Digital Commons Network^™

Fusion, 2017, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Human Ipsc-Derived Cerebellar Neurons From A Patient With Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks, Sam Nayler, Joseph Powell, Darya Vanichkina, Othmar Korn, Christine Wells, Ryan J. Taft, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Ataxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and …

Visual Neurons In The Superior Colliculus Innervated By Islet2+ Or Islet2− Retinal Ganglion Cells Display Distinct Tuning Properties, Rachel Kay, Jason W. Triplett

Pediatrics Faculty Publications

Throughout the visual system, different subtypes of neurons are tuned to distinct aspects of the visual scene, establishing parallel circuits. Defining the mechanisms by which such tuning arises has been a long-standing challenge for neuroscience. To investigate this, we have focused on the retina’s projection to the superior colliculus (SC), where multiple visual neuron subtypes have been described. The SC receives inputs from a variety of retinal ganglion cell (RGC) subtypes; however, which RGCs drive the tuning of different SC neurons remains unclear. Here, we pursued a genetic approach that allowed us to determine the tuning properties of neurons innervated …

Characterization, Regulation, And Targeting Of Erythroid Progenitors In Normal And Disordered Human Erythropoiesis, B. M. Dulmovits, J. Hom, A. Narla, N. Mohandas, L. Blanc

Journal Articles

No abstract provided.

Unraveling Macrophage Heterogeneity In Erythroblastic Islands, K. G. Seu, J. Papoin, R. Fessler, J. Hom, G. Huang, N. Mohandas, L. Blanc, T. A. Kalfa

Journal Articles

No abstract provided.

Nicotinic Acetylcholine Receptor-Mediated Protection Of The Rat Heart Exposed To Ischemia Reperfusion, S. A. Mavropoulos, N. S. Khan, A. C. J. Levy, B. T. Faliks, C. P. Sison, V. A. Pavlov, Y. Zhang, K. Ojamaa

Journal Articles

No abstract provided.

The Effect Of K562-Il21-2 Plasma Membrane Particles On The Proliferation Of Natural Killer Cells To Fight Cancer, Michelle Prophete

Honors Undergraduate Theses

Immunotherapy has emerged as a current and future paradigm of cancer treatment, which utilizes the body’s immune system to eradicate cancer. Natural Killer (NK) cells as part of the innate immune system have immense potential in their anti-tumor cytotoxic activities and host cell surveillance properties. NK cells comprise approximately five to fifteen percent of peripheral blood lymphocytes and can be proliferated in vitro using recently developed methods with co-cultures with feeder cells (derived from engineered tumor cells) or plasma membrane (PM) particles, produced from the fore mentioned feeder cells, in combination with soluble cytokines. For efficient growth and maintenance of …

Employing The Enzyme Cofactor Function Of Ascorbic Acid To Affect Oncogenic Pathways In Human Melanoma: Modulating Hypoxia Inducible Factor-1Α And Dna Demethylation To Reduce Malignant Potential, Adam Patrick Fischer

Theses, Dissertations and Capstones

Dioxygenase enzymes such as the HIF hydroxylases (PHD1-3, FIH) and the Ten-eleven translocation (TET1-3) enzymes regulate the activity of the hypoxia inducible factor-1_a (HIF1_a) transcription factor and the DNA methylation status of cells, respectively. Aberrant accumulation and activation of HIF-1_a can allow malignant cells to acquire attributes that promote progression, chemotherapy resistance, and survival, while aberrant hypermethylation of gene promoters can silence the expression of tumor suppressor genes essential to preventing tumorigenesis. Inadequate levels of intracellular ascorbic acid (AA), a necessary cofactor for optimal dioxygenase enzyme function, could potentiate these tumorigenic conditions. In fact, plasma levels …

Characterization Of Malt1 Inhibitors And Their Effect On Leukemic Cell Growth Properties, Christina Snyder

Graduate School of Biomedical Sciences Theses and Dissertations

Leukemia is the most common childhood cancer, with a combined 40,000 predicted new cases in the United States in 2016 [8]. The two most common subtypes are acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) [9-11]. The commercially available inhibitor of Bruton’s tyrosine kinase (BTK) has shown promising results in clinical trials for CLL because of the importance of BCR signaling in CLL [12-15]. Recent studies suggest that the outgrowth of BTK inhibitor resistant clonal cells in some CLL patients results in a treatment-refractory phenotype [16-18]. MALT1, a protein involved in BCR activation of the NF-κB pathway that functions …

Hippocampal Astrocytes In Migrating And Wintering Semipalmated Sandpiper, Dario Carvalho-Paulo, Nara G De Morais Magalhães, Diego De Almeida Miranda, Daniel G Diniz, Ediely P Henrique, Isis A M Moraes, Patrick D C Pereira, Mauro A D De Melo, Camila M De Lima, Marcus A De Oliveira, Cristovam Guerreiro-Diniz, David F Sherry, Cristovam W P Diniz

Brain and Mind Institute Researchers' Publications

Seasonal migratory birds return to the same breeding and wintering grounds year after year, and migratory long-distance shorebirds are good examples of this. These tasks require learning and long-term spatial memory abilities that are integrated into a navigational system for repeatedly locating breeding, wintering, and stopover sites. Previous investigations focused on the neurobiological basis of hippocampal plasticity and numerical estimates of hippocampal neurogenesis in birds but only a few studies investigated potential contributions of glial cells to hippocampal-dependent tasks related to migration. Here we hypothesized that the astrocytes of migrating and wintering birds may exhibit significant morphological and numerical differences …

“Whatever It Takes To Beat Parkinson’S”: A Controversial Approach For Symptom Relief, Sondra M. Deskins

WRIT: Journal of First-Year Writing

It is known that there is no cure for Parkinson's disease. So, physicians who treat Parkinson's patients must decide what is the best treatment option for the patients symptoms to improve their quality of life. Currently, there are pharmaceutical options for treatment, but they include adverse side effects. What if there were a way to treat patients for the side effects as well as improve the patient's symptoms? The recent commotion around the legalization of marijuana, both recreational and medicinal, has caused interest among patients and physicians. One must decide if the benefits of using marijuana as a form of …

A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signalling In Htlv-1-Associated Neuroinflammation., Soraya Maria Menezes, Fabio E Leal, Tim Dierckx, Ricardo Khouri, Daniele Decanine, Gilvaneia Silva-Santos, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely Adult T-cell Leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fashi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP …

Uncorrelated Neural Firing In Mouse Visual Cortex During Spontaneous Retinal Waves, Matthew Colonnese, Jing Shen, Yasunobu Murata

Pharmacology and Physiology Faculty Publications

Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column. To study this we used single-shank multi-electrode array recordings of spontaneous activity …

Endovascular Embolization In The Management Of Traumatic Andpostoperative Abdominopelvic Bleeding: A Single-Center Experience, Di̇lek Sağlam, Hasan Di̇nç, Abdulkadi̇r Gündüz, Ayşegül Cansu, Mehmet Hali̇l Öztürk

Turkish Journal of Medical Sciences

Background/aim: Endovascular embolization is widely used instead of surgery in the treatment of traumatic and postoperative abdominopelvic bleeding. The objective of this study is to evaluate the efficiency of computed tomography in the determination of active bleeding and the efficiency of endovascular embolization in traumatic and postoperative abdominopelvic bleeding. Materials and methods: Thirty-one patients admitted to our hospital with traumatic and postoperative abdominopelvic bleeding between January 2006 and September 2012 and treated with endovascular embolization were retrospectively enrolled in the study. In 15 hemodynamically stable patients, abdominal computed tomography was performed to detect the presence and/or localization of the hemorrhage. …

Risk Factors For Colistin-Associated Nephrotoxicity And Mortality In Critically Ill Patients, Hüseyi̇n Özkarakaş, Işil Köse, Çi̇ler Zi̇nci̇rci̇oğlu, Si̇bel Ersan, Gürsel Ersan, Ni̇met Şenoğlu, Şükran Köse, Riza Hakan Erbay

Turkish Journal of Medical Sciences

Background/aim: Colistin is gaining popularity against multidrug-resistant bacteria. The primary concern with colistin is its nephrotoxicity (NT). The aim of this study was to evaluate the incidence and risk factors for NT and to evaluate the risk factors for mortality in the toxicity group. Materials and methods: NT was defined according to the RIFLE criteria. Data of patients who did or did not develop NT were compared. Positive and negative predictive values, risk ratio, and correlation coefficients were calculated. Results: NT was seen in 39 patients (70%). Hypoalbuminemia, old age, and the use of vasopressors (VPs) were associated with NT. …

Unknown Vascular Compression Of The Airway In Patients With Congenitalheart Disease And Persistent Lower Respiratory Symptoms, Tuğba Şi̇şmanlar Eyüboğlu, Ayşe Tana Aslan, Çi̇ğdem Öztunali, Fatma Sedef Tunaoğlu, Ayşe Deni̇z Oğuz, Serdar Kula, Betül Emi̇ne Deri̇nkuyu, Öznur Leman Boyunaga

Turkish Journal of Medical Sciences

Background/aim: Airway compression (AC) by vascular structures is an important complication of congenital heart disease (CHD) that often goes unrecognized. It is not easy to identify whether CHD patients require additional invasive examinations or not. Therefore, the present study aims to develop an AC diagnostic algorithm for CHD patients. Materials and methods: CHD patients with persistent respiratory symptoms that were treated between January 2007 and December 2015 were retrospectively reviewed. The following data were recorded for all CHD patients with AC: age, cardiac anomalies, the compressed structure, the airway diameter ratio (ADR), the compressing structure(s), treatment, and follow-up.Results: During the …

The Microbial Ecosystem Of Beer Spoilage And Souring: Competition And Cooperation In The Age Of Bioinformatics, Andrew Kettring

Electronic Theses and Dissertations

The brewing industry generates $350 billion in revenue in the US annually, representing 1.9% of the gross domestic product. Spoilage is a persistent problem throughout production and distribution that causes economic loss, and is therefore meticulously avoided. Contrarily, artisanal sour beers are necessarily produced by a diverse variety of these spoilage organisms metabolically interacting in symbiosis as a microbial ecosystem. We sought to gain insight into factors driving assembly of microbial communities by testing a long-debated Darwinian hypothesis. A collection of community members were screened in co-culture and novel bioinformatics tools were developed to predict observed interactions. A fundamental understanding …

The Role Of Frabin (Fgd4) In Aggressive Prostate Cancer, Alexia M. Bossan

Honors Undergraduate Theses

A major problem in prostate cancer (PCa) management is the development of drug resistance. It is known that there are changes in PCa biology upon prolonged treatment with drugs, including anti-androgen drugs that alter cellular signaling processes leading to the development of castration resistant PCa. MicroRNAs (miRNAs) are regulatory molecules that modulate gene expression through inhibition of protein translation and modulate cellular functions. Altered expression of miRNAs is often noted in drug resistant cancer including PCa. Studies from our laboratory have identified a number of down-regulated miRNAs in PCa, including miR-l 7-92a miRNAs. Frabin (FGD4) is a target of the …

An Rnai Screen To Identify Components Of A Polyamine Transport System, Adam J. Foley

Honors Undergraduate Theses

Polyamines, specifically putrescine, spermidine, and spermine, are small cationic molecules found in all organisms. Cells can biosynthetically make these molecules, or alternatively, they can be transported from the extracellular environment. Malignant cells have been shown to require relatively high amounts of polyamines. There is a chemotherapeutic agent, DFMO, used to block the biosynthesis of polyamines. Many malignant cells can circumvent DFMO therapy by activating their transport system. A potential solution is to simultaneously block biosynthesis and transport of polyamines. However, little is known about the polyamine transport system in higher eukaryotes.

This thesis aims to add to the basic biological …

Tryptophan 375 Stabilizes The Outer-Domain Core Of Gp120 For Hiv Vaccine Immunogen Design, Duoyi Hu, Dane Bowder, Wenzhong Wei, Jesse Thompson, Mark A. Wilson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a …

Gold Nanoparticles In Clp Model And Mechanism In Bone Marrows Derived Macrophages Cell For Sepsis Severity Attenuation, Sujittra Taratummarat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Sepsis is still a major worldwide- public health problem as a leading cause of the high mortality rate condition. Sepsis is the inflammatory condition in host due to bacterial infections. Sepsis severity depends on the individual's immune responses and the organism virulence factor. The current strategies for sepsis treatment are based, mainly on, symptomatic treatment with antibiotics. However, the adjuvant therapy in sepsis is interesting. Gold nanoparticles are anti-inflammatory drug from the ancient time which is still currently used for the treatment of rheumatoid arthritis. Thus, we hypothesized that gold nanoparticles could be effective in reducing an inflammation in sepsis …

Preferential Lineage-Specific Differentiation Of Osteoblast-Derived Induced Pluripotent Stem Cells Into Osteoprogenitors, Casey L. Roberts, Silvia S. Chen, Angela C. Murchison, Rebecca A. Ogle, Michael P. Francis, Roy C. Ogle, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

While induced pluripotent stem cells (iPSCs) hold great clinical promise, one hurdle that remains is the existence of a parental germ-layer memory in reprogrammed cells leading to preferential differentiation fates. While it is problematic for generating cells vastly different from the reprogrammed cells' origins, it could be advantageous for the reliable generation of germ-layer specific cell types for future therapeutic use. Here we use human osteoblast-derived iPSCs (hOB-iPSCs) to generate induced osteoprogenitors (iOPs). Osteoblasts were successfully reprogrammed and demonstrated by endogenous upregulation of Oct4, Sox2, Nanog, TRA-1-81, TRA-16-1, SSEA3, and confirmatory hPSC Scorecard Algorithmic Assessment. The hOB-iPSCs formed embryoid bodies …

Electrosensitization Increases Antitumor Effectiveness Of Nanosecond Pulsed Electric Fields In Vivo, Claudia Muratori, Andrei G. Pakhomov, Loree Heller, Maura Casciola, Elena Gianulis, Sergey Grigoryev, Shu Xiao, Olga N. Pakhomova

Bioelectrics Publications

Nanosecond pulsed electric fields are emerging as a new modality for tissue and tumor ablation. We previously reported that cells exposed to pulsed electric fields develop hypersensitivity to subsequent pulsed electric field applications. This phenomenon, named electrosensitization, is evoked by splitting the pulsed electric field treatment in fractions (split-dose treatments) and causes in vitro a 2- to 3-fold increase in cytotoxicity. The aim of this study was to show the benefit of split-dose treatments for in vivo tumor ablation by nanosecond pulsed electric field. KLN 205 squamous carcinoma cells were embedded in an agarose gel or grown subcutaneously as tumors …

Characterization Of Molecular Pathways Involved In The Production Of Class-Switched Antibodies, Arthur James Vanvalkenburg

All ETDs from UAB

This dissertation research describes two independent characterizations of molecular pathways involved in the manufacture of class-switched antibodies and differentiation of B cells involving the adaptor protein Hematopoietic SRC Homology 2 Domain-containing protein (HSH2) and the surface molecule CD19. HSH2 is dynamically expressed in different subsets of B cells, showing high expression in B1 and MZ B cells and low expression in GC B cells. Experiments involving HSH2 transgenic mice have determined that HSH2 may act as a rheostat regulating the production of class-switched antibodies. Various factors that stimulate B cell activation and differentiation induce HSH2 expression, although regulation of HSH2 …

The Cytotoxicity Of Essential Oils On Mcf-7 Breast Cancer Cells, Desalyn Johnson, Shaylee Green

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Synaptotagmin C2b Ca2+-Binding Loops Impose Distinct Exocytosis Phenotypes, Michael W. Schmidtke

Wayne State University Theses

Regulated exocytosis from chromaffin cells in the adrenal medulla plays a critical role in maintaining organismal homeostasis. In the absence of stress, these cells release physiologically relevant substances into the blood stream only in limited quantities, whereas stressful conditions result in a rapid deluge of signaling molecules used, for example, to increase heart rate and pain tolerance. Although the cellular mechanisms governing the switch from low-level to stress-induced secretion are not well understood, recent evidence has implicated the exocytotic Ca2+-sensing protein Synaptotagmin (Syt) in this role.

Two isoforms of Syt are expressed in chromaffin cells (Syt-1 and Syt-7), and each …

Biomarker And Shear Stress In Secondary Pediatric Pulmonary Hypertension, Ayhan Pektaş, Fatma Rana Olguntürk, Serdar Kula, Erman Çi̇lsal, Ayşe Deni̇z Oğuz, Fatma Sedef Tunaoğlu

Turkish Journal of Medical Sciences

Background/aim: Endothelial dysfunction, tissue damage, inflammation, and microthrombosis are involved in the pathogenesis of pulmonary hypertension (PH), which may be present as a complication of congenital heart diseases. This study aims to identify how indicators of endothelial dysfunction (shear stress), tissue damage (brain natriuretic peptide and troponin T), inflammation (C-reactive protein (CRP)), and microthrombosis (D-dimer and von Willebrand factor) are altered in children with congenital left-to-right shunting. Materials and methods: This is a review of 25 children who developed PH due to congenital left-to-right shunting, 40 children who underwent corrective surgery for congenital left-to-right shunting, and 40 healthy children.Results: Serum …

Detoxification Of Mitochondrial Oxidants And Apoptotic Signaling Are Facilitated By Thioredoxin-2 And Peroxiredoxin-3 During Hyperoxic Injury, Benjamin J. Forred, Darwin R. Daugaard, Brianna K. Titus, Ryan R. Wood, Miranda J. Floen, Michelle L. Booze, Peter F. Vitiello

School of Veterinary and Biomedical Sciences: Faculty Publications

Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2). The goal of this study was to understand the role of the mitochondrial thioredoxin system and mitochondrial injuries during …

Doxorubicin-Conjugated Dexamethasone Induced Mcf-7 Apoptosis Without Entering The Nucleus And Able To Overcome Mdr-1-Induced Resistance, Kamontip Chaikomon

Chulalongkorn University Theses and Dissertations (Chula ETD)

Doxorubicin is a common chemotherapeutic drug that generally uses in many solid and hematologic malignancies. The main mechanism of doxorubicin is inhibition of topoisomerase II that occurs in the nucleus. Currently, doxorubicin resistant cancer cells which have decreased accumulation of intracellular doxorubicin resulting from an efflux pump, P-glycoprotein encoded by multidrug resistant gene. Several studies reported many different ways to overcome doxorubicin resistance. In this study, we conjugated 3'amino group of doxorubicin to dexamethasone molecule. Despite of lower cytotoxic activity in MCF-7 cells, the conjugated product, DexDOX, exerted its actions in the different fashion to doxorubicin. DexDOX rapidly induced MCF-7 …

The Skin Microbiome: Impact Of Modern Environments On Skin Ecology, Barrier Integrity, And Systemic Immune Programming, Susan Prescott, Danica-Lea Larcombe, Alan Logan, Christina West, Wesley Burks, Luis Caraballo, Michael Levin, Eddie Van Etten, Pierre Horwitz, Anita Kozyrskyj, Dianne Campbell

Research outputs 2014 to 2021

Skin barrier structure and function is essential to human health. Hitherto unrecognized functions of epidermal keratinocytes show that the skin plays an important role in adapting whole-body physiology to changing environments, including the capacity to produce a wide variety of hormones, neurotransmitters and cytokine that can potentially influence whole-body states, and quite possibly, even emotions. Skin microbiota play an integral role in the maturation and homeostatic regulation of keratinocytes and host immune networks with systemic implications. As our primary interface with the external environment, the biodiversity of skin habitats is heavily influenced by the biodiversity of the ecosystems in which …