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Title: Identifying and characterizing the immune cell populations of Atlantic bottlenose dolphins (Tursiops truncatus).
Creator: Bible, Brittany, Nouri-Shirazi, Mahyar, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Recently, there has been an increase in marine mammal mortalities, most commonly Atlantic bottlenose dolphins, Tursiops truncatus, which is an alarming indication of the health status of the marine ecosystem. Studies have demonstrated that some free-ranging dolphins exhibit a suppressed immune system possibly because of exposure to contaminants or infectious microorganisms. However, this research has been limited due to a lack of commercially available marine-specific antibodies. Therefore,...
Show moreRecently, there has been an increase in marine mammal mortalities, most commonly Atlantic bottlenose dolphins, Tursiops truncatus, which is an alarming indication of the health status of the marine ecosystem. Studies have demonstrated that some free-ranging dolphins exhibit a suppressed immune system possibly because of exposure to contaminants or infectious microorganisms. However, this research has been limited due to a lack of commercially available marine-specific antibodies. Therefore, the first chapter of this thesis aims to identify cross-reactive terrestrial-specific antibodies that could be used to phenotype and compare the immune cell populations of dolphins under human care and free-ranging dolphins. The second chapter aims to utilize terrestrial-specific growth factors and dendritic cell (DC) surface markers to generate, characterize, and compare ex vivo DCs from peripheral blood mononuclear cells (PBMCs) of dolphins under human care and free-ranging dolphins. In summary, I have identified differences within the PBMCs and ex vivo generated DCs of dolphins under human care and free-ranging dolphins that could potentially shed light on the impact of environmental contaminants and infectious microorganisms on immune cells which could lead to increased morbidity and mortality.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004347, http://purl.flvc.org/fau/fd/FA00004347
Subject Headings: Bottlenose dolphin -- Physiology, Dolphins -- Physiology, Marine animals -- North Atlantic Ocean -- Identification., Marine mammals -- Atlantic Coast (U.S.), Marine mammals -- Effect of water pollution on, Marine mammals -- North Atlantic Ocean -- Identification
Format: Document (PDF)

Title: Mitochondrial regulation pathways in the lens: pink1/parkin- and bnip3l-mediated mechanisms.
Creator: Aktan, Kerem, Kantorow, Marc, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: The mitochondrion is the powerhouse of the cell. Therefore, it is critical to the homeostasis of the cell that populations of mitochondria that are damaged or in excess are degraded. The process of targeted elimination of damaged or excess mitochondria by autophagy is called mitophagy. In this report, analysis of the mitophagy regulators PINK1/PARKIN and BNIP3L and their roles are assessed in the lens. PARKIN, an E3 ubiquitin ligase, has been shown to play a role in directing damaged...
Show moreThe mitochondrion is the powerhouse of the cell. Therefore, it is critical to the homeostasis of the cell that populations of mitochondria that are damaged or in excess are degraded. The process of targeted elimination of damaged or excess mitochondria by autophagy is called mitophagy. In this report, analysis of the mitophagy regulators PINK1/PARKIN and BNIP3L and their roles are assessed in the lens. PARKIN, an E3 ubiquitin ligase, has been shown to play a role in directing damaged mitochondria for degradation. While BNIP3L, an outer mitochondrial membrane protein, increases in expression in response to excess mitochondria and organelle degradation during cellular differentiation. We have shown that PARKIN is both induced and translocates from the cytoplasm to the mitochondria in human epithelial lens cells upon oxidative stress exposure. In addition, our findings also show that overexpression of BNIP3L causes premature clearance of mitochondria and other organelles, while loss of BNIP3L results in lack of clearance. Prior to this work, PARKIN mediated mitophagy had not been shown to act as a protective cellular response to oxidative stress in the lens. This project also resulted in the novel finding that BNIP3L-mediated mitophagy mechanisms are required for targeted organelle degradation in the lens.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004427, http://purl.flvc.org/fau/fd/FA00004427
Subject Headings: Cellular signal transduction, Eye -- Diseases -- Etiology, Mitochondrial pathology, Mitophagy, Molecular chaperones, Oxidative stress -- Prevention, Protein folding
Format: Document (PDF)

Title: Characterization of RNase in Mycoplasma genitalium and study of its possible role in tRNA processing.
Creator: Lalonde, Maureen S., Florida Atlantic University, Li, Zhongwei, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Exoribonucleases degrade RNA and are important in RNA metabolism and gene expression. Mycoplasma genitalium, a bacterium with the smallest genome known, has only one identified exoribonuclease, RNase R (MgR). In this work RNA degradation properties of purified MgR were examined. As observed in Escherichia coli RNase R (EcR) studies, MgR degrades poly(A), rRNA, and oligoribonucleotides in 3'--->5' direction, though its substrate specificity and optimal activity requirements vary. Interestingly...
Show moreExoribonucleases degrade RNA and are important in RNA metabolism and gene expression. Mycoplasma genitalium, a bacterium with the smallest genome known, has only one identified exoribonuclease, RNase R (MgR). In this work RNA degradation properties of purified MgR were examined. As observed in Escherichia coli RNase R (EcR) studies, MgR degrades poly(A), rRNA, and oligoribonucleotides in 3'--->5' direction, though its substrate specificity and optimal activity requirements vary. Interestingly, MgR is sensitive to 2-O-methylation stopping downstream of such modifications in native rRNA and synthetic oligoribonucleotides. MgR removes the 3' trailer sequence from a tRNA precursor of M. genitalium and generates products equal to the mature tRNA, demonstrating a role of MgR in tRNA maturation. The 3' terminal CCA sequence and the acceptor stem of tRNA play a role in determining the formation of such products by MgR. These results suggest multiple functions of RNase R in RNA metabolism in Mycoplasma.
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Date Issued: 2006
PURL: http://purl.flvc.org/fcla/dt/13317
Subject Headings: Gene expression, RNA-protein interactions, Cellular control mechanisms, Ribonucleases--Analysis, Cell membranes
Format: Document (PDF)

Title: Posttranscriptional regulation of tropomyosin expression by myofibril inducing RNA (MIR) during axolotl embryonic heart development.
Creator: Jia, Pingping, Florida Atlantic University, Lemanski, Larry F., Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: A naturally-occurring recessive lethal mutation in axolotls, Ambystoma mexicanum, is an intriguing model for studying tropomyosin expression regulation. Homozygous embryos(c/c) form hearts that are deficient in tropomyosin, lack organized myofibrils and fail to beat. Previous studies have shown that a non-coding RNA gene, MIR (Myofibril Inducing RNA), is sufficient to rescue the non-beating homozygous recessive mutant hearts by promoting sarcomeric tropomyosin expression that leads to...
Show moreA naturally-occurring recessive lethal mutation in axolotls, Ambystoma mexicanum, is an intriguing model for studying tropomyosin expression regulation. Homozygous embryos(c/c) form hearts that are deficient in tropomyosin, lack organized myofibrils and fail to beat. Previous studies have shown that a non-coding RNA gene, MIR (Myofibril Inducing RNA), is sufficient to rescue the non-beating homozygous recessive mutant hearts by promoting sarcomeric tropomyosin expression that leads to formation of organized myofibrils and beating hearts. Real time RT-PCR reveals that mutant hearts express the same level mRNA of the alpha-tropomyosin and TM4 type tropomyosin (ATmC-3) gene as normal embryonic hearts. These genes show no differences with regard to the splicing patterns of normal and mutant. Using protease inhibitor LLnL and E-64d treatments and two-dimensional Western blots of normal and mutant hearts, it is found that mutant hearts express all tropomyosin protein isoforms as normal hearts but protein expression are at low levels. These studies suggest that there is a failure in the translational or posttranslational control mechanisms for tropomyosin protein synthesis in cardiac mutant axolotl hearts during development.
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Date Issued: 2006
PURL: http://purl.flvc.org/fcla/dt/13380
Subject Headings: Medical genetics, Molecular biology, Cell differentiation, Gene expression, Axolotls--Development, Heart--Growth--Molecular aspects
Format: Document (PDF)

Title: Topological Specificity in Inhibitor Recognition by Matrix Metalloproteinases.
Creator: Lauer-Fields, Janelle, Florida Atlantic University, Brew, Keith, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Alterations in activities of one family of proteases, the metzincins have been implicated in an array of physiological and pathological processes. In the present study, metzincin inhibitors were developed by utilizing topologically constrained peptides and pseudopeptides. The endothelin-family framework was used to develop a disulfideconstrained topology. This framework was chosen due to its three-dimensional similarity with a family of endogenous metzincin inhibitors, the tissue inhibitors...
Show moreAlterations in activities of one family of proteases, the metzincins have been implicated in an array of physiological and pathological processes. In the present study, metzincin inhibitors were developed by utilizing topologically constrained peptides and pseudopeptides. The endothelin-family framework was used to develop a disulfideconstrained topology. This framework was chosen due to its three-dimensional similarity with a family of endogenous metzincin inhibitors, the tissue inhibitors of metalloproteases (TIMPs). The collagenous triple-helix was chosen as a second framework, because only a subset of proteolytic enzymes have the capacity to bind and hydrolyze a triple-helix. Both templates were successfully modified to generate an array of inhibitors. These inhibitors displayed subnanomolar to micromolar apparent Ki values, while being moderately selective metzincin inhibitors. In both cases the threedimensional structure was determined to be important for activity. This work encourages the further development of both frameworks as metzincin inhibitors.
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Date Issued: 2007
PURL: http://purl.flvc.org/fau/fd/FA00000867
Subject Headings: Metalloproteinases--Inhibitors, Proteolytic enzymes, Extracellular matrix proteins
Format: Document (PDF)

Title: Fetal and Adult Human Heart RNA Promotes Myofibrillogenesis and Stimulates a Heart Beat in Cardiac Non-function Mutant Mexican Axolotl Hearts in Organ Culture.
Creator: Rueda-de-Leon, Elena, Lemanski, Larry F., Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: The Mexican axolotl (Ambystoma mexicanum) carries a cardiac lethal mutation resulting in mutant embryos with no heartbeat. This homozygous recessive gene results in tropomyosin deficiency and absence of organized myofibrils. Co-culturing mutant hearts with bioactive RNA, termed myofibril-inducing RNA (MIR), from normal axolotl embryonic anterior endoderm causes the mutant hearts to beat. It is hypothesized that the secondary structure of the MIR binds a specific protein(s) and this is...
Show moreThe Mexican axolotl (Ambystoma mexicanum) carries a cardiac lethal mutation resulting in mutant embryos with no heartbeat. This homozygous recessive gene results in tropomyosin deficiency and absence of organized myofibrils. Co-culturing mutant hearts with bioactive RNA, termed myofibril-inducing RNA (MIR), from normal axolotl embryonic anterior endoderm causes the mutant hearts to beat. It is hypothesized that the secondary structure of the MIR binds a specific protein(s) and this is required to synthesize tropomyosin and form organized myofibrils. In this study mutant hearts are co-cultured with human fetal and adult heart total RNA to assess rescue of the mutant hearts. Results show that both human fetal and adult heart total RNA rescue the mutant condition in a manner similar to the MIR. Thus, the MIR human functional homologs induce events leading to normal heart differentiation and function. This finding may help people with heart muscle damage regain normal heart function again.
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Date Issued: 2007
PURL: http://purl.flvc.org/fau/fd/FA00000823
Subject Headings: Axolotls--Development, Heart--Hypertrophy, Molecular genetics--Research, Ibises--Reproduction
Format: Document (PDF)

Title: Mechanisms of placental dysfunction during Plasmodium falciparum infection in pregnancy.
Creator: Goldberg, Valentina, Oleinikov, Andrew, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Placental malaria infection, during which infected red blood cells sequester in the placenta, is a substantial cause of pregnancy-related complications in areas where malaria is endemic. Accumulation of infected red blood cells creates an inflammatory environment and induces an immune response that can be deleterious to the placenta. This response can cause complications that include low birth weight, which is a major risk factor for neonatal and infant death. A decrease in the megalin...
Show morePlacental malaria infection, during which infected red blood cells sequester in the placenta, is a substantial cause of pregnancy-related complications in areas where malaria is endemic. Accumulation of infected red blood cells creates an inflammatory environment and induces an immune response that can be deleterious to the placenta. This response can cause complications that include low birth weight, which is a major risk factor for neonatal and infant death. A decrease in the megalin transport and signaling system has been demonstrated to be linked with placental malaria infection and to be connected with low birth weight pathology. In this study we analyze the abundance of a protein related to megalin, LRP1 (LDL receptor related protein 1) in pregnancy malaria. Protein expression was analyzed in placental tissue samples by immunofluorescence staining. A statistically significant decrease was observed in the expression of LRP1 in placental samples of patients stratified by presence of placental malaria infection and infants born with low birth weight. Findings were supported using an in vitro cell model of placental syncytial trophoblast during malarial infection. In this model BeWo cell line was incubated with erythrocytes infected with malaria parasite CS2 line that is known for binding to malaria placental receptor. LRP1 expression in BeWo cells was analyzed by immunostaining and Western Blot, and a reduction was found by both methods. Analysis of LRP1 mRNA levels by RT-qPCR revealed no difference compared to control samples, indicating that changes happen at the protein level.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013375
Subject Headings: Plasmodium falciparum, Placenta, Pregnancy Complications, Parasitic, Malaria
Format: Document (PDF)

Title: Mechanisms of Placental Dysfunction in Pregnancy Malaria.
Creator: Lybbert, Jared, Oleinikov, Andrew V., Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: The molecular mechanisms by which pregnancy malaria affects the outcome of fetal development are unknown. Megalin, which has been well studied in kidney, has high expression in the placenta from early stages to term, and is proposed to be an important factor in extensive maternofetal exchange during development of the fetus. Pregnancy malaria (PM) is characterized by inflammation in placenta and is associated with low birthweight (LBW), stillborn birth, and other pathologies. It is...
Show moreThe molecular mechanisms by which pregnancy malaria affects the outcome of fetal development are unknown. Megalin, which has been well studied in kidney, has high expression in the placenta from early stages to term, and is proposed to be an important factor in extensive maternofetal exchange during development of the fetus. Pregnancy malaria (PM) is characterized by inflammation in placenta and is associated with low birthweight (LBW), stillborn birth, and other pathologies. It is hypothesized that PM disturbs megalin function/expression/distribution in the brush boarder of syncytiotrophoblast which, in turn, may contribute significantly to pathology of LBW. Our studies show that the presence of infected erythrocytes in placenta at the time of delivery negatively affects protein abundance for megalin and Dab2. This is the first report associating the abundance of placental megalin system proteins with the birth weight of newborn babies, and associating PM with changes in megalin system protein abundance.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004520, http://purl.flvc.org/fau/fd/FA00004520
Subject Headings: Birth weight, Low, Critical care medicine, Fetus -- Diseases -- Molecular diagnosis, Pregnancy -- Complications, Prenatal diagnosis, Stillbirth
Format: Document (PDF)

Title: PHOTORECEPTOR DEGENERATION AND ABNORMAL RETINAL VASCULOGENESIS.
Creator: Nguyen, Matthew, Shen, Wen, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Abnormal vasculature in the retina, specifically tortuous blood vessels, are common to many of the most prevalent retinal degenerative diseases currently affecting millions across the world. The mechanisms of their formation and development in the context of retinal degenerative disease, however, are still poorly understood. The rd1 and rd10 mice are relatively well-studied animal models of retinal degenerative disease, however, there lacks a systematic characterization of vascular changes co...
Show moreAbnormal vasculature in the retina, specifically tortuous blood vessels, are common to many of the most prevalent retinal degenerative diseases currently affecting millions across the world. The mechanisms of their formation and development in the context of retinal degenerative disease, however, are still poorly understood. The rd1 and rd10 mice are relatively well-studied animal models of retinal degenerative disease, however, there lacks a systematic characterization of vascular changes co-related to photoreceptor degeneration in the rd1 and rd10 retina. Here, we utilize advancements in confocal microscopy, immunohistochemistry, and image analysis software in order to systematically characterize vascular changes before and after retinal development in the rd1 and rd10 mice. We show that there are plexus specific changes in the retinal vasculature that parallel photoreceptor degeneration. Such information will be of particular use to future studies investigating the role of vascular changes in retinal degenerative disease therapies.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013818
Subject Headings: Retinal Degeneration, Retinal Vessels--pathology, Retina—Diseases, Photoreceptors
Format: Document (PDF)

Title: EFFECT OF G-CSF GENE THERAPY IN A MICROGLIA MODEL OF STROKE.
Creator: Velasquez Saldarriaga, Esteban, Wu, Jang-Yen, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Cerebrovascular events (stroke) are a significant cause of morbidity and mortality worldwide. Ischemic stroke accounts for ~85% of all strokes and is caused by the blockade of blood flow to a certain area of the brain, resulting in oxygen and nutrient deprivation and ultimately cell death. Cerebral ischemia induces a strong neuroinflammatory response that contributes to tissue damage and is driven by changes in the gene expression profile and phenotype of brain cells including neurons,...
Show moreCerebrovascular events (stroke) are a significant cause of morbidity and mortality worldwide. Ischemic stroke accounts for ~85% of all strokes and is caused by the blockade of blood flow to a certain area of the brain, resulting in oxygen and nutrient deprivation and ultimately cell death. Cerebral ischemia induces a strong neuroinflammatory response that contributes to tissue damage and is driven by changes in the gene expression profile and phenotype of brain cells including neurons, astrocytes, and microglia. Microglia are the resident immune and phagocytic cells of the central nervous system. They rapidly respond to ischemia by migrating to the site of injury and modulating the inflammatory response there. Although microglia may play a deleterious role in the acute phase of stroke, evidence suggests that they play an important role in the reduction of excitotoxic injury as well as in neurogenesis during the tissue regeneration phase. Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that has shown beneficial effects in models of ischemic stroke. G-CSF exerts its neuroprotective effects through different mechanisms including mobilization of haemopoietic stem cells, angiogenesis, neurogenesis, anti-inflammation, and anti-apoptosis. However, its effect on microglia is not well understood yet. The main objective of this project was to evaluate the protective and anti-inflammatory effect of G-CSF gene therapy against glutamate cytotoxicity in the human microglial clone 3 cell line (HMC3). Our results show that although G-CSF gene therapy did not significantly protect HMC3 cells against glutamate induced cell death, it reduced the expression levels of pro-inflammatory proteins NF-κB p65, IL-1β and IL-6, while increasing the phosphorylation of Akt, a regulator of cell survival and proliferation.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013821
Subject Headings: Stroke, Granulocyte Colony-Stimulating Factor, Cerebrovascular disease, Microglia
Format: Document (PDF)

Title: IDENTIFICATION OF ANTI-ADHESION SMALL MOLECULES, WHICH INHIBIT SEQUESTRATION OF PLASMODIUM-FALCIPARUM INFECTED ERYTHROCYTES, USING A TWO-STEP APPROACH.
Creator: Visitdesotrakul, Pimnitah S., Oleinikov, Andrew, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: A hallmark trait of P. falciparum malaria is sequestration, in which parasite infected erythrocytes (IEs) adhere to the vasculature, causing organ failure and death. Current antimalarials only kill the parasites, necessitating development of anti-adhesion drugs. Using our two-step approach, we can efficiently screen for anti-adhesion small molecules. Screenings of 75libraries using Bio-Plex 200 identified the most active TPI libraries, which were deconvoluted to single compounds. Screenings...
Show moreA hallmark trait of P. falciparum malaria is sequestration, in which parasite infected erythrocytes (IEs) adhere to the vasculature, causing organ failure and death. Current antimalarials only kill the parasites, necessitating development of anti-adhesion drugs. Using our two-step approach, we can efficiently screen for anti-adhesion small molecules. Screenings of 75libraries using Bio-Plex 200 identified the most active TPI libraries, which were deconvoluted to single compounds. Screenings library TPI 1319 yielded 3 inhibiting non-optimized compounds, each of which inhibits binding between two receptors, CSA and ICAM1, and their binding PfEMP1 domains. Two compounds deconvoluted from TPI 2103 prevent binding between PfEMP1 and ICAM1. Cytoadhesion assays with live IEs support the results seen with Bio-Plex, with best hits showing inhibition below 200 nM. Cytotoxicity testing of active compounds showed minimaltoxicity. Identified hits appear to be amenable to Structure Activity Relationship studies to develop powerful anti-adhesion drugs to treat severe malaria.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013698
Subject Headings: Plasmodium falciparum, Sequestration, Malaria
Format: Document (PDF)

Title: THERAPEUTIC STRATEGIES USING SULINDAC AND G-CSF GENE THERAPY FOR NEUROLOGICAL DISEASE.
Creator: Chen, Belinda, Prentice, Howard, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Alzheimer’s disease is a neurodegenerative disease that causes cognitive dysfunction and leads to progressive memory loss and behavioral impairment. About 60% to 80% of dementia cases are attributed to Alzheimer’s disease and currently afflict about 50 million people worldwide. Although it primarily affects people over the age of 65, a person’s risk for developing Alzheimer’s disease earlier can depend on factors such as a family history (genetic inheritance) or experiencing an ischemic...
Show moreAlzheimer’s disease is a neurodegenerative disease that causes cognitive dysfunction and leads to progressive memory loss and behavioral impairment. About 60% to 80% of dementia cases are attributed to Alzheimer’s disease and currently afflict about 50 million people worldwide. Although it primarily affects people over the age of 65, a person’s risk for developing Alzheimer’s disease earlier can depend on factors such as a family history (genetic inheritance) or experiencing an ischemic stroke event. Current treatments for Alzheimer’s disease include behavioral therapy and drug treatment that can lessen the severity of symptoms but cannot stop progression indefinitely. Sulindac is a non-steroidal anti-inflammatory drug that, by a mechanism independent of its anti-inflammatory properties, has shown to express a preconditioning response to protect from oxidative damage. Granulocyte colony stimulating factor is a hematopoietic glycoprotein that can stimulate the production of granulocytes and stem cells that has proven to provide neuroprotection in models of ischemic stroke via mechanisms including anti-apoptosis and anti-inflammation. In this in vitro study, the potential neuroprotective effects of Sulindac is measured against the effects of oxidative stress when subjected to hypoxia and reperfusion. Regarding un-transfected SHSY-5Y cells, hypoxia was demonstrated to lower cell viability starting at a period of 12 hours. It was found that a low concentration of Sulindac (200 uM) was effective in protecting SHSY-5Y cells against oxidative stress and overall lowering the rate of cell death in the event of hypoxic and reperfusion injury. When SHSY-5Y cells were transfected with Swedish APP mutation, cell viability was also markedly decreased in hypoxic conditions. However when treated with a concentration of 600 uM of Sulindac, cell viability levels were near matched with its normoxic counterparts
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Date Issued: 2022
PURL: http://purl.flvc.org/fau/fd/FA00014021
Subject Headings: Sulindac, Granulocyte-colony stimulating factor, Genetic Therapy, Alzheimer Disease
Format: Document (PDF)

Title: HIV-1 INFECTION MODULATES CD4+ T CELL GENE EXPRESSION TO INDUCE A QUIESCENT PHENOTYPE.
Creator: Mauer, Christopher, Caputi, Massimo, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: The largest barrier to treatment of HIV-1 infection is the establishment of a viral reservoir constituted mostly by quiescent latently infected CD4+ T cells. This reservoir is formed through two processes: i) the infection of resting CD4+ T cells; both naïve and memory, ii) the infection of activated CD4+ T cells which then become quiescent infected cells. One goal of this project was to understand the gene expression changes occurring in naïve CD4+ T cells following activation and subsequent...
Show moreThe largest barrier to treatment of HIV-1 infection is the establishment of a viral reservoir constituted mostly by quiescent latently infected CD4+ T cells. This reservoir is formed through two processes: i) the infection of resting CD4+ T cells; both naïve and memory, ii) the infection of activated CD4+ T cells which then become quiescent infected cells. One goal of this project was to understand the gene expression changes occurring in naïve CD4+ T cells following activation and subsequent HIV-1 infection and how this may contribute to the establishment of a latent infection in these cells. Utilizing RNA-Seq and a series of validation assays we have identified several genes which are regulated in opposite directions during activation versus infection which we termed DEOC genes. The DEOC genes include a group of physically- and functionally-associated proteins which are key regulators of T cell activation, the cell cycle, cellular proliferation, and cellular quiescence, suggesting that modulation of these DEOC genes may help transition the infected-activated cell from an activated state to a quiescent/resting state to induce a latent infection.
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Date Issued: 2022
PURL: http://purl.flvc.org/fau/fd/FA00014033
Subject Headings: HIV-1, Virus Latency
Format: Document (PDF)

Title: SRSF1 IS AN RNA-BINDING PROTEIN THAT FUNCTIONS AS A TRANSCRIPTIONAL ACTIVATOR.
Creator: Paz, Sean, Caputi, Massimo, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Serine/Arginine splicing factor 1 (SRSF1) is an RNA-binding protein (RBP) with multiple functions in RNA biogenesis. SRSF1 plays a prominent role in oncogenesis, immune function, and response to several physiological stimuli. To date, the role of SRSF1 as a regulator of mRNA splicing has been largely considered the main mechanism driving its biological functions and its role in disease. We have now characterized SRSF1’s role in Human Immunodeficiency Virus Type I (HIV-1) transcription. SRSF1...
Show moreSerine/Arginine splicing factor 1 (SRSF1) is an RNA-binding protein (RBP) with multiple functions in RNA biogenesis. SRSF1 plays a prominent role in oncogenesis, immune function, and response to several physiological stimuli. To date, the role of SRSF1 as a regulator of mRNA splicing has been largely considered the main mechanism driving its biological functions and its role in disease. We have now characterized SRSF1’s role in Human Immunodeficiency Virus Type I (HIV-1) transcription. SRSF1 interacts with the 7SK small nuclear ribonucleoprotein (snRNP) to mobilize and activate the positive transcription-elongation factor (P-TEFb), which is then positioned on the HIV-1 promoter to increase the processivity of RNA polymerase II (RNAPolII) and promote the release of the negative regulators of transcription DSIF/NELF. Next, we defined the role of SRSF1 in the transcription of cellular genes utilizing an RNA sequencing (RNASeq) time course approach was used to detect changes in the transcriptome in response to SRSF1 overexpression. RNASeq data analysis revealed a subset of genes that were upregulated in response to SRSF1 overexpression. Nuclear run-on and qPCR assays experimentally validated 28 of these genes.
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Date Issued: 2022
PURL: http://purl.flvc.org/fau/fd/FA00014112
Subject Headings: Transcription Factors, Serine-Arginine Splicing Factors, RNA-Binding Proteins, HIV
Format: Document (PDF)

Title: To identify the functional domains of BNIP3L required for elimination of MT, ER and GA to form mature lens fiber cells.
Creator: Zabizhin, Rachel, Brennan, Lisa, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: The structure and transparency of the eye lens are vital for focusing light onto the retina for vision. Lens fiber cells undergo a cellular remodeling program that removes mitochondria (MT), endoplasmic reticulum (ER), and Golgi apparatus (GA) to form mature transparent lens fiber cells. Previous studies established a requirement for the mitochondrial outer membrane protein BNIP3L for the elimination of these non-nuclear organelles in the lens; however, the precise molecular pathways for...
Show moreThe structure and transparency of the eye lens are vital for focusing light onto the retina for vision. Lens fiber cells undergo a cellular remodeling program that removes mitochondria (MT), endoplasmic reticulum (ER), and Golgi apparatus (GA) to form mature transparent lens fiber cells. Previous studies established a requirement for the mitochondrial outer membrane protein BNIP3L for the elimination of these non-nuclear organelles in the lens; however, the precise molecular pathways for BNIP3L function remain to be elucidated. BNIP3L contains multiple functional domains whose analysis may illuminate its lens mechanisms including the LIR, BH3, and TM domains. These domains each play an important role in regulation of autophagosome formation and initiation of autophagy. To test each domain’s functionality for BNIP3L-dependent organelle elimination, we designed site-directed mutagenesis studies to delete each domain and test the resulting mutants in initiating the degradation of organelles in ex vivo cultured embryonic chick lenses.
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Date Issued: 2022
PURL: http://purl.flvc.org/fau/fd/FA00014087
Subject Headings: Eye, Lens, Crystalline
Format: Document (PDF)

Title: DEVELOPMENT OF A HIFI-Α LENS SPECIFIC KNOCKOUT MOUSE AS A MODEL FOR HYPOXIA DRIVEN LENS DIFFERENTIATION.
Creator: Adele, Adedamola, Kantorow, Marc, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: During eye lens development the lens receives oxygen from a network of capillaries that comprise of the tunica vasculosa lentis and the anterior pupillary membrane. In development there is regression of this capillaries with the vitreous and aqueous humor, which is the lens only source of oxygen, leaving the lens in low oxygen state. The lens contains a decreasing oxygen gradient from the surface to the core that parallels the differentiation of immature surface epithelial cells into mature...
Show moreDuring eye lens development the lens receives oxygen from a network of capillaries that comprise of the tunica vasculosa lentis and the anterior pupillary membrane. In development there is regression of this capillaries with the vitreous and aqueous humor, which is the lens only source of oxygen, leaving the lens in low oxygen state. The lens contains a decreasing oxygen gradient from the surface to the core that parallels the differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia and the master regulator of the hypoxic response, hypoxia-inducible transcription factor 1 alpha (HIF1a), in the regulation of genes required for lens fiber cell differentiation, structure, and transparency. Previous studies by our lab discovered the HIF1a-dependent gene expression patterns of lens genes by utilizing a Multiomics approach that integrated analysis from CUT&RUN, RNA-seq, and ATACseq. Additionally, our lab also established a hypoxia and HIF1a-dependent mechanism for the non-nuclear organelle degradation process required to form mature transparent fiber cells.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014167
Subject Headings: Cell differentiation, Lens, Crystalline, Eye lens
Format: Document (PDF)

Title: THE EFFECT OF S81 WITHIN THE MINIMAL ESSENTIAL REGION (MER) OF THE BNIP3L PROTEIN IN ACTIVATING ORGANELLE DEGRADATION TO DRIVE FIBER LENS DIFFERENTIATION.
Creator: Yang, Judy, Kantorow, Marc, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Lens differentiation begins with epithelial cells that undergo the process of cellular differentiation and remodelling into fiber cells (Bassnet et al., 2011; Menko 2002; Wride, 2011) that then will undergo terminal remodelling processes to eliminate their cellular organelles to achieve mature lens structure and transparency. We sought to determine if Serine 81, within the minimal essential region (MER) of the BNIP3L protein, is required for organelle elimination. Previous studies have shown...
Show moreLens differentiation begins with epithelial cells that undergo the process of cellular differentiation and remodelling into fiber cells (Bassnet et al., 2011; Menko 2002; Wride, 2011) that then will undergo terminal remodelling processes to eliminate their cellular organelles to achieve mature lens structure and transparency. We sought to determine if Serine 81, within the minimal essential region (MER) of the BNIP3L protein, is required for organelle elimination. Previous studies have shown that levels of phosphorylated P38 MAPK and ERK ½ peaked in the same region as phosphorylated S81 BNIP3L levels, the equatorial epithelium, where organelle degradation is initiated. The use of specific inhibitors of P38 MAPK (SB203580) or ERK ½ (U0126 or PD99089) and P38 MAPK activator Ansiomycin will be used to determine if P38 MAPK or ERK ½ phosphorylates BNIP3L at S81 to induce mitophagy of mitochondria, endoplasmic reticulum, and Golgi apparatus.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014166
Subject Headings: Lens, Crystalline, Cell differentiation, Eye lens
Format: Document (PDF)

Title: CHARACTERIZATION OF BAZ1B, A TARGET PROTEIN OF CHEMOTHERAPEUTIC RESISTANCE IN CANCER.
Creator: Toussaint, Mohamed-Tamar, Grant, Patrick, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Epigenetic dysregulation has been implicated in oncogenesis, with post-translational histone modifications being linked to cancer progression. WSTF/BAZ1B forms chromatin-remodeling complexes with other proteins and lowers cancer survival outcomes. Treatment resistance causes >90 % of all cancer deaths. In particular, cancers develop tolerance to cisplatin-induced genotoxicity. It is hypothesized that the BAZ1B bromodomain, PHD finger, and DDT domain recognize epigenetic modifications,...
Show moreEpigenetic dysregulation has been implicated in oncogenesis, with post-translational histone modifications being linked to cancer progression. WSTF/BAZ1B forms chromatin-remodeling complexes with other proteins and lowers cancer survival outcomes. Treatment resistance causes >90 % of all cancer deaths. In particular, cancers develop tolerance to cisplatin-induced genotoxicity. It is hypothesized that the BAZ1B bromodomain, PHD finger, and DDT domain recognize epigenetic modifications, contributing to cisplatin resistance in cancers. To test this, the domains were expressed in Rosetta 2 BL21(DE3) and Rosetta 2 BL21(DE3) PLysS Escherichia coli strains. Soluble proteins were extracted, purified, and then analyzed using pulldown assays and modified histone peptide arrays. The DDT and PHD finger domains were found to bind to specific histone modifications with the DDT domain also displayed DNA-binding properties. Some of the identified histone modifications have known roles/correlations in normal and cancer cells, implicating BAZ1B as an agent in oncogenesis, treatment resistance, and as a therapeutic target.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014296
Subject Headings: Cancer, Epigenetics, Histones
Format: Document (PDF)

Title: CHARACTERIZATION OF DIFFERENTIATED HUMAN NEUROBLASTOMA SH-SY5Y CELLS IN CULTURE.
Creator: Condikey, Siri, Prentice, Howard, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases affecting an estimated 20 million worldwide. The primary pathology of AD is the progressive loss of basal forebrain cholinergic neurons, which is responsible for the cognitive decline experienced by AD patients. The mechanisms underlying this selective vulnerability have not been fully elucidated. Furthermore, oxidative stress is a key factor behind the pathology of AD leading to this neuronal loss. The current...
Show moreAlzheimer’s disease (AD) is one of the most common neurodegenerative diseases affecting an estimated 20 million worldwide. The primary pathology of AD is the progressive loss of basal forebrain cholinergic neurons, which is responsible for the cognitive decline experienced by AD patients. The mechanisms underlying this selective vulnerability have not been fully elucidated. Furthermore, oxidative stress is a key factor behind the pathology of AD leading to this neuronal loss. The current literature suggests that there are limited in-vitro models available to accurately simulate the hallmark symptoms of Alzheimer's disease (AD). The SH-SY5Y cell line has been used extensively to study neuronal stress responses but the undifferentiated cell type has been predominantly used. Undifferentiated SH-SY5Y versus differentiated SH-SY5Y have been shown to have different interaction, expression and localization with AD hallmark, amyloid-b -42. This project sought to use differentiated cholinergic cells from the line SH-SY5Y to further isolate and elucidate, in-vitro, the mechanisms behind the oxidative stress response, a key stressor in the pathology of AD. Building upon previous studies, a protocol to differentiate SH-SY5Y cells with retinoic acid (RA) and neurotrophin (BDNF) to mature neurons of the cholinergic phenotype was optimized and implemented. The results showed successful differentiation into the cholinergic phenotype as evidenced via immunofluorescence imaging of choline acetyl transferase (ChAT) expression and mature neurite morphology. To simulate oxidative stress, we exposed both undifferentiated and differentiated SH-SY5Y cells to hypoxic conditions. Results indicated a stress response to mild hypoxic conditions with higher sensitivity in cholinergic differentiated SH-SY5Y. Understanding these hallmark mechanisms behind oxidative stress is crucial to developing mechanism-based therapeutics for AD.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014347
Subject Headings: Alzheimer Disease, Cholinergic Neurons, Alzheimer Disease--pathology
Format: Document (PDF)

Title: KLEINE-LEVIN SYNDROME: INVESTIGATING THE IMMUNO-REACTIVITY OF PATIENT SERA TOWARDS VARIOUS BRAIN AREAS.
Creator: Hamper, Michael C., Wei, Jianning, Hartmann, James, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Kleine-Levin Syndrome (KLS) is an extremely rare neurological disorder characterized by episodes of uncontrollable hypersomnia and various cognitive and behavioral abnormalities. There is neither a definitive etiology nor definite treatment modalities. Immunological studies for this condition are extremely limited, and this present study aims to investigate a potential autoimmune mechanism that underlies KLS. To achieve this, western blot and dot-blot assays analyzed the immunoreactivity of...
Show moreKleine-Levin Syndrome (KLS) is an extremely rare neurological disorder characterized by episodes of uncontrollable hypersomnia and various cognitive and behavioral abnormalities. There is neither a definitive etiology nor definite treatment modalities. Immunological studies for this condition are extremely limited, and this present study aims to investigate a potential autoimmune mechanism that underlies KLS. To achieve this, western blot and dot-blot assays analyzed the immunoreactivity of patients and control sera towards various brain tissue areas. Western blot did not show immunoreactivity with IgG-depleted brain tissue lysate. However, dot-blot assays revealed a significantly greater level of immunoreactivity with KLS patient sera towards the dorsolateral prefrontal cortex, hypothalamus, and parieto-temporal areas compared to KLS-negative sera. These areas have previously been shown to be hypo-perfused in KLS patients. Future studies are necessary to identify the specific antibodies that may be autoreactive in KLS patients.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014359
Subject Headings: Kleine-Levin Syndrome, Autoantibodies, Hypersomnia, Nervous System Diseases
Format: Document (PDF)

FAU Theses and Dissertations (75)	+ -
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Cellular signal transduction (14)	+ -
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Cellular control mechanisms (5)	+ -
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Charles E. Schmidt College of Science (11)	+ -

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