pictures of their own body or of the body of another person according to how they perceived the body (subjective task) or how others perceived it (intersubjective task). In keeping with previous reports, at baseline, we found an overall underestimation of body size. Crucially, EBA-rTMS increased the underestimation bias when participants adjusted the images according to how others perceived their own or the other woman's body, suggesting a specific role of EBA in allocentric body representations. Conversely, TPJ-rTMS increased the underestimation bias when participants adjusted the body of another person, either a familiar other or a close friend, in both subjective and intersubjective tasks, suggesting an involvement of TPJ in representing others' bodies. These effects were body-specific, since no TMS-induced modulation was observed when participants judged a familiar object. The results suggest that right EBA and TPJ play active and complementary roles in the complex interaction between the perceptions of one's own and other people's body.

High levels of lactate are positively associated with the prognosis and mortality in patients with heart attack. Endothelial-to-mesenchymal transition (EndoMT) plays an important role in cardiac fibrosis. Here, we report that lactate exerts a previously unknown function that increases cardiac fibrosis and exacerbates cardiac dysfunction by promoting EndoMT following myocardial infarction (MI). Treatment of endothelial cells with lactate disrupts endothelial cell function and induces mesenchymal-like function following hypoxia by activating the TGF-β/Smad2 pathway. Mechanistically, lactate induces an association between CBP/p300 and Snail1, leading to lactylation of Snail1, a TGF-β transcription factor, through lactate transporter monocarboxylate transporter (MCT)-dependent signaling. Inhibiting Snail1 diminishes lactate-induced EndoMT and TGF-β/Smad2 activation after hypoxia/MI. The MCT inhibitor CHC mitigates lactate-induced EndoMT and Snail1 lactylation. Silence of MCT1 compromises lactate-promoted cardiac dysfunction and EndoMT after MI. We conclude that lactate acts as an important molecule that up-regulates cardiac EndoMT after MI via induction of Snail1 lactylation.

Skeletal muscle is a primary contributor to body mass and whole-body energy metabolism. It is an adaptive tissue with the ability to fluctuate in size and mechanical properties in response to stimulus. Health conditions involving chronic elevated inflammation levels often feature metabolic inflexibility and losses in skeletal muscle mass. Mononuclear stem cells, termed satellite cells, are mitotic and serve to donate nuclei to muscle fibers to enable skeletal muscle adaptation. Despite the well-characterized nature of satellite cell activation, proliferation, and differentiation, the underlying mechanisms regulating this process is not fully understood. Recent characterization of cytokines secreted by skeletal muscle in an endocrine type fashion has led to discoveries of inflammatory cytokines influencing satellite cell function. However, how the autocrine production and secretion of these cytokines during proliferation and differentiation in humans and their correlation with myogenic transcription factors is not well understood. Our study used satellite cells cultured from the vastus lateralis of 12 male human research subjects, and ELISA analysis to measure levels of TNF-α and IL-6 across proliferation, early differentiation, and late differentiation. Additionally, mRNA levels of Pax7, MyoD, myogenin, IL-6, TNF-α, and TGF-β were assessed in satellite cells cultured from a subset of two endurance trained and two sedentary individuals from the larger group of 12 human subjects. The novelty of our study is the large number of human research subjects and simultaneous analysis of inflammatory cytokine secretion, mRNA inflammatory cytokine expression, and myogenic transcription factor mRNA expression. Results showed an 83% decrease in IL-6 protein secretion 24 hours after exposure to differentiation media (p-value <0.05) before increasing 50-fold after 7 day of exposure to differentiation media (p-value < 0.05). Myogenin and TGF-β mRNA expression levels were positively correlated (R2 = 0.5814, p-value < 0.0001). A negative correlation was found between IL-6 and MyoD (R2 = 0.2473, p – value = 0.0257). After 1 day of exposure to differentiation media, satellite cells from endurance trained subjects exhibited higher levels of TGF-β mRNA expression compared to sedentary satellite cells of sedentary subjects of the same age and levels of adiposity (p-value < 0.05). Results support a potential relationship in humans satellite cells between myogenic transcription factors and inflammatory cytokines, however, further study is necessary in order to investigate the underlying mechanisms behind the correlations. / Master of Science / Skeletal muscle is responsible for conscious, voluntary movement. In addition, the tissue is responsible for the majority of energy expenditure in the human body. Skeletal muscle is able to adapt to exercise programs through the fusion of undifferentiated stem cells – called satellite cells – in the skeletal muscle fiber. In long-term diseased conditions, the immune response involves chronic rises in inflammation and results in the loss of skeletal muscle and corresponding loss of ability to move. A shorter rise in inflammation is also linked with the positive exercise response. Our study features satellite cells harvested from muscle samples of 12 male human research participants. We were interested in evaluating the relationships between the expression and secretion of two proteins associated with inflammation and regulation of the satellite cell cycle. The two proteins of interest in our study are tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). We also measure the gene expression of another inflammatory protein, transforming growth factor beta (TGF-β). In order to know where the cells were in their life cycle, we measured expression of genes associated with the division (Pax7), early fusion (MyoD), and late fusion of satellite cells (myogenin). Our study found a decrease in IL-6 secretion and expression as the process of satellite cells turning into muscle fibers was initiated. Additionally, a 50-fold increase in IL-6 expression was found at day 7 compared to day 0 of the satellite cell cycle. Additionally, we found a positive correlation between TGF-β and myogenin and a negative correlation between IL-6 and MyoD. Although we found correlations between satellite cell cycle genes and inflammation genes, more research is necessary to see if there is a pathway causing this relationship.

No / Medicines management services provided by community pharmacists have been proposed as one means to ensure that patients receive all the medicines they may benefit from in the English National Health Service. These services may also offer ways of addressing the historic under-utilization of community pharmacists' clinical skills and expertise. Medicines management services differ significantly from the dispensing and medicines sales roles traditionally associated with community pharmacy, particularly in relation to the provision for pharmacists to make recommendations to both patients and doctors about pharmacological treatment and lifestyle management. This paper describes patients' experiences of a medicines management service provided by community pharmacists for people with coronary heart disease, delivered in England. It draws on findings from semistructured, face-to-face interviews with 49 patients recruited from pilot sites delivering the service. Findings suggest that although patients cautiously welcomed the opportunity to consult with a pharmacist about their medicines, they had reservations about them making recommendations about treatment, and many still regarded the doctor as the health professional 'in charge' of their medicines. The implications of these findings are discussed in light of the developing sociological literature on pharmacy and medicines usage.

No / When formulating an estimate of event time, the human sensory system has been shown to possess a degree of perceptual flexibility. Specifically, the perceived relative timing of auditory and visual stimuli is, to some extent, a product of recent experience. It has been suggested that this form of sensory recalibration may be peculiar to the audiovisual domain. Here we investigate how adaptation to sensory asynchrony influences the perceived temporal order of audiovisual, audiotactile and visuotactile stimulus pairs. Our data show that a brief period of repeated exposure to asynchrony in any of these sensory pairings results in marked changes in subsequent temporal order judgments: the point of perceived simultaneity shifts toward the level of adaptation asynchrony. We find that the size and nature of this shift is very similar in all three pairings and that sensitivity to asynchrony is unaffected by the adaptation process. In light of these findings we suggest that a single supramodal mechanism may be responsible for the observed recalibration of multisensory perceived time.

No / The luminance and colour gradients across an image are the result of complex interactions between object shape, material and illumination. Using such variations to infer object shape or surface colour is therefore a difficult problem for the visual system. We know that changes to the shape of an object can affect its perceived colour, and that shading gradients confer a sense of shape. Here we investigate if the visual system is able to effectively utilise these gradients as a cue to shape perception, even when additional cues are not available. We tested shape perception of a folded card object that contained illumination gradients in the form of shading and more subtle effects such as inter-reflections. Our results suggest that observers are able to use the gradients to make consistent shape judgements. In order to do this, observers must be given the opportunity to learn suitable assumptions about the lighting and scene. Using a variety of different training conditions, we demonstrate that learning can occur quickly and requires only coarse information. We also establish that learning does not deliver a trivial mapping between gradient and shape; rather learning leads to the acquisition of assumptions about lighting and scene parameters that subsequently allow for gradients to be used as a shape cue. The perceived shape is shown to be consistent for convex and concave versions of the object that exhibit very different shading, and also similar to that delivered by outline, a largely unrelated cue to shape. Overall our results indicate that, although gradients are less reliable than some other cues, the relationship between gradients and shape can be quickly assessed and the gradients therefore used effectively as a visual shape cue.