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Title: Expression of tear lipocalin and MMPs in the lacrimal gland and their implication in dry eye disease.
Creator: Kota, Smitha J., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Tear lipocalin is a member of the lipocalin superfamily. Homologues have been identified in different species. In this study 18kDa lipocalin protein was identified in lacrimal fluid from New Zealand white rabbits. Densitometric analysis revealed that lacrimal fluid from sexually mature female showed significantly higher expression of lipocalin than the sexually mature male. The sexually mature rabbits had higher expression of lipocalin compared to the juveniles. However no significant...
Show moreTear lipocalin is a member of the lipocalin superfamily. Homologues have been identified in different species. In this study 18kDa lipocalin protein was identified in lacrimal fluid from New Zealand white rabbits. Densitometric analysis revealed that lacrimal fluid from sexually mature female showed significantly higher expression of lipocalin than the sexually mature male. The sexually mature rabbits had higher expression of lipocalin compared to the juveniles. However no significant differences in expression of lipocalin was detected between the juvenile male and female rabbits. Matrix metalloproteinses are members of the metzincin family. Gelatinases (MMP-2 & MMP-9) are known to degrade the extracellular matrix. Sexually mature female animals showed the highest expression of gelatinases. Higher expression of MMP-9 was detected in the epithelial (acinar) cell culture supernatants. Higher expression of MMP-2 was detected in the interstitial (lymphocyte) cell culture supernatants from the lacrimal gland.
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Date Issued: 2003
PURL: http://purl.flvc.org/fcla/dt/13101
Subject Headings: Biology, Molecular
Format: Document (PDF)

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: Design considerations in high-throughput automation for biotechnology protocols.
Creator: Cardona, Aura, Roth, Zvi S., Florida Atlantic University, College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description: In this dissertation a computer-aided automation design methodology for biotechnology applications is proposed that leads to several design guidelines. Because of the biological nature of the samples that propagate in the automation line, a very specific set of environmental and maximum allowed shelf time conditions have to be followed to obtain good yield. In addition all biotechnology protocols require precise sequence of steps, the samples are scarce and the reagents are costly, so no...
Show moreIn this dissertation a computer-aided automation design methodology for biotechnology applications is proposed that leads to several design guidelines. Because of the biological nature of the samples that propagate in the automation line, a very specific set of environmental and maximum allowed shelf time conditions have to be followed to obtain good yield. In addition all biotechnology protocols require precise sequence of steps, the samples are scarce and the reagents are costly, so no waste can be afforded.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004272, http://purl.flvc.org/fau/fd/FA00004272
Subject Headings: Biotechnological process control, Biotechnological process monitoring, Molecular biology -- Automation, Molecular biology -- Technique, Molecular cloning -- Technique, Pharmacognosy
Format: Document (PDF)

Title: Synthetic Analogues of the Microtubule-Stabilizing Agent (+)-Discodermolide: Preparation and Biological Activity.
Creator: Gunasekera, Sarath P., Mickel, Stuart J., Daeffler, Robert, Niederer, Daniel, Wright, Amy E., Linley, P. A., Pitts, Tara P.
Date Issued: 2004
PURL: http://purl.flvc.org/FCLA/DT/3164107
Subject Headings: Microtubules, Cancer --Research, Biopharmaceutics, Molecular biology, Stereochemistry
Format: Document (PDF)

Title: Knockdown of dynactin's p150[Glued] subunit abrogates microtubule organization.
Creator: Roeckner, Jared Todd., Harriet L. Wilkes Honors College
Abstract/Description: Dynactin is a multifunctional protein complex composed of at least 11 different subunits. Dynactin functions as a cofactor for cytoplasmic dynein facilitating long-range vesicle movements, microtubule anchoring, endomembrane localization, and mitotic progression. Previous studies have shown that dynactin binds to microtubules at the centrosome maintaining a radial array in interphase. The p150Glued subunit contains two distinct microtubule-binding sequences named CAP-Gly and Basic. While both...
Show moreDynactin is a multifunctional protein complex composed of at least 11 different subunits. Dynactin functions as a cofactor for cytoplasmic dynein facilitating long-range vesicle movements, microtubule anchoring, endomembrane localization, and mitotic progression. Previous studies have shown that dynactin binds to microtubules at the centrosome maintaining a radial array in interphase. The p150Glued subunit contains two distinct microtubule-binding sequences named CAP-Gly and Basic. While both domains can interact with microtubule, CAP-Gly has a much greater affinity for binding to microtubules, suggesting that the two domains may be active for different dynactin-based functions within the cell. Using siRNA, we found that knockdown of p150Glued was sufficient to alter the maintenance of radial microtubule arrays, cause an increase in centrosome number and mitotic index. In the future we will replace the endogenous protein with versions lacking the CAP-Gly or Basic domains to investigate the contribution of each to microtubule anchoring and cytoskeletal architecture.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/209998
Subject Headings: Cytoskeletal proteins, Cell organelles, Formation, Microtubules, Molecular biology
Format: Document (PDF)

Title: Contributions of dynactin's p150[Glued] subunit's binding domains to microtubule anchoring at the centrosome.
Creator: Schneider, Rebecca., Harriet L. Wilkes Honors College
Abstract/Description: Intracellular transport carries out very important roles within the cell including mitosis, organization, and organelle function. In order for effective transport using the motor protein dynein, a cofactor named dynactin is required. Of dynactin's many subunits, p150[Glued] holds the most responsibility for effective microtubule organization throughout the cell and the necessary anchoring at the centrosome. P150[Glued] holds two areas of high binding potential, the CAP-Gly region and the...
Show moreIntracellular transport carries out very important roles within the cell including mitosis, organization, and organelle function. In order for effective transport using the motor protein dynein, a cofactor named dynactin is required. Of dynactin's many subunits, p150[Glued] holds the most responsibility for effective microtubule organization throughout the cell and the necessary anchoring at the centrosome. P150[Glued] holds two areas of high binding potential, the CAP-Gly region and the Basic region. Each of these binding domains have different binding potentials and affinities for microtubules. The CAP-Gly region binds tightly the microtubules for a longer period of tiem ; the Basic region binds loosely to microtubules. Throughout the course of my research, I manipulated these two regions binding affinity for microtubules and evaluated the resulting cells ability to effectively organize microtubules and anchor them properly at the centrosome.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3359326
Subject Headings: Cytoskeletal proteins, Microtubules, Centrosomes, Cell organelles, Formation, Molecular biology, Tubulins
Format: Document (PDF)

Title: Dynactin is a processivity factor for dynein in vivo.
Creator: Fulton, Edward., Harriet L. Wilkes Honors College
Abstract/Description: Dynein is a motor protein responsible for microtubule-based minus-end directed trafficking in eukaryotic cells. Dynactin is a protein complex involved in mitosis, embryonic development, intracellular trafficking and anchoring microtubules at the centrosome. While dynactin is widely recognized to improve the array of cargo with which dynein can associate, there has been some dispute over whether dynactin, which binds both dynein and microtubules, improves the distance that dynein can travel...
Show moreDynein is a motor protein responsible for microtubule-based minus-end directed trafficking in eukaryotic cells. Dynactin is a protein complex involved in mitosis, embryonic development, intracellular trafficking and anchoring microtubules at the centrosome. While dynactin is widely recognized to improve the array of cargo with which dynein can associate, there has been some dispute over whether dynactin, which binds both dynein and microtubules, improves the distance that dynein can travel processively in the act of cargo trafficking before it dissociates from its microtubule. In this study, we compare movement parameters of wild type dynein-based vesicle movements with movements in cells where expression of dynactin's microtubule binding subunit, p150glued, has been knocked down. We find that dynactin does act as a processivity factor for dynein by increasing the distance that dynein can travel smoothly in a single movement event, but does not increase dynein's velocity.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/209990
Subject Headings: Cell organelles, Formation, Microtubules, Cytoskeletal proteins, Molecular biology
Format: Document (PDF)

Title: You keep me hangin' on: dynactin's p24 is essential for microtube anchoring.
Creator: Le, Ariel., Harriet L. Wilkes Honors College
Abstract/Description: Dynactin is a multisubunit protein complex that functions as a processivity cofactor to cytoplasmic dynein, assisting in vesicle transport and cell division. Independent of dynein,dynactin also serves to anchor microtubules to the centrosome. The functions of the majority of dynactin's subunits have been described to a certain degree ; however, the p24 subunit remains largely uncharacterized. Among the few things that are known about p24 are that it has a predicted molecular weight of about...
Show moreDynactin is a multisubunit protein complex that functions as a processivity cofactor to cytoplasmic dynein, assisting in vesicle transport and cell division. Independent of dynein,dynactin also serves to anchor microtubules to the centrosome. The functions of the majority of dynactin's subunits have been described to a certain degree ; however, the p24 subunit remains largely uncharacterized. Among the few things that are known about p24 are that it has a predicted molecular weight of about 20,822 Da, forms an a-helix, and binds directly to the p150[Glued] subunit. In order to explore its function further, we have performed shRNA-mediated knockdown, and fluorescent microscopy. We observe that microtubule disorganization is amplified due to the loss of p24. Our findings support the model that p24 serves as reinforcement to stabilize p150[Glued] at the centrosome.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3355592
Subject Headings: Cytoskeletal proteins, Cell organellles, Formation, Microtubules, Molecular 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: Statistical physics inspired methods to assign statistical significance in bioinformatics and proteomics: From sequence comparison to mass spectrometry based peptide sequencing.
Creator: Alves, Gelio, Florida Atlantic University, Yu, Yi-Kuo
Abstract/Description: After the sequencing of many complete genomes, we are in a post-genomic era in which the most important task has changed from gathering genetic information to organizing the mass of data as well as under standing how components interact with each other. The former is usually undertaking using bioinformatics methods, while the latter task is generally termed proteomics. Success in both parts demands correct statistical significance assignments for results found. In my dissertation. I study two...
Show moreAfter the sequencing of many complete genomes, we are in a post-genomic era in which the most important task has changed from gathering genetic information to organizing the mass of data as well as under standing how components interact with each other. The former is usually undertaking using bioinformatics methods, while the latter task is generally termed proteomics. Success in both parts demands correct statistical significance assignments for results found. In my dissertation. I study two concrete examples: global sequence alignment statistics and peptide sequencing/identification using mass spectrometry. High-performance liquid chromatography coupled to a mass spectrometer (HPLC/MS/MS), enabling peptide identifications and thus protein identifications, has become the tool of choice in large-scale proteomics experiments. Peptide identification is usually done by database searches methods. The lack of robust statistical significance assignment among current methods motivated the development of a novel de novo algorithm, RAId, whose score statistics then provide statistical significance for high scoring peptides found in our custom, enzyme-digested peptide library. The ease of incorporating post-translation modifications is another important feature of RAId. To organize the massive protein/DNA data accumulated, biologists often cluster proteins according to their similarity via tools such as sequence alignment. Homologous proteins share similar domains. To assess the similarity of two domains usually requires alignment from head to toe, ie. a global alignment. A good alignment score statistics with an appropriate null model enable us to distinguish the biologically meaningful similarity from chance similarity. There has been much progress in local alignment statistics, which characterize score statistics when alignments tend to appear as a short segment of the whole sequence. For global alignment, which is useful in domain alignment, there is still much room for exploration/improvement. Here we present a variant of the direct polymer problem in random media (DPRM) to study the score distribution of global alignment. We have demonstrate that upon proper transformation the score statistics can be characterized by Tracy-Widom distributions, which correspond to the distributions for the largest eigenvalue of various ensembles of random matrices.
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Date Issued: 2006
PURL: http://purl.flvc.org/fcla/dt/12194
Subject Headings: Molecular biology--Data processing, Bioinformatics, Proteomics, Genomics
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: 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: 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: Effects of small molecule modulators and Phospholipid Liposomes on βeta-amyloid (1-40) Amyloidogenesis.
Creator: Morris, Clifford, Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Beta-Amyloid (1-40) (Aβ40) is an aggregation prone protein, which undergoes a nucleation-dependent aggregation process causing the pathological neurodegeneration by amyloid plaque formation implicated in Alzheimer’s disease. In this thesis, we investigated the effects of small molecule modulators extracted from the marine invertebrate Pseudopterogorgia elisabethae on the Aβ40 amyloidogenic process using in- vitro ThT fluorescence assay and atomic force microscopy. We also investigated the...
Show moreBeta-Amyloid (1-40) (Aβ40) is an aggregation prone protein, which undergoes a nucleation-dependent aggregation process causing the pathological neurodegeneration by amyloid plaque formation implicated in Alzheimer’s disease. In this thesis, we investigated the effects of small molecule modulators extracted from the marine invertebrate Pseudopterogorgia elisabethae on the Aβ40 amyloidogenic process using in- vitro ThT fluorescence assay and atomic force microscopy. We also investigated the effects of neutral and anionic phospholipid liposomes on Aβ40 aggregation. Our results show that a marine natural product Pseudopterosin-A and its derivatives can suppress and modulate the Aβ40 aggregation process. Furthermore, our results demonstrate that a neutral phospholipid liposome inhibits Aβ40 fibril formation, whereas the anionic liposomes promote it.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004453, http://purl.flvc.org/fau/fd/FA00004453
Subject Headings: Aggregation (Chemistry), Alzheimer's disease -- Pathogenesis, Alzheimer's disease -- Research, Amyloid beta protein, Molecular biology, Molecular dynamics, Prions, Proteins -- Metabolism -- Disorders
Format: Document (PDF)

Title: cTnI N-Terminal deletion: an agent for rescuing restrictive cardiomyopathy, a disease caused by mutations of Cardiac Troponin I.
Creator: Getfield, Cecile A., Huang, Xupei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Restrictive cardiomyopathy (RCM) is represented in part by left ventricular stiffness and diastolic dysfunction. Missense mutations of the cardiac troponin I (cTnI) gene cause idiopathic RCM. These mutations are located in the C-terminus of cTnI and affect cardiac relaxation. Transgenic mouse models presenting the pathology observed in clinical patients with RCM have been generated previously and express the mutant cTnI in their hearts. RCM-linked mutations increase cardiac myofilament Ca2+...
Show moreRestrictive cardiomyopathy (RCM) is represented in part by left ventricular stiffness and diastolic dysfunction. Missense mutations of the cardiac troponin I (cTnI) gene cause idiopathic RCM. These mutations are located in the C-terminus of cTnI and affect cardiac relaxation. Transgenic mouse models presenting the pathology observed in clinical patients with RCM have been generated previously and express the mutant cTnI in their hearts. RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity and promote diastolic dysfunction in the heart. Previous studies using double transgenic mice (cTnI/R193H/ND) showed that ventricular relaxation is enhanced in the cTnI/R193H transgenic mice. In this study, another double transgenic mouse model, (cTnI/R193H/ND/KO), provides an avenue to investigate its rescuing effects on RCMlinked mutations in the cTnI /R193H/KO mouse. Use of molecular biological techniques, transgenic animal developments and murine echocardiography in this study has culminated into a greater understanding of RCM and diastolic dysfunction.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004196, http://purl.flvc.org/fau/fd/FA00004196
Subject Headings: Biochemical markers -- Diagnostic use, Cardiovascular system -- Pathophysiology, Coronary heart disease -- Molecular diagnosis, Mice as laboratory animals, Molecular biology
Format: Document (PDF)

Title: Studies of Site-Specific Dynamics of Aβ Amyloid Formation and Effect of Macromolecules on Aβ Amyloidogenesis.
Creator: Liu, Haiyang, Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The aim of this dissertation was 1) to explore early stage aggregation kinetic behavior of Amyloid-β 1-40 (Aβ1-40) by incorporation of unnatural amino acid pcyanophenylalanine as a site-specific fluorescence reporter, 2) to explore the effect of macromolecules on the aggregation of Aβ1-40. Chapter One provides an introduction of Alzheimer’s disease as an amyloidogenic disease, amyloidogenic peptide and amyloid formation. Details were shown about the research progress of Aβ1-40 aggregation and...
Show moreThe aim of this dissertation was 1) to explore early stage aggregation kinetic behavior of Amyloid-β 1-40 (Aβ1-40) by incorporation of unnatural amino acid pcyanophenylalanine as a site-specific fluorescence reporter, 2) to explore the effect of macromolecules on the aggregation of Aβ1-40. Chapter One provides an introduction of Alzheimer’s disease as an amyloidogenic disease, amyloidogenic peptide and amyloid formation. Details were shown about the research progress of Aβ1-40 aggregation and Aβ1-40’s interaction with polyelectrolytes, and how treatments studies were designed. In Chapter two, using Aβ1-23 as a model molecule, the distinct site-specific dynamics was identified, during amyloid formation, and the structural characteristics of amyloid fibrils were defined by using an unnatural amino acid, p-cyanophenylalanine, as a sensitive fluorescent and Raman probe. The results reveal distinct local environmental changes of specific residues during the aggregation of Aβ1-23. The results also suggest that an edge-to-face aromatic interaction between the F4 and F19 residues from the adjacent in-register β-strands plays a key role in the conformational conversion to form and stabilize β-sheet structure. In Chapter Three, p-cyanophenylalanine was incorporated in the full sequence of Aβ1-40. Site-specific information from p-cyanophenylalanine fluorescence was studied and summarized. In Chapter Four, the inhibiting effect of an anionic polyelectrolyte poly(4- styrenesulfonate) (PSS) on the aggregation of Aβ1-40 peptide was reported. The results demonstrate the strong inhibition potential of PSS on the aggregation of Aβ1-40. Additional studies indicate that the presence of both aliphatic backbone as well as aromatic side chain group in PSS is essential for its inhibition activity. In Chapter Five, it was investigated the effect of two polyelectrolytes, chitosan (CHT) and N-trimethyl chitosan chloride (TMC), on the aggregation of Aβ1-40. Results show that both CHT and TMC exhibit a concentration-dependent decrease of amyloid aggregation suggesting their application as amyloid assembly inhibitors. Their binding mechanism was investigated by computational modeling which shows that Aβ1-40 monomer was primarily stabilized by electrostatic interactions with charged amine and quaternary amines of CHT and TMC respectively. Chapter Six, describes all experimental procedures and instrument setup in detail.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004769, http://purl.flvc.org/fau/fd/FA00004769
Subject Headings: Alzheimer's disease--Research., Alzheimer's disease--Pathogenesis., Molecular biology., Molecular dynamics., Prions., Amyloid beta-protein.
Format: Document (PDF)

Title: Mechanism and treatment of restrictive cardiomyopathy.
Creator: Jean-Charles, Pierre-Yves, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Restrictive cardiomyopathy (RCM) is a cardiac muscle disorder characterized by increased ventricular stiffness and diastolic dysfunction. Patients with RCM often present severe cardiac problems which usually lead to heart failure and sudden death. No effective treatment is available for RCM which makes the finding of novel efficient therapies an urgent necessity. Great progress in molecular biology techniques and advances in transgenic animal development provide great opportunities for the...
Show moreRestrictive cardiomyopathy (RCM) is a cardiac muscle disorder characterized by increased ventricular stiffness and diastolic dysfunction. Patients with RCM often present severe cardiac problems which usually lead to heart failure and sudden death. No effective treatment is available for RCM which makes the finding of novel efficient therapies an urgent necessity. Great progress in molecular biology techniques and advances in transgenic animal development provide great opportunities for the study of RCM and other cardiovascular diseases encountered in clinical patients.... Our laboratory is among the first to generate transgenic mouse models of RCM based on cardiac troponin I (cTnI) missense mutations. In this study, transgenic mice that suffer from RCM have been generated to understand the factors behind the diastolic dysfunction associated with that myocardial disease.... The information obtained from this study allows a better understanding of the role of troponin in RCM and the factors behind the physiopathology of the disease. It will also offer a therapeutic strategy taking into account the physiological characteristic of RCM.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3358554
Subject Headings: Biochemical markers -- Diagnostic use, Cardiovascular system -- Pathophysiology, Coronary heart disease -- Molecular diagnosis, Mice as laboratory animals, Molecular biology
Format: Document (PDF)

Title: DFT calculations of Amide 1 vibrational frequencies for a model peptide.
Creator: Lantz, Richard, Stillman, Storm, Terentis, Andrew C.
Date Issued: 2012-04-06
PURL: http://purl.flvc.org/fcla/dt/3348894
Subject Headings: Density Functional Theory (DFT), Molecular biology, Amides --chemistry, Biomolecular methods, Biochemistry, Amide-I modes
Format: Document (PDF)

Title: FSTL-1 secreted by mesenchymal stem cells increases cell viability of human aortic endothelial cells under hypoxic stress.
Creator: Eid, Nibal., Harriet L. Wilkes Honors College
Abstract/Description: Human mesenchymal stem cells (MSCs) are being evaluated for the treatment of a broad array of diseases due to their ability to secrete a variety of therapeutically beneficial paracrine-acting factors. For example, MSC conditioned media (MSC-CM) has been shown to inhibit hypoxia-induced apoptosis in human aortic endothelial cells (HAECs) via activation of the P13-AKT pathway. However, the factors secreted by MSCs responsible for this effect have yet to be identified. Recent studies have shown...
Show moreHuman mesenchymal stem cells (MSCs) are being evaluated for the treatment of a broad array of diseases due to their ability to secrete a variety of therapeutically beneficial paracrine-acting factors. For example, MSC conditioned media (MSC-CM) has been shown to inhibit hypoxia-induced apoptosis in human aortic endothelial cells (HAECs) via activation of the P13-AKT pathway. However, the factors secreted by MSCs responsible for this effect have yet to be identified. Recent studies have shown that the glycoprotein Follistatin-like 1 (FSTL1) activates the P13-AKT pathway by binding to the receptor disco-interacting protein (DIP2A) expressed on the surface of cells. Based on our data indicating that MSCs constitutively secrete high quantities of FSTL1, we hypothesize that this protein principally mediates the anti-apoptopic effect of MSC-CM on HAECs. Loss-of-function studies employing siRNA-mediated knockdown of the protein and neutralizing antibodies will be used to assess the role of FSTL1 in growth and survival of HAECs following exposure to hypoxic stress.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3359296
Subject Headings: Stem cells, Transplantation, Molecular biology, Gene therapy, Coronary heart disease, Prevention, Stress (Physiology)
Format: Document (PDF)

Title: Investigation of talin head-tail interactions.
Creator: Butyn, Amber., Harriet L. Wilkes Honors College
Abstract/Description: Talin is a ubiquitous, high-molecular-weight, flexible protein that plays a critical role in focal adhesions by activating, as well as connecting, integrins to the actin cytoskeleton. Talin's inactive auto-inhibitory state is speculated to be one of its modes of regulation inside the cell and is achieved through its head-tail interactions. In order to decipher the stability of this interaction, the head domain (residues 206-405) was cloned into a modified pET28m vector while the tail domains ...
Show moreTalin is a ubiquitous, high-molecular-weight, flexible protein that plays a critical role in focal adhesions by activating, as well as connecting, integrins to the actin cytoskeleton. Talin's inactive auto-inhibitory state is speculated to be one of its modes of regulation inside the cell and is achieved through its head-tail interactions. In order to decipher the stability of this interaction, the head domain (residues 206-405) was cloned into a modified pET28m vector while the tail domains (residues 1654-2344 and 2225-2344) were cloned into the pET32a vector to obtain octa-histidine tagged and un-tagged peptide, respectively. Neither co-expression nor pull-down using the His-tagged head domain was successful in purifying a stable head-tail complex. Our results indicate rather weak interactions between the talin head and rod domains and hence, under our experimental conditions, do not lead to a stable auto-inhibitory complex that can be purified for further studies.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/209984
Subject Headings: Membrane proteins, Structure-activity relationships, Cell membranes, Physiology, Molecular biology, Cell interaction, Developmental cytology
Format: Document (PDF)

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