Medicine and Health Sciences Commons^™

Declining Incidence Of Stroke And Dementia: Coincidence Or Prevention Opportunity?, Luciano A. Sposato, Moira K. Kapral, Jiming Fang, Sudeep S. Gill, Daniel G. Hackam, Lauren E. Cipriano, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

The Transient Receptor Potential Melastatin 2 (Trpm2) Channel Contributes To Beta-Amyloid Oligomer-Related Neurotoxicity And Memory Impairment, Valeriy G. Ostapchenko, Megan Chen, Monica S. Guzman, Yu-Feng Xie, Natalie Lavine, Jue Fan, Flavio H. Beraldo, Amanda C. Martyn, Jillian C. Belrose, Yasuo Mori, John F. Macdonald, Vania F. Prado, Marco A. M. Prado, Michael F. Jackson

Anatomy and Cell Biology Publications

In Alzheimer's disease, accumulation of soluble oligomers of beta-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with beta-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of …

Hyperactivity And Attention Deficits In Mice With Decreased Levels Of Stress-Inducible Phosphoprotein 1 (Stip1), Flavio H. Beraldo, Anu Thomas, Benjamin Kolisnyk, Pedro H. Hirata, Xavier De Jaeger, Amanda C. Martyn, Jue Fan, Daniela F. Goncalves, Matthew F. Cowan, Talal Masood, Vilma R.. Martins, Robert Gros, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a cochaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test …

Expert And Crowd-Sourced Validation Of An Individualized Sleep Spindle Detection Method Employing Complex Demodulation And Individualized Normalization, Laura B. Ray, Stephane Sockeel, Melissa Soon, Arnaud Bore, Ayako Myhr, Bobby Stojanoski, Rhodri Cusack, Adrian M. Owen, Julien Doyon, Stuart M. Fogel

Anatomy and Cell Biology Publications

A spindle detection method was developed that: (1) extracts the signal of interest (i.e., spindle-related phasic changes in sigma) relative to ongoing "background" sigma activity using complex demodulation, (2) accounts for variations of spindle characteristics across the night, scalp derivations and between individuals, and (3) employs a minimum number of sometimes arbitrary, user-defined parameters. Complex demodulation was used to extract instantaneous power in the spindle band. To account for intra- and inter individual differences, the signal was z-score transformed using a 60 s sliding window, per channel, over the course of the recording. Spindle events were detected with a z-score …

Evidence For Differential Viral Oncolytic Efficacy In An In Vitro Model Of Epithelial Ovarian Cancer Metastasis, Jessica G. Tong, Yudith R. Valdes, John W. Barrett, John C. Bell, David Stojdl, Grant Mcfadden, J. Andrea Mccart, Gabriel E. Dimattia, Trevor G. Shepherd

Anatomy and Cell Biology Publications

Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses—Myxoma virus, double-deleted vaccinia virus, and Maraba virus—using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and …

Deletion Of Panx3 Prevents The Development Of Surgically Induced Osteoarthritis, Paxton M. Moon, Silvia Penuela, Kevin Barr, Sami Khan, Christopher L. Pin, Ian Welch, Mukundan Attur, Steven B. Abramson, Dale W. Laird, Frank Beier

Anatomy and Cell Biology Publications

© 2015, Springer-Verlag Berlin Heidelberg. Abstract: Osteoarthritis (OA) is a highly prevalent, disabling joint disease with no existing therapies to slow or halt its progression. Cartilage degeneration hallmarks OA pathogenesis, and pannexin 3 (Panx3), a member of a novel family of channel proteins, is upregulated during this process. The function of Panx3 remains poorly understood, but we consistently observed a strong increase in Panx3 immunostaining in OA lesions in both mice and humans. Here, we developed and characterized the first global and conditional Panx3 knockout mice to investigate the role of Panx3 in OA. Interestingly, global Panx3 deletion produced no …

Beclin-1 Expression Is Retained In High-Grade Serous Ovarian Cancer Yet Is Not Essential For Autophagy Induction In Vitro, Rohann J.M. Correa, Yudith R. Valdes, Trevor G. Shepherd, Gabriel E. Dimattia

Anatomy and Cell Biology Publications

Background: Autophagy is a conserved cellular self-digestion mechanism that can either suppress or promote cancer in a context-dependent manner. In ovarian cancer, prevalent mono-allelic deletion of BECN1 (a canonical autophagy-inducer) suggests that autophagy is impaired to promote carcinogenesis and that Beclin-1 is a haploinsufficient tumor suppressor. Nonetheless, autophagy is known to be readily inducible in ovarian cancer cells. We sought to clarify whether Beclin-1 expression is in fact disrupted in ovarian cancer and whether this impacts autophagy regulation.

Methods: BECN1 expression levels were assessed using The Cancer Genome Atlas (TCGA) datasets from 398 ovarian high-grade serous cystadenocarcinomas (HGSC) and protein …

Whole-Retina Reduced Electrophysiological Activity In Mice Bearing Retina-Specific Deletion Of Vesicular Acetylcholine Transporter, Jake Bedore, Amanda C. Martyn, Anson K. C. Li, Eric A. Dolinar, Ian S. Mcdonald, Stuart G. Coupland, Vania F. Prado, Marco A. Prado, Kathleen A. Hill

Anatomy and Cell Biology Publications

Background: Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina. Methods & Results A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina-targeted (embryonic day …

Increased Expression Of Simple Ganglioside Species Gm2 And Gm3 Detected By Maldi Imaging Mass Spectrometry In A Combined Rat Model Of A Beta Toxicity And Stroke, Sarah Caughlin, Jeffrey D. Hepburn, Dae Hee Park, Kristina Jurcic, Ken K. -C. Yeung, David F. Cechetto, Shawn N. Whitehead

Anatomy and Cell Biology Publications

The aging brain is often characterized by the presence of multiple comorbidities resulting in synergistic damaging effects in the brain as demonstrated through the interaction of Alzheimer's disease (AD) and stroke. Gangliosides, a family of membrane lipids enriched in the central nervous system, may have a mechanistic role in mediating the brain's response to injury as their expression is altered in a number of disease and injury states. Matrix-Assisted Laser Desorption Ionization (MALDI) Imaging Mass Spectrometry (IMS) was used to study the expression of A-series ganglioside species GD1a, GM1, GM2, and GM3 to determine alteration of their expression profiles in …

Intact Lkb1 Activity Is Required For Survival Of Dormant Ovarian Cancer Spheroids, Teresa M. Peart, Yudith R. Valdes, Rohann J.M. Correa, Elena Fazio, Monique Bertrand, Jacob Mcgee, Michel Prefontaine, Akira Sugimoto, Gabriel E. Dimattia, Trevor G. Shepherd

Anatomy and Cell Biology Publications

Metastatic epithelial ovarian cancer (EOC) cells can form multicellular spheroids while in suspension and disperse directly throughout the peritoneum to seed secondary lesions. There is growing evidence that EOC spheroids are key mediators of metastasis, and they use specific intracellular signalling pathways to control cancer cell growth and metabolism for increased survival. Our laboratory discovered that AKT signalling is reduced during spheroid formation leading to cellular quiescence and autophagy, and these may be defining features of tumour cell dormancy. To further define the phenotype of EOC spheroids, we have initiated studies of the Liver kinase B1 (LKB1)-5′-AMP-activated protein kinase (AMPK) …

Increased Airway Reactivity And Hyperinsulinemia In Obese Mice Are Linked By Erk Signaling In Brain Stem Cholinergic Neurons, Luiz O. S. Leiria, Fernanda M. Arantes-Costa, Marina C. Calixto, Eduardo C. Alexandre, Rodrigo F. Moura, Franco Folli, Carla M. Prado, Marco Antonio Prado, Vania F. Prado, Licio A. Velloso, Jose Donato Jr., Edson Antunes, Milton A. Martins, Mario J. A. Saad

Anatomy and Cell Biology Publications

Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR). In obesity-associated asthma, AHR may be regulated by non-T(H)2 mechanisms. We hypothesized that airway reactivity is regulated by insulin in the CNS, and that the high levels of insulin associated with obesity contribute to AHR. We found that intracerebroventricular (ICV)-injected insulin increases airway reactivity in wild-type, but not in vesicle acetylcholine transporter knockdown (VAChT KDHOM-/-), mice. Either neutralization of central insulin or inhibition of extracellular signal-regulated kinases (ERK) normalized airway reactivity in hyperinsulinemic obese mice. These effects were mediated by insulin in cholinergic nerves located …

Human Severe Sepsis Cytokine Mixture Increases Beta 2-Integrin-Dependent Polymorphonuclear Leukocyte Adhesion To Cerebral Microvascular Endothelial Cells In Vitro, Chris Blom, Brittany L. Deller, Douglas D. Fraser, Eric K. Patterson, Claudio M. Martin, Bryan Young, Patricia C. Liaw, Payam Yazdan-Ashoori, Angelica Oritz, Brian Webb, Greg Kilmer, David E. Carter, Gediminas Cepinskas

Anatomy and Cell Biology Publications

Introduction: Sepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood-brain barrier dysfunction. Thus, our objectives were to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro. Methods: The concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and …

Effect Of Gamma Radiation On Growth And Mycotoxins Production Of Alternaria Alternata, Danny Karlet

Anatomy and Cell Biology Publications

The ubiquitous genus Alternaria contains many species that are able to invade cereals, oleaginous plants and other crops. Alternaria alternata is considered one of the most important species and can produce several mycotoxins under favourable conditions of temperature and humidity, including the economically important toxins: alternariol (AOH) and alternariol monomethyl ether (AME). The aim of this study was to evaluate the radio-sensitivity of Alternaria alternata spores through different gamma radiation doses. A. alternata growth and the production of AOH and AME were then analyzed. After fungal irradiation with 2 kGy, 5 kGy and 7 kGy, the spores were suspended with …

Critical Care Capacity In Canada: Results Of A National Cross-Sectional Study, Robert A. Fowler, Philip Abdelmalik, Gordon Wood, Denise Foster, Noel Gibney, Natalie Bandrauk, Alexis F. Turgeon, Francois Lamontagne, Anand Kumar, Ryan Zarychanski, Rob Green, Sean M. Bagshaw, Henry T. Stelfox, Ryan Foster, Peter Dodek, Susan Shaw, John Granton, Bernard Lawless, Andrea Hill, Louise Rose, Neill K. Adhikari, Damon C. Scales, Deborah J. Cook, John C. Marshall, Philippe Jouvet

Anatomy and Cell Biology Publications

Introduction: Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity. Methods: After the 2009-2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability …

Pulmonary Inflammation Is Regulated By The Levels Of The Vesicular Acetylcholine Transporter, Nathalia M. Pinheiro, Claudia J. C. P. Miranda, Adenir Perini, Niels O. S. Camara, Soraia K. P. Costa, Maria Isabel C. Alonso-Vale, Luciana C. Caperuto, Iolanda F. L. C. Tiberio, Marco A. M. Prado, Milton A. Martins, Vania F. Prado, Carla M. Prado

Anatomy and Cell Biology Publications

Acetylcholine (ACh) plays a crucial role in physiological responses of both the central and the peripheral nervous system. Moreover, ACh was described as an anti-inflammatory mediator involved in the suppression of exacerbated innate response and cytokine release in various organs. However, the specific contributions of endogenous release ACh for inflammatory responses in the lung are not well understood. To address this question we have used mice with reduced levels of the vesicular acetylcholine transporter (VAChT), a protein required for ACh storage in secretory vesicles. VAChT deficiency induced airway inflammation with enhanced TNF-alpha and IL-4 content, but not IL-6, IL-13 and …

Nicotine Receptors Mediating Sensorimotor Gating And Its Enhancement By Systemic Nicotine, Farena Pinnock, Daniel Bosch, Tyler Brown, Nadine Simons, John R. Yeomans, Cleusa Deoliveira, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the …

Skeletal Muscle Fibrosis In The Mdx/Utrn Plus /- Mouse Validates Its Suitability As A Murine Model Of Duchenne Muscular Dystrophy, Kelly M. Gutpell, William T. Hrinivich, Lisa M. Hoffman

Anatomy and Cell Biology Publications

Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and …

Habituation Mechanisms And Their Importance For Cognitive Function, Susanne Schmid, Donald A. Wilson, Catharine H. Rankin

Anatomy and Cell Biology Publications

No abstract provided.

3d Mr Ventricle Segmentation In Pre-Term Infants With Post-Hemorrhagic Ventricle Dilation, Wu Qiu, Jing Yuan, Jessica Kishimoto, Yimin Chen

Anatomy and Cell Biology Publications

Intraventricular hemorrhage (IVH) or bleed within the brain is a common condition among pre-term infants that occurs in very low birth weight preterm neonates. The prognosis is further worsened by the development of progressive ventricular dilatation, i.e., post-hemorrhagic ventricle dilation (PHVD), which occurs in 10-30% of IVH patients. In practice, predicting PHVD accurately and determining if that specific patient with ventricular dilatation requires the ability to measure accurately ventricular volume. While monitoring of PHVD in infants is typically done by repeated US and not MRI, once the patient has been treated, the follow-up over the lifetime of the patient is …

Quantification Of Cerebral Ventricle Volume Change Of Preterm Neonates Using 3d Ultrasound Images, Yimin Chen, Jessica Kishimoto, Wu Qiu, Sandrine De Ribaupierre, Aaron Fenster, Bernard Chiu

Anatomy and Cell Biology Publications

Intraventricular hemorrhage (IVH) is a major cause of brain injury in preterm neonates. Quantitative measurement of ventricular dilation or shrinkage is important for monitoring patients and in evaluation of treatment options. 3D ultrasound (US) has been used to monitor the ventricle volume as a biomarker for ventricular dilation. However, volumetric quantification does not provide information as to where dilation occurs. The location where dilation occurs may be related to specific neurological problems later in life. For example, posterior horn enlargement, with thinning of the corpus callosum and parietal white matter fibres, could be linked to poor visuo-spatial abilities seen in …

Temperamental Variation In Learned Irrelevance In Humans, Aleksandra Gruszka, Adrian M. Owen

Anatomy and Cell Biology Publications

BACKGROUND Learned irrelevance (LIRR) represents one of the mechanisms of attentional set-shifting and refers to the inability to attend to, or to learn about, any aspect of a stimulus previously experienced as irrelevant. Although it has been extensively studied in the context of clinical populations, not much is known about LIRR effects in relation to normal variation in individual differences. The present study was designed to assess how temperamental factors may modulate LIRR. PARTICIPANTS AND PROCEDURES Sixty-eight healthy volunteers performed a visual discrimination learning task modelled after Wisconsin Card Sorting Test. To test the susceptibility to learned irrelevance, participants were …