Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa,
2018
University of Nebraska- Lincoln
Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti
Nebraska Center for Virology: Faculty Publications
We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus (HPV) genotyping assay to fill the need for rapid and low‐cost HPV detection in Sub‐ Saharan Africa. This method allows high throughput genotyping and simultaneous detection of 14 high‐risk and two low‐risk HPV types, by PCR amplification of HPV DNAs in a single reaction tube. In this study, we describe stepwise experiments to validate the multiplex HPV PCR assay for determination of HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay performance was evaluated by determination of intra‐laboratory reproducibility, sensitivity, and specificity. Further performance was assessed by …
Discovery Of A Non-Nucleoside Rna Polymerase
Inhibitor For Blocking Zika Virus Replication
Through In Silico Screening,
2018
University of Nebraska-Lincoln
Discovery Of A Non-Nucleoside Rna Polymerase Inhibitor For Blocking Zika Virus Replication Through In Silico Screening, Aryamav Pattnaik, Nicholas Palermo, Bikash R. Sahoo, Zhe Yuan, Duoyi Hu, Arun S. Annamalai, Hiep L. X. Vu, Ignacio Correas, Pavan Kumar Prathipati, Christopher J. Destache, Qingsheng Li, Fernando A. Osorio, Asit K. Pattnaik, Shi-Hua Xiang
Nebraska Center for Virology: Faculty Publications
Zika virus (ZIKV), an emerging arbovirus, has become a major human health concern globally due to its association with congenital abnormalities and neurological diseases. Licensed vaccines or antivirals against ZIKV are currently unavailable. Here, by employing a structure-based approach targeting the ZIKV RNA-dependent RNA polymerase (RdRp), we conducted in silico screening of a library of 100,000 small molecules and tested the top ten lead compounds for their ability to inhibit the virus replication in cell-based in vitro assays. One compound, 3-chloro-N-[({4-[4-(2-thienylcarbonyl)-1-piperazinyl]phenyl}amino)carbonothioyl]-1-benzothiophene-2-carboxamide (TPB), potently inhibited ZIKV replication at submicromolar concentrations. Molecular docking analysis suggests that …
Role Of Oxidized Extracellular Vesicles As Early Biomarkers And Inflammatory Mediators In Chemotherapy-Induced Normal Tissue Injury,
2018
University of Kentucky
Role Of Oxidized Extracellular Vesicles As Early Biomarkers And Inflammatory Mediators In Chemotherapy-Induced Normal Tissue Injury, Chontida Yarana
Theses and Dissertations--Toxicology and Cancer Biology
Significant advances in the efficacy of cancer therapy have been accompanied by an escalation of side effects that result from therapy-induced injury to normal tissues. Patients with high grade cancer or metastasis are often treated with chemotherapy, 50% of which are associated with reactive oxygen species generation and cellular oxidative stress. Heart is the normal tissue most susceptible to chemotherapy-induced oxidative stress and heart disease is the most common leading cause of death in cancer survivors. However, early and sensitive biomarkers to identify heart disease are still lacking. Extracellular vesicles (EVs) are released from cells during oxidative stress and send …
Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases,
2018
Edith Cowan University
Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, Ian James Martins
Research outputs 2014 to 2021
Biotherapeutics and nutritional therapy are essential for the treatment of endoplasmic reticulum (ER) stress in diabetes and neurodegenerative diseases. Oxidative stress and nutrient excess may induce ER stress associated with activation of the unfolded protein response and connected to cell death. The heat shock gene Sirtuin 1 (Sirt 1) is important to the heat shock response with amyloid beta aggregation associated with the induction of mitophagy and ER stress in neuron cells. Genomic medicine that activates nuclear Sirt 1 is essential for the prevention of mitochondrial apoptosis and ER stress. Inhibitors such as drugs, alcohol, excess caffeine and palmitic acid …
Saturation Mutagenesis Reveals Manifold Determinants Of Exon Definition.,
2018
Columbia University; Jackson Laboratory, Bar Harbor, ME
Saturation Mutagenesis Reveals Manifold Determinants Of Exon Definition., Shengdong Ke, Vincent Anquetil, Jorge Rojas Zamalloa, Alisha Maity, Anthony Yang, Mauricio A. Arias, Sergey Kalachikov, James J Russo, Jingyue Ju, Lawrence A. Chasin
Student Papers, Posters & Projects
To illuminate the extent and roles of exonic sequences in the splicing of human RNA transcripts, we conducted saturation mutagenesis of a 51-nt internal exon in a three-exon minigene. All possible single and tandem dinucleotide substitutions were surveyed. Using high-throughput genetics, 5560 minigene molecules were assayed for splicing in human HEK293 cells. Up to 70% of mutations produced substantial (greater than twofold) phenotypes of either increased or decreased splicing. Of all predicted secondary structural elements, only a single 15-nt stem-loop showed a strong correlation with splicing, acting negatively. The in vitro formation of exon-protein complexes between the mutant molecules and …
The Role Of Pro-Inflammatory Mediators Ifnβ And Prostaglandin E2 In Suppression Of Innate Immunity To Listeria Monocytogenes,
2018
University of Kentucky
The Role Of Pro-Inflammatory Mediators Ifnβ And Prostaglandin E2 In Suppression Of Innate Immunity To Listeria Monocytogenes, Michelle G. Pitts
Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics
As a foodborne pathogen, Listeria monocytogenes (Lm) encounters many barriers to invasion and dissemination in the host that may change the nature of host response. Lm has been most commonly studied using intravenous (i.v.) inoculation, however, a method that delivers a bolus of bacteria directly to the bloodstream. Thus, little is known about what systemic and local mediators are triggered during the natural course of infection and how these may impact susceptibility. Our laboratory used foodborne transmission of Lm in mice to assess whether the method of transmission and the specific organ microenvironment could affect infection-induced secretion of …
Cellular Senescence Is Induced By The Environmental Neurotoxin Paraquat And Contributes To Neuropathology Linked To Parkinson’S Disease,
2018
Touro University California
Cellular Senescence Is Induced By The Environmental Neurotoxin Paraquat And Contributes To Neuropathology Linked To Parkinson’S Disease, Shankar J. Chinta, Georgia Woods, Marco Demaria, Anand Rane, Ying Zou, Amanda Mcquade, David T. Madden
Faculty Publications & Research of the TUC College of Pharmacy
Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson’s disease (PD). Therapies based on PQ’s presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects against …
Ultrastructure Of Meelsvirus: A Nuclear Virus Of
Arrow Worms (Phylum Chaetognatha)
Producing Giant "Tailed" Virions,
2018
Truman State University
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 …
Role Of Mir-489 In Her2 Positive Breast Cancer,
2018
University of South Carolina
Role Of Mir-489 In Her2 Positive Breast Cancer, Yogin Patel
Theses and Dissertations
Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several micro RNAs (miRs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRs dysregulated in HER2-positive breast cancer cells. Molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenicity and tumor growth in xenograft mice. Mechanistically, …
Role Of Cox2 In Cellular Senescence,
2018
University of South Carolina
Role Of Cox2 In Cellular Senescence, Mingxiao Feng
Theses and Dissertations
The survivors of childhood cancers are often associated with adverse late effects including hypoplasia, fatigue, and infertility, which are characteristics of aging. However, the underlying mechanisms of the late effects of chemotherapy are still elusive. We have found that transgenic cyclooxygenase-2 (COX2) expression causes premature aging phenotypes. Since COX2 expression is highly induced by various chemotherapeutic agents, we further investigated the possible link between COX2 and the late effects of chemotherapy. Treatment of juvenile wild-type mice with doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, resulted in premature aging phenotypes and escalated cellular senescence level in various tissues. We found that tissue …
Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis.,
2018
Virginia Commonwealth University
Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh
Theses and Dissertations
Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …
Cortactin Phosphorylation By Casein Kinase 2 Regulates Actin Related Protein 2/3 Complex Activity And Invadopodia Function,
2018
West Virginia University
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 …
Arl2bp, A Novel Ciliopathy Protein, Is Required For Cilia Microtubule Formation,
2018
West Virginia University
Arl2bp, A Novel Ciliopathy Protein, Is Required For Cilia Microtubule Formation, Abigail Ruth Moye
Graduate Theses, Dissertations, and Problem Reports (ETD)
Cilia are specialized organelles essential for cellular function. Not surprisingly, mutations in cilia- related genes are linked to multi-syndromic diseases termed ciliopathies. These include blinding diseases such as retinitis pigmentosa (RP). One such novel gene is ARL2BP (ARL2-binding protein) and is linked to RP and situs inversus (organ reversal) in humans, a phenotype produced by defects in the nodal cilia of developing embryos. Defects in photoreceptor cilia, as well as situs inversus in human patients, suggest that ARL2BP plays an invaluable role in the structure and function of cilia. However little is known about the role for this protein in …
Brain Is A Potential Sanctuary For Subtype C
Hiv-1 Irrespective Of Art Treatment Outcome,
2018
University of Nebraska-Lincoln
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 …
Mucosal Antibody Responses To Vaccines
Targeting Siv Protease Cleavage Sites Or Fulllength
Gag And Env Proteins In Mauritian
Cynomolgus Macaques,
2018
University of Manitoba
Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo
Nebraska Center for Virology: Faculty Publications
HIV mutates rapidly and infects CD4+ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4+ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …
Brain Is A Potential Sanctuary For Subtype C
Hiv-1 Irrespective Of Art Treatment Outcome,
2018
University of Nebraska-Lincoln
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 …
Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability
In Primate Immunodeficiency Viruses,
2018
University of Nebraska-Lincoln
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 …
Non-Naturally Occurring Porcine
Reproductive And Respiratory
Syndrome Virus (Prrsv) And
Methods Of Using,
2018
University of Nebraska-lincoln
Non-Naturally Occurring Porcine Reproductive And Respiratory Syndrome Virus (Prrsv) And Methods Of Using, Hiep Lai Xuan Vu, Fernando Osorio, William W. Laegreid, Asit K. Pattnaik, Fangrui Ma
Nebraska Center for Virology: Faculty Publications
A non-naturally occurring porcine reproductive and respiratory syndrome virus (PRRSV) is provided herein, and methods of making and using the non-naturally occurring PRRSV also are provided.
Targeting Ribosome Assembly Factors Selectively Protects P53 Positive Cells From Chemotherapeutic Agents,
2017
Rowan University
Targeting Ribosome Assembly Factors Selectively Protects P53 Positive Cells From Chemotherapeutic Agents, Russell T. Sapio, Anastasiya Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J. Manna, N. Minkovsky, Dimitri G Pestov
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Many chemotherapeutic agents act in a nondiscriminatory fashion, targeting both cancerous and noncancerous cells in Sphase and Mphase. One approach to reduce the toxic side effects in normal tissue is to exploit the differences in p53 functionality between cancerous and noncancerous cells. For example, activating p53 signaling by nongenotoxic means can transiently arrest noncancerous p53 positive cells in G1 phase and protect them from the cytotoxic effects of chemotherapeutic drugs. However, since most cancerous cells have faulty p53 signaling, they will proceed to cycle, and continue to be affected by the drug. In this study we asked if this G1‐phase …
The Role Of Mapk And Scf In The Destruction Of Med13 In Cyclin C Mediated Cell Death,
2017
Rowan University School of Osteopathic Medicine
The Role Of Mapk And Scf In The Destruction Of Med13 In Cyclin C Mediated Cell Death, David C Stieg, Stephen D Willis, Joseph Scuorzo, Mia Song, Vidyaramanan Ganesan, Randy Strich, Katrina F Cooper
Rowan-Virtua School of Osteopathic Medicine Departmental Research
In response to stress, the yeast1 and mammalian2 cyclin C translocate from the nucleus to the cytoplasm, where it associates with the GTPase Drp1/Dnm1 to drive mitochondrial fragmentation and apoptosis. Therefore, the decision to release cyclin C represents a key life or death decision. In unstressed cells, the cyclin C‐Cdk8 kinase regulates transcription by associating with the Mediator of RNA polymerase II. We previously reported that the Mediator component Med13 anchors cyclin C in the nucleus3. Loss of Med13 function leads to constitutive cytoplasmic localization of cyclin C, resulting in fragmented mitochondria, hypersensitivity to stress and …
