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Title: Cytogenetic of chromosomal synteny evaluation: bioinformatic applications towards screening of chromosomal aberrations/ genetic disorder.
Creator: Sharma, Sandhya, Neelakanta, Perambur S., Florida Atlantic University, College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description: The research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study...
Show moreThe research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study addresses: (i) Cytogenetic framework of syntenic correlation and, (ii) applying information-theoretics to determine entropy-dictated synteny across an exhaustive set of orthologs of the test pairs of species.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004331, http://purl.flvc.org/fau/fd/FA00004331
Subject Headings: Cytogenetics, Genetic screening, Human chromosome abnormalities, Medical genetics, Molecular biology, Molecular diagnosis, Molecular genetics, Mutation (Biology)
Format: Document (PDF)

Title: RNA oxidative damage and ribosomal RNA surveillance under oxidative stress.
Creator: Liu, Min, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: We have studies oxidative damage of RNA, a major type of cellular macromolecules. RNA is a primary target of reactive oxygen species (ROS). Under oxidative stress, most nucleic acid damages in Escherichia coli (E.coli) are present in RNA as shown by high levels of 8-oxo-G, an oxidized form of guanine. Increased RNA oxidation is closely correlated to cell death under oxidative stress. Surprisingly, neither RNA structure nor association with proteins protects RNA from oxidation... Our results...
Show moreWe have studies oxidative damage of RNA, a major type of cellular macromolecules. RNA is a primary target of reactive oxygen species (ROS). Under oxidative stress, most nucleic acid damages in Escherichia coli (E.coli) are present in RNA as shown by high levels of 8-oxo-G, an oxidized form of guanine. Increased RNA oxidation is closely correlated to cell death under oxidative stress. Surprisingly, neither RNA structure nor association with proteins protects RNA from oxidation... Our results demonstrate a major role for RNA degradation in controlling oxidized RNA. We have identified activities that may work in specific pathways for selectively degrading damaged RNA. These activities may play pivotal rold in controlling oxidized RNA and protecting cells under oxidative stress.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3355620
Subject Headings: RNA, Metabolism, Cellular signal transduction, Genetic translation, Molecular biology
Format: Document (PDF)

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

Title: Creation of an aconitase overexpression strain of Saccharomyces cerevisiae for lifespan analysis.
Creator: Nunes, Steve., Harriet L. Wilkes Honors College
Abstract/Description: In my thesis work, I attempted to construct a plasmid that would allow stable integration of genes into the Saccharomyces cerevisiae yeast genome under the control of the repressible TetO promoter. The yeast ACO1 gene was cloned under the control of the TetO operator and the tTA transactivator. This construct was inserted into yeast cells in order to observe the effects of aconitase overexpression on aging. Unfortunately, the transformed cells appeared incapable of aconitase expression as...
Show moreIn my thesis work, I attempted to construct a plasmid that would allow stable integration of genes into the Saccharomyces cerevisiae yeast genome under the control of the repressible TetO promoter. The yeast ACO1 gene was cloned under the control of the TetO operator and the tTA transactivator. This construct was inserted into yeast cells in order to observe the effects of aconitase overexpression on aging. Unfortunately, the transformed cells appeared incapable of aconitase expression as determined by glutamic acid auxptrophy, a phenotype of aconitase mutants. We have sequenced the pIT1ACO1 plasmid and have found many abnormalities in the promoter region. If the plasmid can be made to function as intended, the resulting yeast strain can be used in the future to determine if aconitase plays an important role in cellular aging.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3359306
Subject Headings: Yeast fungi, Research, Methodology, Microbial genetics, Genetic engineering, Aging, Molecular aspects, Cell metabolism, Mutation (Biology)
Format: Document (PDF)

Title: The Application of Yeast Three-Hybrid Technology in the Mexican Axolotl (Ambystoma mexicanum) System.
Creator: Maier, Jennifer A., Lemanski, Larry F., Florida Atlantic University
Abstract/Description: The Mexican axolotl, Ambystoma mexicanum, possesses a naturally-occurring lethal mutation, designated gene "c", for cardiac non-function. Hearts form but fail to beat, lack organized myofibrils, and are deficient in tropomyosin. Treatment with a noncoding RNA MIR (Myofibril-Inducing RNA) rescues this defect in organ culture. Rescued mutant hearts have restored tropomyosin, form organized myofibrils, and beat vigorously. Studies to elucidate the mechanism of MIR heart rescue are underway....
Show moreThe Mexican axolotl, Ambystoma mexicanum, possesses a naturally-occurring lethal mutation, designated gene "c", for cardiac non-function. Hearts form but fail to beat, lack organized myofibrils, and are deficient in tropomyosin. Treatment with a noncoding RNA MIR (Myofibril-Inducing RNA) rescues this defect in organ culture. Rescued mutant hearts have restored tropomyosin, form organized myofibrils, and beat vigorously. Studies to elucidate the mechanism of MIR heart rescue are underway. Current evidence suggests that MIR acts by binding with at least two proteins. The yeast three-hybrid system is being used to screen an axolotl eDNA library for these two proteins and other possible MIR-binding candidates. This is a method utilizing two hybrid proteins and a hybrid RNA. An interaction between these three components will activate the expression of reporter genes, whose activity is assayed through phenotypical and biochemical methods. In this study, the protocol for yeast three-hybrid technology is being established for analyzing the MIR in the Mexican axolotl, cardiac mutant animal model.
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Date Issued: 2007
PURL: http://purl.flvc.org/fau/fd/FA00000793
Subject Headings: Axolotls--Development, Heart--Hypertrophy, Genetic translation, Molecular genetics--Research
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: Diversity and selection in the major histocompatibility complex: DQA and immune function in IRL and Atlantic bottlenose dolphins (Tursiops truncatus).
Creator: Ferrer, Tatiana., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The Major Histocompatibility Complex (MHC) encodes proteins critical to the vertebrate immune response; therefore MHC diversity is an indicator of population health. I have (1) Isolated exon 2 of the class II gene DQA in Tursiops truncatus in the North Indian River Lagoon (IRL) (n=17), South IRL (n=29) and adjacent Atlantic waters (n=20), (2) assessed genetic variability between groups, (3) developed a method to genotype individuals, (4) typed 11 unique alleles in 66 individuals, (5) detected...
Show moreThe Major Histocompatibility Complex (MHC) encodes proteins critical to the vertebrate immune response; therefore MHC diversity is an indicator of population health. I have (1) Isolated exon 2 of the class II gene DQA in Tursiops truncatus in the North Indian River Lagoon (IRL) (n=17), South IRL (n=29) and adjacent Atlantic waters (n=20), (2) assessed genetic variability between groups, (3) developed a method to genotype individuals, (4) typed 11 unique alleles in 66 individuals, (5) detected geographic patterns of diversity between estuarine and coastal individuals (FST=0.1255, p<0.05), (6) found evidence of positive selection centered in the binding pockets P1, P6 and P9 of the peptide binding region (w=2.08), (7) found that patterns of polymorphism did not closely match patterns of diversity in neutral markers, (8) performed a pilot study with Orcinus orca. The initial findings highlight the need for further comparative work and suggest that silent mutations are not neutral.
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Date Issued: 2013
PURL: http://purl.flvc.org/fcla/dt/3362335
Subject Headings: Major histocompatibility complex, Immunogenetics, Molecular genetics, Endocrine disrupting chemicals, Dolphins, Geographical distribution, Population genetics, Social behavior in animals
Format: Document (PDF)

Title: Correlation between specific carcinogenic chemicals and specific mitotic defects and the restorative role of antioxidants.
Creator: Yates, Travis., Harriet L. Wilkes Honors College
Abstract/Description: The progression of cancerous cells towards a more aggressive tumor can be linked to external elements called carcinogens. The goal of this project is to examine the correlation between exposure to specific carcinogens and an increase of mitotic defects. These defects can manifest as lagging chromosomes, multipolar spindles, and anaphase bridges. Some of these instabilities are associated with the formation of reactive oxygen species (ROS), which are known to damage DNA. The potential for...
Show moreThe progression of cancerous cells towards a more aggressive tumor can be linked to external elements called carcinogens. The goal of this project is to examine the correlation between exposure to specific carcinogens and an increase of mitotic defects. These defects can manifest as lagging chromosomes, multipolar spindles, and anaphase bridges. Some of these instabilities are associated with the formation of reactive oxygen species (ROS), which are known to damage DNA. The potential for damage to the genome can be averted via antioxidants. Using the oral cancer cell line UPCI:SCC103, we established a baseline for the mitotic defects in the absence and presence of various ROS-inducing carcinogens using DAPI-stained fixed cells examined by immunofluorescent microscopy, The cells were treated with varying concentrations of the antioxidants, Vitamin C, (Sb(B-Carotene, and Vitamin E. The reactive oxygen scavengers significantly reduced the number of mitotic defects. A possible link between the carcinogens and lagging chromosomes was established.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/210007
Subject Headings: Cellular signal transduction, Genetic regulation, Antioxidants, Therapeutic use, Apoptosis, Molecular aspects, Cancer, Chemoprevention
Format: Document (PDF)

Title: The effect of mutated aconitase on yeast longevity.
Creator: Kwan, CJ., Harriet L. Wilkes Honors College
Abstract/Description: Aconitase is an important enzyme in the citric Acid Cycle, is needed for maintenance of mitochondrial DNA, is a key regulator of iron in the cell, and is very sensitive to oxidative stress. We have isolatd the yeast ACO1 gene, which codes for aconitase, and randomly mutated it to create a mutant library of cells each expressing a different version of ACO1. We will select for oxidative stress resistant aconitase in S. cerevisiae by subjecting strains to successive rounds of heat shock and...
Show moreAconitase is an important enzyme in the citric Acid Cycle, is needed for maintenance of mitochondrial DNA, is a key regulator of iron in the cell, and is very sensitive to oxidative stress. We have isolatd the yeast ACO1 gene, which codes for aconitase, and randomly mutated it to create a mutant library of cells each expressing a different version of ACO1. We will select for oxidative stress resistant aconitase in S. cerevisiae by subjecting strains to successive rounds of heat shock and competitive growth against other mutants. The "winner" of this competition will then be analyzed for which version of aconitase it is expressing, which may lead to increased longevity.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3359310
Subject Headings: Yeast fungi, Research, Microbial genetics, Aging, Molecular aspects, Mutation (Biology), Cell metabolism
Format: Document (PDF)

Title: Biological Computation: the development of a genomic analysis pipeline to identify cellular genes modulated by the transcription / splicing factor srsf1.
Creator: Clark, Evan, Asghar, Waseem, Florida Atlantic University, College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description: SRSF1 is a widely expressed mammalian protein with multiple functions in the regulation of gene expression through processes including transcription, mRNA splicing, and translation. Although much is known of SRSF1 role in alternative splicing of specific genes little is known about its functions as a transcription factor and its global effect on cellular gene expression. We utilized a RNA sequencing (RNA-¬‐Seq) approach to determine the impact of SRSF1 in on cellular gene expression and...
Show moreSRSF1 is a widely expressed mammalian protein with multiple functions in the regulation of gene expression through processes including transcription, mRNA splicing, and translation. Although much is known of SRSF1 role in alternative splicing of specific genes little is known about its functions as a transcription factor and its global effect on cellular gene expression. We utilized a RNA sequencing (RNA-¬‐Seq) approach to determine the impact of SRSF1 in on cellular gene expression and analyzed both the short term (12 hours) and long term (48 hours) effects of SRSF1 expression in a human cell line. Furthermore, we analyzed and compared the effect of the expression of a naturally occurring deletion mutant of SRSF1 (RRM12) to the full-¬‐length protein. Our analysis reveals that shortly after SRSF1 is over-¬‐expressed the transcription of several histone coding genes is down-¬‐regulated, allowing for a more relaxed chromatin state and efficient transcription by RNA Polymerase II. This effect is reversed at 48 hours. At the same time key genes for the immune pathways are activated, more notably Tumor Necrosis Factor-¬‐Alpha (TNF-¬‐α), suggesting a role for SRSF1 in T cell functions.
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Date Issued: 2017
PURL: http://purl.flvc.org/fau/fd/FA00004858, http://purl.flvc.org/fau/fd/FA00004858
Subject Headings: Gene expression., Computational biology., Markov processes., Bioinformatics., Genetic engineering., Molecular biology.
Format: Document (PDF)

Title: DISCOVERY OF GENES AND MOLECULAR PROCESSES THAT ARE IMPORTANT FOR THE PATHOGENESIS OF ALZHEIMER’S DISEASE.
Creator: Kwakye, Alexander, Li, Zhongwei, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Alzheimer’s Disease (AD) is a complex brain disorder that affects at least one in every ten persons aged 65 and above worldwide. The pathogenesis of this disorder remains elusive. In this work, we utilized a rich set of publicly available gene expression data to elucidate the genes and molecular processes that may underlie its pathogenesis. We developed a new ranking score to prioritize molecular pathways enriched in differentially expressed genes during AD. After applying our new ranking...
Show moreAlzheimer’s Disease (AD) is a complex brain disorder that affects at least one in every ten persons aged 65 and above worldwide. The pathogenesis of this disorder remains elusive. In this work, we utilized a rich set of publicly available gene expression data to elucidate the genes and molecular processes that may underlie its pathogenesis. We developed a new ranking score to prioritize molecular pathways enriched in differentially expressed genes during AD. After applying our new ranking score, GO categories such as cotranslational protein targeting to membrane, SRP-dependent cotranslational protein targeting to membrane, and spliceosomal snRNP assembly were found to be significantly associated with AD. We also confirm the protein-protein interaction between APP, NPAS4 and ARNT2 and explain that this interaction could be implicated in AD. This interaction could serve as a theoretical framework for further analyses into the role of NPAS4 and other immediate-early genes in AD pathogenesis.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013541
Subject Headings: Alzheimer's disease, Alzheimer's disease--Genetic aspects, Alzheimer's disease--Molecular aspects, Alzheimer's disease--Pathogenesis
Format: Document (PDF)

Title: DNA fingerprints of human oral microbiome: a first step towards early diagnosis of oral diseases.
Creator: Chakraborty, Shreyasee, Esiobu, Nwadiuto, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: This study evaluated the stability of oral bacteria in healthy subjects and documented community shifts in smokers and oral/periodontal disease by employing PCR-RFLP, DGGE and sequence analysis of the 16S rDNA gene from metagenomes and plate-wash (cultured) bacteria of oral wash from 15 participants,. A stable core of bacterial DNA fingerprint was detected within and between subjects and did not change over time when analyzed in smokers and healthy non-smokers. Signature bands in smokers, non...
Show moreThis study evaluated the stability of oral bacteria in healthy subjects and documented community shifts in smokers and oral/periodontal disease by employing PCR-RFLP, DGGE and sequence analysis of the 16S rDNA gene from metagenomes and plate-wash (cultured) bacteria of oral wash from 15 participants,. A stable core of bacterial DNA fingerprint was detected within and between subjects and did not change over time when analyzed in smokers and healthy non-smokers. Signature bands in smokers, non-smokers and periodontal disease subjects were evident suggesting the presence of potential indicators of health and poor oral health. Taxon diversity was higher in smokers including members of the genera Rothia, Synechococcus, Neisseria, Thiomargarita and Pyrobaculum but highest in periodontal disease. The two techniques successfully aligned the subjects within appropriate categories (based on their oral microbial genetic patterns)confirming their diagnostic suitability.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004184, http://purl.flvc.org/fau/fd/FA00004184
Subject Headings: Molecular microbiology., Mouth--Microbiology., Bacterial genetics., Cellular signal transduction., Microbial genomics.
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.
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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: Genetic differentiation among populations of bald eagles, Haliaeetus leucocephalus.
Creator: Helmick, Ericka Elizabeth., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The bald eagle, Haliaeetus leucocephalus, population declined dramatically in the early 20th century reducing the population from tens of thousands of birds within the lower 48 states, to
Show moreThe bald eagle, Haliaeetus leucocephalus, population declined dramatically in the early 20th century reducing the population from tens of thousands of birds within the lower 48 states, to <450 pairs of birds, effectively inducing a population bottleneck. The overall population has recovered and was removed from the endangered species list in 2007. This study investigates whether such overall population statistics are appropriate descriptors for this widespread species. I investigated the genetic differentiation between three populations of bald eagles from Alaska, North Florida and Florida Bay using both mitochondrial and nuclear DNA loci to determine whether discrete subpopulations comprise the broad range. Significant FST values, for both mtDNA and microsatellites, were found between both Florida populations and Alaska, but not within Florida populations. Results indicate that there is strong population structure, rejecting the null hypothesis of a panmictic population. Future conservation efforts should focus on subpopulations rather than the overall population.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3171395
Subject Headings: Wildlife conservation, Birds, Molecular genetics, Gene targeting, Developmental biology, Biochemical markers
Format: Document (PDF)

Title: Inflammatory response in stress and the role of autophagy in breast cancer.
Creator: Onwuha-Ekpete, Lillian C., Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: We attempted to understand the molecular regulators that impact inflammation using a rat model of human sensation-seeking/risk-taking trait for drug and stress vulnerability, based on their exploratory behavior displaying high rates (HRs) or low rates of locomotor reactivity (LRs) to environmental stress. We found that HRs have a pro-inflammatory phenotype as indicated by increased protein expression of the inflammatory cytokine TNF-(Sa(B. Furthermore, we found that HRs have a lower gene...
Show moreWe attempted to understand the molecular regulators that impact inflammation using a rat model of human sensation-seeking/risk-taking trait for drug and stress vulnerability, based on their exploratory behavior displaying high rates (HRs) or low rates of locomotor reactivity (LRs) to environmental stress. We found that HRs have a pro-inflammatory phenotype as indicated by increased protein expression of the inflammatory cytokine TNF-(Sa(B. Furthermore, we found that HRs have a lower gene expression of the glucocorticoid receptor and histone deacetylase 2 which are known to play an immunosuppressive role. Autophagy (macroautophagy) is a homeostatic process needed for cell maintenance, growth and proliferation and known to assist in tumor survival. FYVE and coiled-coil domain containing 1 (FYCO1) is a novel protein implicated to assist in the plus-end directed trafficking and fusion of autophagosomes. In these studies, we show that FYCO1 gene expression among human breast cell lines of varying degrees of malignancy.
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Date Issued: 2012
PURL: http://purl.flvc.org/fcla/dt/3362042
Subject Headings: Breast, Cancer, Genetic aspects, Cancer, Molecular aspects, Carcinogenesis, Cellular signal transduction, Stress (Physiology)
Format: Document (PDF)

Title: Structure-function relationships in eukaryotic and prokaryotic family 6 glycosyltransferases.
Creator: Tumbale, Percy., Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Carbohydrate Active Enzyme family 6 (CA6) glycosyltransferases (GTs) are type II transmembrane proteins localized in the Golgi apparatus. CA6 GTs have a GT-A fold, a type of structure that resembles the Rossman fold and catalyze the transfer either galactose (Gal) or N-acetylgalactosamine (GalNAc) from the UDP nucleotide sugar to an non-reducing terminal Gal or GalNAc on an acceptor via an a-1,3 linkage. In this reaction, the anomeric configuration of the sugar moiety of the donor is retained...
Show moreCarbohydrate Active Enzyme family 6 (CA6) glycosyltransferases (GTs) are type II transmembrane proteins localized in the Golgi apparatus. CA6 GTs have a GT-A fold, a type of structure that resembles the Rossman fold and catalyze the transfer either galactose (Gal) or N-acetylgalactosamine (GalNAc) from the UDP nucleotide sugar to an non-reducing terminal Gal or GalNAc on an acceptor via an a-1,3 linkage. In this reaction, the anomeric configuration of the sugar moiety of the donor is retained in the product. CA6 GTs includes the histo-blood group A and B GTs, a-galactosyltransferase (a3GT), Forssman glycolipid synthase (FS), isogloboside 3 synthase (iGb3) in mammals. a3GT and its products (a-Gal epitode) are present in most mammals but are absent in humans and old world primates because of inactivating mutations. The absence of a3GT and its products results in the production of anti-a-Gal epitope natural antibodies in these species., Up to date, the catalytic mechanisms of the CA6 GTs are not well understood. Based on previous structural and mutagenesis studies of bovine aB3GT, we investigated active site residues (His315, Asp316, Ser318, His319, and Lys359) that are highly conserved among CA6 GTs. We have also investigated the role of the C-terminal region by progressive C-terminal truncations. Findings from these studies clarify the functional roles of these residues in structure, catalysis, and specificity in these enzymes and have implications for their catalytic mechanisms. GTs are useful tools in synthesis of glycans for various applications in science and medicine. Methods for the large scale production of pure glycans are continuously being developed. We created a limited randomized combinatorial library based on knowledge of structural information and sequence analysis of the enzyme and its mammalian homologues., Two GalNAc-specific variants were identified from the library and one Glc-specific variant was identified by site-direct mutagenesis. The glycosyltransferase activities of these variants are expected to be improved by further screens of libraries which are designed using the variants as templates. The mammalian CA6 GTs that have been characterized to date are metal-independent and require the divalent cation, Mn2+ for activity. In some recently-discovered bacterial CA6 GTs, the DXD sequence that is present in eukaryotic GTs is replaced by NXN. We cloned and expressed one of these proteins from Bacteroides ovatus, a bacterium that has been linked with inflammatory bowel disease. Functional characterization shows it is a metal-independent monomeric GT that efficiently catalyzes the synthesis of oligosaccharides similar to human blood group A glycan., Mutational studies indicated that despite the lack of a metal cofactor there are similarities in structure-function relationships between the bacterial and vertebrate family 6 GTs.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186686
Subject Headings: Molecular biology, Mathematical models, Glycotransferase genes, Biological transport, Proteins, Synthesis, Evolutionary genetics
Format: Document (PDF)

Title: Characterization of Cellular Proteins Binding HIV's Rev Responsive Element (RRE).
Creator: Dhir, Neetika, Caputi, Massimo, Florida Atlantic University
Abstract/Description: The RRE is a sequence of the HIV genome which is required for the export of the unspliced mRNA from the nucleus to the cytoplasm. Previous studies show that RRE on the HIV mRNA binds directly to Rev which then interacts with Ran and CRM 1 to form an export complex. Our results indicate that Ran can interact with the RRE in the absence of Rev and CRM 1 but in the presence of other factor(s) present in the nuclear extract. Ran-GEF or RCC 1 seems to be a potential mediating factor. Our results...
Show moreThe RRE is a sequence of the HIV genome which is required for the export of the unspliced mRNA from the nucleus to the cytoplasm. Previous studies show that RRE on the HIV mRNA binds directly to Rev which then interacts with Ran and CRM 1 to form an export complex. Our results indicate that Ran can interact with the RRE in the absence of Rev and CRM 1 but in the presence of other factor(s) present in the nuclear extract. Ran-GEF or RCC 1 seems to be a potential mediating factor. Our results suggest that Ran binds directly to RCC 1 and that the binding is disrupted by addition of excess nucleotides and magnesimn. Our suggestion is that Ran and RCC 1 are members of an alternate export pathway present in the HIV. Our observation that the binding is nonspecific makes us speculate that this export pathway may be present in other cell types as well.
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Date Issued: 2007
PURL: http://purl.flvc.org/fau/fd/FA00000742
Subject Headings: AIDS (Disease)--Genetic aspects, AIDS (Disease)--Molecular aspects, Medical virology, Immunoinformatics
Format: Document (PDF)

Title: Functional analysis of Drosophila and human follistatin domains and their role in growth inhibition.
Creator: Shah, Ripal., Florida Atlantic University, Haerry, Theodor E.
Abstract/Description: Follistatin (FS) proteins are highly conserved inhibitors of Activins, members of the Transforming Growth Factor beta (TGF-beta) family, which play prominent roles in patterning and cell proliferation, and can contribute to tumor formation. Comparison of FS from Drosophila (dFS) and humans (hFS) in flies shows that hFS is less active. The goal of this thesis is to test three possible mechanisms: dFS might be more stable and turn over at a lower rate, exhibit a stronger affinity for ligands,...
Show moreFollistatin (FS) proteins are highly conserved inhibitors of Activins, members of the Transforming Growth Factor beta (TGF-beta) family, which play prominent roles in patterning and cell proliferation, and can contribute to tumor formation. Comparison of FS from Drosophila (dFS) and humans (hFS) in flies shows that hFS is less active. The goal of this thesis is to test three possible mechanisms: dFS might be more stable and turn over at a lower rate, exhibit a stronger affinity for ligands, or diffuse less because of stronger interaction with the extracellular matrix. We generated chimeric proteins of dFS and hFS by exchanging individual protein domains. Our results suggest that the increased activity is likely due to ligand binding. Based on the recent structure of the hFS-Activin complex, we speculate that stronger interactions with heparin sulfate in the extracellular matrix may also contribute to the increased activity of dFS.
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Date Issued: 2005
PURL: http://purl.flvc.org/fcla/dt/13282
Subject Headings: Cell differentiation, Drosophila--Cytology, Molecular genetics, Reproduction--Physiological aspects, Glycoproteins
Format: Document (PDF)

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

Title: The role of bacterial lipopolysaccharide in the production of the lupus B cell phenotype.
Creator: Nikolic, Veljko., Florida Atlantic University, Hartmann, James X.
Abstract/Description: The purpose of this study was to determine the effect of bacterial lipopolysaccharide (LPS) on the expression of RP105 (CD180) in human B lymphocytes from normal, leukemic, and lupus patients. The percentage of cells that express RP105 on their surface increased following a 24 hour exposure to LPS. However, continued exposure for a total of four days resulted in a marked decrease in the expression of this receptor molecule. Human B cells were purified by a combination of density gradient and...
Show moreThe purpose of this study was to determine the effect of bacterial lipopolysaccharide (LPS) on the expression of RP105 (CD180) in human B lymphocytes from normal, leukemic, and lupus patients. The percentage of cells that express RP105 on their surface increased following a 24 hour exposure to LPS. However, continued exposure for a total of four days resulted in a marked decrease in the expression of this receptor molecule. Human B cells were purified by a combination of density gradient and negative magnetic bead selection and maintained in culture with and without LPS. Enzyme linked immunoassay for the detection of anti-dsDNA antibodies following LPS treatment of isolated B cells was negative. The percentage of RP105 positive or negative B cells from lupus patients could not be accurately determined because too few B cells were available from these lymphopenic patients following negative selection.
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Date Issued: 2004
PURL: http://purl.flvc.org/fcla/dt/13177
Subject Headings: Microbial polysaccharides, Bacterial genetics, Systemic lupus erythematosus--Etiology, Systemic lupus erythematosus--Molecular aspects
Format: Document (PDF)

FAU Theses and Dissertations (27)	+ -
Honors Student Theses (4)	+ -
FAU College Collections (2)	+ -

Cellular signal transduction (8)	+ -
Molecular aspects (8)	+ -
Mutation (Biology) (8)	+ -
Aging (4)	+ -
Medical genetics (4)	+ -

Molecular biology (4)	+ -
Molecular genetics (4)	+ -
Aging--Molecular aspects. (3)	+ -
Apoptosis (3)	+ -
Axolotls--Development (3)	+ -
Cancer (3)	+ -
Cell differentiation (3)	+ -
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Cellular signal transduction. (3)	+ -
Gene expression. (3)	+ -
Genetic aspects (3)	+ -
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Mitochondrial pathology (3)	+ -
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Aging -- Molecular aspects (2)	+ -
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Apoptosis--Molecular aspects (2)	+ -
Apoptosis. (2)	+ -
Autophagic vacuoles. (2)	+ -
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Caenorhabditis elegans--Molecular genetics. (2)	+ -
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Gene expression--Research--Methodology (2)	+ -

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thesis (4)	+ -

Florida Atlantic University (18)	+ -
Charles E. Schmidt College of Science (12)	+ -
Department of Biological Sciences (12)	+ -
Charles E. Schmidt College of Medicine (6)	+ -
Department of Biomedical Science (6)	+ -

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