Exposure To The Rxr Agonist Sr11237 In Early Life Causes Disturbed Skeletal Morphogenesis In A Rat Model,
2019
Western University
Exposure To The Rxr Agonist Sr11237 In Early Life Causes Disturbed Skeletal Morphogenesis In A Rat Model, Holly Dupuis, Michael Andrew Pest, Ermina Hadzic, Thin Xuan Vo, Daniel B. Hardy, Frank Beier
Physiology and Pharmacology Publications
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. …
Piezo1: Proteins For Mechanotransduction And Integration Of Endothelial Shear Stress & Intravascular Pressure,
2019
The University of Western Ontario
Piezo1: Proteins For Mechanotransduction And Integration Of Endothelial Shear Stress & Intravascular Pressure, Juan Garcia Robledo M.D.
Electronic Thesis and Dissertation Repository
Piezo proteins are transmembrane ion channels, specialized in detecting mechanosensitive stimuli and transduce mechanical forces into biochemical signals. Piezo proteins research has helped understand physiological mechanisms, but the integrative role that Piezo1 plays in the regulation of the microvasculature has remained unstudied. Our main objective was to characterize ex vivo microvascular responses to the blockade of Piezo1 mechanotransduction in male (n=29) and female (n=24) Sprague-Dawley (SD) rats. Gracilis arterioles (GA) and middle cerebral arterioles (MCA) were harvested for ex-vivo vessel preparations. After vessel viability confirmation, every vessel was submitted to myogenic and flow challenges under control conditions and after Grammostola …
Low Birth Weight And Post-Natal Diet Induced Alterations In Skeletal Muscle Oxygen Consumption And Fiber Type Composition,
2019
The University of Western Ontario
Low Birth Weight And Post-Natal Diet Induced Alterations In Skeletal Muscle Oxygen Consumption And Fiber Type Composition, Megan Cedrone
Electronic Thesis and Dissertation Repository
Adverse in utero and postnatal conditions can increase susceptibility to metabolic syndrome (MS). Altered muscle respiration contributes to MS, but the effects of restricted oxygen and nutrients in utero on skeletal muscle mitochondria remain unknown. In this study guinea pig sows underwent uterine artery ablations mid-gestation, producing fetuses with low birth weight (LBW). Soleus muscle was collected near term or at four months of age, from LBW and control fetuses and offspring, where the offspring were fed either a Western Diet (WD) or a control diet (CD). Soleus muscles from LBW fetuses exhibit lower maximal respiration rates than normal birth …
Targeting Pathogenic Lafora Bodies In Lafora Disease Using An Antibody-Enzyme Fusion,
2019
University of Kentucky
Targeting Pathogenic Lafora Bodies In Lafora Disease Using An Antibody-Enzyme Fusion, M. Kathryn Brewer, Annette M. Uittenbogaard, Grant L. Austin, Dyann M. Segvich, Anna Depaoli-Roach, Peter J. Roach, John J. Mccarthy, Zoe R. Simmons, Jason A. Brandon, Zhengqiu Zhou, Jill Zeller, Lyndsay E. A. Young, Ramon C. Sun, James R. Pauly, Nadine M. Aziz, Bradley L. Hodges, Tracy R. Mcknight, Dustin D. Armstrong, Matthew S. Gentry
Molecular and Cellular Biochemistry Faculty Publications
Lafora disease (LD) is a fatal childhood epilepsy caused by recessive mutations in either the EPM2A or EPM2B gene. A hallmark of LD is the intracellular accumulation of insoluble polysaccharide deposits known as Lafora bodies (LBs) in the brain and other tissues. In LD mouse models, genetic reduction of glycogen synthesis eliminates LB formation and rescues the neurological phenotype. Therefore, LBs have become a therapeutic target for ameliorating LD. Herein, we demonstrate that human pancreatic α-amylase degrades LBs. We fused this amylase to a cell-penetrating antibody fragment, and this antibody-enzyme fusion (VAL-0417) degrades LBs in vitro and dramatically reduces LB …
White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups,
2019
University of Kentucky
White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha
Sanders-Brown Center on Aging Faculty Publications
Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and …
System Dynamics To Investigate Opioid Use And Chiropractic Care For Chronic Musculoskeletal Pain,
2019
Canadian Memorial Chiropractic College
System Dynamics To Investigate Opioid Use And Chiropractic Care For Chronic Musculoskeletal Pain, Marion Mcgregor, Alexandra Nielsen, Chadwick Chung, Mark Fillery, Wayne Wakeland, Silvano Mior
Systems Science Faculty Publications and Presentations
Objective: The purpose of this investigation was to create a system dynamics (SD) model, including published data and required assumptions, as a tool for future research identifying the role of chiropractic care in the management of chronic, nonmalignant pain in a Canadian population. Methods: We present an illustrative case description of how we evaluated the feasibility of conducting a large-scale clinical trial to assess the impact of chiropractic care in mitigating excessive opioid use in Canada. We applied SD modeling using current evidence and key assumptions where such evidence was lacking. Modeling outcomes were highlighted to determine which potential …
Poly(Ester Amide) Particles For Controlled Delivery Of Celecoxib,
2019
The University of Western Ontario
Poly(Ester Amide) Particles For Controlled Delivery Of Celecoxib, Ian J. Villamagna, Trent N. Gordon, Mark B. Hurtig, Frank Beier, Elizabeth R. Gillies
Physiology and Pharmacology Publications
© 2019 Wiley Periodicals, Inc. Many potential pharmacological treatments for osteoarthritis can result in undesirable side effects due to the systemic administration of drugs, making the direct delivery of drugs to joints an attractive alternative. Poly(ester amide)s (PEAs) have been shown to exhibit promising properties for the development of particle-based intra-articular delivery vehicles. However, a limited range of PEA structures has been investigated. In this study, we prepared and characterized the properties of two different PEA particles composed of l-phenylalanine, sebacic acid, and either 1,4-butanediol or 1,8-octanediol (PBSe and POSe, respectively). The anti-inflammatory drug celecoxib (CXB) was encapsulated into the …
Technical Freediving: An Emerging Breath-Hold Diving Technique,
2019
University of Florida
Technical Freediving: An Emerging Breath-Hold Diving Technique, Derek Covington, Robert H. Lee, Steven Toffel, Alberto Bursian, Kirk Krack, Chris Giordano
Journal of Human Performance in Extreme Environments
Technical freediving can be defined as freediving augmented by the use of oxygen-enriched gases or oxygen before, during, or after a freedive. As a result of these techniques, breath-hold divers can visit and enjoy underwater wrecks, reefs, and other diving locations previously located at depths unreachable to apnea divers. By pre-breathing oxygen-enriched gases in conjunction with hyperventilation—which decreases the partial pressure of carbon dioxide (PCO2)—the technical freediver now has additional oxygen to facilitate aerobic respiration during the dive. In addition, pre-breathing oxygen decreases tissue nitrogen tensions, which limits inert gas loading and decreases the risk of decompression sickness (DCS). Finally, …
Δ9-Tetrahydrocannabinol Leads To Endoplasmic Reticulum Stress And Mitochondrial Dysfunction In Human Bewo Trophoblasts.,
2019
Western University
Δ9-Tetrahydrocannabinol Leads To Endoplasmic Reticulum Stress And Mitochondrial Dysfunction In Human Bewo Trophoblasts., Tina Lojpur, Zachary Easton, Sergio Raez-Villanueva, Steven Laviolette, Alison C Holloway, Daniel B Hardy
Physiology and Pharmacology Publications
While studies have demonstrated that the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC) alone induces placental insufficiency and fetal growth restriction, the underlying mechanisms remain elusive. Given that both (i) endoplasmic reticulum (ER) stress in pregnancy and (ii) gestational exposure to Δ9-THC leads to placental deficiency, we hypothesized that Δ9-THC may directly induce placental ER stress, influencing trophoblast gene expression and mitochondrial function. BeWo human trophoblast cells treated with Δ9-THC (3-30 μM) led to a dose-dependent increase in all ER stress markers and CHOP; these effects could be blocked with CB1R/CB2R antagonists. Moreover, expression of ER stress-sensitive genes ERRγ, VEGFA, …
Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells,
2019
UConn Health Center
Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells, Tyler Hanna, Suzy Torti Ph. D, Frank Torti M.D., Mph, Nicole Farra Ph. D.
Honors Scholar Theses
The iron regulatory axis has consistently been shown to be perturbed in cancer cell lines relative to non-cancerous cell lines. As cancer cells rapidly divide and grow, they require iron to fuel many intracellular processes, including DNA replication and protein synthesis. Three-dimensional cell culture is an increasingly popular method of culture that purportedly more accurately mimics the in vivo microenvironment of cancers over traditional two-dimensional culture. This project was prompted by previous lab results to investigate differential iron regulatory gene expression in 2D and 3D spheroid culture models. We replicated the findings that the gene hepcidin is induced in 3D …
Increasing Upstream Chromatin Long-Range Interactions May Favor Induction Of Circular Rnas In Lysopc-Activated Human Aortic Endothelial Cells.,
2019
Temple University; Duke University
Increasing Upstream Chromatin Long-Range Interactions May Favor Induction Of Circular Rnas In Lysopc-Activated Human Aortic Endothelial Cells., Angus Li, Yu Sun, Charles Drummer, Yifan Lu, Daohai Yu, Yan Zhou, Xinyuan Li, Simone J. Pearson, Candice Johnson, Catherine Yu, William Y. Yang, Kevin Mastascusa, Xiaohua Jiang, Jianxin Sun, Thomas Rogers, Wenhui Hu, Hong Wang, Xiaofeng Yang
Center for Translational Medicine Faculty Papers
Circular RNAs (circRNAs) are non-coding RNAs that form covalently closed continuous loops, and act as gene regulators in physiological and disease conditions. To test our hypothesis that proatherogenic lipid lysophosphatidylcholine (LPC) induce a set of circRNAs in human aortic endothelial cell (HAEC) activation, we performed circRNA analysis by searching our RNA-Seq data from LPC-activated HAECs, and found: (1) LPC induces significant modulation of 77 newly characterized cirRNAs, among which 47 circRNAs (61%) are upregulated; (2) 34 (72%) out of 47 upregulated circRNAs are upregulated when the corresponding mRNAs are downregulated, suggesting that the majority of circRNAs are upregulated presumably via …
Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report,
2019
Duquesne University
Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report, Brielle Corrente
Graduate Student Research Symposium
Usually not diagnosed until open laparotomy, aortoduodenalfistulas (ADF) are one of the rarest complications of intestinal transplant surgery. With an incidence rate of only 0.04% at autopsy and only 250 documented cases since the early 1800’s, aortoduodenal fistulas are the most deadly complications of intestinal transplantation with a mortality rate of 100% without surgical intervention. A 39 year old, two-time multi-visceral transplant African American female patient suffered from a primary aortoduodenal fistula formation in a primary modified multi-visceral transplant aortic stump graft site. With emergency open laparotomy repair, revascularization of the secondary multi-visceral transplant was performed, saving the life of …
Crf Mediates Stress-Induced Pathophysiological High-Frequency Oscillations In Traumatic Brain Injury,
2019
Robarts Research Institute
Crf Mediates Stress-Induced Pathophysiological High-Frequency Oscillations In Traumatic Brain Injury, Chakravarthi Narla, Paul S. Jung, Francisco Bautista Cruz, Michelle Everest, Julio Martinez-Trujillo, Michael O. Poulter
Physiology and Pharmacology Publications
Copyright © 2019 Narla et al. It is not known why there is increased risk to have seizures with increased anxiety and stress after traumatic brain injury (TBI). Stressors cause the release of corticotropin-releasing factor (CRF) both from the hypothalamic pituitary adrenal (HPA) axis and from CNS neurons located in the central amygdala and GABAergic interneurons. We have previously shown that CRF signaling is plastic, becoming excitatory instead of inhibitory after the kindling model of epilepsy. Here, using Sprague Dawley rats we have found that CRF signaling increased excitability after TBI. Following TBI, CRF type 1 receptor (CRFR1)-mediated activity caused …
The Purification Of Human Adult Progenitor Cell Types To Promote Angiogenesis,
2019
The University of Western Ontario
The Purification Of Human Adult Progenitor Cell Types To Promote Angiogenesis, Stephen E. Sherman
Electronic Thesis and Dissertation Repository
Cellular transplantation strategies have aimed to combat critical limb ischemia (CLI) by inducing endogenous blood vessel regeneration. Transplantation of mesenchymal stromal cells (MSC) for CLI has proven safe and well-tolerated but demonstrated only modestly improved clinical outcomes explained in part by a lack of MSC survival and/or potency in ischemic tissues. This thesis focuses on the development of improved transplantation strategies for patients with CLI utilizing purified pro-angiogenic subsets of MSC and endothelial colony forming cells (ECFC) seeded within decellularized adipose tissue (DAT) bioscaffolds. First, I investigated whether purification of bone marrow-derived MSC based on a conserved stem cell function, …
Initial Characterization Of The Indole-3-Carboxamide Bic-154 As A Fast Onset And Reversible Orai Channel Blocker,
2019
Wright State University - Main Campus
Initial Characterization Of The Indole-3-Carboxamide Bic-154 As A Fast Onset And Reversible Orai Channel Blocker, Tetyana Zhelay, Kalina Szteyn, Elisa Liardo, Jae Eun Cheong, Steffi Koerner, Anil Ekkati, Lijun Sun, J. Ashot Kozak
Neuroscience, Cell Biology & Physiology Faculty Publications
Calcium ion elevations are required for human T-lymphocyte proliferation in response to antigen recognition by a T-cell receptor. Calcium influx through the plasma membrane is necessary for efficient T-cell proliferation and effector function. The calcium channels responsible for Ca2+ influx in lymphocytes have been identified and Orai interacting with ER Ca2+ sensor STIM were shown to be crucial for persistent calcium mobilization. Loss-of-function mutations in Orai1 or STIM1 result in severe combined immunodeficiency (SCID) with muscle hypotonia. Suppression of calcium influx through Orai/STIM channels gives rise to various lymphoproliferative defects. Thus, deletion of Orai or STIM in mice results in …
Naktide Targeted To Adipocytes Ameliorates Western Diet Induced Obesity,
2019
Marshall University
Naktide Targeted To Adipocytes Ameliorates Western Diet Induced Obesity, Rebecca D. Pratt
Theses, Dissertations and Capstones
Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. It is believed that cellular oxidant stress plays a key role in both the development and maintenance of obesity as well as its associated comorbidities such as diabetes, cardiovascular disease, and nonalcoholic steatohepatitis (NASH). We have previously reported that systemic administration of pNaKtide, which targets the Na/K-ATPase oxidant amplification loop was able to decrease oxidative stress and adiposity in mice fed a high fat and fructose supplemented western diet (WD). As adipocytes are believed to play an active role in the development of obesity and …
The Effects Of Methylphenidate (Ritalin) On The Neurophysiology Of The Monkey Caudal Prefrontal Cortex,
2019
Institut-Hôpital Neurologique de Montréal
The Effects Of Methylphenidate (Ritalin) On The Neurophysiology Of The Monkey Caudal Prefrontal Cortex, Sébastien Tremblay, Florian Pieper, Adam Sachs, Ridha Joober, Julio Martinez-Trujillo
Physiology and Pharmacology Publications
© 2019 Tremblay et al. Methylphenidate (MPH), commonly known as Ritalin, is the most widely prescribed drug worldwide to treat patients with attention deficit disorders. Although MPH is thought to modulate catecholamine neurotransmission in the brain, it remains unclear how these neurochemical effects influence neuronal activity and lead to attentional enhancements. Studies in rodents overwhelmingly point to the lateral prefrontal cortex (LPFC) as a main site of action of MPH. To understand the mechanism of action of MPH in a primate brain, we recorded the responses of neuronal populations using chronic multielectrode arrays implanted in the caudal LPFC of two …
Maternal Protein Restriction During Perinatal Life Affects Lung Mechanics And The Surfactant System During Early Postnatal Life In Female Rats.,
2019
Western University
Maternal Protein Restriction During Perinatal Life Affects Lung Mechanics And The Surfactant System During Early Postnatal Life In Female Rats., Reza Khazaee, Lynda A Mccaig, Cory Yamashita, Daniel B Hardy, Ruud A W Veldhuizen
Physiology and Pharmacology Publications
Limited information is available on how fetal growth retardation (FGR) affects the lung in the neonatal period in males and females. This led us to test the hypothesis that FGR alters lung mechanics and the surfactant system during the neonatal period. To test this hypothesis a model of FGR was utilized in which pregnant rat dams were fed a low protein diet during both the gestation and lactation period. We subsequently analyzed lung mechanics using a FlexiVent ventilator in male and female pups at postnatal day 7 and 21. Lung lavage material was obtained at postnatal day 1, 7 and …
Redox Biology In Physiology And Disease,
2019
University of Nebraska Medical Center
Redox Biology In Physiology And Disease, Matthew C. Zimmerman, Adam J. Case
Journal Articles: Cellular & Integrative Physiology
No abstract provided.
Autonomic And Redox Imbalance Correlates With T-Lymphocyte Inflammation In A Model Of Chronic Social Defeat Stress,
2019
University of Nebraska Medical Center
Autonomic And Redox Imbalance Correlates With T-Lymphocyte Inflammation In A Model Of Chronic Social Defeat Stress, Cassandra M. Moshfegh, Safwan K. Elkhatib, Christopher W. Collins, Allison J. Kohl, Adam J. Case
Journal Articles: Cellular & Integrative Physiology
Patients diagnosed with post-traumatic stress disorder (PTSD) are at a significantly elevated risk of developing comorbid inflammatory conditions, but the mechanisms underlying this predilection remain unclear. Our previous work has shown that T-lymphocytes exposed to elevated levels of norepinephrine (NE) displayed a pro-inflammatory signature reminiscent of an autoreactive phenotype. With this, we hypothesized that the increased sympathetic tone observed during psychological trauma may be promoting pro-inflammatory T-lymphocytes, which causes a predisposition to comorbid inflammatory conditions. Here, we examined the consequences of psychological trauma on splenic T-lymphocytes using a mouse model of repeated social defeat stress. Social defeat led to anxiety-like …
