Endothelial Agonists Stimulate Vwf Release In Vitro And Trigger Ttp In Vivo, 2013 University of Iowa
Endothelial Agonists Stimulate Vwf Release In Vitro And Trigger Ttp In Vivo, Gilbert Van Schaeffer
Theses and Dissertations
Von Willebrand factor (VWF) is a plasma glycoprotein that can bind collagen at a wound site as well as circulating platelets. VWF forms high molecular weight multimers (>20,000 kDa). VWF can also form VWF strings that appear to be attached to the endothelial surface and are capable of binding platelets. These strings are only observed in vitro and in vivo in the absence of the VWF-cleaving protease ADAMTS13. Deficiency in ADAMTS13 results in thrombotic thrombocytopenic purpura (TTP), a clotting disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction, neurological dysfunction and fever. Patients suffering from TTP demonstrate VWF-and platelet-rich ...
Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, 2013 Florida International University
Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, Lorenzo P. Menzel
FIU Electronic Theses and Dissertations
The immune systems of cnidaria are important to study for two reasons: to gain a better understanding of the evolution of immune responses, and to provide a basis to partially redress the precipitous world-wide die-offs of reef corals, some of which have been attributed to diseases and stress. Many immune responses share ancient evolutionary origins and are common across many taxa.
Using Swiftia exserta, an azooxanthellate ahermatypic local octocoral, as a proxy model organism to study aspects of innate immunity in corals and cnidaria allows us to address both of the reasons listed above while not using endangered species. Utilizing ...
The Mechanisms And Consequences Of Gene Suppression During The Unfolded Protein Response, 2013 University of Iowa
The Mechanisms And Consequences Of Gene Suppression During The Unfolded Protein Response, Angela Marie Arensdorf
Theses and Dissertations
The endoplasmic reticulum (ER) facilitates the synthesis, assembly and quality control of all secretory, transmembrane, and resident proteins of the endomembrane system. An accumulation of unfolded proteins or a disruption in the specialized folding environment within the organelle causes ER stress, thus impairing the folding capacity of the ER. In response to this stress, the ER initiates a signaling cascade called the unfolded protein response (UPR) in an attempt to restore ER homeostasis.
The vertebrate UPR is propagated by three ER-resident transmembrane proteins (i.e., PERK, IRE1α, and ATF6α), each initiating a signaling cascade that ultimately culminates in production of ...
Focal Adhesion Kinase Signaling Regulates Highly Productive Transduction Of Adeno-Associated Virus Through Integrin-Mediated Endocytosis, Paul Michael Kaminsky
Theses and Dissertations
Recombinant adeno-associated virus (rAAV) is a widely used gene therapy vector. Although a wide range of rAAV serotypes can effectively enter most cell types, their transduction efficiencies (i.e., transgene expression) can vary widely depending on the target cell type. Integrins play important roles as co-receptors for rAAV infection, however, it remains unclear how integrin-dependent and -independent mechanisms of rAAV endocytosis influence the efficiency of intracellular virus processing and ultimately transgene expression. In this thesis, I examined the contribution of integrin-mediated endocytosis to transduction of fibroblasts by rAAV2. I found that promoting AAV2/integrin binding with Mn++ greatly enhanced (~17-fold ...
Flash4 Dark Reference Images, 2013 M.D. Anderson Cancer Center
Flash4 Dark Reference Images, George Mcnamara
Hamamatsu FLASH4.0 dark reference images, acquired with 10 second exposure times, no light to camera. Camera offset (set by Hamamatsu( is ~100 (the average intensity of the first image is always ~1 intensity level higher - an odd feature, but trivial in practice for a 16-bit camera).
George McNamara, Ph.D.
Single Cells Analyst at L.J.N. Cooper Lab
University of Texas M.D. Anderson Cancer Center
Identification Of Rtl1, A Retrotransposon-Derived Imprinted Gene, As A Novel Driver Of Hepatocarcinogenesis, Jesse D Riordan, Vincent W Keng, Barbara R Tschida, Todd E Scheetz, Jason B Bell, Kelly M Podetz-Pedersen, Catherine D Moser, Neal G Copeland, Nancy A Jenkins, Lewis R Roberts, David A Largaespada, Adam J Dupuy
Department of Anatomy and Cell Biology Publications
We previously utilized a Sleeping Beauty (SB) transposon mutagenesis screen to discover novel drivers of HCC. This approach identified recurrent mutations within the Dlk1-Dio3 imprinted domain, indicating that alteration of one or more elements within the domain provides a selective advantage to cells during the process of hepatocarcinogenesis. For the current study, we performed transcriptome and small RNA sequencing to profile gene expression in SB–induced HCCs in an attempt to clarify the genetic element(s) contributing to tumorigenesis. We identified strong induction of Retrotransposon-like 1 (Rtl1) expression as the only consistent alteration detected in all SB–induced tumors with ...
Functional Analysis Of A Putative Membrane-Bound Endo-Β-1,4-Glucanase From Panicum Virgatum, 2013 University of Tennessee - Knoxville
Functional Analysis Of A Putative Membrane-Bound Endo-Β-1,4-Glucanase From Panicum Virgatum, Joshua N Grant, Jonathan D. Willis, Neal Stewart
EURēCA: Exhibition of Undergraduate Research and Creative Achievement
Cellulose is the most abundant carbohydrate in the world and is degraded by the synergistic action of multiple enzymes. One large family of enzymes capable of hydrolyzing cellulose is glycoside hydrolase family 9 (GH9), which includes several endoglucanases. Recent research into the molecular biology of plants has revealed certain genes coding for endo-β-1,4-glucanases (EGases). The EGases in plants are primarily functional during cell elongation through wall stress relaxation. GH9 enzymes have been found in insects, bacteria, oomycetes, and fungi. In insects, EGases enable the organism to digest cellulose; in fungi, EGases are suspected to play an important role in ...
Video Codec Performance (Excel Spreadsheet), 2013 M.D. Anderson Cancer Center
Video Codec Performance (Excel Spreadsheet), George Mcnamara
Video codec performance (Excel spreadsheet). Movie was made in 2005-2006 when I worked at City of Hope National Medical Center. VTLF refers to Video Timelapse Light Facility. Videos were outputted from MetaMorph as AVI files. Personally, I always recommend uncompressed video files fro scientific uses. I also encourage posting the original scientific data format (ex. .lsm, .zvi, .lif, .stk).
Pubspectra Tattletales, 2013 M.D. Anderson Cancer Center
Pubspectra Tattletales, George Mcnamara
Tattletales for Multiplex Fluorescent Reporters in Single Cells for Metabolomics
As of April 2013: L.J.N. Cooper & D.A. Lee Cellular Immunotherapy Lab, University of Texas M.D. Anderson Cancer Center, Houston, TX
Email: email@example.com, firstname.lastname@example.org
Tattletales is my concept for spatial multiplexing many fluorescent protein (FP) biosensors in the same live cell. For example, there are excellent FP biosensors to Ca++ ions, pH, glucose, ribose, glutamine, glutamate, ATP, redox, ROS, pyruvate, cAMP, cGMP, IP3, PI(3,4,5)P3, cell cycle indicators (Fucci2), PKA, PKC, photsphatases, caspase(s) [1, 2]. However, these are typically used one biosensor per experiment, due in part to flooding the cell with soluble biosensor. That is, conventionally, either a metabolite (glucose) reporter or a signal transduction (Ca++) reporter can be imaged. By flooding the cell with the reporter, signal to noise ratio is compromized by autofluorescence.
Tattletales takes advantage of spatial multiplexing to both increase the number of different reporters, and improve signal to noise ratio by localizing each biosensor to a small volume. I started with the observation by Robinett et al  who localized 512 GFP-nls-LacI to a 256 LacO array as a 200 nm diameter diffraction limited spot (nuclear background due to overexpression). Many thousands of DNA binding proteins, of known sequence specifities, exist (LacI, TetR, GalR, etc for cell line studies; ZF-FPs, TALE-FPs to STRs, telomere repeat binding factors-FPs, etc for primary cells) and can be fused (as cDNAs) to different fluorescent proteins and FP biosensors.
Many biosensors are available as affinity series [1, 4], now enabling extended dynamic range. I realized that spatial multiplexing of many DNA binding protein-reporters by localizing to different spots in the cell nucleus and distinguished by combinatorial addressing, where N address colors provide 2^N addresses (example, 3 colors is 2^3 = 8 combinations). Multiplexing ...
Abnormal Trafficking Of Endogenously Expressed Bmpr2 Mutant Allelic Products In Patients With Heritable Pulmonary Arterial Hypertension, Andrea L Frump, Jonathan W. Lowery Ph.D., Rizwan Hamid, Eric D Austin, Mark De Caestecker
Faculty Publications and Research
More than 200 heterozygous mutations in the type 2 BMP receptor gene, BMPR2, have been identified in patients with Heritable Pulmonary Arterial Hypertension (HPAH). More severe clinical outcomes occur in patients with BMPR2 mutations by-passing nonsense-mediated mRNA decay (NMD negative mutations). These comprise 40% of HPAH mutations and are predicted to express BMPR2 mutant products. However expression of endogenous NMD negative BMPR2 mutant products and their effect on protein trafficking and signaling function have never been described. Here, we characterize the expression and trafficking of an HPAH-associated NMD negative BMPR2 mutation that results in an in-frame deletion of BMPR2 EXON2 ...
Evaluation Of Antibiotic Resistance Emerging From Use Of Antibiotics In Cafos, 2013 Xavier University
Evaluation Of Antibiotic Resistance Emerging From Use Of Antibiotics In Cafos, J. R. Robbins, D. Hellman, N. Pease, M. Costello
No abstract provided.
Embryonic Stem Cells Are Redirected To Non-Tumorigenic Epithelial Cell Fate By Interaction With The Mammary Microenvironment, Corinne A. Boulanger, Robert D. Bruno, David L. Mack, Monica Gonzales, Nadia P. Castro, David S. Salomon, Gilbert H. Smith
Medical Diagnostics & Translational Sciences Faculty Publications
Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+) progeny interspersed with normal mammary cell progeny in the mammary epithelial ...
Ferret Cftr Processing And Function, 2012 University of Iowa
Ferret Cftr Processing And Function, John T. Fisher
Theses and Dissertations
The most common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation is δF508 and this causes cystic fibrosis (CF). Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiologic mechanisms in CF and developing therapies. New CF models in the pig and ferret have been generated that develop lung, pancreatic, liver, and intestinal pathologies that reflect disease in CF patients. Species-specific biology in the processing of CFTR has demonstrated that pig and mouse δF508-CFTR proteins are more effectively processed to the apical membrane of airway epithelia than human δF508-CFTR. The processing behavior of ferret wild-type (WT) and ...
Cancer Gene Discovery And Immunosurveillance Studies Using Sleeping Beauty Mouse Models, 2012 University of Iowa
Cancer Gene Discovery And Immunosurveillance Studies Using Sleeping Beauty Mouse Models, Laura Marie Rogers
Theses and Dissertations
Cancer is the second leading cause of death in the United States. The majority of cases are caused by sporadic somatic mutation, which leads to cellular transformation over time. Therefore, cancer gene identification is a major focus of current research efforts. Understanding how key driver mutations result in cancer could lead to the design of better targeted therapies.
The Sleeping Beauty (SB) transposon system can be used to identify driver mutations in a variety of tumor types. SB mutagenesis mimics the sporadic accumulation of somatic mutations found in spontaneous human cancers. This system also has an additional benefit over chemical ...
Halloween 2012 Jack O'Lanterns Trick Or Treat, 2012 M.D. Anderson Cancer Center
Halloween 2012 Jack O'Lanterns Trick Or Treat, George Mcnamara
Halloween 2012 makes trick or treating more visual and interactive than in past years.
the download is a ZIP file containing three files.
Print out the (unnumbered) image on as large and nice printer paper as possible - I used glossy 44" wide here in Miami (University of Miami, MillerSchool of Medicine, Calder Library, Biomedical Communications dept - I also made another print on "fabric", also 44" wide to take with me to an HHMI Janelia Farm conference on 'turning images into knowledge' that ends on Oct 31 - might stay up for a second conference, "GFP..." that start Nov 4).
The other ...
Mcnamara 20120831fri-20120904tue Cosmic Ray Particles By Ccd Imaging, 2012 M.D. Anderson Cancer Center
Mcnamara 20120831fri-20120904tue Cosmic Ray Particles By Ccd Imaging, George Mcnamara
McNamara 20120831Fri-20120904Tue Cosmic Ray Particles by CCD imaging.zip contains image files in support of a Microscopy Today article - please see
Cosmic Ray Particles Images With Orca-Ii Erg, 2012 M.D. Anderson Cancer Center
Cosmic Ray Particles Images With Orca-Ii Erg, George Mcnamara
Cosmic ray particles image series acquired using a Hamamatsu ORCA-II ERG scientific grade CCD camera, cooled to -60 C. Each image is a consecutive 600 second (10 minute) exposure time with no light to the camera.
While processing the data, I discoverd that the background changed around planes 25 and 227 (see Excel file and jpeg screenshots), so I also processed only planes 025-227 (203 planes total, 2030 minutes, 33.83 hours). the CCD industry "rule of thumb" for a "typical" CCD sensor (i.e. 1/3" CCD) is that one cosmic ray particle strikes a sensor approximately every 30 ...
Transcription Factor Activator Protein 2 In Development And Disease Of The Neural Crest, 2012 University of Iowa
Transcription Factor Activator Protein 2 In Development And Disease Of The Neural Crest, Eric Scott Van Otterloo
Theses and Dissertations
The neural crest (NC) is a vertebrate specific early embryonic stem-cell population that forms an array of derivatives in the developing embryo. These cells are induced from the developing ectoderm at the boundary of the neural plate and non-neural ectoderm (termed the neural plate border). After initial induction the NC migrate along predefined routes within the developing embryo and upon reaching their destination begin to differentiate into this myriad of derivatives. These derivatives include neurons, glia, cartilage, bone, connective tissue and pigmented melanocytes, among others. Through genetic studies a variety of genes important in these various stages of NC development ...
Identification Of Genes Contributing To Preterm Birth: Insights From Genetic, Transcriptomic, And Epigenetic Analyses, Jinsil Kim
Theses and Dissertations
Preterm birth (PTB) is a global public health problem that has significant adverse effects on neonatal mortality and morbidity. Progress in understanding the pathological mechanisms underlying PTB has been greatly hampered by the complex and polygenic nature of the disease. As a result, a multifaceted approach may hold promise for identifying true causal factors. The main objective of this thesis is to identify genes that play a role in the etiology of PTB using experimental data derived from different molecular levels (genome, transcriptome, and epigenome). To achieve this goal, we performed association studies using a candidate gene approach to identify ...
Ral Gtpases Regulate Biogenesis Of Cell Polarity, 2012 University of Iowa
Ral Gtpases Regulate Biogenesis Of Cell Polarity, C. Clayton Hazelett
Theses and Dissertations
Cell polarity is the asymmetric distribution of organelles that almost all cells use to separate individual processes and perform complex functions. Although the manner in which cells are polarized is very diverse, the processes necessary to assume polarized phenotypes are similar in many cell types. Epithelial cell polarization is of particular importance, as these cells serve form linings of organs and act as barriers distinguishing different compartments. Furthermore, loss of epithelial polarization occurs in some disease states and may result in cell invasion through underlying matrix. During initial polarization, vesicle trafficking is indispensible for assembly of structures, including apical junctional ...