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2018

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Articles 481 - 510 of 525

Full-Text Articles in Cell and Developmental Biology

Identifying The Role Of The Type-Ii Transmembrane Serine Protease Tmprss13 In Breast Cancer, Andrew Stevan Murray Jan 2018

Identifying The Role Of The Type-Ii Transmembrane Serine Protease Tmprss13 In Breast Cancer, Andrew Stevan Murray

Wayne State University Dissertations

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in women in the United States. Breast cancer progression is accompanied by increased expression of extracellular and cell surface proteases that are capable of degrading the extracellular matrix as well as cleaving and activating downstream targets. These proteolytic processes are critically involved in modifying the tissue microenvironment of the breast, which is necessary for cancer cell invasion and eventual dissemination of cancer cells to other organs. Therefore, identifying novel proteases that promote tumor progression is critical to create new approaches for developing improved breast …


Developing Small-Molecule Ribosomal Sensors, Joseph Noble Jan 2018

Developing Small-Molecule Ribosomal Sensors, Joseph Noble

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

No abstract provided.


Controlling Platelet Secretion To Modulate Hemostasis And Thrombosis, Smita Joshi Jan 2018

Controlling Platelet Secretion To Modulate Hemostasis And Thrombosis, Smita Joshi

Theses and Dissertations--Molecular and Cellular Biochemistry

Upon vascular injury, activated blood platelets fuse their granules to the plasma membrane and release cargo to regulate the vascular microenvironment, a dynamic process central to platelet function in many critical processes including hemostasis, thrombosis, immunity, wound healing, angiogenesis etc. This granule- plasma membrane fusion is mediated by a family of membrane proteins- Soluble N-ethyl maleimide Attachment Receptor Proteins(SNAREs). SNAREs that reside on vesicle (v-SNAREs) /Vesicle-Associated Membrane Proteins(VAMPs) interact with target/t-SNAREs forming a trans-bilayer complex that facilitates granule fusion. Though many components of exocytic machinery are identified, it is still not clear how it could be manipulated to prevent …


Elucidating The Role Of Nidogen In The Fusion Of The Choroid Fissure, Nicholas W. Carrara Jan 2018

Elucidating The Role Of Nidogen In The Fusion Of The Choroid Fissure, Nicholas W. Carrara

Theses and Dissertations--Biology

In the developing embryo, the timely fusion of opposing epithelial sheets into one uniform layer denotes the completion of several developmental events. Failure of this epithelial sheet fusion event (ESF) within the choroid fissure (CF) is associated with the congenital disorder Ocular Coloboma, and is one of the leading causes of pediatric blindness. A requirement for a highly coordinated dismantling of the basement membrane (BM) to allow for fusion to occur is undoubted, however the underlying mechanisms of this process are poorly understood. Due to its BM crosslinking capabilities, I have hypothesized that the regulation of nidogen plays a crucial …


Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara Jan 2018

Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara

Markey Cancer Center Faculty Publications

Background

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

Methods

We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m 2; every …


Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo Jan 2018

Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …


Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Eun Hee Kwon, Peter Julius, Qingsheng Li, John T. West, Charles Wood Jan 2018

Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Eun Hee Kwon, Peter Julius, Qingsheng Li, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Subtype C HIV-1 is responsible for the largest proportion of people living with HIV-1 infection. However, there is limited information about the roles of the brain and its cell types as a potential sanctuary for this subtype and how the sanctuary may be affected by the administration of anti-retroviral therapy (ART). To address this issue, we collected postmortem brain tissues from ART treated HIV-1 infected Zambian individuals who experienced complete viral suppression and those who did not. Tissues from various brain compartments were collected from each individual as frozen and formalin-fixed paraffin embedded brain specimens, for detection and quantification of …


Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Peter Julius, Qingsheng Li, John T. West, Charles Wood Jan 2018

Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Peter Julius, Qingsheng Li, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Subtype C HIV-1 is responsible for the largest proportion of people living with HIV-1 infection. However, there is limited information about the roles of the brain and its cell types as a potential sanctuary for this subtype and how the sanctuary may be affected by the administration of anti-retroviral therapy (ART). To address this issue, we collected postmortem brain tissues from ART treated HIV-1 infected Zambian individuals who experienced complete viral suppression and those who did not. Tissues from various brain compartments were collected from each individual as frozen and formalin-fixed paraffin embedded brain specimens, for detection and quantification of …


Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability In Primate Immunodeficiency Viruses, Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang Jan 2018

Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability In Primate Immunodeficiency Viruses, Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV. Changes that reduced the hydrophobicity of these V3 residues resulted in increased gp120 shedding and …


Ultrastructure Of Meelsvirus: A Nuclear Virus Of Arrow Worms (Phylum Chaetognatha) Producing Giant "Tailed" Virions, George L. Shinn, Brianna L. Bullard Jan 2018

Ultrastructure Of Meelsvirus: A Nuclear Virus Of Arrow Worms (Phylum Chaetognatha) Producing Giant "Tailed" Virions, George L. Shinn, Brianna L. Bullard

Nebraska Center for Virology: Faculty Publications

Most known giant viruses, i.e., viruses producing giant virions, parasitize amoebae and other unicellular eukaryotes. Although they vary in the level of dependence on host nuclear functions, their virions self-assemble in the host cell's cytoplasm. Here we report the discovery of a new prototype of giant virus infecting epidermal cells of the marine arrow worm Adhesisagitta hispida. Its 1.25 μm-long virions self-assemble and accumulate in the host cell's nucleus. Conventional transmission electron microscopy reveals that the virions have a unique bipartite structure. An ovoid nucleocapsid, situated in a broad "head" end of the virion is surrounded by a thin …


Development Of Septic Polysynovitis And Uveitis In Foals Experimentally Infected With Rhodococcus Equi, Laura Huber, Steeve Giguère, Londa J. Berghaus, Amanda Hanafi, Sarah Vitosh-Sillman, Sarah L. Czerwinski Jan 2018

Development Of Septic Polysynovitis And Uveitis In Foals Experimentally Infected With Rhodococcus Equi, Laura Huber, Steeve Giguère, Londa J. Berghaus, Amanda Hanafi, Sarah Vitosh-Sillman, Sarah L. Czerwinski

School of Veterinary and Biomedical Sciences: Faculty Publications

Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of …


Alkaline Stabilization Of Manure Slurry Inactivates Porcine Epidemic Diarrhea Virus, Erin E. Stevens, Daniel N. Miller, Bethany A. Brittenham, Sarah J. Vitosh-Sillman, Bruce W. Brodersen, Virginia L. Jin, John D. Loy, Amy M. Schmidt Jan 2018

Alkaline Stabilization Of Manure Slurry Inactivates Porcine Epidemic Diarrhea Virus, Erin E. Stevens, Daniel N. Miller, Bethany A. Brittenham, Sarah J. Vitosh-Sillman, Bruce W. Brodersen, Virginia L. Jin, John D. Loy, Amy M. Schmidt

School of Veterinary and Biomedical Sciences: Faculty Publications

Hydrated lime manure treatment was evaluated to determine porcine epidemic diarrhea virus (PEDV) susceptibility to alkaline stabilization. At pH 10, PEDV decreased (quantitative polymerase chain reaction) and lost infectivity (swine bioassay). Although ammonium decreased above pH 9 (up to 25%), alkaline stabilization managed to control potential infection from manure sources.


Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry Identification Of Moraxella Bovoculi And Moraxella Bovis Isolates From Cattle, Kara Robbins, Aaron M. Dickey, Michael L. Clawson, John Dustin Loy Jan 2018

Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry Identification Of Moraxella Bovoculi And Moraxella Bovis Isolates From Cattle, Kara Robbins, Aaron M. Dickey, Michael L. Clawson, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious bovine keratoconjunctivitis (IBK) is an economically significant disease caused by Moraxella bovis. Moraxella bovoculi, although not reported to cause IBK, has been isolated from the eyes of cattle diagnosed with IBK. Identification of M. bovis and M. bovoculi can be performed using biochemical or DNA-based approaches, both of which may be time consuming and inconsistent between laboratories. We conducted a comparative evaluation of M. bovoculi and M. bovis identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with a database provided by Bruker Daltonics (termed the BDAL database), the BDAL database supplemented with spectra generated in …


Circadian Behavioral Responses To Light And Optic Chiasm-Evoked Glutamatergic Epscs In The Suprachiasmatic Nucleus Of Iprgc Conditional Vglut2 Knock-Out Mice, Michael G. Moldavan, Patricia J. Sollars, Michael R. Lasarev, Charles N. Allen, Gary E. Pickard Jan 2018

Circadian Behavioral Responses To Light And Optic Chiasm-Evoked Glutamatergic Epscs In The Suprachiasmatic Nucleus Of Iprgc Conditional Vglut2 Knock-Out Mice, Michael G. Moldavan, Patricia J. Sollars, Michael R. Lasarev, Charles N. Allen, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN. vGlut2 has been conditionally deleted in ipRGCs in mice [conditional knock-outs (cKOs)] and their aberrant photoentrainment and residual attenuated light responses have been ascribed to ipRGC PACAP release. However, …


Development Of A Multiplex Real-Time Pcr Assay Using Two Thermocycling Platforms For Detection Of Major Bacterial Pathogens Associated With Bovine Respiratory Disease Complex From Clinical Samples, John Dustin Loy, Laura Leger, Aspen M. Workman, Michael L. Clawson, Ece Bulut, Bing Wang Jan 2018

Development Of A Multiplex Real-Time Pcr Assay Using Two Thermocycling Platforms For Detection Of Major Bacterial Pathogens Associated With Bovine Respiratory Disease Complex From Clinical Samples, John Dustin Loy, Laura Leger, Aspen M. Workman, Michael L. Clawson, Ece Bulut, Bing Wang

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine respiratory disease complex (BRDC) is one of the most significant diseases of cattle. Bacterial pathogens involved in BRDC include Mannheimia haemolytica, Mycoplasma bovis, Histophilus somni, and Pasteurella multocida. We developed and evaluated a multiplexed real-time hydrolysis probe (rtPCR) assay using block-based Peltier and rotary-based thermocycling on lung tissue, nasal swabs, and deep nasopharyngeal swabs. The rtPCR results were compared to culture or a gel-based M. bovis PCR using statistical analysis to determine optimum quantification cycle (Cq) cutoffs to maximize agreement. The limits of detection were 1.2–12 CFU/reaction for each pathogen. M. haemolytica was the most prevalent organism detected …


Coordinated Regulation Of Transcription By Ccpa And The Staphylococcus Aureus Twocomponent System Hptrs, Joseph M. Reed, Sean Olson, Danielle F. Brees, Caitlin E. Griffin, Ryan A. Grove, Paul J. Davis, Stephen D. Kachman, Jiri Adamec, Greg A. Somerville Jan 2018

Coordinated Regulation Of Transcription By Ccpa And The Staphylococcus Aureus Twocomponent System Hptrs, Joseph M. Reed, Sean Olson, Danielle F. Brees, Caitlin E. Griffin, Ryan A. Grove, Paul J. Davis, Stephen D. Kachman, Jiri Adamec, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

The success of Staphylococcus aureus as a pathogen is due in part to its ability to adapt to changing environmental conditions using signal transduction pathways, such as metaboliteresponsive regulators and two-component systems. S. aureus has a two-component system encoded by the gene pair sav0224 (hptS) and sav0223 (hptR) that regulate the hexose phosphate transport (uhpT) system in response to extracellular glucose-6-phosphate. Glycolytic intermediates such as glucose-6-phosphate are important carbon sources that also modulate the activity of the global metabolite-responsive transcriptional regulator CcpA. Because uhpT has a putative CcpA binding site in its promoter and …


Novel Docosahexaenoic Acid Ester Of Phloridzin Inhibits Proliferation And Triggers Apoptosis In An In Vitro Model Of Skin Cancer, Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe, Mihalis I. Panayiotidis Jan 2018

Novel Docosahexaenoic Acid Ester Of Phloridzin Inhibits Proliferation And Triggers Apoptosis In An In Vitro Model Of Skin Cancer, Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability …


Whole Genome Sequencing Of Moraxella Bovoculi Reveals High Genetic Diversity And Evidence For Interspecies Recombination At Multiple Loci, Aaron M. Dickey, Gennie Schuller, John D. Loy, Michael L. Clawson Jan 2018

Whole Genome Sequencing Of Moraxella Bovoculi Reveals High Genetic Diversity And Evidence For Interspecies Recombination At Multiple Loci, Aaron M. Dickey, Gennie Schuller, John D. Loy, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovoculi is frequently cultured from the ocular secretions and conjunctiva of cattle with Infectious Bovine Keratoconjunctivitis (IBK). Previous work has shown that single nucleotide polymorphism (SNP) diversity in this species is quite high with 81,284 SNPs identified in eight genomes representing two distinct genotypes isolated from IBK affected eyes (genotype 1) and the nasopharynx of cattle without clinical IBK signs (genotype 2), respectively. The goals of this study were to identify SNPs from a collection of geographically diverse and epidemiologically unlinked M. bovoculi strains from the eyes of IBK positive cattle (n = 183) and another from the eyes …


Differential Modulation Of Human Gabac‑Ρ1 Receptor By Sulfur‑Containing Compounds Structurally Related To Taurine, Lenin David Ochoa‑De La Paz, Martin González‑Andrade, Herminia Pasantes‑Morales, Rodrigo Franco, Rubén Zamora‑Alvarado, Edgar Zenteno, Hugo Quiroz‑Mercado, Roberto Gonzales‑Salinas, Rosario Gulias‑Cañizo Jan 2018

Differential Modulation Of Human Gabac‑Ρ1 Receptor By Sulfur‑Containing Compounds Structurally Related To Taurine, Lenin David Ochoa‑De La Paz, Martin González‑Andrade, Herminia Pasantes‑Morales, Rodrigo Franco, Rubén Zamora‑Alvarado, Edgar Zenteno, Hugo Quiroz‑Mercado, Roberto Gonzales‑Salinas, Rosario Gulias‑Cañizo

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: The amino acid taurine (2-Aminoethanesulfonic acid) modulates inhibitory neurotransmitter receptors. This study aimed to determine if the dual action of taurine on GABAC- ρ1R relates to its structure. To address this, we tested the ability of the structurally related compounds homotaurine, hypotaurine, and isethionic acid to modulate GABAC- ρ1R.

Results: In Xenopus laevis oocytes, hypotaurine and homotaurine partially activate heterologously expressed GABAC- ρ1R, showing an increment in its deactivation time with no changes in channel permeability, whereas isethionic acid showed no effect. Competitive assays suggest that hypotaurine and homotaurine compete for the GABA-binding site. In addition, their effects were …


Using Art And Story To Explore How Primary School Students In Rural Tanzania Understand Planetary Health: A Qualitative Analysis, Elizabeth Vanwormer, Jesca Mlawa, Elizabeth Komba, Christopher Gustafson, Hilda Mrema, Jenny M. Dauer Jan 2018

Using Art And Story To Explore How Primary School Students In Rural Tanzania Understand Planetary Health: A Qualitative Analysis, Elizabeth Vanwormer, Jesca Mlawa, Elizabeth Komba, Christopher Gustafson, Hilda Mrema, Jenny M. Dauer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background The global planetary health community increasingly recognises the need to prepare students to investigate and address connections between environmental change and human health. As we strive to support education on planetary health themes for students of all ages, understanding students’ concepts of linkages between the health of people and animals, and their shared environments might advance educational approaches. Children living in villages bordering Ruaha National Park in Iringa Region, Tanzania, have direct experience of these connections as they share a water-stressed but biodiverse environment with domestic animals and wildlife. Livelihoods in these villages depend predominantly on crop and livestock …


Tellurite Resistance In Shiga Toxin-Producing Escherichia Coli , Gentry L. Lewis, Quentin R. Jorgensen, John Dustin Loy, Rodney A. Moxley Jan 2018

Tellurite Resistance In Shiga Toxin-Producing Escherichia Coli , Gentry L. Lewis, Quentin R. Jorgensen, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Potassium tellurite ( K2TeO3) is an effective selective agent for O157:H7 Shiga toxin-producing Escherichia coli (STEC), whereas tellurite resistance in non-O157 STEC is variable with information on O45 minimal. High-level K2TeO3 resistance in STEC is attributable to the ter gene cluster with terD an indicator of the cluster’s presence. Polymerase chain reactions for terD and K2TeO3 minimum inhibitory concentration (MIC) determinations in broth cultures were conducted on 70 STEC and 40 non-STEC control organisms. Sixty-six STEC strains (94.3%) were terD+ compared to 28 control organisms (70.0%; P < 0.001). The prevalence of terD in …


Epitope Mapping Of Serca2a Identifies An Antigenic Determinant That Induces Mainly Atrial Myocarditis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Rajkumar Rajasekaran, Muhammad Z. Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S. Nandi, Paras K. Mishra, Raymond A. Sobel, Jennifer L. Strande, David Steffen, Jay Reddy Jan 2018

Epitope Mapping Of Serca2a Identifies An Antigenic Determinant That Induces Mainly Atrial Myocarditis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Rajkumar Rajasekaran, Muhammad Z. Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S. Nandi, Paras K. Mishra, Raymond A. Sobel, Jennifer L. Strande, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Sarcoplasmic/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a …


Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack Jan 2018

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …


The Effect Of Stress Induced Premature Senescence On The Expression Of Heterogeneous Ribonucleoieoprotein, Yuriy Pechenyy Jan 2018

The Effect Of Stress Induced Premature Senescence On The Expression Of Heterogeneous Ribonucleoieoprotein, Yuriy Pechenyy

Dissertations and Theses

The role of heterogeneous nuclear ribonucleoproteins (hnRNP) in cellular senescence is yet to be defined. Cellular senescence is a terminal growth arrest in somatic cells. It is thought to be the consequence of telomeric shortening that acts as a DNA damage signal. Conversely, cells induced into premature senescence (SIPS) by oxidative stress, is independent of telomere attrition. Premature senescence has been proposed to be physiologically relevant as it can be induced by treatment with chemotherapeutic agents. In particular, we are studying the roles of hnRNP A1 and A2 in the maintenance of the senescence phenotype. hnRNPs are a family of …


Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque Jan 2018

Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque

Dissertations and Theses

The thymus serves as the primary lymphoid organ responsible for the development and selection of a self-tolerant T cell repertoire. In paradox to its critical functions for the adaptive immune response, the thymus undergoes a profound age associated decline beginning in early adult life resulting in significant decline in T-cell function.Thymic epithelial cells (TECs) are the most critical component of the thymic microenvironment and undergo rapid turn-over, so understanding the cellular mechanisms responsible for the maintenance of TEC number and organization will be critical in counteracting age associated involution, particularly in cancer patients, due to enhanced degeneration in response to …


Effects Of Diabetes On Ovarian Cancer: Data Analysis And Modeling Study, Claire Belay Jan 2018

Effects Of Diabetes On Ovarian Cancer: Data Analysis And Modeling Study, Claire Belay

Theses and Dissertations

Ovarian cancer has one of the highest mortality rates of all gynecological cancers [13]. Further knowledge of risk factors for the growth of ovarian tumors would be beneficial in both the treatment and prevention of this type of cancer. Previous research has shown a positive correlation between diabetes and prostate tumor growth [22], The first aim of this study was to determine the effect of diabetes of ovarian tumor growth. The second aim was to develop a model to predict ovarian tumor growth based on the microenvironment within a patient’s body. The hypothesis was that there would be a positive …


An Optimized Solid-Phase Reduction And Capture Strategy For The Study Of Reversibly-Oxidized Cysteines And Its Application To Metal Toxicity, John Andrew Hitron Jan 2018

An Optimized Solid-Phase Reduction And Capture Strategy For The Study Of Reversibly-Oxidized Cysteines And Its Application To Metal Toxicity, John Andrew Hitron

Theses and Dissertations--Toxicology and Cancer Biology

The reversible oxidation of cysteine by reactive oxygen species (ROS) is both a mechanism for cellular protein signaling as well as a cause of cellular injury and death through the generation of oxidative stress. The study of cysteine oxidation is complicated by the methodology currently available to isolate and enrich oxidized-cysteine containing proteins. We sought to simplify this process by reducing the time needed to process samples and reducing sample loss and contamination risk.

We accomplished this by eliminating precipitation steps needed for the protocol by (a) introducing an in-solution NEM-quenching step prior to reduction and (b) replacing soluble dithiothreitol …


Cortactin Phosphorylation By Casein Kinase 2 Regulates Actin Related Protein 2/3 Complex Activity And Invadopodia Function, Steven Michael Markwell Jan 2018

Cortactin Phosphorylation By Casein Kinase 2 Regulates Actin Related Protein 2/3 Complex Activity And Invadopodia Function, Steven Michael Markwell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Malregulation of the actin cytoskeleton enhances tumor cell motility and invasion. The actin-binding protein cortactin facilitates branched actin network formation through activation of the actin-related protein (Arp) 2/3 complex. Arp2/3 complex activation is responsible for driving increased migration and extracellular matrix (ECM) degradation by governing invadopodia formation and activity. While cortactin-mediated activation of Arp2/3 complex and invadopodia regulation has been well established, signaling pathways responsible for governing cortactin binding to Arp2/3 are unknown. In this dissertation we identify casein kinase (CK) 2α phosphorylation of cortactin as a negative regulator of Arp2/3 binding. CK2α directly phosphorylates cortactin at a conserved threonine …


Deciphering The Role Of Adrenergic Hormones In Embryonic Cardiac Calcium Signaling And Metabolism, Jessica Peoples Jan 2018

Deciphering The Role Of Adrenergic Hormones In Embryonic Cardiac Calcium Signaling And Metabolism, Jessica Peoples

Electronic Theses and Dissertations

The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are critical regulators of mammalian cardiovascular physiology. NE and EPI mediate stress responses to enhance cardiovascular function, however dysregulation of adrenergic signaling leads to heart failure, congenital heart malformations, and sudden cardiac death. Adrenergic hormone-expressing cells were found in the early embryonic heart, and NE has been determined essential for embryonic cardiac development. Despite extensive work in adults, the regulatory roles and adrenergic targets of these hormones during embryonic cardiac development have not yet been fully determined. Prior transcriptomic studies from our lab showed that expression of signal transduction and metabolic genes …


Modulation Of Autophagy In Gbm Cells By Clinical Doses Of Gamma Radiation, Devron Ozgen Jan 2018

Modulation Of Autophagy In Gbm Cells By Clinical Doses Of Gamma Radiation, Devron Ozgen

Graduate Research Theses & Dissertations

Glioblastoma (GBM) is a highly aggressive cancer that forms from the astrocytes of the brain. Poor prognosis and rather unsuccessful treatment regimens have left researchers and patients looking for new therapeutic strategies to combat this dreadful disease. Following tumor resection and radiotherapy combined with temozolomide, survival only remains around 15 months. Recurrence is very commonly seen, and urgently needs to be further understood. Autophagy is an important mechanism within cancer cells, which allows for cellular organelle/amino acid recycling and thus contributes to energy metabolism. Autophagy machinery has been shown to control cell death within cancer cells, leading to our interest …