Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, 2017 Nankai University
Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, Tianzheng Zhang, Ying Wang, Li Zhang, Bin Liu, Jinhui Xie, Charles Wood, Jinzhong Wang
Kaposi’s sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN ...
Therapeutic Application Of Carbon Monoxide In Acute Limb Compartment Syndrome, 2017 The University of Western Ontario
Therapeutic Application Of Carbon Monoxide In Acute Limb Compartment Syndrome, Aurelia Bihari
Electronic Thesis and Dissertation Repository
Acute limb compartment syndrome (CS), a devastating complication of musculoskeletal trauma, develops in response to elevation of the pressure within a closed osseofascial compartment, producing muscle- and limb-threatening ischemia. Full decompression of all involved compartments by fasciotomy is the current gold-standard therapy, but it must be performed within a surgical window of 6-8 hours, before tissue damage becomes permanent.
Carbon monoxide (CO), a byproduct of heme metabolism, has been shown protective in ischemia. While inhalation of CO leads to elevation of carboxyhemoglobin (COHb), recent development of transitional metal carbonyls, CO-releasing molecules (CO-RMs), particularly the water-soluble CORM-3, delivers CO in a ...
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, 2017 Western University
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, Kevin X. Zhou, Luana Langlois, Ashmita Singh, John Prince
Western Research Forum
Measuring pH is one of the most commonly used techniques in both the laboratory as well as the field due to its importance in a multitude of biochemical processes. Traditional methods of measuring pH may be highly developed in accuracy and precision but often involve disruption of the environment. Biological markers offer an alternative that allows for long-term pH monitoring. This innovative approach allows for vast applications such as in the manufacturing, food processing and research industries. Under moderate acidic conditions, the asr (acid shock RNA) gene is highly inducible and has been demonstrated to be crucial for growth at ...
Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, 2017 The University of Western Ontario
Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, Mario Cepeda
Electronic Thesis and Dissertation Repository
Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease that affects cell function via proteolytic and non-proteolytic mechanisms such as promoting degradation of the extracellular matrix (ECM) or augmentation of cell migration and viability, respectively. MT1-MMP has been implicated in metastatic progression ostensibly due to its ability to degrade ECM components and to allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) that inhibit substrate catalysis as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by ...
Reactivation Of Hiv-1 Proviruses In Immune-Compromised Mice Engrafted With Human Voa-Negative Cd4+ T Cells, 2017 University of Nebraska-Lincoln
Reactivation Of Hiv-1 Proviruses In Immune-Compromised Mice Engrafted With Human Voa-Negative Cd4+ T Cells, Zhe Yuan, Guobin Kang, Wuxun Lu, Qingsheng Li
Background: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses.
Methods: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted ...
Distinct Transcriptome Profiles Of Gag-Specific Cd8+ T Cells Temporally Correlated With The Protection Elicited By Sivδnef Live Attenuated Vaccine, 2017 University of Nebraska - Lincoln
Distinct Transcriptome Profiles Of Gag-Specific Cd8+ T Cells Temporally Correlated With The Protection Elicited By Sivδnef Live Attenuated Vaccine, Wuxun Lu, Yanmin Wu, Fangrui Ma, R. Paul Johnson, Qingsheng Li
The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: macaques are not protected at 3±5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific ...
Preferential Lineage-Specific Differentiation Of Osteoblast-Derived Induced Pluripotent Stem Cells Into Osteoprogenitors, 2017 Old Dominion University
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
Medical Diagnostics & Translational Sciences Faculty 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 ...
The Nucleolar Protein Nucleophosmin Undergoes Liquid-Liquid Phase Separation With Arginine-Rich Nucleolar Proteins Through Weak, Multivalent Electrostatic Interactions, 2016 University of Tennessee Health Science Center
The Nucleolar Protein Nucleophosmin Undergoes Liquid-Liquid Phase Separation With Arginine-Rich Nucleolar Proteins Through Weak, Multivalent Electrostatic Interactions, Jaclyn Alicia Cika
Theses and Dissertations (ETD)
Nucleoli are nuclear membrane-less organelles that are the sites for ribosome biogenesis and serve as sensors of cellular stress. Weak, multivalent protein-protein interactions and interactions between disordered, low complexity domains (LCDs) and rRNA have been shown to promote liquid-liquid phase separation (LLPS) in vitro, suggesting a basis for the liquid-like behavior of nucleoli. Nucleophosmin (NPM1), a multifunctional and highly abundant nucleolar protein, exhibits structural features associated with LLPS suggesting a role in nucleolar organization. Specifically, NPM1 forms a pentamer through its N-terminal oligomerization domain and can bind to rRNA through its C-terminal nucleic acid binding domain. Multiple acidic tracts throughout ...
The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., 2016 University of Louisville
The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary
Electronic Theses and Dissertations
The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current ...
Immune Monitoring In Recipients Of Combined Living Donor Kidney And Hematopoietic Stem/Facilitating Cell Transplants., 2016 University of Louisville
Immune Monitoring In Recipients Of Combined Living Donor Kidney And Hematopoietic Stem/Facilitating Cell Transplants., Mark Dewayne Badder
Electronic Theses and Dissertations
Solid organ transplantation coupled with a hematopoietic stem cell transplant from the organ donor allows for the recipient to cease immunosuppressive therapy after transplant via a chimeric immune system. This beneficial effect of stem cell transplants is negatively affected by graft versus host disease (GVHD). Better understanding of the donor and recipient’s immune system is vital to mitigating graft versus host disease and induction of donor chimerism without GVHD. In this study, flow cytometry was used to characterize immune cells of the recipients’ before and up to eighteen months post transplantation. The recipients were categorized into their respective chimeric ...
Seniors Welcome! Avoiding The Trap Of Age Limits In Health Research, 2016 Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Research Institute
Seniors Welcome! Avoiding The Trap Of Age Limits In Health Research, Arshad Jahangir
Journal of Patient-Centered Research and Reviews
The guest editor introduces this specialty issue of the Journal of Patient-Centered Research and Reviews, which focuses on cardiovascular diseases in the elderly. The reality of an aging population has increased the need for better evidence-based medicine in older patients. However, randomized controlled trials frequently exclude such patients, especially those with comorbidities, from study. This practice ignores the fact that physiologic changes to the cardiovascular system caused by the aging process and aging-associated diseases create clinical dilemmas distinct from those in younger patients. Considering the rising costs of health care and growing incidence of cardiovascular disease, research efforts and resources ...
Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, 2016 Surgical Breast Oncology, Aurora Health Care
Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra
Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and ...
Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., 2016 University of Louisville
Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., Erik Anderson Korte
Electronic Theses and Dissertations
Glomerulonephritis (GN) is the most common cause of end-stage renal disease worldwide and is characterized by deposition of immune complex, inflammation, proteinuria and podocyte damage. Immunosuppressive therapy is effective in less than 50% of patients, indicating that immunological activity is not the only relevant cause of kidney injury. While methods have been described for neutrophil-mediated immune activation, specific glomerular mechanisms for recruitment of neutrophils and development of GN have not been determined. Here I present a pathogenic mechanism for the development of GN involving a novel podocyte-neutrophil axis and reveal the importance of glomerular NF-κB inhibition by the ubiquitin binding ...
Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, 2016 University of Arkansas, Fayetteville
Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, Laura E. Fitzgerald
Biological Sciences Undergraduate Honors Theses
Clostridium difficile (C. difficile) is a gram-positive bacterium that comprises part of the healthy human gut microbiome. When it gains sufficient access to peptides, C. difficile flourishes and releases tissue-damaging toxins, which cause inflammation of the colon that can develop into a Clostridium difficile Infection (CDI).10 The Ivey Laboratory believes that the best tactic in preventing CDIs is stopping peptide ingestion, which theoretically could be accomplished by manipulating the oligopeptide permease (App) system.7 In order to verify that altering the App system would successfully impede peptide uptake, first the expression of the app Promoter Region (appProR) of ...
Inside Exploration, 2016 College Scholars Program
Inside Exploration, Reagan E. Long
University of Tennessee Honors Thesis Projects
No abstract provided.
Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall
Electronic Theses and Dissertations
Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral ...
Heme Oxygenase-1 Induction Improves Cardiac Function Following Myocardial Ischemia By Reducing Oxidative Stress, Yossi Issan, Ran Kornowski, Dan Aravot, Asher Shainberg, Michal Laniado-Schwartzman, Komal Sodhi, Nader G. Abraham, Edith Hochhauser
Nader G. Abraham
Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation.
In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage ...
Association Of Epstein-Barr Virus With Nasopharyngeal Carcinoma And Current Status Of Development Of Cancer-Derived Cell Lines, Charles A. Gullo Phd, Wong Kein Low, Gerrard Teoh
It is well known that the Epstein-Barr virus (EBV) contributes directly to tumourigenesis in nasopharyngeal carcinoma (NPC), primarily in the undifferentiated form of NPC (WHO type III; UNPC or UC), which is commonly found in South East Asia. Unfortunately, research in NPC has been severely hampered by the lack of authentic EBV-positive (EBV+) human NPC cell lines for study. Since 1975, there have been more than 20 reported NPC cell lines. However, many of these NPC-derived cell lines do not express EBV transcripts in long-term culture, and therefore that finding may dispute the fundamental theory of NPC carcinogenesis. In fact ...
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, 2016 Northwestern Polytechnical University
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han
Pharmacy Faculty Articles and Research
The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no ...
Design, Synthesis, And Evaluation Of Chitosan Conjugated Ggrgdsk Peptides As A Cancer Cell-Targeting Molecular Transporter, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, Zenat A. Nagieb, Keykavous Parang, Rakesh Tiwari
Pharmacy Faculty Articles and Research
Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using (sulfo-SMCC) bifunctional linker affording COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, 1H NMR, 13C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of cell-impermeable cargoes (e.g., FAM and F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian ...