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Mechanisms Regulating Stem Cell Phenotype In Infantile Hemangioma, Niamh Richmond 2016 The University of Western Ontario

Mechanisms Regulating Stem Cell Phenotype In Infantile Hemangioma, Niamh Richmond

Electronic Thesis and Dissertation Repository

Infantile hemangiomas (IHs) are benign vascular neoplasms characterized by the differentiation of multipotential stem cells (hemSCs) into endothelial cells during the early proliferative phase, and later into adipocytes during spontaneous involution. Transforming growth factor-β (TGFβ) has been shown to be significantly elevated upon IH involution and this coincides with repression of a developmentally-regulated transcription factor T-box 2 (TBX2). These findings implicate both TGFβ and TBX2 in mediating hemSC differentiation during IH evolution. The aim of my study is to understand the role of TGFβ and TBX2 in hemSC differentiation. I performed immunofluorescence staining to localize TBX2 protein in sectioned IH ...


Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri 2016 Regenerative Medicine Center, Aurora Research Institute, Aurora Health Care

Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri

Indrajit Choudhuri

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs. Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of ...


Glial Cell Involvement In Early Alzheimer's Disease, Rachel Y. De La Torre 2016 Portland State University

Glial Cell Involvement In Early Alzheimer's Disease, Rachel Y. De La Torre

PSU McNair Scholars Online Journal

Glial cells, the resident immune cells of the brain, are important for brain health as they represent a critical function both in brain injury as well as in brain development and maintenance. Following brain injury, glia quickly respond by cleaning up neuronal and synaptic debris. In addition to their role as the cleaning cell of the brain, recent research has shown that during development, glia also shape and fine-tune neural connections by eliminating weak synapses fated for removal. However, whether glial cells also continue to remodel synaptic architecture in the adult brain is unclear. Moreover, synaptic pruning and loss are ...


Priming Cardiovascular Stem Cells For Transplantation Using Short-Term Hypoxia, Ivan Hernandez 2016 California State University - San Bernardino

Priming Cardiovascular Stem Cells For Transplantation Using Short-Term Hypoxia, Ivan Hernandez

Electronic Theses, Projects, and Dissertations

Conventional medical treatments fail to address the underlying problems associated with the damage inflicted by a coronary event. Thus, the long-term prognosis of patients admitted for heart failure is disheartening, with reported survival rates of 25 percent. Recent advances in stem cell research highlight the potential benefits of autologous stem cell transplantation for stimulating repair in heart tissue. However, a majority of those suffering from cardiovascular diseases are older adults whose autologous cells no longer possess optimum functional capacity. Additional work is needed to identify the optimal cell types or conditions that will promote cardiovascular regeneration across all age groups ...


Expression Of Heme Oxygenase-1 In Thick Ascending Loop Of Henle Attenuates Angiotensin Ii-Dependent Hypertension, David E. Stec, Heather A. Drummond, Moneete U. Gousette, Megan V. Storm, Nader G. Abraham, Eva Csongradi 2016 Marshall University

Expression Of Heme Oxygenase-1 In Thick Ascending Loop Of Henle Attenuates Angiotensin Ii-Dependent Hypertension, David E. Stec, Heather A. Drummond, Moneete U. Gousette, Megan V. Storm, Nader G. Abraham, Eva Csongradi

Nader G. Abraham

Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments. Medullary HO activity, but not cortical HO activity, was significantly higher in transgenic mice than control mice. Enhanced TALH HO-1 attenuated the hypertension induced by Ang ...


The Structure And Regulation Of Cullin 2 Based E3 Ubiquitin Ligases And Their Biological Functions., Weijia Cai, Haifeng Yang 2016 Thomas Jefferson University, Department of Pathology and Cell Biology

The Structure And Regulation Of Cullin 2 Based E3 Ubiquitin Ligases And Their Biological Functions., Weijia Cai, Haifeng Yang

Department of Pathology, Anatomy and Cell Biology Faculty Papers

BACKGROUND: Cullin-RING E3 ubiquitin ligase complexes play a central role in targeting cellular proteins for ubiquitination-dependent protein turnover through 26S proteasome. Cullin-2 is a member of the Cullin family, and it serves as a scaffold protein for Elongin B and C, Rbx1 and various substrate recognition receptors to form E3 ubiquitin ligases.

MAIN BODY OF THE ABSTRACT: First, the composition, structure and the regulation of Cullin-2 based E3 ubiquitin ligases were introduced. Then the targets, the biological functions of complexes that use VHL, Lrr-1, Fem1b, Prame, Zyg-11, BAF250, Rack1 as substrate targeting subunits were described, and their involvement in diseases ...


Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton 2016 East Tennessee State Universtiy

Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton

Electronic Theses and Dissertations

Endogenous and exogenous agents that can damage DNA are a constant threat to genome stability in all living cells. In response, cells have evolved an array of mechanisms to repair DNA damage or to eliminate the cells damaged beyond repair. One of these mechanisms is nucleotide excision repair (NER) which is the major repair pathway responsible for removing a wide variety of bulky DNA lesions. Deficiency, or mutation, in one or several of the NER repair proteins is responsible for many diseases, including cancer. Prokaryotic NER involves only three proteins to recognize and incise a damaged site, while eukaryotic NER ...


In Vitro Investigation Of The Effect Of Exogenous Ubiquitin On Processes Associated With Atherosclerosis, Chase W. Mussard 2016 East Tennessee State University

In Vitro Investigation Of The Effect Of Exogenous Ubiquitin On Processes Associated With Atherosclerosis, Chase W. Mussard

Undergraduate Honors Theses

Atherosclerosis, characterized by the build-up of cholesterol, immune cells and cellular debris within arterial walls, is accelerated following myocardial infarction by poorly understood mechanisms. Ubiquitin, a small, well-studied intracellular protein involved in protein turnover via the proteasome pathway, has recently been shown to exert extracellular effects on cardiac myocytes, in vitro, and in mice undergoing myocardial remodeling. This study investigates the potential role of extracellular ubiquitin in atherosclerosis by determining its effects on two critical atherosclerotic processes: the migration of vascular smooth muscles cells and the uptake of modified LDL by monocyte/macrophages in foam cell formation. In the presence ...


Cell-Based Therapies For Ischemic Cardiomyopathy : Investigations Of Intramyocardial Retention And Safety Of High Dose Intracoronary Delivery Of C-Kit Positive Cardiac Progenitor Cells, And Therapeutic Utility Of A Novel Population Of Cardiac Mesenchymal Stem Cells Expressing Stage-Specific Embryonic Antigen-3 (Ssea-3)., Matthew C. L. Keith 2016 University of Louisville

Cell-Based Therapies For Ischemic Cardiomyopathy : Investigations Of Intramyocardial Retention And Safety Of High Dose Intracoronary Delivery Of C-Kit Positive Cardiac Progenitor Cells, And Therapeutic Utility Of A Novel Population Of Cardiac Mesenchymal Stem Cells Expressing Stage-Specific Embryonic Antigen-3 (Ssea-3)., Matthew C. L. Keith

Electronic Theses and Dissertations

Over the last decade attempts at reducing morbidity and mortality of patients with chronic heart failure have been made via the development and implementation of novel cell based therapies. Substantial advances in cell based therapies with indications of efficacy have been shown along with a robust safety profile. Despite these advances, there is a substantial unmet need for novel therapies, specifically addressing repair and regeneration of the damaged or lost myocardium and its vasculature. Accordingly, cardiac cell-based therapies have gained attention. Various cell-types have been utilized, including bone marrow-derived mononuclear cells, bone marrow-derived mesenchymal stem cells, mobilized CD34+ cells, and ...


Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen 1980- 2016 University of Louisville

Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen 1980-

Electronic Theses and Dissertations

Alcohol consumption can cause alcoholic liver disease (ALD), which remains a major cause of morbidity and mortality in the United States. Chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Acrolein forms protein adducts and triggers endoplasmic reticulum (ER) stress and hepatocyte apoptosis, which are recognized etiologic factors in ALD. Several studies have established the critical role of the gut-liver axis in ALD pathogenesis, wherein alcohol-induced gut barrier dysfunction contributes to liver injury. This study investigates, in vitro and in vivo, the ...


Inhibition Of The Pi3k/Akt Signaling Pathway Increases Efficacy Of Doxorubicin And Its Derivative Ad198 In Bladder And Oral Cancers, Dmitriy Smolensky 2016 University of Tennessee - Knoxville

Inhibition Of The Pi3k/Akt Signaling Pathway Increases Efficacy Of Doxorubicin And Its Derivative Ad198 In Bladder And Oral Cancers, Dmitriy Smolensky

Doctoral Dissertations

Doxorubicin (Dox) is a successful chemotherapy to treat various cancers, including bladder and oral cancers. Many patients initially respond to Dox-based regimens, however often cancers become resistant. A novel derivatives of Dox, e.g. N-benzyladriamycin-14-valerate (AD198), have been developed to overcome Dox-induced drug resistance and cardiotoxicity. The purpose of this thesis was to determine the efficacy of AD198 and Dox in bladder and oral cancers in vitro.

Part-I of this dissertation focuses on the bladder cancer, including discussing risk factors, diagnosis, staging, and current treatment options, following by a description of altered molecular mechanisms responsible cancer progression. This section also ...


Ho-1 Induction Improves The Type-1 Cardiorenal Syndrome In Mice With Impaired Angiotensin Ii–Induced Lymphocyte Activation, Sumit R. Monu, Paola Pesce, Komal Sodhi, Massimo Boldrin, Nitin Puri, Larisa Fedorova, David Sacerdoti, Stephen J. Peterson, Nader G. Abraham, Attallah Kappas 2016 Marshall University

Ho-1 Induction Improves The Type-1 Cardiorenal Syndrome In Mice With Impaired Angiotensin Ii–Induced Lymphocyte Activation, Sumit R. Monu, Paola Pesce, Komal Sodhi, Massimo Boldrin, Nitin Puri, Larisa Fedorova, David Sacerdoti, Stephen J. Peterson, Nader G. Abraham, Attallah Kappas

Nader G. Abraham

Type-1 cardiorenal syndrome, characterized by acute kidney dysfunction secondary to cardiac failure and renal arteriolar vasoconstriction, is mediated by the renin–angiotensin–aldosterone axis and sympathetic nervous system activation. Previous reports indicate that angiotensin II modulates immune function and causes recruitment and activation of T-lymphocytes. The goal of this study was to evaluate the effects of postischemic heart failure on renal morphology and circulation and the beneficial effects of heme oxygenase-1 (HO-1) induction in T-lymphocyte–suppressed severe combined immune deficiency (SCID) mice. Mice were divided into 4 groups: sham, myocardial infarction (MI), MI treated with an HO-1 inducer, cobalt protoporphyrin ...


The Cell Surface Receptor Slam Controls T Cell And Macrophage Functions, Ninghai Wang, Abhay Satoskar, William Faubion, Susumu Okamoto, Stefan Feske, Charles A. Gullo PhD, Kareem Clarke, Miriam Rodriguez Sosa, Arlene H. Sharpe, Cox Terhorst 2016 Marshall University, Huntington, WV

The Cell Surface Receptor Slam Controls T Cell And Macrophage Functions, Ninghai Wang, Abhay Satoskar, William Faubion, Susumu Okamoto, Stefan Feske, Charles A. Gullo Phd, Kareem Clarke, Miriam Rodriguez Sosa, Arlene H. Sharpe, Cox Terhorst

Charles Gullo

Signaling lymphocyte activation molecule (SLAM), a glycoprotein expressed on activated lymphocytes and antigen-presenting cells, has been shown to be a coregulator of antigen-driven T cell responses and is one of the two receptors for measles virus. Here we show that T cell receptor–induced interleukin (IL)-4 secretion by SLAM−/− CD4+ cells is down-regulated, whereas interferon γ production by CD4+ T cells is only slightly up-regulated. Although SLAM controls production of IL-12, tumor necrosis factor, and nitric oxide in response to lipopolysaccharide (LPS) by macrophages, SLAM does not regulate phagocytosis and responses to peptidoglycan or CpG. Thus, SLAM acts as ...


Inhibition Of Proliferation And Induction Of Apoptosis In Multiple Myeloma Cell Lines By Cd137 Ligand Signaling, Charles A. Gullo PhD, Liang Kai Koh, Wan Lu Pang, Kian Tong Ho, Shi Hao Tan, Herbert Schwarz 2016 Marshall Univeristy

Inhibition Of Proliferation And Induction Of Apoptosis In Multiple Myeloma Cell Lines By Cd137 Ligand Signaling, Charles A. Gullo Phd, Liang Kai Koh, Wan Lu Pang, Kian Tong Ho, Shi Hao Tan, Herbert Schwarz

Charles Gullo

Background

Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells, and the second most prevalent blood cancer. At present there is no cure for MM, and the average prognosis is only three to five years. Current treatments such as chemotherapy are able to prolong a patient's life but rarely prevent relapse of the disease. Even hematopoietic stem cell transplants and novel drug combinations are often not curative, underscoring the need for a continued search for novel therapeutics. CD137 and its ligand are members of the Tumor Necrosis Factor (TNF) receptor and TNF superfamilies, respectively. Since CD137 ligand cross-linking ...


Cardiac Tissue Engineering: Using Induced Pluripotent Stem Cells To Repair Damaged Cardiac Tissue, Megan Lenz 2016 College of Saint Benedict/Saint John's University

Cardiac Tissue Engineering: Using Induced Pluripotent Stem Cells To Repair Damaged Cardiac Tissue, Megan Lenz

Celebrating Scholarship & Creativity Day

Heart Disease is the number one cause of death in the United States and affects many individuals on a daily basis. The purpose of this research was to explore possible tissue regeneration therapies that aim to improve and recover function of damaged myocardial tissue commonly seen as a side-effect of chronic heart disease. Cardiac tissue engineering using induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) is a relatively new method that involves dedifferentiating cells from any tissue of the host into pluripotent stem cells. These cells are then guided to be differentiated into functioning myocardial cells that can be used to ...


Gaining Competencies During Early Medical Training: Medical Students As Teaching Assistants In Dissection-Based Anatomy Course, Martin T. Brown, Bruce Fenderson, Guiyan Zhang 2016 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Gaining Competencies During Early Medical Training: Medical Students As Teaching Assistants In Dissection-Based Anatomy Course, Martin T. Brown, Bruce Fenderson, Guiyan Zhang

Pathology, Anatomy and Cell Biology Posters

Introduction and Objectives

  • In 2002, ACGME identified six ACGME Core Competencies: patient care; medical knowledge; practice-based learning and improvement; interpersonal and communication skills; professionalism; and systems-based practice.
  • AAMC recommended lists of similar competencies for the curricula of medical schools. Competency based curricula have been widely implemented in medical schools.
  • Effective shifting in the graduate medical educational programs has been reported in various clinical specialties.
  • There is a lack of reported efforts and development on competency training in early preclinical years of medical education.

Objectives:

  • To explore methods for strengthening medical students’ competency training during preclinical undergraduate medical education.
  • To measure ...


Use Of Propensity Score Matching To Identify A Strong Association Between Strategic Concentration To Mitochondria-Sr Associations Of The Mitochondrial Ca2+ Uniporter: Ca2+ Uptake Hotspots In The Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Kinkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Shen, György Csordás 2016 MitoCare Center, Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA

Use Of Propensity Score Matching To Identify A Strong Association Between Strategic Concentration To Mitochondria-Sr Associations Of The Mitochondrial Ca2+ Uniporter: Ca2+ Uptake Hotspots In The Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Kinkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Shen, György Csordás

Pathology, Anatomy and Cell Biology Posters

Introduction:

  • Control of the mitochondrial ATP production by SR-derived Ca2+ signals includes local, nanodomain Ca2+ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).
  • Ca2+ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca2+-activated Ca2+ channel complex.
  • The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).


Review Of "The Human Embryonic Stem Cell Debate: Science, Ethics, And Public Policy (Basic Bioethics)," Edited By Suzanne Holland, Karen Lebacqz, And Laurie Zoloth, James Steele 2016 FranklinPierce Law Center

Review Of "The Human Embryonic Stem Cell Debate: Science, Ethics, And Public Policy (Basic Bioethics)," Edited By Suzanne Holland, Karen Lebacqz, And Laurie Zoloth, James Steele

University of New Hampshire Law Review

[Excerpt] "Perhaps like others, I started The Human Embryonic Stem Cell Debate not knowing many of the finer points of embryonic stem cell research, but I certainly had an opinion. This issue is far more complex than I had initially imagined. The editors do a commendable effort of compiling a sample of the innumerable arguments surrounding the debate."


Micu1 Regulation Of Mitochondrial Ca(2+) Uptake Dictates Survival And Tissue Regeneration., Anil Noronha Antony, Melanie Paillard, Cynthia Moffat, Egle Juskeviciute, Jason Correnti, Brad Bolon, Emanual Rubin, MD, György Csordás, Erin L Seifert, Jan B. Hoek, György Hajnóczky 2016 MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University

Micu1 Regulation Of Mitochondrial Ca(2+) Uptake Dictates Survival And Tissue Regeneration., Anil Noronha Antony, Melanie Paillard, Cynthia Moffat, Egle Juskeviciute, Jason Correnti, Brad Bolon, Emanual Rubin, Md, György Csordás, Erin L Seifert, Jan B. Hoek, György Hajnóczky

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Mitochondrial Ca(2+) uptake through the recently discovered Mitochondrial Calcium Uniporter (MCU) is controlled by its gatekeeper Mitochondrial Calcium Uptake 1 (MICU1). However, the physiological and pathological role of MICU1 remains unclear. Here we show that MICU1 is vital for adaptation to postnatal life and for tissue repair after injury. MICU1 knockout is perinatally lethal in mice without causing gross anatomical defects. We used liver regeneration after partial hepatectomy as a physiological stress response model. Upon MICU1 loss, early priming is unaffected, but the pro-inflammatory phase does not resolve and liver regeneration fails, with impaired cell cycle entry and extensive ...


Structure-Activity Relationships Governing The Interaction Of Nanoparticles With Mammalian Cells- Predictive Models For Toxicology And Medical Appliancesd, Marcus A. Maher 2016 Dublin Institute of Technology

Structure-Activity Relationships Governing The Interaction Of Nanoparticles With Mammalian Cells- Predictive Models For Toxicology And Medical Appliancesd, Marcus A. Maher

Doctoral

Nanoscience is seen as one of the key enabling technologies of the 20th century and as its range of applications increases it is important to look at how nanomaterials interact with biological environments. Some of these interactions have given rise to toxic effects and thus, the creation of the field of nanotoxicology, it has also been noted that current methods of evaluating toxicity may not be sufficient to keep up with the rapidly emerging range of nanomaterials becoming available. It is clear that alternatives are necessary. In this thesis, a phenomenological rate equation model is constructed to simulate nanoparticle uptake ...


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