Medicine and Health Sciences Commons^™

Expression Of Ski Can Act As A Negative Feedback Mechanism On Retinoic Acid Signaling, Meaghan A. Melling, Charlotte R.C. Friendship, Trevor G. Shepherd, Thomas A. Drysdale

Paediatrics Publications

Background: Retinoic acid signaling is essential for many aspects of early development in vertebrates. To control the levels of signaling, several retinoic acid target genes have been identified that act to suppress retinoic acid signaling in a negative feedback loop. The nuclear protein Ski has been extensively studied for its ability to suppress transforming growth factor-beta (TGF-β) signaling but has also been implicated in the repression of retinoic acid signaling. Results: We demonstrate that ski expression is up-regulated in response to retinoic acid in both early Xenopus embryos and in human cell lines. Blocking retinoic acid signaling using a retinoic …

Prefrontal Neurons Of Opposite Spatial Preference Display Distinct Target Selection Dynamics., Therese Lennert, Julio C Martinez-Trujillo

Brain and Mind Institute Researchers' Publications

Neurons in the primate dorsolateral prefrontal cortex (dlPFC) of one hemisphere are selective for the location of attended targets in both visual hemifields. Whether dlPFC neurons with selectivity for opposite hemifields directly compete with each other for target selection or instead play distinct roles during the allocation of attention remains unclear. We explored this issue by recording neuronal responses in the right dlPFC of two macaques while they allocated attention to a target in one hemifield and ignored a distracter on the opposite side. Forty-nine percent of the recorded neurons were target location selective. Neurons selective for contralateral targets (58%) …

Decoding The Neural Mechanisms Of Human Tool Use., Jason P Gallivan, D Adam Mclean, Kenneth F Valyear, Jody C Culham

Brain and Mind Institute Researchers' Publications

Sophisticated tool use is a defining characteristic of the primate species but how is it supported by the brain, particularly the human brain? Here we show, using functional MRI and pattern classification methods, that tool use is subserved by multiple distributed action-centred neural representations that are both shared with and distinct from those of the hand. In areas of frontoparietal cortex we found a common representation for planned hand- and tool-related actions. In contrast, in parietal and occipitotemporal regions implicated in hand actions and body perception we found that coding remained selectively linked to upcoming actions of the hand whereas …

The Human Brain Processes Syntax In The Absence Of Conscious Awareness., Laura Batterink, Helen J Neville

Brain and Mind Institute Researchers' Publications

Syntax is the core computational component of language. A longstanding idea about syntactic processing is that it is generally not available to conscious access, operating autonomously and automatically. However, there is little direct neurocognitive evidence on this issue. By measuring event-related potentials while human observers performed a novel cross-modal distraction task, we demonstrated that syntactic violations that were not consciously detected nonetheless produced a characteristic early neural response pattern, and also significantly delayed reaction times to a concurrent task. This early neural response was distinct from later neural activity that was observed only to syntactic violations that were consciously detected. …

The Function Of The Left Angular Gyrus In Mental Arithmetic: Evidence From The Associative Confusion Effect, Roland H. Grabner, Daniel Ansari, Karl Koschutnig, Gernot Reishofer, Franz Ebner

Paediatrics Publications

While the left angular gyrus (lAG) has been repeatedly implicated in mental arithmetic, its precise functional role has not been established. On the one hand, it has been speculated that the lAG is involved in task-specific processes. On the other hand, the observation of relative deactivation during arithmetic has led to the contention that differential lAG activation reflects task-unrelated difficulty effects associated with the default mode network (DMN). Using functional magnetic resonance imaging, we investigated the neural correlates of the associative confusion effect that allowed us to dissociate effects of task difficulty and task-related arithmetic processes on lAG activation. The …

Umbilical Uptakes And Transplacental Concentration Ratios Of Amino Acids In Severe Fetal Growth Restriction, Timothy R.H. Regnault, Barbra De Vrijer, Henry L. Galan, Randall B. Wilkening, Frederick C. Battaglia, Giacomo Meschia

Paediatrics Publications

Background: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia. Methods: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group). Results: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus. The combined uptake of glucose, lactate, and AAs, expressed as nutrient/oxygen quotients, was reduced almost to 1.00 (FGR: 1.05 vs. C: 1.32, P …

Molecular Mechanisms Underlying Rb Protein Function, Frederick A. Dick, Seth M. Rubin

Paediatrics Publications

Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define …

Three-Dimensional Segmentation Of Three-Dimensional Ultrasound Carotid Atherosclerosis Using Sparse Field Level Sets., E Ukwatta, J Yuan, D Buchanan, B Chiu, J Awad, W Qiu, G Parraga, A Fenster

Medical Biophysics Publications

PURPOSE: Three-dimensional ultrasound (3DUS) vessel wall volume (VWV) provides a 3D measurement of carotid artery wall remodeling and atherosclerotic plaque and is sensitive to temporal changes of carotid plaque burden. Unfortunately, although 3DUS VWV provides many advantages compared to measurements of arterial wall thickening or plaque alone, it is still not widely used in research or clinical practice because of the inordinate amount of time required to train observers and to generate 3DUS VWV measurements. In this regard, semiautomated methods for segmentation of the carotid media-adventitia boundary (MAB) and the lumen-intima boundary (LIB) would greatly improve the time to train …

Shared Neural Substrates Of Emotionally Enhanced Perceptual And Mnemonic Vividness, Rebecca M. Todd, Taylor W. Schmitz, Josh Susskind, Adam K. Anderson

Brain and Mind Institute Researchers' Publications

It is well known that emotionally salient events are remembered more vividly than mundane ones. Our recent research has demonstrated that such memory vividness is due in part to the subjective experience of emotional events as more perceptually vivid, an effect we call emotion-enhanced vividness, or EEV. The present study built on previously reported research in which fMRI data were collected while participants rated relative levels of visual noise overlaid on emotionally salient and neutral images. Ratings of greater EEV were associated with greater activation in the amygdala, visual cortex, and posterior insula. In the present study, we measured BOLD …

On The Role Of Abnormal Dl(Co) In Ex-Smokers Without Airflow Limitation: Symptoms, Exercise Capacity And Hyperpolarised Helium-3 Mri, Miranda Kirby, Amir Owrangi, Sarah Svenningsen, Andrew Wheatley, Harvey O Coxson, Nigel A M Paterson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

BACKGROUND: The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood.

OBJECTIVE: We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD.

METHODS: We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St George's Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and …

Defining The Efficacy Of Aortic Root Enlargement Procedures: A Comparative Analysis Of Surgical Techniques, Katie L. Losenno, Jill J. Gelinas, Marjorie Johnson, Michael W. A. Chu

Anatomy and Cell Biology Publications

Background: Aortic root enlargement (ARE) procedures are believed to allow implantation of larger valve prostheses; however, little evidence exists to support the specific efficacy of various techniques. Methods: Using a cadaveric model, 20 adult (72.4 +/- 15.3 years) hearts were stratified into 4 groups based on annular diameter: <20 mm, 20-22 mm, 22-24 mm, and >24 mm. Each heart underwent an aortic valve replacement following a Nicks, Manougian, aortoventriculoplasty and modified Bentall procedure, with appropriate reversals between procedures. Results: All 4 groups experienced similar increases in annular diameter (P = 0.43) and prosthesis size implanted (P = 0.51) with each enlargement technique. The Nicks, Manougian, modified Bentall …

A Magnetic-Resonance-Imaging-Compatible Remote Catheter Navigation System., Mohammad Ali Tavallaei, Yogesh Thakur, Syed Haider, Maria Drangova

Medical Biophysics Publications

A remote catheter navigation system compatible with magnetic resonance imaging (MRI) has been developed to facilitate MRI-guided catheterization procedures. The interventionalist's conventional motions (axial motion and rotation) on an input catheter - acting as the master - are measured by a pair of optical encoders, and a custom embedded system relays the motions to a pair of ultrasonic motors. The ultrasonic motors drive the patient catheter (slave) within the MRI scanner, replicating the motion of the input catheter. The performance of the remote catheter navigation system was evaluated in terms of accuracy and delay of motion replication outside and within …

Hidden Surveillance On Consumer Health Information Websites, Jacquelyn A. Burkell, Alexandre Fortier

FIMS Publications

Behavioural tracking presents a significant privacy risk to Canadians, particularly when their online behaviours reveal sensitive information that could be used to discriminate against them. This concern is particularly relevant in the context of online health information seeking, since searches can reveal details about health conditions and concerns that the individual may wish to keep private. The privacy threats are exacerbated because behavioural tracking mechanisms are large invisible to users, and many are unaware of the strategies and mechanisms available to track online behaviour. In this project, we seek to document the behavioural tracking practices of consumer health websites, and …

Relationships Amongst Osteoarthritis Biomarkers, Dynamic Knee Joint Load, And Exercise: Results From A Randomized Controlled Pilot Study, Michael A. Hunt, Courtney L. Pollock, Virginia Byers Kraus, Tore Saxne, Sue Peters, Janet L. Huebner, Eric C. Sayre, Jolanda Cibere

Physical Therapy Publications

Background

Little is known about the relationships of circulating levels of biomarkers of cartilage degradation with biomechanical outcomes relevant to knee osteoarthritis (OA) or biomarker changes following non-pharmacological interventions. The objectives of this exploratory, pilot study were to: 1) examine relationships between biomarkers of articular cartilage degradation and synthesis with measures of knee joint load during walking, and 2) examine changes in these biomarkers following 10 weeks of strengthening exercises.

Methods

Seventeen (8 male, 9 female; 66.1 +/- 11.3 years of age) individuals with radiographically-confirmed medial tibiofemoral OA participated. All participants underwent a baseline testing session where serum and urine …

Children First: It’S Time To Change! Mental Health Promotion, Prevention, And Treatment Informed By Public Health, And Resiliency Approaches, Vicki Schwean, Susan Rodger

Journal Articles

Although the importance of healthy mental development in children and youth is not disputed, the mental health needs of far too many Canadian children are being ignored. Within the context of recent federal and provincial calls for systemic reform of the mental health care systems for children and youth, we underscore the necessity for ongoing innovation, development, education, and evaluation. This article describes our aims to establish demonstration and research sites focused on promising frameworks that draw from systems of care, public health, and resiliency approaches.

Microglia-Derived Tnfα Induces Apoptosis In Neural Precursor Cells Via Transcriptional Activation Of The Bcl-2 Family Member Puma, J. Guadagno, X. Xu, M. Karajgikar, A. Brown, S.P. Cregan

Paediatrics Publications

Neuroinflammation is a common feature of acute neurological conditions such as stroke and spinal cord injury, as well as neurodegenerative conditions such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Previous studies have demonstrated that acute neuroinflammation can adversely affect the survival of neural precursor cells (NPCs) and thereby limit the capacity for regeneration and repair. However, the mechanisms by which neuroinflammatory processes induce NPC death remain unclear. Microglia are key mediators of neuroinflammation and when activated to induce a pro-inflammatory state produce a number of factors that could affect NPC survival. Importantly, in the present study we demonstrate …

Molecular Imaging To Target Transplanted Muscle Progenitor Cells, Kelly Gutpell, Rebecca Mcgirr, Lisa Hoffman

Anatomy and Cell Biology Publications

Duchenne muscular dystrophy (DMD) is a severe genetic neuromuscular disorder that affects 1 in 3,500 boys, and is characterized by progressive muscle degeneration(1, 2). In patients, the ability of resident muscle satellite cells (SCs) to regenerate damaged myofibers becomes increasingly inefficient(4). Therefore, transplantation of muscle progenitor cells (MPCs)/myoblasts from healthy subjects is a promising therapeutic approach to DMD. A major limitation to the use of stem cell therapy, however, is a lack of reliable imaging technologies for long-term monitoring of implanted cells, and for evaluating its effectiveness. Here, we describe a non-invasive, real-time approach to evaluate the success of myoblast …

Large Area Periodic, Systematically Changing, Multishape Nanostructures By Laser Interference Lithography And Cell Response To These Topographies, Erden Ertorer, Fartash Vasefi, Joel Keshwah, Mohamadreza Najiminaini, Christopher Halfpap, Uwe Langbein, Jeffrey J. L. Carson, Douglas W. Hamilton, Silvia Mittler

Anatomy and Cell Biology Publications

The fabrication details to form large area systematically changing multishape nanoscale structures on a chip by laser interference lithography (LIL) are described. The feasibility of fabricating different geometries including dots, ellipses, holes, and elliptical holes in both x- and y- directions on a single substrate is shown by implementing a Lloyd's interferometer. The fabricated structures at different substrate positions with respect to exposure time, exposure angle and associated light intensity profile are analyzed. Experimental details related to the fabrication of symmetric and biaxial periodic nanostructures on photoresist, silicon surfaces, and ion milled glass substrates are presented. Primary rat calvarial osteoblasts …

Chronic Obstructive Pulmonary Disease: More Imaging, More Phenotyping...Better Care?, Damien Pike, Grace Parraga

Medical Biophysics Publications

No abstract provided.

Conditional Sox9 Ablation Reduces Chondroitin Sulfate Proteoglycan Levels And Improves Motor Function Following Spinal Cord Injury, William M. Mckillop, Magdalena Dragan, Andreas Schedl, Arthur Brown

Paediatrics Publications

Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation would result in reduced CSPG expression after spinal cord injury and that this would lead to increased neuroplasticity and improved locomotor recovery. Control and Sox9 conditional knock-out mice were subject to a 70 kdyne contusion spinal cord injury at thoracic …

Hd-Cnv: Hotspot Detector For Copy Number Variants., Jenna L Butler, Marjorie Elizabeth Osborne Locke, Kathleen A Hill, Mark Daley

Brain and Mind Institute Researchers' Publications

SUMMARY: Copy number variants (CNVs) are a major source of genetic variation. Comparing CNVs between samples is important in elucidating their potential effects in a wide variety of biological contexts. HD-CNV (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input. It creates a unique graphical representation of the data, as well as summary spreadsheets and UCSC (University of California, Santa Cruz) Genome Browser track files. The interval graph, when viewed with other software …

Synaptic Scaffold Evolution Generated Components Of Vertebrate Cognitive Complexity, Jess Nithianantharajah, Noboru H. Komiyama, Andrew Mckechanie, Mandy Johnstone, Douglas H. Blackwood, David St.Clair, Richard D. Emes, Louie N. Van De Lagemaat, Lisa M. Saksida, Timothy J. Bussey, Seth G. Grant

Brain and Mind Institute Researchers' Publications

The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive …

Differential Effects Of Parkinson's Disease And Dopamine Replacement On Memory Encoding And Retrieval., Alex A Macdonald, Ken N Seergobin, Adrian M Owen, Ruzbeh Tamjeedi, Oury Monchi, Hooman Ganjavi, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

Increasingly memory deficits are recognized in Parkinson's disease (PD). In PD, the dopamine-producing cells of the substantia nigra (SN) are significantly degenerated whereas those in the ventral tegmental area (VTA) are relatively spared. Dopamine-replacement medication improves cognitive processes that implicate the SN-innervated dorsal striatum but is thought to impair those that depend upon the VTA-supplied ventral striatum, limbic and prefrontal cortices. Our aim was to examine memory encoding and retrieval in PD and how they are affected by dopamine replacement. Twenty-nine PD patients performed the Rey Auditory Verbal Learning Test (RAVLT) and a non-verbal analogue, the Aggie Figures Learning Test …

African Probiotic Yoghurt Network : Western Heads East Internship Report, Emily Trudell

Business and Social Enterprise

The purpose of this report is to explain to all stakeholders, and especially Western Heads East (WHE), the progression of my internship work with APYN alongside the progression of APYN’s establishment as an organization during the second half of my internship,to provide APYN with a recordof the activities we worked on together, and tohand over the documents APYN and I produced collaboratively to APYN to help guide future organizational decisions. I will begin with a review of my planning workshop, from which my two main activities stemmed, and then provide descriptions and analysis surrounding each one in the body of …

Susceptibility To Fatty Acid-Induced Β-Cell Dysfunction Is Enhanced In Prediabetic Diabetes-Prone Biobreeding Rats: A Potential Link Between Β-Cell Lipotoxicity And Islet Inflammation, Christine Tang, Anthony E. Naassan, Astrid Chamson-Reig, Khajag Koulajian, Tracy T. Goh, Frederick Yoon, Andrei I. Oprescu, Husam Ghanim, Gary F. Lewis, Paresh Dandona, Marc Y. Donath, Jan A. Ehses, Edith Arany, Adria Giacca

Paediatrics Publications

β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity maybe synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth …

Progastrin Stimulates Colonic Cell Proliferation Via Cck2r- And Β-Arrestin-Dependent Suppression Of Bmp2, Guangchun Jin, C. Benedikt Westphalen, Yoku Hayakawa, Daniel L. Worthley, Samuel Asfaha, Xiangdong Yang, Xiaowei Chen, Yiling Si, Hongshan Wang, Yagnesh Tailor, Richard A. Friedman, Timothy C. Wang

Paediatrics Publications

Background & Aims Progastrin stimulates colonic mucosal proliferation and carcinogenesis through the cholecystokinin 2 receptor (CCK2R) - partly by increasing the number of colonic progenitor cells. However, little is known about the mechanisms by which progastrin stimulates colonic cell proliferation. We investigated the role of bone morphogenetic proteins (BMPs) in progastrin induction of colonic cell proliferation via CCK2R. Methods We performed microarray analysis to compare changes in gene expression in the colonic mucosa of mice that express a human progastrin transgene, gastrin knockout mice, and C57BL/6 mice (controls); the effects of progastrin were also determined on in vitro colonic crypt …

Mice That Express Human Interleukin-8 Have Increased Mobilization Of Immature Myeloid Cells, Which Exacerbates Inflammation And Accelerates Colon Carcinogenesis, Samuel Asfaha, Alexander N. Dubeykovskiy, Hiroyuki Tomita, Xiangdong Yang, Sarah Stokes, Wataru Shibata, Richard A. Friedman, Hiroshi Ariyama, Zinaida A. Dubeykovskaya, Sureshkumar Muthupalani, Russell Ericksen, Harold Frucht, James G. Fox, Timothy C. Wang

Paediatrics Publications

Background & Aims: Interleukin (IL)-8 has an important role in initiating inflammation in humans, attracting immune cells such as neutrophils through their receptors CXCR1 and CXCR2. IL-8 has been proposed to contribute to chronic inflammation and cancer. However, mice do not have the IL-8 gene, so human cancer cell lines and xenograft studies have been used to study the role of IL-8 in colon and gastric carcinogenesis. We generated mice that carry a bacterial artificial chromosome that encompasses the entire human IL-8 gene, including its regulatory elements (IL-8Tg mice). Methods: We studied the effects of IL-8 expression in APCmin+/- mice …

Dietary Exposures And Allergy Prevention In High-Risk Infants, Edmond S. Chan, Carl Cummings, Mark Feldman, Ruth B. Grimes, Barbara Grueger, Larry B. Pancer, Anne Rowan Legg, Ellen P. Wood, Fabian P. Gorodzinsky, Nestor Cisneros, Janet Roberts, Adelle Atkinson, Zave Chad, Marie Josée Francoeur, Linda Kirste, Douglas Mack, Marie Noel Primeau, Timothy Vander Leek, Wade Watson

Paediatrics Publications

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk for developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps …

The Health And Well-Being Of Indigenous Drug And Alcohol Workers: Results From A National Australian Survey, Ann M. Roche, Vinita Duraisingam, Allan Trifonoff, Amanda Tovell

Aboriginal Policy Research Consortium International (APRCi)

The increasing demand for alcohol and other drug (AOD) treatment services among the Australian Indigenous population, complex organisational challenges and limitations, and high unemployment rates are likely to negatively impact Indigenous AOD workers' health and well-being. Building the capacity of Indigenous AOD workers is vital, as they play a crucial role in the delivery of treatment services and offer essential support to their communities. A national online survey was conducted to examine organisational, workplace and individual factors that might contribute to levels of stress and well-being among workers who provide services to Indigenous clients. A total of 294 eligible surveys …

Development Of A 3d Ultrasound System To Investigate Post-Hemorrhagic Hydrocephalus In Pre-Term Neonates, J. Kishimoto, D. Lee, K. St. Lawrence, W. Romano, A. Fenster, S. De Ribaupierre

Anatomy and Cell Biology Publications

Clinical intracranial ultrasound (US) is performed as a standard of care on neonates at risk of intraventricular hemorrhaging (IVH) and is also used after a diagnosis to monitor for potential ventricular dilation. However, it is difficult to estimate the volume of ventricles with 2D US due to their irregular shape. We developed a 3D US system to be used as an adjunct to a clinical system to investigate volumetric changes in the ventricles of neonates with IVH. Our system has been found have an error of within 1% of actual distance measurements in all three directions and volume measurements of …