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Title: Vascular endothelial growth factor (VEGF), BCL-2, and BAX expression in fibropapilloma tumor tissue and skin tissue of sea turtles.
Creator: Bancalari-Schmidlapp, Angela., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: In sea turtles, the study of the etiology and development of fibropapillomatosis is not fully understood. Sea turtle fibropapillomatosis is a disease characterized by the proliferation of skin fibropapillomas and occasional internal fibromas. In this study, sea turtle fibropapilloma tumor and healthy tissue samples were used to look at VEGF, BCL-2 and Bax expression. Cancer tumors have a well established pattern of protein expression that involves overexpression of vascular endothelial growth...
Show moreIn sea turtles, the study of the etiology and development of fibropapillomatosis is not fully understood. Sea turtle fibropapillomatosis is a disease characterized by the proliferation of skin fibropapillomas and occasional internal fibromas. In this study, sea turtle fibropapilloma tumor and healthy tissue samples were used to look at VEGF, BCL-2 and Bax expression. Cancer tumors have a well established pattern of protein expression that involves overexpression of vascular endothelial growth factor (VEGF), responsible for the growth of new blood vessels, and a high BCL-2 to Bax ratio that leads to uncontrolled cell proliferation. Real time PCR was used to analyze VEGF expression, and Western blot techniques were used to measure BCL-2 and Bax expression. The results indicated that expression of VEGF was not significantly higher in tumor vs. skin tissue. For the differential expression of BCL-2 and Bax, the results were not in agreement with the established levels found in cancer studies, showing no significant change in BCL-2 expression and significantly higher levels of Bax in tumor vs. healthy tissue.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/209981
Subject Headings: Sea turtles, Physiology, Cancer, Pathophysiology, Vascular endothelial growth factors, Pathophysiology, Cellular signal transduction
Format: Document (PDF)

Title: A comprehensive study of mammalian SNAG transcription family members.
Creator: Chiang, Cindy Chung-Yue., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Transcriptional regulation by the family of SNAG (Snail/Gfi-1) zinc fingers has been shown to play a role in various developmental states and diseases. These transcriptional repressors have function in both DNA- and protein-binding, allowing for multiple interactions by a single family member. This work aims to characterize the SNAG members Slug, Smuc, Snail, Scratch, Gfi-1, Gfi-1B, and IA-1 in terms of both DNA-protein and protein-protein interactions. The specific DNA sequences to which the...
Show moreTranscriptional regulation by the family of SNAG (Snail/Gfi-1) zinc fingers has been shown to play a role in various developmental states and diseases. These transcriptional repressors have function in both DNA- and protein-binding, allowing for multiple interactions by a single family member. This work aims to characterize the SNAG members Slug, Smuc, Snail, Scratch, Gfi-1, Gfi-1B, and IA-1 in terms of both DNA-protein and protein-protein interactions. The specific DNA sequences to which the zinc finger regions bind were determined for each member, and a general consensus of TGCACCTGTCCGA, was developed for four of the members. Via these studies, we also reveal thebinding affinities of E-box (CANNTG) sequences to the members, since this core is found for multiple members' binding sites. Additionally, protein-protein interactions of SNAG members to other biological molecules were investigated. The Slug domain and Scratch domain have unknown function, yet through yeast two-hybrid screening, we were able to determine protein interaction partners for them as well as for other full length SNAG members. These protein-interacting partners have suggested function as corepressors during transcriptional repression. The comprehensive information determined from these studies allow for a better understanding of the functional relationship between SNAG-ZFPs and other genes. The collected data not only creates a new profile for each member investigated, but it also allows for further studies to be initiated from the results.
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Date Issued: 2012
PURL: http://purl.flvc.org/fcla/dt/3342041
Subject Headings: Cellular signal transduction, Zinc-finger proteins, Synthesis, Metalloproteins, Synthesis, Genetic transcription, Regulation
Format: Document (PDF)

Title: A role for polynucleotide phosphorylase in protecting cells and controlling RNA quality under oxidative stress.
Creator: Wu, Jinhua., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: RNA damage occurring under oxidative stress has been shown to cause RNA dysfunction and must be detrimental to cells and organisms. We propose that damaged RNA can be removed by specific RNA surveillance activities. In this work, we investigated the role of polynucleotide phosphorylase (PNPase), a 3'->5' exoribonuclease, in protecting the cells against oxidative stress and eliminating oxidatively-damaged RNA. Previously, it was reported that E. coli PNPase has a higher affinity to poly(8-oxoG...
Show moreRNA damage occurring under oxidative stress has been shown to cause RNA dysfunction and must be detrimental to cells and organisms. We propose that damaged RNA can be removed by specific RNA surveillance activities. In this work, we investigated the role of polynucleotide phosphorylase (PNPase), a 3'->5' exoribonuclease, in protecting the cells against oxidative stress and eliminating oxidatively-damaged RNA. Previously, it was reported that E. coli PNPase has a higher affinity to poly(8-oxoG:A). We further confirmed that E. coli PNPase can specifically bind to an oxidized RNA with a high affinity. An E. coli strain deficient in PNPase (pnp) is hypersensitive to hydrogen peroxide (H2O2). Importantly, the level of H2O2-induced RNA damage, measured by the content of 8-hydroxyguanosine, increases significantly in the pnp mutant cells. Consistent with the notion that PNPase plays a direct role in these processes, introduction of the pnp gene encoding E. coli PNPase can restore the viability and RNA oxidation level of the pnp mutant cells in response to H2O2 treatment. Interestingly, degradosome-association is not required for PNPase to protect cell against oxidative stress. PNPase is evolutionary conserved in most of organisms of all domains of life. The human polynucleotide phosphorylase (hPNPase) localizes mainly in mitochondria and plays pleiotropic roles in cell differentiation and has been previously shown to bind 8- oxoG-RNA with a high affinity. Here we show that similar to E. coli PNPase, hPNPase plays an indispensable role in protecting HeLa cells against oxidative stress. The viability in HeLa cell and 8-oxoG levels in RNA are inversely correlated in response to H2O2- treatment. After removal of oxidative challenge, the elevated level of 8-oxoG in RNA decreases, suggesting the existence of surveillance mechanism(s) for cleaning up oxidized RNA., We have shown that hPNPase may be responsible for the surveillance of oxidized RNA in mammalian cells.Overexpresion of hPNPase reduces RNA oxidation and increases HeLa cell viability against H2O2 insult. Conversely, hPNPase knockdown decreases the viability and increases 8-oxoG level in HeLa cells exposed to H2O2. Taken together, our results suggest that RNA oxidation is a challenging problem for living organisms, and PNPase may play an important role in protecting both prokaryotic and eukaryotic cells by limiting damage to RNA under oxidative stress.
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Date Issued: 2008
PURL: http://purl.flvc.org/FAU/186302
Subject Headings: RNA, Metabolism, Biopolymers, Physiological transport, Bacterial genetics, Proteins, Synthesis, Cellular signal transduction
Format: Document (PDF)

Title: Uncovering the role of the rodent dorsal hippocampus in spatial and object memory retrieval.
Creator: Rios, Lisa, Charles E. Schmidt College of Science, Department of Psychology
Abstract/Description: Male C7BL/6J mice were implanted with bilateral dorsal CA1 guide cannulae. After confirming that intrahippocampal microinfusion of muscimol impaired hippocampal function, demonstrated by impaired performance in the Morris water maze, the influence of intrahippocampal muscimol was tested in the Novel Object Recognition paradigm. During a test session 24 h after the last habituation/sample session, mice were presented with one familiar object and one novel object. Successful retention of object...
Show moreMale C7BL/6J mice were implanted with bilateral dorsal CA1 guide cannulae. After confirming that intrahippocampal microinfusion of muscimol impaired hippocampal function, demonstrated by impaired performance in the Morris water maze, the influence of intrahippocampal muscimol was tested in the Novel Object Recognition paradigm. During a test session 24 h after the last habituation/sample session, mice were presented with one familiar object and one novel object. Successful retention of object memory was inferred if mice spent more time exploring the novel object than the familiar object. Results demonstrate that muscimol infused into dorsal CA1 region prior to the test session eliminates novel object preference, indicating that the hippocampus is necessary for the retrieval of this non-spatial memory - a topic that has garnered much debate. Understanding the similarities between rodent and human hippocampal function could enable future animal studies to effectively answer questions about diseases and disorders affecting human learning and memory.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3172696
Subject Headings: Rodents as laboratory animals, Memory, Research, Cellular signal transduction, Cognitive neuroscience, Hippocampus (Brain), Space perception
Format: Document (PDF)

Title: aB- crystallin/sHSP is required for mitochondrial function in human ocular tissue.
Creator: McGreal, Rebecca., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The central premise of this dissertation is that the small heat shock protein (sHSP), (Sa(BB-crystallin is essential for lens and retinal pigmented epithelial (RPE) cell function and oxidative stress defense. To date, the mechanism by which it confers protection is not known. We hypothesize that these functions could occur through its ability to protect mitochondrial function in lens and RPE cells. To test this hypothesis, we examined the expression of (Sa(BB-crystallin/sHSP in lens and RPE...
Show moreThe central premise of this dissertation is that the small heat shock protein (sHSP), (Sa(BB-crystallin is essential for lens and retinal pigmented epithelial (RPE) cell function and oxidative stress defense. To date, the mechanism by which it confers protection is not known. We hypothesize that these functions could occur through its ability to protect mitochondrial function in lens and RPE cells. To test this hypothesis, we examined the expression of (Sa(BB-crystallin/sHSP in lens and RPE cells, we observed its localization in the cells, we examined translocation to the mitochondria in these cells upon oxidative stress treatment, we determined its ability to form complexes with and protect cytochrome c (cyt c) against damage, and we observed its ability to preserve mitochondrial function under oxidative stress conditions in lens and RPE cells. In addition to these studies, we examined the effect of mutations of (Sa(BB-crystallin/sHSP on its cellular localization and translocation patterns under oxidative stress, its in vivo and in vitro chaperone activity, and its ability to protect cyt c against oxidation. Our data demonstrated that (Sa(BB-crystallin/sHSP is expressed at high levels in the mitochondria of lens and RPE cells and specifically translocates to the mitochondria under oxidative stress conditions. We demonstrate that (Sa(BB-crystallin/sHSP complexes with cyt c and protects it against oxidative inactivation. Finally, we demonstrate that (Sa(BB-crystallin/sHSP directly protects mitochondria against oxidative inactivation in lens and RPE cells. Since oxidative stress is a key component of lens cataract formation and age-related macular degeneration (AMD), these data provide a new paradigm for understanding the etiology of these diseases.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3342242
Subject Headings: Mitochondrial pathology, Chemical mutagenesis, Oxidative stress, Prevention, Cellular signal transduction, Eye, Diseases, Etiology, Molecular chaperones
Format: Document (PDF)

Title: Protective Mechanisms of Granulocyte-Colony Stimulating Factor Against Experimental Models of Stroke.
Creator: Menzie-Suderam, Janet, Wu, Jang-Yen, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biomedical Science
Abstract/Description: Ischemic stroke has a multiplicity of pathophysiological mechanisms. Granulocyte-colony stimulating factor (G-CSF) is an endogenous growth factor that exerts a diverse range of neuroprotection against ischemic stroke. Several lines of evidence demonstrated the contribution of endoplasmic reticulum (ER) in apoptotic cell death involving ischemia. Cell culture of undifferentiated PC12 cells were subjected to 10mM glutamate and selected doses of G-CSF (25ng/ml, 50ng/ml, 100ng/ml and 250ng/ml)...
Show moreIschemic stroke has a multiplicity of pathophysiological mechanisms. Granulocyte-colony stimulating factor (G-CSF) is an endogenous growth factor that exerts a diverse range of neuroprotection against ischemic stroke. Several lines of evidence demonstrated the contribution of endoplasmic reticulum (ER) in apoptotic cell death involving ischemia. Cell culture of undifferentiated PC12 cells were subjected to 10mM glutamate and selected doses of G-CSF (25ng/ml, 50ng/ml, 100ng/ml and 250ng/ml) for 24 hours. Cell viability, expression of the G-CSF receptor and expression level of CHOP were assessed in vitro. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Rats were subcutaneously injected with G-CSF (n= 15; 50ug/kg body weight) 24 hours post-MCAO for 4 days. Vehicle treated rats were administered 5% dextrose for 1 day (n=4) or 4 days (n=16). Sham-operated rats (n=9) were not subjected to MCAO. Neurological deficit and infarct volume were measured while expression levels of pAKT, Bcl2, Bax, Bak, cleaved caspase-3, GRP78, ATF4, ATF6, p-p38MAPK, pJNK, CHOP and HSP27 were analyzed by western blotting. In vitro G-CSF receptor was expressed on undifferentiated PC12 cell, and an optimal dose of 50 ng/ml G-CSF significantly protected these cells against glutamate-induced cytotoxicity (P < 0.05). G-CSF significantly down-regulated (P < 0.01) the ER stressinduced pro-apoptotic marker CHOP in vitro. In vivo, G-CSF reduced infarct volume to 50% while significantly improved neurological deficit compared to vehicle rats. G-CSF significantly (P < 0.05) up-regulated pro-survival proteins pAKT and Bcl2 while downregulating pro-apoptotic proteins Bax, Bak and cleaved caspase 3 in the ischemic brain. It also significantly (P < 0.05) downregulated the ER intraluminal stress sensor GRP78, proteins of ER stress induced intracellular pathway; ATF4, ATF6, p-p38MAPK, pJNK and the ER stress induced apoptotic marker CHOP, which suggests that ER stress is being ameliorated by G-CSF treatment. G-CSF also reduced the level of HSP27, providing additional evidence of cellular stress reduction. G-CSF treatment increased cell survival by attenuating both general pro-apoptotic proteins and specific effector proteins in the ER stress induced apoptotic pathways. Our data has provided new insight into the anti-apoptotic mechanism of G-CSF, especially as it relates to ER stress induced apoptosis in ischemia.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004795, http://purl.flvc.org/fau/fd/FA00004795
Subject Headings: Cerebral ischemia--Protection., Apoptosis., Rats as laboratory animals., Cellular signal transduction., Oxidation-reduction reaction.
Format: Document (PDF)

Title: Relationships of fibroblast growth factor 21 with inflammation and insulin resistance in response to acute exercise in obese individuals.
Creator: Slusher, Aaron L., Huang, Chun-Jung, Florida Atlantic University, College of Education, Department of Exercise Science and Health Promotion
Abstract/Description: Obesity is associated with elevated levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), contributing to systemic insulin resistance. Fibroblast growth factor 21 (FGF21) is a vital metabolic and inflammatory regulator, however circulating FGF21 concentrations are elevated in obese individuals. Acute aerobic exercise increases systemic FGF21 in normal-weight individuals, however the effect of acute aerobic exercise on plasma FGF21 response and...
Show moreObesity is associated with elevated levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), contributing to systemic insulin resistance. Fibroblast growth factor 21 (FGF21) is a vital metabolic and inflammatory regulator, however circulating FGF21 concentrations are elevated in obese individuals. Acute aerobic exercise increases systemic FGF21 in normal-weight individuals, however the effect of acute aerobic exercise on plasma FGF21 response and the relationships with inflammation (IL-6 and TNF-α), insulin resistance, and energy expenditure in obese individuals is unknown. Following 30 minutes of treadmill running at 75% VO2max, plasma FGF21 response, as indicated by area-under-the-curve “with respect to increase” (AUCi) analyses, was attenuated in 12 obese compared to 12 normalweight subjects. Additionally, FGF21 AUCi positively correlated with glucose AUCi, total relative energy expenditure, and relative VO2max, suggesting that cardiorespiratory fitness levels may predict FGF21 response, contributing to the enhanced regulation of glucose and energy metabolism.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004229, http://purl.flvc.org/fau/fd/FA00004229
Subject Headings: Fibroblast growth factor., Cell differentiation., Cellular signal transduction., Obesity--Health aspects., Metabolic syndrome--Pathophysiology.
Format: Document (PDF)

Title: Heterologous expression and purification of cell function components -: an effort towards developing an antigen-capture ELISA diagnostics for metastatic cancers.
Creator: Irvine, Michael., Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Metastatic cancers are problematic because they spread throughout the body. A crucial step in cancer metastasis is the separation of the cancer cells from their surrounding normal cells. This occurs due to suppression or destruction of cell adhesion molecules such as E-cadherin, occludin, and various claudins. The Snail and Slug transcription factors play a direct role in suppressing these cell adhesion molecules through their SNAG repression domain. We explored the possibility of developing...
Show moreMetastatic cancers are problematic because they spread throughout the body. A crucial step in cancer metastasis is the separation of the cancer cells from their surrounding normal cells. This occurs due to suppression or destruction of cell adhesion molecules such as E-cadherin, occludin, and various claudins. The Snail and Slug transcription factors play a direct role in suppressing these cell adhesion molecules through their SNAG repression domain. We explored the possibility of developing an ELISA diagnostics capable of detecting soluble E-cadherin, occludin, and claudin fragments in the serum of cancer patients. Using several bioinformatics tools, unique extracellular antigenic sequences were identified on claudins-1, 4, 16, occludin, and E-cadherin. These sequences were cloned as GST fusion proteins, expressed, and purified in large quantities to raise antibodies. In parallel, expression profiling of metastatic cancer cell lines was carried out to derive a correlation between Snail-Slug expression and suppression of cell adhesion molecules.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/369191
Subject Headings: Cellular signal transduction, Extracellular matrix proteins, Genetic transcription, Research, Metalloproteinases, Inhibitors
Format: Document (PDF)

Title: Molecular characterization of ARID and DDT domain.
Creator: MacDonald, Emmanuel., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Transcriptional regulation of genes is vital to cell success making it an important aspect of research. Transcriptional regulation can occur in many ways; transcription factors bind to the promoter region and block transcription, disrupt an activator protein, or interact with histones to lead to higher order chromatin. Plant HomeoDomain can recognize and bind to different methylation states of histone tails. PHD proteins use other functional regions to carry out functions. Two associated...
Show moreTranscriptional regulation of genes is vital to cell success making it an important aspect of research. Transcriptional regulation can occur in many ways; transcription factors bind to the promoter region and block transcription, disrupt an activator protein, or interact with histones to lead to higher order chromatin. Plant HomeoDomain can recognize and bind to different methylation states of histone tails. PHD proteins use other functional regions to carry out functions. Two associated domains having DNA-binding capacity were characterized in this study; the ARID domains of JARID1A and JARID1C and the DDT domains of BAZ1A, BAZ1B and BAZ2A. These genes are important because of their roles in various diseases such as cancer. The consensus sequences for BAZ1A-DDT is GGACGGRnnGG, GnGAGRGCRnnGGnG, RAGGGGGRnG and CRYCGGT. Consensus sequences for BAZ1B-DDT were CGnCCAnCTTnTGGG and YGCCCCTCCCCnR. Consensus sequences for BAZ2A-DDT were TACnnAGCnY and CnnCCRGCnRTGnYY. Consensus sequence for JARID1A-ARID was GnYnGCGYRCYnCnG. Consensus sequences for JARID1C-ARID was RGGRGCCRGGY.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2705077
Subject Headings: Genetic transcription, Regulation, Transcription factors, Zinc-finger proteins, Synthesis, Cellular signal transduction, Gene expression
Format: Document (PDF)

Title: Methionine sulfoxide reductases: studies on the reducing requirements and role in the metabolism of sulindac.
Creator: Brunell, David J., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is...
Show moreThe methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is thioredoxin (Trx), although high levels of dithiothreitol (DTT) can be used as the reductant in vitro. In contrast, certain MsrB enzymes show less than 10% of the activity with Trx as compared to DTT. This raises the possibility that in animal cells Trx may not be the direct hydrogen donor for the MsrB enzymes. Studies with bovine liver extracts have shown that thionein, the apoprotein of metallothionein, can function as a reductant for the Msr proteins. Certain selenium compounds such as selenocystamine and selenocystine can also serve as potent reducing agents for the Msr enzymes. Since an increased activity of Msr enzymes can reduce the level of oxidative damage in tissues, compounds that could activate Msr may have therapeutic potential. A high-throughput screening assay has been developed to screen large chemical libraries to find activators of MsrA, as well as specific inhibitors that could be useful research tools. This study will be done in collaboration with The Scripps Florida Research Institute. Sulindac was originally developed as a non-steroidal anti-inflammatory drug but has also shown efficacy in the treatment of certain cancers. The S epimer of sulindac is known to be reduced by MsrA, but the enzymes responsible for reduction of the R epimer are not known., An activity has been purified from rat liver which is capable of reducing the R epimers of sulindac, free Met(O) and a dabsylated Met(O) substrate, the latter suggesting that this enzyme may have properties similar t o the MsrB enzymes. The oxidation of the epimers of sulindac to sulindac sulfone has also been characterized, and the members of the cytochrome P450 family involved in the oxidation have been identified.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/227979
Subject Headings: Cellular signal transduction, Proteins, Chemical modification, Biochemical markers, Oxidation-reduction reaction
Format: Document (PDF)

Title: Peroxiredoxin 3 and Methionine sulfoxide reductase A are Essential for Lens Cell Viability by Preserving Lens Cell Mitochondrial Function through Repair of Cytochrome c.
Creator: Lee, Wanda, Florida Atlantic University, Kantorow, Marc, Charles E. Schmidt College of Science, Department of Biomedical Science
Abstract/Description: The central premise of this dissertation is that mitochondrial antioxidant enzymes are essential to lens cell viability by preserving lens cell mitochondria and protecting and/or repairing lens cell proteins, and two mitochondrial-specific antioxidant enzymes, Peroxiredoxin 3 (PRDX3) and Methionine sulfoxide reductase A (MsrA), are explored. In this dissertation, we will examine the expression ofPRDX3 in the human lens, its colocalization to the lens cell mitochondria, its ability to be...
Show moreThe central premise of this dissertation is that mitochondrial antioxidant enzymes are essential to lens cell viability by preserving lens cell mitochondria and protecting and/or repairing lens cell proteins, and two mitochondrial-specific antioxidant enzymes, Peroxiredoxin 3 (PRDX3) and Methionine sulfoxide reductase A (MsrA), are explored. In this dissertation, we will examine the expression ofPRDX3 in the human lens, its colocalization to the lens cell mitochondria, its ability to be induced by H20 2-oxidative stress, and speculate how PRDX3 function/sf could affect the lens. We will also examine the reduced levels of MsrA by targeted gene silencing and its effect on reactive oxygen species production and mitochondrial membrane potential in human lens cells to determine its role in mitochondrial function in the lens. Lastly, we will examine the ability of MsrA to repair and restore function to a critical mitochondrial protein, Cytochrome c. The collective evidence strongly indicates that the loss of mitochondrial-specific enzymes, such as PRDX3 and MsrA, are responsible for increased reactive oxygen species levels, decreased mitochondrial membrane potential, protein aggregation and lens cell death, and further indicates that mitochondrial repair, protective, and reducing systems play key roles in the progression of age-related cataract and other agerelated diseases.
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Date Issued: 2008
PURL: http://purl.flvc.org/fau/fd/FA00000868
Subject Headings: Genetic regulation, Proteins--Chemical modification, Cellular signal transduction, Eye--Physiology, Mitochondrial pathology
Format: Document (PDF)

Title: Taurine inhibits glutamate-induced excitotoxicity through a calpain dependent pathway.
Creator: Leon, Rebecca, Prentice, Howard, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Taurine, an endogenous ammo acid and neuromodulator, has been found to be neuroprotective against numerous forms of neurotoxicity including glutamate-induced excitotoxicity. Previously we have shown that taurine inhibits glutamate-induced calcium influx through VGCCs and NMDA receptors. Although the neuroprotective effects of taurine against excitotoxicity have been attributed to its intracellular Ca2+ regulatory functions, the complete mechanism underling taurine neuroprotection has remained...
Show moreTaurine, an endogenous ammo acid and neuromodulator, has been found to be neuroprotective against numerous forms of neurotoxicity including glutamate-induced excitotoxicity. Previously we have shown that taurine inhibits glutamate-induced calcium influx through VGCCs and NMDA receptors. Although the neuroprotective effects of taurine against excitotoxicity have been attributed to its intracellular Ca2+ regulatory functions, the complete mechanism underling taurine neuroprotection has remained unclear. Using primary rat cortical neuronal cell cultures, we have determined key cytosolic components to the mechanism of taurine neuroprotection. In this study we have found that taurine inhibits excitotoxicity by suppressing glutamate-induced elevations in [Ca2+]i, preventing calpain activation, and inhibiting reductions in Bel- 2:Bax ratios and consequently activation of the intrinsic pathway.
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Date Issued: 2008
PURL: http://purl.flvc.org/fau/fd/FA00000788
Subject Headings: Cellular signal transduction, Taurine--Physiological effect, Proteolytic enzymes--Research
Format: Document (PDF)

Title: Methionine sulfoxide reductase (Msr) deficiency leads to a reduction of dopamine levels in Drosophila.
Creator: Hernandez, Caesar, Binninger, David, Weissbach, Herbert, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Biological homeostasis relies on protective mechanisms that respond to cellular oxidation caused primarily by free radical reactions. Methionine sulfoxide reductases (Msr) are a class of enzymes that reverse oxidative damage to methionine in proteins. The focus of this study is on the relationship between Msr and dopamine levels in Drosophila. Dopaminergic neurons in Drosophila have comparable roles to those found in humans. A deficit in dopamine leads to the onset of many neurological...
Show moreBiological homeostasis relies on protective mechanisms that respond to cellular oxidation caused primarily by free radical reactions. Methionine sulfoxide reductases (Msr) are a class of enzymes that reverse oxidative damage to methionine in proteins. The focus of this study is on the relationship between Msr and dopamine levels in Drosophila. Dopaminergic neurons in Drosophila have comparable roles to those found in humans. A deficit in dopamine leads to the onset of many neurological disorders including the loss of fine motor control—a neurodegenerative condition characteristic of Parkinson’s disease (PD). We found that dopamine levels in the heads of MsrAΔ/ΔBΔ/Δ mutants are significantly reduced in comparison to MsrA ⁺/⁺ B⁺/⁺ heads. In addition, wefound protein and expression levels are markedly reduced in an Msr-deficient system. Our findings suggest an important role for the Msr system in the CNS.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004202, http://purl.flvc.org/fau/fd/FA00004202
Subject Headings: Cellular signal transduction, Dopamine -- Receptors, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Proteins -- Chemical modification
Format: Document (PDF)

Title: Cells and cocktails: antioxidants rescue carcinogen induced mitotic defects in both chromosomally stable and unstable cells.
Creator: Griffin, Isabel Sloan., Harriet L. Wilkes Honors College
Abstract/Description: Tumor cells are characterized by an increase in genomic instability, brought about by both chromosomal rearrangement and chromosomal instability. Both of these broad changes can be induced by exposure to carcinogens. During mitosis, cells can exhibit early and late lagging chromosomes, multipolar spindles or anaphase bridges, all of which contribute to genomic rearrantement. We have studied the link between exposure to carcinogen and prevalence of mitotic defect in both chromosomally stable...
Show moreTumor cells are characterized by an increase in genomic instability, brought about by both chromosomal rearrangement and chromosomal instability. Both of these broad changes can be induced by exposure to carcinogens. During mitosis, cells can exhibit early and late lagging chromosomes, multipolar spindles or anaphase bridges, all of which contribute to genomic rearrantement. We have studied the link between exposure to carcinogen and prevalence of mitotic defect in both chromosomally stable and unstable cell lines as well as ecamined the restorative effects of antioxidants in preventing mitotic defects. We have exposed MES-SA uterine cancer cells to vinyl chloride followed by exposure to an antioxidant : ascorbic acid, B-carotene, or lycopene. Treated cells were then scored for the prevalence of mitotic defects within the population and compared to controls. We have also investigated whether pre-treatment with the antioxidants will weaken the effects of carcinogen exposure in these cell lines.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3359304
Subject Headings: Cellular signal transduction, Cell differentiation, Medical genetics, Cancer, Genetic aspects, Antioxidants, Therapeutic use, Cancer, Chemoprevention, Apoptosis, Molecular aspects, Genetic regulation
Format: Document (PDF)

Title: Comprehensive study of the ZAD family of zinc finger transcription factors in Drosophila melanogaster.
Creator: Krystel, Joseph., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The zinc finger associated domain (ZAD) family of transcription factors from Drosophila melanogaster is not well described in the literature, in part because it is very difficult to study by traditional mutagenesis screens. Bioinformatic studies indicate this is due to overlapping functions remaining after a recent evolutionary divergence. I set out to use in vitro-binding techniques to identify the characteristics of the ZAD family and test this theory. I have constructed glutathione S...
Show moreThe zinc finger associated domain (ZAD) family of transcription factors from Drosophila melanogaster is not well described in the literature, in part because it is very difficult to study by traditional mutagenesis screens. Bioinformatic studies indicate this is due to overlapping functions remaining after a recent evolutionary divergence. I set out to use in vitro-binding techniques to identify the characteristics of the ZAD family and test this theory. I have constructed glutathione S-transferase (GST)-ZAD domain chimeric proteins for use in pull down protein binding assays,and GST-Zinc finger (ZnF) array domain chimera for electrophoretic mobility shift assays (EMSA). Protein binding assays indicated two putative conserved interactors, similar to the analogous KRAB system in mammals. ... Competitive bindings were carried out to show a specificity of binding conferred by the identified conserved positions. While the consensus binding sites show relatively few similarities, the predicted target genes identified by the consensus binding sites show significant overlap. The nature of this overlap conforms to the known characteristics of the ZAD family but points to a more positive selection to maintain conservation of function.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3355627
Subject Headings: Cellular signal transduction, Drosophila melanogaster, Cytogenetics, Transcription factors, Zinc-finger proteins, Synthesis, Genetic transcription, Regulation, Gene expression
Format: Document (PDF)

Title: Elucidation of the features of the zinc finger associated domain (ZAD) family of transportation factors in Drosophila melanogaster.
Creator: Krystel, Joseph., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The zinc finger associated domain (ZAD) containing family of transcription factors is not well described in the literature, in part because it is very difficult to study by mutagenesis. We used in vitro-binding techniques to identify characteristics of the ZAD family, by constructing glutathione Stransferase (GST)-ZAD domain chimeric proteins for use in protein binding assays, and GST-Zinc finger array domain chimera for binding site selections. Protein binding assays indicated a possible...
Show moreThe zinc finger associated domain (ZAD) containing family of transcription factors is not well described in the literature, in part because it is very difficult to study by mutagenesis. We used in vitro-binding techniques to identify characteristics of the ZAD family, by constructing glutathione Stransferase (GST)-ZAD domain chimeric proteins for use in protein binding assays, and GST-Zinc finger array domain chimera for binding site selections. Protein binding assays indicated a possible shared cofactor, as seen in the analogous KRAB system in mammals. DNA binding assays have provided a consensus binding sequence for five of the ZAD proteins, consistent with previously reported work on ZAD and unpublished work on mammalian transcription factors. Research is ongoing with an additional ~50 ZAD proteins to more fully map the binding characters of ZAD proteins.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186768
Subject Headings: Cellular signal transduction, Drosophila melanogaster, Cytogenetics, Transcription factors, Zinc-finger proteins, Synthesis, Genetic transcription, Regulation, Gene expression
Format: Document (PDF)

Title: Identification of longitudinals lacking (LOLA) target genes in Drosophila melanogaster.
Creator: Qureshi, Bazila., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Longitudinals lacking gene (LOLA) is a transcription factor that is involved in a variety of axon guidance decisions in Drosophila melanogaster nervous system. Besides having a role as an epigenetic silencer and in the programmed cell death in Drosophila's ovary, this gene is also an example of complex transcription unit. LOLA is a transcription repressor and can generate 17 DNA - binding isoforms, through alternative splicing, each containing distinct zinc-finger proteins. This unique...
Show moreLongitudinals lacking gene (LOLA) is a transcription factor that is involved in a variety of axon guidance decisions in Drosophila melanogaster nervous system. Besides having a role as an epigenetic silencer and in the programmed cell death in Drosophila's ovary, this gene is also an example of complex transcription unit. LOLA is a transcription repressor and can generate 17 DNA - binding isoforms, through alternative splicing, each containing distinct zinc-finger proteins. This unique DNAbinding binding sequence to which LOLA-ZFP binds has been determined for four of the lola isoforms F, J, P and K. Also, bioinformatics' tool approach has been taken to identify the target genes that are regulated by these four LOLA splice variants. Future work will be done for the five other LOLA isoforms to categorize their putative DNA-binding sequences and subsequently their protein interactions.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2684893
Subject Headings: Transcription factors, Cellular signal transduction, Zinc-finger proteins, Synthesis, Genetic transcription, Regulation, Drosophila melanogaster, Cytogenetics, Gene expression
Format: Document (PDF)

Title: Identification and characterization of mutations in the Drosophila mitochondrial translation elongation factor iconoclast.
Creator: Trivigno, Catherine F., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Mitochondrial disorders resulting from defects in oxidative phosphorylation are the most common form of inherited metabolic disease. Mutations in the human mitochondrial translation elongation factor GFM1 have recently been shown to cause the lethal pediatric disorder Combined Oxidative Phosphorylation Deficiency Syndrome (COXPD1). Children harboring mutations in GFM1 exhibit severe developmental, metabolic and neurological abnormalities. This work describes the identification and extensive...
Show moreMitochondrial disorders resulting from defects in oxidative phosphorylation are the most common form of inherited metabolic disease. Mutations in the human mitochondrial translation elongation factor GFM1 have recently been shown to cause the lethal pediatric disorder Combined Oxidative Phosphorylation Deficiency Syndrome (COXPD1). Children harboring mutations in GFM1 exhibit severe developmental, metabolic and neurological abnormalities. This work describes the identification and extensive characterization of the first known mutations in iconoclast (ico), the Drosophila orthologue of GFM1. Expression of human GFM1 can rescue ico null mutants, demonstrating functional conservation between the human and fly proteins. While point mutations in ico result in developmental defects and death during embryogenesis, animals null for ico survive until the second or third instar larval stage. These results indicate that in addition to loss-of-function consequences, point mutations in ico appear to produce toxic proteins with antimorphic or neomorphic effects. Consistent with this hypothesis, transgenic expression of a mutant ICO protein is lethal when expressed during development and inhibits growth when expressed in wing discs. In addition, animals with a single copy of an ico point mutation are more sensitive to acute hyperthermic or hypoxic stress. Removal of the positively-charged tail of the protein abolishes the toxic effects of mutant ICO, demonstrating that this domain is necessary for the harmful gain-of-function phenotypes observed in ico point mutants., Further, expression of GFP-tagged constructs indicates that the C-terminal tail enhances ectopic nuclear localization of mutant ICO, suggesting that mislocalization of the protein may play a role in the antimorphic effects of mutant ICO. Taken together, these results illustrate that in addition to loss-of-function effects, gain-of-function effects can contribute significantly to the pathology caused by mutation in mitochondrial translation elongation factors.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2705081
Subject Headings: Drosophila melanogaster, Cytogenetics, Mutation (Biology), Mitochondrial DNA, Cell metabolism, Cellular signal transduction, Oxidation, Physiological, Genetic transcription, Regulation
Format: Document (PDF)

Title: Temporal response of creatine kinase and fibroblast growth factor-21 to high and low repetition resistance training programs.
Creator: Blanco, Rocky, Zourdos, Michael C., Florida Atlantic University, College of Education, Department of Exercise Science and Health Promotion
Abstract/Description: The purpose of this study was to examine the acute and temporal response of CK- MM and FGF-21 to 3-day/wk. different repetition-range, volume-equated resistance training programs over 8-weeks in previously trained males. Sixteen trained, college- aged males were counterbalanced into high (DUP-HR) or low (DUP-LR) repetition groups. Subjects performed the squat and bench press 3x/wk. for 8 weeks. Blood samples were collected at various intervals throughout the study. Trained individuals did not...
Show moreThe purpose of this study was to examine the acute and temporal response of CK- MM and FGF-21 to 3-day/wk. different repetition-range, volume-equated resistance training programs over 8-weeks in previously trained males. Sixteen trained, college- aged males were counterbalanced into high (DUP-HR) or low (DUP-LR) repetition groups. Subjects performed the squat and bench press 3x/wk. for 8 weeks. Blood samples were collected at various intervals throughout the study. Trained individuals did not elicit significant acute or chronic changes in CK-MM or FGF-21 following training and the lack of change was present in both groups. Additionally, neither biomarker correlated with changes in 1RM strength. There was a very strong correlation between acute mean (r=0.95) and acute percentage change (r=0.97) increase from pre training to post training in week #1. Additionally, a moderate correlation in percentage change was observed (r=0.59) of both biomarkers from pre training to 48 hours post training in week #2.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004429, http://purl.flvc.org/fau/fd/FA00004429
Subject Headings: Bioenergetics, Cellular signal transduction, Fibroblast growth factors, Metabolic syndrome -- Pathophysiology, Protein kinases -- Inhibitors -- Therapeutic use
Format: Document (PDF)

Title: The Impact of Pharmacological Targeting of Abnormal Tumor Metabolism with 3-Bromopyruvate on Dendritic Cell Mediated Tumoral Immunity.
Creator: Lang, Kevin, Hartmann, James X., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Studies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the...
Show moreStudies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the immune system. Immunogenic cell death is critical to eliciting an effective adaptive immune response that selectively kills additional target cells and generates immunological memory. We demonstrated that 3-bromopyruvate induced apoptosis in a number of different murine breast cancer cell lines, including the highly metastatic 4T1 line. The dying tumor cells stimulated immature dendritic cells (DCs) of the immortal JAWS II cell line to produce high levels of the pro-inflammatory cytokine IL-12, and increased their expression of key co-stimulatory molecules CD80 and CD86. The activated dendritic cells showed increased uptake of fragments from dying tumor cells that correlated with the increased levels of calreticulin on the surface and release of high group motility box 1 (HMGB1) of the latter following 3-BP treatment. Additionally, the anti-phagocytic signal CD47 present on breast cancer cells was reduced by treatment with 3-bromopyruvate when compared to the levels on untreated 4T1 cells. 3-BP treated breast cancer cells were able to activate dendritic cells through TLR4 signaling. Signaling was dependent on both the expression of surface calreticulin and on the extracellular release of high mobility group box 1 protein (HMGB1) during the process of immunogenic cell death. Killing by 3-BP was compared to mitoxantrone and doxorubicin, among the few chemotherapeutics that induce immunogenic cell death. 3-BP killing was likewise compared to camptothecin, a compound that fails to induce immunogenic cell death. Importantly, 3-BP did not markedly decrease the levels of the key peptide presenting molecule MHC I on DCs that were co-cultivated with dying tumor cells. Treatment of the highly aggressive triple negative BT-20 human breast cancer cell line with 3-BP also induced an immunogenic cell death, activating human dendritic cells in vitro.
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Date Issued: 2017
PURL: http://purl.flvc.org/fau/fd/FA00004834
Subject Headings: Apoptosis., Cellular signal transduction., Cell death., Breast--Cancer--Treatment., Carrier proteins., Cancer--Molecular aspects., Biological interfaces.
Format: Document (PDF)

FAU Theses and Dissertations (69)	+ -
Honors Student Theses (9)	+ -
HBOI Faculty Contributions (1)	+ -

Cellular signal transduction (67)	+ -
Cellular signal transduction. (12)	+ -
Genetic transcription (12)	+ -
Regulation (10)	+ -
Cancer (9)	+ -

Gene expression (9)	+ -
Research (8)	+ -
Cellular control mechanisms (7)	+ -
Drosophila melanogaster (7)	+ -
Synthesis (7)	+ -
Transcription factors (7)	+ -
Apoptosis (6)	+ -
Mitochondrial pathology (6)	+ -
Molecular aspects (6)	+ -
Mutation (Biology) (6)	+ -
Zinc-finger proteins (6)	+ -
Cytogenetics (5)	+ -
Genetic aspects (5)	+ -
Genetic regulation (5)	+ -
Metabolism (5)	+ -
Oxidative stress (5)	+ -
Proteins (5)	+ -
Apoptosis. (4)	+ -
Cell division (4)	+ -
Cellular control mechanisms. (4)	+ -
Hippocampus (Brain) (4)	+ -
Mice as laboratory animals (4)	+ -
Oxidation-reduction reaction (4)	+ -
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thesis (9)	+ -
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Charles E. Schmidt College of Science (51)	+ -
Department of Biological Sciences (39)	+ -
Florida Atlantic University (28)	+ -
Department of Biomedical Science (16)	+ -
Charles E. Schmidt College of Medicine (12)	+ -

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