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Environmental Signaling Through The Target Of Rapamycin Complex 1 (Torc1) And The Regulation Of Epigenetic Mechanisms, Jason J. Workman 2016 University of Tennessee Health Science Center

Environmental Signaling Through The Target Of Rapamycin Complex 1 (Torc1) And The Regulation Of Epigenetic Mechanisms, Jason J. Workman

Theses and Dissertations (ETD)

The gene expression profile of a eukaryotic cell is responsive to a variety of extracellular stimuli, including nutrient availability, which allows cells to toggle between anabolism and catabolism based on the favorability of their environment. Much of this information is relayed through signaling complexes, such as the target of rapamycin complex 1 (TORC1), to downstream chromatin modifying enzymes. These enzymes impact the gene regulatory process through altered histone post-translation modifications, changes in chromatin structure, and docking of chromatin regulatory complexes. Yet, despite preliminary studies suggesting that TORC1 affects epigenetic mechanisms, including histone H3 lysine 56 acetylation (H3K56ac), almost nothing is ...


Mirna-145 Increases Therapeutic Sensibility To Gemcitabine Treatment Of Pancreatic Adenocarcinoma Cells., Yong Lin, Xin Ge, Yiyang Wen, Zhu-Mei Shi, Qiu-Dan Chen, Min Wang, Ling-Zhi Liu, Bing-Hua Jiang, Yuan Lu 2016 Department of Laboratory Medicine, Huashan Hospital of Fudan University, Shanghai, China; The Department of Clinical Laboratory, Central Laboratory, Jing'an District Centre Hospital of Shanghai, Huashan Hospital of Fudan University Jing'An Branch, Shanghai, China

Mirna-145 Increases Therapeutic Sensibility To Gemcitabine Treatment Of Pancreatic Adenocarcinoma Cells., Yong Lin, Xin Ge, Yiyang Wen, Zhu-Mei Shi, Qiu-Dan Chen, Min Wang, Ling-Zhi Liu, Bing-Hua Jiang, Yuan Lu

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Pancreatic adenocarcinoma is one of the most leading causes of cancer-related deaths worldwide. Although recent advances provide various treatment options, pancreatic adenocarcinoma has poor prognosis due to its late diagnosis and ineffective therapeutic multimodality. Gemcitabine is the effective first-line drug in pancreatic adenocarcinoma treatment. However, gemcitabine chemoresistance of pancreatic adenocarcinoma cells has been a major obstacle for limiting its treatment effect. Our study found that p70S6K1 plays an important role in gemcitabine chemoresistence. MiR-145 is a tumor suppressor which directly targets p70S6K1 for inhibiting its expression in pancreatic adenocarcinoma, providing new therapeutic scheme. Our findings revealed a new mechanism underlying ...


Integrated Live Imaging And Molecular Profiling Of Embryoid Bodies Reveals A Synchronized Progression Of Early Differentiation., Jonathan Boxman, Naor Sagy, Sirisha Achanta, Rajanikanth Vadigepalli, Iftach Nachman 2016 Tel Aviv University

Integrated Live Imaging And Molecular Profiling Of Embryoid Bodies Reveals A Synchronized Progression Of Early Differentiation., Jonathan Boxman, Naor Sagy, Sirisha Achanta, Rajanikanth Vadigepalli, Iftach Nachman

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Embryonic stem cells can spontaneously differentiate into cell types of all germ layers within embryoid bodies (EBs) in a highly variable manner. Whether there exists an intrinsic differentiation program common to all EBs is unknown. Here, we present a novel combination of high-throughput live two-photon imaging and gene expression profiling to study early differentiation dynamics spontaneously occurring within developing EBs. Onset timing of Brachyury-GFP was highly variable across EBs, while the spatial patterns as well as the dynamics of mesendodermal progression following onset were remarkably similar. We therefore defined a 'developmental clock' using the Brachyury-GFP signal onset timing. Mapping snapshot ...


Performance Of Creatinine And Chloride On The Epoc Analyzer, Lilah Evans, Susanne Gallo, Stacey K. Mardekian, Barbara Goldsmith, PhD, FACB 2016 Thomas Jefferson University Hospitals, Philadelphia, PA, USA

Performance Of Creatinine And Chloride On The Epoc Analyzer, Lilah Evans, Susanne Gallo, Stacey K. Mardekian, Barbara Goldsmith, Phd, Facb

Pathology, Anatomy and Cell Biology Posters

BACKGROUND

The epoc Blood Analysis System (Alere, Orlando, FL) performs blood gases, electrolytes, and metabolites using a Blood Gas Electrolyte and Metabolite (BGEM) Test Card panel on 92 uL of whole blood. The BGEM test card uses potentiometric sensors to measure sodium, potassium, ionized calcium, pH, pCO2; amperometric sensors to measure pO2, glucose, and lactate; and a conductometric sensor to measure hematocrit. Results are available in 3-10 minutes, depending upon the time between calibration and patient testing. TJUH implemented the epoc in its ICUs in 2012 to provide Point of Care (POC) results. Alere recently added creatinine and chloride sensors ...


Activated Clotting Time (Act): Comparison Of The Hemochron Signature Elite And The Abbott I-Stat, Lilah Evans, Susanne Gallo, Joseph J. Leo, Barbara Goldsmith, PhD, FACB 2016 Thomas Jefferson University Hospitals, Philadelphia, PA, USA

Activated Clotting Time (Act): Comparison Of The Hemochron Signature Elite And The Abbott I-Stat, Lilah Evans, Susanne Gallo, Joseph J. Leo, Barbara Goldsmith, Phd, Facb

Pathology, Anatomy and Cell Biology Posters

BACKGROUND

ACT is commonly used for heparin anticoagulation monitoring during procedures including cardiopulmonary bypass surgery, coronary angioplasty, and interventional radiology. To prevent thrombosis, moderate to high levels of heparin anticoagulation are required. The Hemochron Signature Elite (HSE, Accriva Diagnostics, formerly ITC, San Diego, CA) was implemented at TJUH as a replacement for the older model Hemochron Response (Accriva/ITC Model HRS.110, San Diego, CA). Operating room (OR) perfusionists reported irreproducible high results using HSE that could not be explained clinically. In consideration of use of i-STAT analyzers (Abbott Point of Care, Princeton, NJ) as an alternative to HSE, we ...


Exome-Based Variant Detection In Core Promoters., Yeong C. Kim, Jian Cui, Jiangtao Luo, Fengxia Xiao, Bradley Downs, San Ming Wang 2016 University of Nebraska Medical Center

Exome-Based Variant Detection In Core Promoters., Yeong C. Kim, Jian Cui, Jiangtao Luo, Fengxia Xiao, Bradley Downs, San Ming Wang

Journal Articles: Genetics, Cell Biology & Anatomy

Core promoter controls the initiation of transcription. Core promoter sequence change can disrupt transcriptional regulation, lead to impairment of gene expression and ultimately diseases. Therefore, comprehensive characterization of core promoters is essential to understand normal and abnormal gene expression in biomedical studies. Here we report the development of EVDC (Exome-based Variant Detection in Core promoters) method for genome-scale analysis of core-promoter sequence variation. This method is based on the fact that exome sequences contain the sequences not only from coding exons but also from non-coding region including core promoters generated by random fragmentation in exome sequencing process. Using exome data ...


Cytojournal Quiz Cases: Publishing Open-Access, Pubmed-Searchable Cytopathology Cases With Educational Messages, Katherine G. Akers, Vinod B. Shidham 2016 Wayne State University

Cytojournal Quiz Cases: Publishing Open-Access, Pubmed-Searchable Cytopathology Cases With Educational Messages, Katherine G. Akers, Vinod B. Shidham

Library Scholarly Publications

No abstract provided.


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 ...


Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay 2016 Loma Linda University

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It ...


Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue 2016 Loma Linda University

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of ...


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 ...


Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida 2016 Wright State University - Main Campus

Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in ...


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 ...


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 ...


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 ...


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 ...


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