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Full-Text Articles in Biology

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters Mar 2023

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …


Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka Jan 2021

Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka

Legacy Theses & Dissertations (2009 - 2024)

Ricin is a highly lethal protein toxin derived from the seeds of the castor plant, Ricinus communis. It is a Type II ribosome inactivating protein (RIP), meaning it is a heterodimer with one subunit, ricin toxin B (RTB), that mediates cell surface attachment and intracellular trafficking and a second subunit, ricin toxin A (RTA), that irreversibly shuts down protein synthesis in the cytosol. During trafficking, RTA and RTB necessarily separate in the endoplasmic reticulum, wherein RTA unfolds and translocates into the cytosol where it refolds into an enzymatically active conformation. RTA is remarkably fast acting and efficient, with few molecules …


Tunel Apoptotic Cell Detection In Stony Coral Tissue Loss Disease (Sctld): Evaluation Of Potential And Improvements, E. Murphy Mcdonald Dec 2020

Tunel Apoptotic Cell Detection In Stony Coral Tissue Loss Disease (Sctld): Evaluation Of Potential And Improvements, E. Murphy Mcdonald

All HCAS Student Capstones, Theses, and Dissertations

Stony coral tissue loss disease (SCTLD) is a highly lethal coral disease that has caused a dramatic loss of coral tissue along the Florida Reef Tract and throughout the Wider Caribbean. This study seeks to understand whether programmed cell death (apoptosis) is involved in the pathology of the highly virulent SCTLD tissue loss lesion. Tissues from diseased colonies of Pseudodiploria strigosa collected in 2018 and 2020 were stained using the terminal deoxyribonucleotidyltransferase (TdT) mediated dUTP-biotin nick end labeling (TUNEL) assay to visualize areas of programmed cell death. The archived tissue samples collected in 2018 exhibited a significantly higher degree of …


Rac1 And Ire1 Are Required To Prevent Early Loss Of Intestinal Homeostasis In Drosophila Melanogaster, Mauricio M. Ortega May 2016

Rac1 And Ire1 Are Required To Prevent Early Loss Of Intestinal Homeostasis In Drosophila Melanogaster, Mauricio M. Ortega

Dissertations, Masters Theses, Capstones, and Culminating Projects

No abstract available


Optimization Of Fluorescent Phagocytic Assay Using Apoptotic Cells, Jacob L. Brown, Jason R. Leigh, Ryan Marquardt, Cambria R. Puffenberger, Daniel J. Stank, Kaleb M. Pauley Apr 2016

Optimization Of Fluorescent Phagocytic Assay Using Apoptotic Cells, Jacob L. Brown, Jason R. Leigh, Ryan Marquardt, Cambria R. Puffenberger, Daniel J. Stank, Kaleb M. Pauley

The Research and Scholarship Symposium (2013-2019)

Sjögren’s Syndrome is a systemic autoimmune disease that primarily affects the exocrine glands and is characterized by severe dry eyes and mouth. Previous studies have shown that there are elevated levels of the microRNA miR-146a in Sjögren’s patients. Mir-146a is a microRNA that has been found to be involved in down regulating inflammation. Yet, in patients with Sjögren’s Syndrome, there is a large upregulation of miR-146a that exists alongside chronic inflammation. This led us to investigate the role of miR-146a in Sjögren’s Syndrome. We found that miR-146a upregulates phagocytosis of E. coli by human macrophages. Therefore, we hypothesized that this …


Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez Jan 2016

Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez

Theses and Dissertations

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …


Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane May 2015

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma7. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …


Investigating The Mechanism Of Nur77-Induced Apoptosis In T Cells, Heather E. Fogarty Jan 2012

Investigating The Mechanism Of Nur77-Induced Apoptosis In T Cells, Heather E. Fogarty

Masters Theses 1911 - February 2014

Nur77 is a member of the orphan nuclear receptor family, where it is known to play an important role in apoptosis in both negative selection in T cells and in cancer cell lines. In the development of T cells, it is critical for the immune system to discriminate self from non-self by eliminating auto-reactive cells. It was originally thought that Nur77 initiated apoptosis by activating downstream gene targets. However, it is now clear that Nur77 has its own distinct role outside of the nucleus and the precise mechanisms by which Nur77 induces apoptosis in T cells still needs to be …


Identification Of Epitopes On Ricin Toxin's Enzymatic Subunit (Rta) Critical For Eliciting Neutralizing Antibodies And Protective Immunity, Joanne Marie O'Hara Jan 2012

Identification Of Epitopes On Ricin Toxin's Enzymatic Subunit (Rta) Critical For Eliciting Neutralizing Antibodies And Protective Immunity, Joanne Marie O'Hara

Legacy Theses & Dissertations (2009 - 2024)

Ricin toxin's enzymatic subunit (RTA) is a 267 amino acid RNA N-glycosidase that selectively depurinates eukaryotic ribosomal RNA and arrests protein synthesis. The crystal structure of RTA revealed that the protein assumes three distinct folding domains (FD). Residues within FD1 and FD2 form RTA's active site pocket and are proposed to interface with ribosomal proteins, while FD3's primary function is to associate with ricin's B subunit (RTB). In this study I sought to identify the regions of RTA that are important in eliciting toxin-neutralizing antibodies (TNA), as this information is critical for current efforts to develop RTA-based subunit vaccines. I …