Cell and Developmental Biology Commons^™

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

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 …

Chemical-Free Technique To Study The Ultrastructure Of Primary Cilium, Ashraf M. Mohieldin, Wissam A. Aboualaiwi, Min Gao, Surya M. Nauli

Pharmacy Faculty Articles and Research

A primary cilium is a hair-like structure with a width of approximately 200 nm. Over the past few decades, the main challenge in the study of the ultrastructure of cilia has been the high sensitivity of cilia to chemical fixation, which is required for many imaging techniques. In this report, we demonstrate a combined high-pressure freezing (HPF) and freeze-fracture transmission electron microscopy (FFTEM) technique to examine the ultrastructure of a cilium. Our objective is to develop an optimal high-resolution imaging approach that preserves cilia structures in their best natural form without alteration of cilia morphology by chemical fixation interference. Our …

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 …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Viewing The Extracellular Matrix: An Imaging Method For Tissue Engineering, Michael Drakopoulos, Sarah Calve

The Summer Undergraduate Research Fellowship (SURF) Symposium

The field of regenerative medicine seeks to create replacement tissues and organs, both to repair deficiencies in biological function and to treat structural damage caused by injury. Scaffoldings mimicking extracellular matrix (ECM), the structure to which cells attach to form tissues, have been developed from synthetic polymers and also been prepared by decellularizing adult tissue. However, the structure of ECM undergoes significant remodeling during natural tissue repair, suggesting that ECM-replacement constructs that mirror developing tissues may promote better regeneration than those modeled on adult tissues. This work investigated the effectiveness of a method of viewing the extracellular matrix of developing …

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 …

The Ctcf Chromatin Organizer Is Required For Hindlimb Development, Katherine L. Rabicki

Electronic Thesis and Dissertation Repository

Mutations in chromatin organizer CTCF were identified in patients with intellectual disability and skeletal defects. Previous studies demonstrated that depletion of CTCF in murine limb mesenchyme results in apoptosis in the forelimb. The role of CTCF in the hindlimb, however, is unknown. My objective was to investigate effects of CTCF deletion on chondrogenesis and skeletal development in the hindlimb. In vitro wild-type micromass cultures demonstrate that chondrocyte gene expression is delayed in the hindlimb when compared to forelimbs. Embryonic Ctcf^Fl/Fl;Prx1Cre mice were investigated, and qRT-PCR and histology were performed on limb buds and long bones. Results show that …

Targeting Il13ralpha2 Activates Stat6-Tp63 Pathway To Suppress Breast Cancer Lung Metastasis, Panagiotis Papageorgis, Sait Ozturk, Arthur W. Lambert, Christiana M. Neophytou, Alexandros Tzatsos, Chen K. Wong, Sam Thiagalingam, Andreas I. Constantinou

Anatomy and Regenerative Biology Faculty Publications

Introduction

Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action.

Methods

An unbiased approach using gene expression profiling of a BLBC progression model and in silicoleveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was …

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) …

Klf4-Sqstm1/P62-Associated Prosurvival Autophagy Contributes To Carfilzomib Resistance In Multiple Myeloma Models., Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 …

Prostate Tumorigenesis Induced By Pten Deletion Involves Estrogen Receptor Beta Repression, Paul Mak, Jianrong Li, Sanjoy Samanta, Cheng Chang, D. Joseph Jerry, Roger J. Davis, Irwin Leav, Arthur M. Mercurio

Arthur M. Mercurio

The role of ERbeta in prostate cancer is unclear, although loss of ERbeta is associated with aggressive disease. Given that mice deficient in ERbeta do not develop prostate cancer, we hypothesized that ERbeta loss occurs as a consequence of tumorigenesis caused by other oncogenic mechanisms and that its loss is necessary for tumorigenesis. In support of this hypothesis, we found that ERbeta is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERbeta is important for tumor formation. ERbeta transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis. …

A Laminin 511 Matrix Is Regulated By Taz And Functions As The Ligand For The Alpha6bbeta1 Integrin To Sustain Breast Cancer Stem Cells, Cheng Chang, Hira Lal Goel, Huijie Gao, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Sulev Ingerpuu, Manuel Patarroyo, Shiliang Cao, Elgene Lim, Junhao Mao, Karen Kulju. Mckee, Peter D. Yurchenco, Arthur M. Mercurio

Arthur M. Mercurio

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer.

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 …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations & Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

The Development Of Skeletal Muscle In Young Horses: An Ultrasonography And Satellite Cell Approach, Emma K. Lavigne

Honors Scholar Theses

Muscle growth in young horses is characterized by an increase in muscle cross-sectional area, which can be accomplished through the activation and differentiation of satellite cells. Satellite cells can be stimulated or inhibited in response to different cytokines and growth factors and are key mediators of muscle hypertrophy and regeneration. The aim of this study was to investigate the growth of the longissimus dorsi (LD) muscle in horses under 5 years of age and to obtain preliminary data on satellite cell behavior in foals. The area, width, height, and subcutaneous fat were measured using ultrasonography at 6-month increments over the …

Live Imaging Of The Ependymal Cilia In The Lateral Ventricles Of The Mouse Brain, Alzahra J. Al Omran, Hannah C. Saternos, Tongyu Liu, Surya M. Nauli, Wissam A. Aboualaiwi

Pharmacy Faculty Articles and Research

Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various neurological deficits. The current ex vivo live imaging of motile ependymal cilia technique allows for a detailed study of ciliary dynamics following several steps. These steps include: mice euthanasia with carbon dioxide according to protocols of The University of Toledo’s Institutional Animal Care and Use Committee (IACUC); craniectomy followed by brain removal and sagittal brain dissection with a vibratome or sharp blade to obtain very thin sections through the brain lateral ventricles, where the ependymal cilia can be visualized. …

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 …

Effects Of Cannabidiol On Contractions And Calcium Signaling In Rat Ventricular Myocytes, Ramez M. Ali, Lina T. Al Kury, Keun-Hang Susan Yang, Anwar Qureshi, Mohanraj Rajesh, Sehamuddin Galadari, Yaroslav M. Shuba, Frank Christopher Howarth, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the Ca2+ sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca2+ currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1 μM) caused a significant decrease in the amplitudes of …

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 …

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …

The Effect Of Active Video Games On The Heart Rate Of Older Adults, Yeon Bai, Shahla M. Wunderlich, Diane M. Hanel

Department of Nutrition and Food Studies Scholarship and Creative Works

Background: Heart rate is used as a health biomarker. This aim of this study was to investigate the effects of playing active video games on the heart rate of older adults, in comparison to the heart rate after common table recreational activity.

Methods: An experimental study with 40 participants was conducted: a control group (n=20) participated in common Pokeno® card games; an experimental group (n=20) played WiiTM bowling. The participants’ pre- and post-activity heart rates were measured and compared between and within groups using t-tests.

Results: The findings signified an 11.9% increase (p

Conclusions: The inclusion of active video games …