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- Title
- Activators and repressors of transcription: using bioinformatics approaches to analyze and group human transcription factors.
- Creator
- Savitskaya, Ala., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Transcription factors are macromolecules that are involved in transcriptional regulation by interacting with specific DNA regions, and they can cause activation or silencing of their target genes. Gene regulation by transcriptional control explains different biological processes such as development, function, and disease. Even though transcriptional control has been of great interest for molecular biology, much still remains unknown. This study was designed to generate the most current list...
Show moreTranscription factors are macromolecules that are involved in transcriptional regulation by interacting with specific DNA regions, and they can cause activation or silencing of their target genes. Gene regulation by transcriptional control explains different biological processes such as development, function, and disease. Even though transcriptional control has been of great interest for molecular biology, much still remains unknown. This study was designed to generate the most current list of human transcription factor genes. Unique entries of transcription factor genes were collected and entered into Microsoft Office 2007 Access Database along with information about each gene. Microsoft Office 2007 Access tools were used to analyze and group collected entries according to different properties such as activator or repressor record, or presence of certain protein domains. Furthermore, protein sequence alignments of members of different groups were performed, and phylogenetic trees were used to analyze relationship between different members of each group. This work contributes to the existing knowledge of transcriptional regulation in humans.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/1930495
- Subject Headings
- Transcription factors, Genetic transcription, Regulation, Cellular signal transduction, DNA microarrays, Bioinformatics
- Format
- Document (PDF)
- Title
- An investigation of membrane transporter proteins in the distal vertebrate retina: excitatory amino acid transporters and sodium potassium chloride cotransporters.
- Creator
- Purpura, Lauren Angeline, Shen, Wen, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Neurons are able to maintain membrane potential and synaptic integrity by an intricate equilibrium of membrane transporter proteins and ion channels. Two membrane proteins of particular importance in the vertebrate retina are the excitatory amino acid transporters (EAATs) which are responsible for the reuptake of glutamate into both glial and neuronal cells and the sodium potassium chloride cotransporters (NKCCs) that are responsible for the uptake of chloride ions into the cell. NKCCs are...
Show moreNeurons are able to maintain membrane potential and synaptic integrity by an intricate equilibrium of membrane transporter proteins and ion channels. Two membrane proteins of particular importance in the vertebrate retina are the excitatory amino acid transporters (EAATs) which are responsible for the reuptake of glutamate into both glial and neuronal cells and the sodium potassium chloride cotransporters (NKCCs) that are responsible for the uptake of chloride ions into the cell. NKCCs are electro-neutral with the uptake of 2 Cl- coupled to an exchange of a potassium and Na+ ion into the cells. Therefore, there is little change of cell membrane potential in the action of NKCCs. In this study the localization and function of EAATs in the distal retina is investigated. Whole cell patch clamp recordings in lower vertebrate retina have demonstrated that EAAT2 is the main synaptic EAATs in rod photoreceptors and it is localized to the axon terminals. Furthermore, the action of the transporter seems to be modified by intracellular calcium concentration. There is also evidence that EAAT2 might be regulated by feedback from the neuron network by glycinergic and GABAergic mechanisms. The second half of this study investigates expression of NKCCs in the retina by western blot analysis and quantitative polymerase chain reaction. There are two forms of NKCCs, NKCC1 and NKCC2. NKCC1 is mostly expressed in the central nervous system and NKCC2 was thought to only be expressed in the kidneys. NKCC1 is responsible for the majority of chloride uptake into neuronal and epithelial cells and NKCC1 is expressed in the distal retina where photoreceptors synapse on second order horizontal and bipolar cells. This study found the expression of NKCC1 in the distal retina to be regulated by temporal light and dark adaptation. Light adaptation increased phosphorylated NKCC1 expression (the active form of the cotransporter). The increase in NKCC1 expression during light adaptation was modulated by dopamine. Specifically, a D1 receptor agonist increased phosphorylated NKCC1 expression. Dopamine is an essential chemical and receptor known for initiating light adaptation in retina. Finally, an NKCC1 knockout mouse model was examined and it revealed that both forms of NKCC are expressed in the vertebrate retina.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004224, http://purl.flvc.org/fau/fd/FA00004224
- Subject Headings
- Biological transport, Carrier proteins, Cellular signal transduction, Neural receptors, Retina -- Cytology
- Format
- Document (PDF)
- Title
- Approaches for raising the level of FOXO3a in animal cells.
- Creator
- Navarro, Diana., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
The turtle is a unique model of anoxic survival. The turtle's brain can tolerate total oxygen deprivation for hours to days as well as prevent high levels of mitochondrial-derived free radicals upon re-oxygenation. Because of its ability to prevent elevated free radical generation, the turtle has also become recognized as a model of exceptional longevity. We are employing the turtle model for an investigation into the regulation of a key antioxidant enzyme system - methionine sulfoxide...
Show moreThe turtle is a unique model of anoxic survival. The turtle's brain can tolerate total oxygen deprivation for hours to days as well as prevent high levels of mitochondrial-derived free radicals upon re-oxygenation. Because of its ability to prevent elevated free radical generation, the turtle has also become recognized as a model of exceptional longevity. We are employing the turtle model for an investigation into the regulation of a key antioxidant enzyme system - methionine sulfoxide reductases (Msrs), primarily MsrA and MsrB. The Msr system is capable of reversing oxidation of methionines in proteins and Msr subtypes have been implicated in protecting tissues against oxidative stress, as well as, enhancing the longevity of organisms from yeast to mammals. Preliminary data, unpublished results, indicate that MsrA protein and transcripts are elevated by anoxia. A recent study on Caenorhabditis elegans demonstrated that FOXO is involved in activation of the MsrA promoter. Using the turtle MsrA promoter sequence we worked to determine which regions in the promoter are necessary for activation by anoxia. The results of the present study were 1) to prepare a TAT-FOXO3a fusion protein which could penetrate animal cells and 2) to construct a FOXO3a expression vector for transcription studies on MsrA expression.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3342243
- Subject Headings
- Cellular signal transduction, Cell proliferation, Oxidative stress, Prevention, Adaptation (Physiology)
- Format
- Document (PDF)
- Title
- Characterization of SNAG-zinc finger protein (ZFP) transcription factors.
- Creator
- Chiang, Cindy Chung-Yue., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Transcriptional regulation is an important area of research due to the fact that it leads to gene expression. Transcription factors associated with the regulation can either be activators or repressors of target genes, acting directly or with the aid of other factors. A majority of transcriptional repressors are zinc finger proteins (ZFPs) which bind to specific DNA sequences. The Snail/Gfi (SNAG) domain family, with members such as Slug, Smuc, Snail, and Scratch, are transcriptional...
Show moreTranscriptional regulation is an important area of research due to the fact that it leads to gene expression. Transcription factors associated with the regulation can either be activators or repressors of target genes, acting directly or with the aid of other factors. A majority of transcriptional repressors are zinc finger proteins (ZFPs) which bind to specific DNA sequences. The Snail/Gfi (SNAG) domain family, with members such as Slug, Smuc, Snail, and Scratch, are transcriptional repressors shown to play a role in various diseases such as cancer. The SNAG transcription factors contain a conserved SNAG repression domain and DNA binding domain zinc fingers. The specific DNA sequences to which each SNAG-ZFP binds, as well as a general consensus -TGCACCTGTCCGA, have been determined. Also, putative protein-protein interactions in which the Slug domain participates has been identified via binding assays. All these results contribute to better understanding of SNAG-ZFP functions.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/186676
- Subject Headings
- Zinc-finger proteins, Synthesis, Metalloproteins, Synthesis, Genetic transcription, Regulation, Cellular signal transduction, Gene expression
- Format
- Document (PDF)
- Title
- Characterization of the MHC II B of the bald eagle.
- Creator
- Smith, Andrew., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
The Major Histocompatibility Complex class II B (MHC II B) gene encodes a protein that is part of the adaptive immune system and critical for the non-self recognition ability of immune cells. This gene has been characterized in the Bald Eagle, ten unique alleles were found in two subpopulations at the geographic extremes of the range margins. Geographic genetic variation is suggested by the presence of population specific alleles. The results showed considerable divergence of groups of Bald...
Show moreThe Major Histocompatibility Complex class II B (MHC II B) gene encodes a protein that is part of the adaptive immune system and critical for the non-self recognition ability of immune cells. This gene has been characterized in the Bald Eagle, ten unique alleles were found in two subpopulations at the geographic extremes of the range margins. Geographic genetic variation is suggested by the presence of population specific alleles. The results showed considerable divergence of groups of Bald Eagle alleles when compared to alleles from other birds of prey. Particular codons within the exon II show signs of balancing selection driving the evolution of the MHC II B. Transcription data showed statistically significant differential expression of alleles. This can be interpreted as meaning a particular locus is being preferentially expressed in blood. The analysis of the polymorphism of this adaptive marker may aid managers of wildlife during this age of global climate change and the biodiversity crisis.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/2979375
- Subject Headings
- Major histocompatibility complex, Cellular signal transduction, Immunogenetics, Genetic polymorphisms
- Format
- Document (PDF)
- Title
- Chronic variable stress affects hippocampal neurotrophic factor gene expression in the novelty-seeking phenotype: epigenetic regulation.
- Creator
- Oztan, Ozge., Charles E. Schmidt College of Medicine
- Abstract/Description
-
Experimentally naive rats exhibit varying degrees of novelty exploration. Some rats display high rates of locomotor reactivity to novelty (high responders; HR), and others display low rates (low responders; LR). The novelty-seeking phenotype (LRHR) is introduced as a model of stress responsiveness. In this thesis I examined effects of chronic variable physical and social stress or control handling on the levels of various neurotrophins in the hippocampus, and changes in mossy fibre terminal...
Show moreExperimentally naive rats exhibit varying degrees of novelty exploration. Some rats display high rates of locomotor reactivity to novelty (high responders; HR), and others display low rates (low responders; LR). The novelty-seeking phenotype (LRHR) is introduced as a model of stress responsiveness. In this thesis I examined effects of chronic variable physical and social stress or control handling on the levels of various neurotrophins in the hippocampus, and changes in mossy fibre terminal fields in LRHR rats. A positive correlation is seen between histone deacetylase 2 and brain-derived neurotrophic factor (BDNF) levels both of which are oppositely regulated in LRHR CA3 fields in response to chronic social stress. Increase in BDNF levels in CA3 field accompanied increase in supra-pyramidal mossy fibre terminal field size (SP-MF) in HRs, and decrease in BDNF levels accompanied decrease in SP-MF volume in LRs. Epigenetic regulation of neurotrophic support underlying these structural changes is discussed.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/215290
- Subject Headings
- Rats as laboratory animals, Cellular signal transduction, Gene expression, Hippocampus (Brain), Physiology, Neural transmission, Genetic regulation
- Format
- Document (PDF)
- Title
- Cleavage of brain glutamic acid decarboxylase 65 by calpain under pathological conditions.
- Creator
- Buddhala, Chandana, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Brain glutamic acid decarboxylase 65 (GAD65) catalyzes the rate-limiting step in the biosynthesis of the major inhibitory neurotransmitter-amino butyric acid (GABA) from the substrate L-glutamic acid. Severe lapse in GABA neurotransmission is one of the etiologies documented in the manifestation of certain neurodegenerative diseases such as epilepsy, Parkinson's disease, Huntington's disease etc. Because GAD65 synthesizes GABA, any modulation of GAD65, therefore, has direct implications on...
Show moreBrain glutamic acid decarboxylase 65 (GAD65) catalyzes the rate-limiting step in the biosynthesis of the major inhibitory neurotransmitter-amino butyric acid (GABA) from the substrate L-glutamic acid. Severe lapse in GABA neurotransmission is one of the etiologies documented in the manifestation of certain neurodegenerative diseases such as epilepsy, Parkinson's disease, Huntington's disease etc. Because GAD65 synthesizes GABA, any modulation of GAD65, therefore, has direct implications on the quanta of GABA released at the synapse. Hence, the major objective of this study was to focus on the regulation of GAD65, with special emphasis on investigating the proteolytic cleavage of fGAD65. Previously, we have shown in vitro that GAD65 was cleaved to form its truncated form (tGAD65), which was more active than the full length form (fGAD65). The enzyme responsible for cleavage was later identified as calpain. Calpain is known to cleave its substrates either under a transient physiologica l stimulus or upon a sustained pathological insult. However, the precise role of calpain cleavage of fGAD65 is poorly understood. In this study, we examined the cleavage of fGAD65 under a range of conditions encompassing both physiological and pathological aspects, including rats under ischemia/reperfusion insult, rat brain synaptosomes or primary neuronal cultures subjected to excitotoxic stimulation with KCl. It was observed that the formation of tGAD65 progressively increased with increasing stimulus concentration. More importantly, cleavage of synaptic vesicle (SV) - associated fGAD65 by calpain was demonstrated, and the resulting tGAD65 harboring the active site of the enzyme was detached from the SVs. Vesicular uptake of the newly synthesized GABA into the SVs was found to be reduced in calpain treated SVs. Furthermore, we also observed that the levels of tGAD65 in the focal cerebral ischemic rat brain tissue increased corresponding to the elevation of local glutamate indica, d by in vivo micro dialysis. Based on these observations, we conclude that calpain cleavage of fGAD65 occurs under pathological conditions.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3342053
- Subject Headings
- Glutamic acids, Antagonists, Proteolytic enzymes, Research, Cellular signal transduction, Calpain, Glutamic acid, Metabolism
- 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.
Show less - 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
- 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.
Show less - 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
- 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.
Show less - 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
- Determining the subcellular localization of a group II p21-activated kinase - PAK6.
- Creator
- John, Ciny, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
p-21-activated kinase 6 (PAK6) is a serine-threonine protein kinase originally identified as an Androgen Receptor (AR) interacting protein. In current study, we determined the subcellular localization of PAK6 through mutational analysis. We have found that the N-terminal CRIB domain is partly responsible for plasma membrane targeting, the region between amino acid residues #292 to #368 is functionally relevant to plasma membrane localization and that amino acid residues #119 through #190 are...
Show morep-21-activated kinase 6 (PAK6) is a serine-threonine protein kinase originally identified as an Androgen Receptor (AR) interacting protein. In current study, we determined the subcellular localization of PAK6 through mutational analysis. We have found that the N-terminal CRIB domain is partly responsible for plasma membrane targeting, the region between amino acid residues #292 to #368 is functionally relevant to plasma membrane localization and that amino acid residues #119 through #190 are responsible for nuclear targeting of PAK6, in addition to a stretch of positively charged N-terminal residues (#2-#11) since mutants lacking this sequence mis-localizes to cytoplasm. In junction forming epithelial cells, PAK6 is demonstrated to co-localize with B-catenin at adherens junctions, suggesting that PAK6 is an activation-dependent event and that PAK6 translocates from plasma membrane to the cytoplasm in response activation via the PKA signal pathway.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3355569
- Subject Headings
- Cellular signal transduction, Serine proteinases, Phosphorylation, Protein kinases, Pathophysiology, Phosphoroproteins, Metabolism
- Format
- Document (PDF)
- Title
- Developmental delays in methionine sulfoxide reductase mutants in Drosophila Melanogaster.
- Creator
- Hausman, William, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Aging is a biological process that has many detrimental effects due to the accumulation of oxidative damage to key biomolecules due to the action of free radicals. Methionine sulfoxide reductase (Msr) functions to repair oxidative damage to methionine residues. Msr comes in two forms, MsrA and MsrB, each form has been shown to reduce a specific enantiomer of bound and free oxidized methionine. Effects of Msr have yet to be studied in the major developmental stages of Drosophila melanogaster...
Show moreAging is a biological process that has many detrimental effects due to the accumulation of oxidative damage to key biomolecules due to the action of free radicals. Methionine sulfoxide reductase (Msr) functions to repair oxidative damage to methionine residues. Msr comes in two forms, MsrA and MsrB, each form has been shown to reduce a specific enantiomer of bound and free oxidized methionine. Effects of Msr have yet to be studied in the major developmental stages of Drosophila melanogaster despite the enzymes elevated expression during these stages. A developmental timeline was determined for MsrA mutant, MsrB mutant, and double null mutants against a wild type control. Results show that the Msr double mutant is delayed approximately 20 hours in the early/mid third instar stage while each of the single mutants showed no significant difference to the wild type. Data suggests that the reasoning of this phenomenon is due to an issue gaining mass.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004200, http://purl.flvc.org/fau/fd/FA00004200
- Subject Headings
- Aging -- Molecular aspects, Cellular signal transduction, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Mutation (Biology), Oxidative stress
- Format
- Document (PDF)
- Title
- Discovery and visualization of co-regulated genes relevant to target diseases.
- Creator
- Lad, Vaibhan., College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
- Abstract/Description
-
In this thesis, we propose to discover co-regulated genes using microarray expression data, as well as providing visualization functionalities for domain experts to study relationships among discovered co-regulated genes. To discover co-regulated genes, we first use existing gene selection methods to select a small portion of genes which are relevant to the target diseases, on which we build an ordered similarity matrix by using nearest neighbor based similarity assessment criteria. We then...
Show moreIn this thesis, we propose to discover co-regulated genes using microarray expression data, as well as providing visualization functionalities for domain experts to study relationships among discovered co-regulated genes. To discover co-regulated genes, we first use existing gene selection methods to select a small portion of genes which are relevant to the target diseases, on which we build an ordered similarity matrix by using nearest neighbor based similarity assessment criteria. We then apply a threshold based clustering algorithm named Spectral Clustering to the matrix to obtain a number of clusters. The genes which are clustered together in one cluster represent a group of co-regulated genes and to visualize them, we use Java Swings as the tool and develop a visualization platform which provides functionalities for domain experts to study relationships between different groups of co-regulated genes; study internal structures within each group of genes, and investigate details of each individual gene and of course for gene function prediction. Results are analyzed based on microarray expression datasets collected from brain tumor, lung cancers and leukemia samples.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/2976447
- Subject Headings
- Genomics, Gene mapping, Cell transformation, Cellular signal transduction
- Format
- Document (PDF)
- Title
- DNAJC25 Pro90Leu J-domain mutation demonstrates decreased chaperone activity in vitro.
- Creator
- Chauss, Daniel C., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Molecular chaperones guide peptide fold conformation throughout the lifetime of the peptide. One network of chaperone proteins involved in this activity, Heat shock protein 70s (Hsp70s), are well characterized at restoring peptide fold, utilizing J-domain containing protein chaperone cofactors to activate Hsp70 activity. DnaJ (Hsp40) homolog, subfamily C, member 25 (DNAJC25) is a class III transmembrane J-domain containing protein that to date is underrepresented in the literature. Recently,...
Show moreMolecular chaperones guide peptide fold conformation throughout the lifetime of the peptide. One network of chaperone proteins involved in this activity, Heat shock protein 70s (Hsp70s), are well characterized at restoring peptide fold, utilizing J-domain containing protein chaperone cofactors to activate Hsp70 activity. DnaJ (Hsp40) homolog, subfamily C, member 25 (DNAJC25) is a class III transmembrane J-domain containing protein that to date is underrepresented in the literature. Recently, Hejtmancik et al. 2012. (unpublished data) have revealed that missense mutation to DNACJ25 at Pro90Leu (P90L) is strongly correlated with inherited Closed-Angle Glaucoma. Inherited mutations are well characterized for Open-Angle Glaucoma, however, prior to this finding, were unknown for Closed-Angle Glaucoma. In this report, analysis of the in vitro chaperone activity of DNAJC25 w+ and P90L is assessed utilizing an Hsp70 mediated Glucose-6-Phosphate Dehydrogenase refolding system, SWISS-MODEL predictions are performed for the J-domain structure of DNAJC25 w+ and P90L with consequent analysis of DNAJC25 Pro90 conservation relative to other type I, II, and III J-domain containing proteins. DNAJC25 P90L demonstrated decreased chaperone activity in vitro compared to w+ DNAJC25.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3342040
- Subject Headings
- Cell physiology, Methodology, Molecular chaperones, Physiological effect, Cellular signal transduction, Proteolytic enzymes
- Format
- Document (PDF)
- Title
- Effects of adolescent stress on depressive- and anxiety-like behaviors and hippocampal mossy fibre-CA3 remodeling in the novelty-seeking phenotype: implications for epigenetic regulation of the BDNF gene.
- Creator
- Oztan, Ozge., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Experimentally naive rats show variance in their locomotor reactivity to novelty, some displaying higher (HR) while others displaying lower (LR) reactivity, associated with vulnerability to stress. LRHR phenotype is proposed as an antecedent to the development of stress hyper responsiveness. Results presented here show emergence of antidepressive-like behavior following peripubertal-juvenile exposure to chronic variable physical (CVP) and chronic variable social stress (CVS) in HR rats, and...
Show moreExperimentally naive rats show variance in their locomotor reactivity to novelty, some displaying higher (HR) while others displaying lower (LR) reactivity, associated with vulnerability to stress. LRHR phenotype is proposed as an antecedent to the development of stress hyper responsiveness. Results presented here show emergence of antidepressive-like behavior following peripubertal-juvenile exposure to chronic variable physical (CVP) and chronic variable social stress (CVS) in HR rats, and depressive-like behavior following CVP in the LRs. The antidepressive-like behavior in HR rats was accompanied by increased levels of acetylated Histone3 (acH3) and acetylated Histone4 (acH4) at the hippocampal brain-derived neurotrophic factor (BDNF) P2 and P4 promoters respectively. This effect may mediate increased mossy fibre (MF) terminal field size, particularly the suprapyramidal mossy fibre projection volume (SP-MF), in the HR animals following both stress regimens. These findings show that chronic variable stress during adolescence induces individual differences in molecular, neuromorphological and behavioral parameters between LRs and HRs, which provides further evidence that individual differences in stress responsiveness is an important factor in resistance or vulnerability to stress-induced depression and/or anxiety.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3360950
- Subject Headings
- Rats as laboratory animals, Anxiety in adolescence, Depression in adolescence, Stress (Psychology), Cellular signal transduction, Hippocampus (Brain), Physiology, Genetic regulation, Gene expression
- Format
- Document (PDF)
- Title
- Elucidating the role of Semaphorin 7A in breast cancer.
- Creator
- Garcia-Areas, Ramon A., lragavarapu-Charyulu, Vijaya, Florida Atlantic University, Charles E Schmidt College of Science, Department of Biomedical Science
- Abstract/Description
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Solid tumors can hijack many of the same programs used in neurogenesis to enhance tumor growth and metastasis, thereby generating a plethora of neurogenesis-related molecules including semaphorins Among them, we have identified Semaphorin7A (SEMA7A) in breast cancer We first used to the DA-3 mammary tumor model to determine the effect of tumor-derived SEMA7A on immune cells We found that tumor-derived SEMA7A can modulate the production of proangiogenic chemokines CXCL2/MIP-2 and CXCL 1, and...
Show moreSolid tumors can hijack many of the same programs used in neurogenesis to enhance tumor growth and metastasis, thereby generating a plethora of neurogenesis-related molecules including semaphorins Among them, we have identified Semaphorin7A (SEMA7A) in breast cancer We first used to the DA-3 mammary tumor model to determine the effect of tumor-derived SEMA7A on immune cells We found that tumor-derived SEMA7A can modulate the production of proangiogenic chemokines CXCL2/MIP-2 and CXCL 1, and prometastatic MMP-9 in macrophages We next aimed to determine the expression and function of SEMA7A in mammary tumor cells We found that SEMA7A is highly expressed in both metastatic human and murine breast cancer cells We show that both TGF-β and hypoxia elicits the production of SEMA 7 A in mammary cells SEMA7 A shRNA silencing in 4T1 cells resulted in decreased mesenchymal markers MMP-3, MMP-13, Vimentin and TGF-β) SEMA7A silenced cells show increased stiffness with reduced migratory and proliferative potential In vivo, SEMA7A silenced 4T1 tumor bearing mice showed decreased tumor growth and metastasis Genetic ablation of host-derived SEMA7A synergized to further decrease the growth and metastasis of 4T1 cells Our findings suggest novel functional roles for SEMA7A in breast cancer and that SEMA7A could be a novel therapeutic target to limit tumor growth and metastasis
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00004802
- Subject Headings
- Breast--Cancer--Diagnosis, Semaphorins, Protein precursors, Cellular signal transduction, Cell receptors
- 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
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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.
Show less - 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
- Function of glycinergic interplexiform cells in rod synaptic transmission.
- Creator
- Jiang, Zheng., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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The interplexiform cells(IP cells) are the most recently discovered neurons in the retina and their function is to provide centrifugal feedback in retina. The anatomical structure of the IP cells has been well studied, but the function of these neurons is largely unknown. I systematically studied the excitatory and inhibitory inputs from IP cells in salamander retina. I found that L-EPSCs in IP cells are mediated by AMPA and NMDA receptors; in addition, L-IPSCs are mediated by glycine...
Show moreThe interplexiform cells(IP cells) are the most recently discovered neurons in the retina and their function is to provide centrifugal feedback in retina. The anatomical structure of the IP cells has been well studied, but the function of these neurons is largely unknown. I systematically studied the excitatory and inhibitory inputs from IP cells in salamander retina. I found that L-EPSCs in IP cells are mediated by AMPA and NMDA receptors; in addition, L-IPSCs are mediated by glycine receptors and GABAC receptors. In response to light, IP cells reaction potentials transiently at the onset and onset of light stimulation. The major neural transmitter of IP cells in salamander retina is glycine. We also studied the distribution and function of glycine transporters. Our result indicates that GlyT1- and GlyT2-like transporters were present in Muller cells and neurons. The glycine feedback at outer plexiform layer (OPL) has effects on both the bipolar cell dendrites and rod photoreceptor terminals. At bipolar cell dendrites, glycine selectively depolarizes rod-dominant On-bipolar cells, and hyperpolarizes Off- bipolar cells. At rod photoreceptor terminals, 10 M glycine activates voltage-gated Ca2+ channels. These effects facilitated glutamate vesicle release in photoreceptors. It increases the sEPSC in OFF bipolar cells. The combined effect of glycine at rod terminals and bipolar cell dendrites leads to enhanced dim light signal transduction in the rod photoreceptor to ganglion cell pathway. This study provides a model that displays the function of centrifugal feedback through IP cells in the retina.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/2708369
- Subject Headings
- Cellular signal transduction, Neurochemistry, Neuroplasticity, Synapses, Retina, Cytology, Visual pathways
- Format
- Document (PDF)
- Title
- Functional roles of L1-Cam/Neuroglian in the nervous system of Drosophila Melanogaster.
- Creator
- Kudumala, Sirisha, Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Neuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic...
Show moreNeuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic connectivity to control the development and maintenance of synaptic connections within neuronal circuits. Here we characterized the essential role of nrg in regulating synaptic structure and function in vivo in a well characterized Drosophila central synapse model neuron, the Giant Fiber (GF) system. Previous studies from our lab revealed that the phosphorylation status of the tyrosine in the Ankyrin binding FIGQY motif in the intracellular domain of Nrg iscrucial for synapse formation of the GF to Tergo-Trochanteral Motor neuron (TTMn) synapse in the GF circuit. The present work provided us with novel insights into the role of Nrg-Ank interaction in regulating Nrg function during synapse formation and maintenance. By utilizing a sophisticated Pacman based genomic rescue strategy we have shown that dynamic regulation of the Neuroglian–Ankyrin interaction is required to coordinate transsynaptic development in the GF–TTMn synapse. In contrast, the strength of Ankyrin binding directly controls the balance between synapse formation and maintenance at the NMJ. Human L1 pathological mutations affect different biological processes distinctively and thus their proper characterization in vivo is essential to understand L1CAM function. By utilizing nrg14;P[nrg180ΔFIGQY] mutants that have exclusive synaptic defects and the previously characterized nrg849 allele that affected both GF guidance and synaptic function, we were able to analyze pathological L1CAM missense mutations with respect to their effects on guidance and synapse formation in vivo. We found that the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation and not for axon guidance while L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004131, http://purl.flvc.org/fau/fd/FA00004131
- Subject Headings
- Cell adhesion molecules, Cellular signal transduction, Cognitive neuroscience, Cognitive neuroscience, Drosophila melanogaster, Molecular neurobiology
- Format
- Document (PDF)
- Title
- GAD 65 and its role in pancreatic tissue survival.
- Creator
- Kumari, Neeta., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
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We employed three genotypes of GAD 65, wildtype (GAD 65 +/+), heterozygous (GAD 65 +/-) and knockout (GAD 65 -/-) to investigate the role of GAD 65 in survival of pancreatic islets. We analyzed the mRNA expression of pro-survival proteins including Bcl2 and Bax in pancreas of wildtype, heterozygous and knockout using Reverse Transcriptase Polymerase Chain Reaction (RTPCR). The level of expression of Bcl2 mRNA was down regulated in knockout mice pancreas and Bax to Bcl2 ratio was found higher...
Show moreWe employed three genotypes of GAD 65, wildtype (GAD 65 +/+), heterozygous (GAD 65 +/-) and knockout (GAD 65 -/-) to investigate the role of GAD 65 in survival of pancreatic islets. We analyzed the mRNA expression of pro-survival proteins including Bcl2 and Bax in pancreas of wildtype, heterozygous and knockout using Reverse Transcriptase Polymerase Chain Reaction (RTPCR). The level of expression of Bcl2 mRNA was down regulated in knockout mice pancreas and Bax to Bcl2 ratio was found higher in knockout mice pancreas suggesting higher cell death rate. However, further studies are required to recognize and understand the specific connections between apoptotic pathways and GAD 65 in pancreatic islets.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3342206
- Subject Headings
- Glutamic acids, Antagonists, Cellular signal transduction, Glutamic acid, Metabolism
- Format
- Document (PDF)