Life Sciences Commons^™

Transplantation Of Pediatric Renal Allografts From Donors Less Than 10 Kg, Nickolas Mitrou, Shahid Aquil, Marie Dion, Vivian Mcalister, Alp Sener, Patrick P. Luke

Anatomy and Cell Biology Publications

Few transplant programs use kidneys from donors with body weight (BW) BW < 10 kg would provide similar transplant outcomes to larger grafts. All pediatric en bloc renal transplants performed at our center between 2001 and 2017 were reviewed (N = 28). Data were stratified by smaller (donor BW < 10 kg; n = 11) or larger donors (BW > 10 kg; n = 17). Renal volume was assessed during follow-up with ultrasound. Demographic characteristics were similar between the 2 groups of recipients. After mean follow-up of 44 months (smaller donors) and 124 months (larger donors), graft and patient outcomes were similar between groups. Serum creatinine at 1, 3, and 5 years was no different between groups. At 1 day posttransplant, mean total renal volume in the smaller donors was 28 +/- 9 mm(3) vs 45 +/- 12 mm(3) (P < .01). By 3 weeks, it was 53 +/- 19 mm(3) (smaller donors) versus 73 +/- 19 mm(3) (larger donors) (P = NS). Complication rates were similar between both groups with 1 case of venous thrombosis in the smaller group. With experience, outcomes are equivalent to those from larger pediatric donors.

Fast And Slow-Twitching Muscles Are Differentially Affected By Reduced Cholinergic Transmission In Mice Deficient For Vacht: A Mouse Model For Congenital Myasthenia, Matheus P.S. Magalhaes-Gomes, Marco A.M. Prado

Anatomy and Cell Biology Publications

Congenital myasthenic syndromes (CMS) result from reduced cholinergic transmission at neuromuscular junctions (NMJs). While the etiology of CMS varies, the disease is characterized by muscle weakness. To date, it remains unknown if CMS causes long-term and irreversible changes to skeletal muscles. In this study, we examined skeletal muscles in a mouse line with reduced expression of Vesicular Acetylcholine Transporter (VAChT, mouse line herein called VAChT-KDHOM). We examined this mouse line for several reasons. First, VAChT plays a central function in loading acetylcholine (ACh) into synaptic vesicles and releasing it at NMJs, in addition to other cholinergic nerve endings. Second, loss …

Pannexin 1 Regulates Adipose Stromal Cell Differentiation And Fat Accumulation, Vanessa R. Lee, Kevin J. Barr, John J. Kelly, Danielle Johnston, Cody F.C. Brown, Kevin P. Robb, Samar Sayedyahossein, Kenneth Huang, Robert Gros, Lauren E. Flynn, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexin 1 (Panx1) is a channel-forming glycoprotein important in paracrine signaling and cellular development. In this study, we discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain and blood markers of obesity as compared to WT controls, except for an increase in glucose and insulin levels. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory …

First Canadian Experience With Robotic Laparoendoscopic Single-Site Vs. Standard Laparoscopic Living-Donor Nephrectomy: A Prospective Comparative Study, Patrick P Luke, Shahid Aquil, Bijad Alharbi, Hemant Sharma, Alp Sener

Anatomy and Cell Biology Publications

INTRODUCTION: We aimed to compare the outcomes of robotic laparoendoscopic single-site living donor nephrectomy (R-LESS LDN) vs. standard laparoscopic living donor nephrectomy (LLDN).

METHODS: Between October 2013 and November 2015, 39 patients were allocated to either standard LLDN (n=25) or R-LESS LDN (n=14). Patient demographics, perioperative outcomes, analgesic requirement, visual analogue scale of pain at postoperative days 1, 3, 7, and 30, and a health-related quality of life and body image questionnaire were prospectively collected.

RESULTS: There were no significant differences in demographics and intraoperative outcomes between the two cohorts. The R-LESS LDN cohort had lower analgesic requirement (p=0.002) and …

Learning Expands The Preplanning Horizon In Finger Sequence Tasks, Neda Kordjazi

Electronic Thesis and Dissertation Repository

Many everyday skills involve the production of complex sequences of movements. However, the dynamics of the interplay between action selection and execution processes in sequential movements is poorly understood.Here, we set out to investigate the extent to which information regarding upcoming actions is utilized by the motor system to preplan into the future and furthermore, how this ability is influenced by learning. We designed a finger sequence taskwhere participants were shown only a fixed number of upcoming cues regarding future presses in every trial (viewing window, W). W varied between 1 (next digit revealed with pressing the current digit – …

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain

Electronic Thesis and Dissertation Repository

Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with …

Cardiodynamic Associations With Resilience In Undergraduate Students And The Effect Of A Mentorship Intervention, Rachel J. Knetsch

Electronic Thesis and Dissertation Repository

The National College Health Assessment (NCHA) indicates that a majority of Canadian university students report feeling overwhelmed, stressed, and anxious during their undergraduate studies. Resilience refers to positive adaptation, or the ability to maintain or regain mental health, despite experiencing adversity (Herrman et al., 2011). While autonomic indices have been used to describe chronic physiological stress, the role of heart rate variability (HRV) as an index of resilience remains unclear. This research tested the hypotheses that (1) there is a relationship between HRV and resilience scoresand (2) a mentorship intervention will improve HRV and resilience outcomes. Fifty-seven first year students …

A Comprehensive Catalog Of Post-Translational Modifications Of Drosophila Melanogaster Hox Protein, Sex Combs Reduced, Anirban Banerjee

Electronic Thesis and Dissertation Repository

During formation of the anterior-posterior axis, Homeotic selector (HOX) proteins determine the identity of Drosophila body segments. HOX proteins are transcription factors that regulate gene expression during development. Besides a highly conserved DNA-binding homeodomain (HD), HOX proteins also contain functionally important, evolutionarily conserved small motifs. These short motifs found in HOX proteins may be Short Linear Motifs (SLiMs). SLiMs are proposed to be sites of phosphorylation and this may regulate the activity of HOX proteins. The primary aim of this work was to develop a comprehensive catalogue of the sites of phosphorylation and other post-translational modifications (PTMs) for Fushi tarazu …

The 2Β Insert Perturbs Folding, Stability And Hydrophobic Exposure Of Stromal Interaction Molecules, Steve Chung

Electronic Thesis and Dissertation Repository

Stromal interaction molecule (STIM)1 and 2 regulate agonist-induced and basal cytosolic calcium (Ca2+) levels through oligomerization and translocation to endoplasmic reticulum (ER)-plasma membrane (PM) junctions. At these junctions, the STIM cytosolic coiled-coil domains couple to PM Orai1 protein subunits to form Ca2+ released activated Ca2+ (CRAC) channels that facilitate store-operated Ca2+ entry (SOCE). One splice variant of STIM2, STIM2β, contains an extra 8-residue (2β insert) located within the coiled-coils and inhibits SOCE through an unresolved mechanism, adding another layer of complexity to Ca2+ regulation in mammals. I hypothesize that the 2β insert perturbs the coiled-coil conformation and dynamics commensurate with …

The Role Of Hand1 In The Development Of The Lateral Plate Mesoderm In Xenopus, Victoria A. Deveau

Electronic Thesis and Dissertation Repository

The transcription factor hand1 is expressed in the heart, lateral plate mesoderm (LPM) and neural crest cells during development. As Hand1-null mice die early in embryogenesis, identification of the precise role of Hand1 in development is difficult. In Xenopus, we observed that hand1 expression patterns correlates very closely with development of LPM derivatives, leading us to hypothesize that hand1 is required for normal LPM development. Using hand1 knockdown and overexpression models in Xenopus, development of LPM derivatives were assessed by whole mount in situ hybridization. I found that hand1 is required for proper heart morphogenesis. Furthermore, hand1 …

The Effects Of Perceived Predation Threat On Stress Response And Memory In Birds, Chlöe S. N. Carter

Electronic Thesis and Dissertation Repository

This study examined how perception of predator cues, across three sensory modalities, affects physiology and behaviour of songbirds. I hypothesized that the perception of predator threat would elicit physiological and behavioural responses in both acute and chronic exposure conditions. My first study examined the responses of wild-caught black-capped chickadees (Poecile atricapillus) and house sparrows (Passer domesticus), as well as lab-bred zebra finches (Taeniopygia guttata), to acute predation cue exposure by coding video recorded behaviour and corticosterone analysis. My second study examined changes in black-capped chickadees’ foraging behaviour and memory retention after chronic exposure to …

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

Adaptation Mechanisms Of Two-Spotted Spider Mite, Tetranychus Urticae, To Arabidopsis Indole Glucosinolates, Golnaz Salehipourshirazi

Electronic Thesis and Dissertation Repository

The two-spotted spider mite Tetranychus urticae Koch is a key agricultural pest that causes significant yield losses in a wide range of economically important crops. Rapid development of resistance to several classes of pesticides in T. urticae necessitates introduction of alternative management strategies to control this pest. Indole glucosinolates (IGs) are secondary metabolites found in Brassicaceae plants (including Arabidopsis thaliana) that have been shown to be effective against T. urticae and could be potential candidates to control spider mites. However, a laboratory population selected on IG-containing Arabidopsis was able to evolve adaptation to this plant. The overall objective of …

Characterizing The Sensorimotor Properties Of A Rapid Visuomotor Reach Movement On Human Upper Limb Muscles, Chao Gu

Electronic Thesis and Dissertation Repository

Humans and other primates rely heavily on vision as a primary sensory input to drive our upcoming volitional motor actions. Our motor system makes so many of these visual-to-motor transformations that they become ubiquitous in our daily lives. However, a central question in systems neuroscience is how does the brain perform these transformations?

Reaching movements have been an ideal model for studying volitional motor control in primates. Broadly, these visually-guided reach movements contain three inherent sensorimotor components: an action selection component, a motor execution component, and a motor learning component. A core assumption is that as reach movements become more …

Cannabinoid Transmission In The Basolateral Amygdala Modulates Prefrontal Cortex And Ventral Hippocampal Activity, Brian J. Pereira

Electronic Thesis and Dissertation Repository

The cannabinoid system is important for maintaining neuron-to-neuron communication within the mammalian brain. One of the most commonly used substances to alter the cannabinoid system is cannabis. Individuals who are exposed to cannabis report having dissociable effects; both positive and negative. High amounts of THC have been commonly associated with the negative effects of cannabis, whereas CBD can be used to counter these. Pre-clinical evidence suggests that the combination of the two compounds can produce a therapeutic benefit for individuals who are susceptible to the effects of THC. The present study investigates whether the combination of THC+CBD can prevent electrophysiological …

Dna Sequence Classification: It’S Easier Than You Think: An Open-Source K-Mer Based Machine Learning Tool For Fast And Accurate Classification Of A Variety Of Genomic Datasets, Stephen Solis-Reyes

Electronic Thesis and Dissertation Repository

Supervised classification of genomic sequences is a challenging, well-studied problem with a variety of important applications. We propose an open-source, supervised, alignment-free, highly general method for sequence classification that operates on k-mer proportions of DNA sequences. This method was implemented in a fully standalone general-purpose software package called Kameris, publicly available under a permissive open-source license. Compared to competing software, ours provides key advantages in terms of data security and privacy, transparency, and reproducibility. We perform a detailed study of its accuracy and performance on a wide variety of classification tasks, including virus subtyping, taxonomic classification, and human haplogroup assignment. …

The Post-Fledging Survival And Movements Of Juvenile Barn Swallows (Hirundo Rustica): An Automated Telemetry Approach, Dean R. Evans

Electronic Thesis and Dissertation Repository

For migratory songbirds, population dynamics are primarily influenced by juvenile or first year survival, but survival between fledging and fall migration is particularly important. Unfortunately, our knowledge of this post-fledging period is largely limited due to the difficulty of tracking juveniles outside the nest. For this thesis, I used automated radio telemetry to track the survival and post-fledging movements of 216 juvenile Barn Swallows (Hirundo rustica) from fledging up until departure for autumn migration in 2016-2017. Average apparent survival was 42% for both broods and nestlings in better body condition had higher survival. Nestlings from second broods migrated …

Hierarchical Variation In Cellulose Decomposition Across Southern Ontario Reference Streams, Jenna R. Webb

Electronic Thesis and Dissertation Repository

The cotton strip assay (CSA) has been promoted as a method of incorporating functional indicators into standardized river assessments by study of organic-matter decomposition. However, operationalization of the CSA as an indicator requires testing the spatial and temporal controls of variance associated with decomposition of cotton strips at regional reference sites. I conducted a hierarchically structured study of decomposition rates in Ontario, Canada. Cotton strips were deployed during the spring, summer and fall in pool and riffle habitats of 22 streams located in three distinct physiographic regions. Partitioning of variation among hierarchical scales associated with rates of decomposition were examined …

The Effect Of Anoxia On Mitochondrial Function In A Hibernator (Ictidomys Tridecemlineatus), Leah Hayward

Electronic Thesis and Dissertation Repository

Hibernation protects mammalian tissues against ischemia-reperfusion injury, but the underlying biochemical mechanisms are unknown. I hypothesized that the mechanisms allowing for mitochondrial metabolic flexibility during hibernation permit anoxia tolerance and contribute to tissue ischemia-reperfusion tolerance. I assessed mitochondrial performance before and after five minutes of anoxia in liver mitochondria isolated from thirteen-lined ground squirrels. I compared this anoxia effect among animals that were summer active (SA), or during hibernation (in torpor or interbout euthermia; IBE). Anoxia decreased state 3 respiration in all groups, but mitochondria isolated from torpid squirrels were least affected; these decreases paralleled decreased activity of electron transport …

Overwintering Biology Of The Brown Marmorated Stink Bug, Halyomorpha Halys (Hemiptera: Pentatomidae), John Ciancio

Electronic Thesis and Dissertation Repository

The invasive crop pest Halyomorpha halys has been established in Ontario since 2012 and poses a significant threat to Canadian agriculture. I investigated the tolerance of H. halys to three stressors - low temperatures, desiccation, and energy depletion - in addition to investigating the role of lab-induced diapause in enhancing stress tolerance. Overwintering H. halys depress their supercooling point to -15.4 °C and LT₅₀ to -17.5 °C after acute (1 h) exposure, however they do not encounter these temperatures while overwintering indoors. Moreover, overwintering H. halys maintain their water balance through a reduction of water loss rates, while conserving …

Lung-Derived Selectins Interact With Cd44 And Enhance The Migration Of Breast Cancer Cells, Sami U. Khan

Electronic Thesis and Dissertation Repository

The lung is among the deadliest sites of breast cancer metastasis. Previous work from our laboratory demonstrated that aggressive CD44-expressing breast cancer cells preferentially metastasize to the lung in vivo, and observed the presence of multiple CD44-interacting proteins in the lung including E-, L- and P-selectin. We hypothesized that lung-derived selectins promote breast cancer migration and/or growth via interactions with CD44. Using an ex vivo model of the soluble lung-microenvironment, we demonstrate that lung-derived selectins enhance in vitro migration but not proliferation of breast cancer cells. Co-immunoprecipitation experiments reveal that CD44 expressed by breast cancer cells in vitro interacts …

The Role Of Cholinergic Midbrain Neurons In Startle And Prepulse Inhibition, Erin Azzopardi, Andrea G. Louttit, Cleusa Deoliveira, Steven R, Laviolette, Susanne Schmid

Anatomy and Cell Biology Publications

One of the two major cholinergic centers of the mammalian brain is located in the midbrain, i.e., the pedunculopontine tegmentum (PPTg) and the adjacent laterodorsal tegmentum. These cholinergic neurons have been shown to be important for e.g., arousal, reward associations, and sleep. They also have been suggested to mediate sensorimotor gating, measured as prepulse inhibition of startle (PPI). PPI disruptions are a hallmark of schizophrenia and are observed in various other psychiatric disorders, where they are associated with, and often predictive of, other cognitive symptoms. PPI has been proposed to be mediated by a short midbrain circuitry including inhibitory cholinergic …

Als Yeast Models-Past Success Stories And New Opportunities, Sonja E. Di Gregorio, Martin L. Duennwald

Anatomy and Cell Biology Publications

In the past two decades, yeast models have delivered profound insights into basic mechanisms of protein misfolding and the dysfunction of key cellular pathways associated with amyotrophic lateral sclerosis (ALS). Expressing ALS-associated proteins, such as superoxide dismutase (SOD1), TAR DNA binding protein 43 (TDP-43) and Fused in sarcoma (FUS), in yeast recapitulates major hallmarks of ALS pathology, including protein aggregation, mislocalization and cellular toxicity. Results from yeast have consistently been recapitulated in other model systems and even specimens from human patients, thus providing evidence for the power and validity of ALS yeast models. Focusing on impaired ribonucleic acid (RNA) metabolism …

Everolimus In Advanced Breast Cancer: A Systematic Review And Meta-Analysis, J Raphael, C Lefebvre, A Allan, J Helou, G Boldt, T Vandenberg

Anatomy and Cell Biology Publications

No abstract provided.

Behavioral Plasticity Of Audiovisual Perception: Rapid Recalibration Of Temporal Sensitivity But Not Perceptual Binding Following Adult-Onset Hearing Loss, Ashley L. Schormans, Brian L. Allaman

Anatomy and Cell Biology Publications

The ability to accurately integrate or bind stimuli from more than one sensory modality is highly dependent on the features of the stimuli, such as their intensity and relative timing. Previous studies have demonstrated that the ability to perceptually bind stimuli is impaired in various clinical conditions such as autism, dyslexia, schizophrenia, as well as aging. However, it remains unknown if adult-onset hearing loss, separate from aging, influences audiovisual temporal acuity. In the present study, rats were trained using appetitive operant conditioning to perform an audiovisual temporal order judgment (TOJ) task or synchrony judgment (SJ) task in order to investigate …

Overall Survival (Os) Implications For Patients With Mcrpc Through Coverage And Adoption Of Nuclear Ar-V7 Testing By Healthcare Systems, J Hornberger, R P. Graf, M Hulling, G Attard, A Allan, R Dittamore, H Scher

Anatomy and Cell Biology Publications

No abstract provided.

Air Pollution: A Silent Common Killer For Stroke And Dementia, Mahmoud R. Azarpazhooh, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

Implementing The Proclamation Of Stroke And Potentially Preventable Dementias, Vladimir Hachinski, Detlev Ganten, Daniel Lackland, Reinhold Kreutz, Konstantinos Tsioufis, Werner Hacke

Anatomy and Cell Biology Publications

Brain health plays a central role in wellbeing and in the management of chronic diseases. Stroke and dementia pose the two greatest threats to brain health, but recent developments suggest the possibility that preventing stroke may also prevent some dementias: 1. A large population study showed a 32% decrease in the incidence of stroke and a concomitant 7% reduction in the incidence of dementia; 2. Treatment of atrial fibrillation resulted not only in stroke reduction, but a 48% decrease in dementia; 3. A hypothesis free analyses has shown that the first phase of Alzheimer disease involves vascular dysregulation, opening the …

Altered Auditory Processing, Filtering, And Reactivity N The Cntnap2 Knock-Out Rat Model For Neurodevelopmental Disorders, Kaela E. Scott, Ashley L. Schormans, Katharine Y. Pacoli, Cleusa De Oliveria, Brian L. Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Sensory processing, and auditory processing in particular, is altered in individuals with neurodevelopmental disorders such as autism spectrum disorders (ASDs). The typical maturation of the auditory system is perturbed in these individuals during early development, which may underlie altered auditory reactivity that persists in later life. Of the many genes that regulate the auditory system development, loss-of-function mutations in the CNTNAP2 gene are strongly associated with language processing deficits and ASD. Therefore, using a novel Cntnap2 knock-out rat model, we tested the impact of Cntnap2 loss on auditory processing, filtering, and reactivity throughout development and young adulthood in male and …

Endothelial Glycocalyx Shedding In Pediatric Diabetic Ketoacidosis, Rufina Ning

Electronic Thesis and Dissertation Repository

Diabetic ketoacidosis (DKA) is a state of severe insulin deficiency resulting in hyperglycemia, ketoacidosis, and inflammation. Children with DKA have an increased risk of microvascular complications (e.g. stroke). The glycocalyx maintains the anti-thrombotic properties of endothelial cells (ECs), however the glycocalyx status is unknown in DKA. We quantified major glycocalyx components: hyaluronic acid (HA), heparan sulfate (HS), chondroitin sulfate (CS), and syndecan-1 in DKA plasma and correlated them with DKA severity. HA/HS were significantly increased in the plasma of DKA patients in comparison to insulin-controlled type-1 diabetics, but only HA correlated to DKA severity. Exogenous addition or removal of HA …