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Title: Roles of troponin I in heart development and cardiac function.
Creator: Du, Jianfeng., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Two major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (~1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site...
Show moreTwo major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (~1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site were critical for the gene expression. Electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays revealed binding proteins to CREB site in nuclear extracts from myocardial cells. Thyroid hormone (T3) caused a significant inhibitory effect on ssTnI expression in myocardial cells. Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI Cv terminus, arginine1 92 histidine (R192H) by cardiac specific expression of the mutated protein (cTnI193His in mouse sequence) in transgenic mice. The main functional alteration detected in cTnI193His mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. Echocardiography revealed a series of changes on the transgenic mice including a reversed E-to-A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. At the age of 12 months, cardiac output in cTnI193His mice was significantly declined, and some transgenic mice showed congestive heart failure. The negative impact of cTnI193His on ventricular contraction and relaxation was further demonstrated in isolated mouse working heart preparations., Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO.The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation. The results demonstrate a critical role of the COOH-terminal domain of cTnI in the diastolic function of cardiac muscle. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM.
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Date Issued: 2008
PURL: http://purl.flvc.org/FAU/186287
Subject Headings: Mice as laboratory animals, Biochemical markers, Diagnostic use, Heart, Diseases, Molecular diagnosis, Cardiovascular system, Pathophysiology
Format: Document (PDF)

Title: CHARACTERIZING THE PHYSICAL PROPERTIES OF LIVING CELLS THROUGH MICROFLUIDIC IMPEDANCE SENSING.
Creator: Galpayage, Dona Kalpani Nisansala Udeni, Lau, Andy W.C., Du, Sarah E., Florida Atlantic University, Department of Physics, Charles E. Schmidt College of Science
Abstract/Description: The purpose of this research is to explore and investigate the biophysical properties of living cells using microfluidics based electrical impedance sensing (EIS) technique. It provides a non-invasive approach to detect label-free biological markers in the regulation of cellular activities even at a molecular level. We specifically focus on the development, testing, and theoretical modeling of electrical impedance spectroscopy for neuroblastoma cells and endothelial cells. First, we...
Show moreThe purpose of this research is to explore and investigate the biophysical properties of living cells using microfluidics based electrical impedance sensing (EIS) technique. It provides a non-invasive approach to detect label-free biological markers in the regulation of cellular activities even at a molecular level. We specifically focus on the development, testing, and theoretical modeling of electrical impedance spectroscopy for neuroblastoma cells and endothelial cells. First, we demonstrate that the EIS technique can be used to monitor the progressive mitochondrial fission/fusion modification in genetically modified human neuroblastoma cell lines. Our results characterize quantitatively the abnormal mitochondrial dynamics through the variations in cytoplasm conductivity. Secondly, we employ a real time EIS method to determine the biophysical properties of the junctions which join one endothelial cell with one another in a monolayer of endothelial cells. In particular, we examine the role of the protein, c-MYC oncogene, in the barrier function. Our results show that the downregulation of c-MYC oncogene enhances the endothelial barrier dysfunction associated with inflammation. Finally, we measure and find that the electrical admittance (the reciprocal of the impedance) of the monolayer of endothelial cellular networks exhibits an anomalous power law of the form, Y ∝ ωα, over a wide range of frequency, with the value of the exponent, α, depending on the severity of the inflammation. We attribute the power law to the changes of the intercellular electric permeability between neighboring endothelial cells. Thus, the inflammation gives rise to relatively smaller values of α compared to that of the no-inflammation group. Furthermore, we propose a simple percolation model of a large R-C network to confirm the emergent of power law scaling behavior of the complex admittance, suggesting that the endothelial network behaves as a complex microstructural network and its electrical properties may be simulated by a large R-C network.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013595
Subject Headings: Microfluidics, Impedance spectroscopy, Cells
Format: Document (PDF)

Title: Aggregation Inhibition and Detection of Alzheimer’s Amyloidogenic and Oligomeric Peptides.
Creator: Elbassal, Esmail A. E., Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Protein aggregation, oligomer and fibril formation is one of the dominant characteristics in the pathogenesis of a number of neurodegenerative diseases, such as Alzheimer’s disease (AD). Inhibition of toxic oligomer and fibril formation is one of the approaches to find potential drug candidates for AD. Additionally, early diagnosis of these amyloid species can provide mechanistic understanding of protein aggregation and thus can pave the way for preventing the onset of AD. The aim of this...
Show moreProtein aggregation, oligomer and fibril formation is one of the dominant characteristics in the pathogenesis of a number of neurodegenerative diseases, such as Alzheimer’s disease (AD). Inhibition of toxic oligomer and fibril formation is one of the approaches to find potential drug candidates for AD. Additionally, early diagnosis of these amyloid species can provide mechanistic understanding of protein aggregation and thus can pave the way for preventing the onset of AD. The aim of this dissertation was 1) to explore the effects of charged cholesterol derivatives on the aggregation kinetic behavior of Amyloid-β40 (Aβ40), 2) to probe Aβ40 oligomer and amyloid formation in vitro using gold nanoparticles (AuNPs), and 3) to monitor the kinetic effect of various natural product molecules on Aβ40 aggregation in vitro. In the first chapter, a general introduction about AD as an amyloidogenic disease, amyloid cascade hypothesis, and the manipulation of Aβ peptides aggregation kinetics using different approaches was presented. In the second chapter, we studied the effects of oppositely charged cholesterol derivatives on the aggregation kinetics of Aβ. In the third chapter, we developed a gold nanoparticles (AuNPs) assay to probe Aβ40 oligomers and amyloid formation. In chapter IV, we monitored the effects of various small molecules on the aggregation kinetics of Aβ40. In chapter V, we discussed the methods and experimental details.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013009
Subject Headings: Alzheimer's disease, Amyloid beta-protein, Oligomers, Protein Aggregates, Neurodegenerative Diseases
Format: Document (PDF)

Title: Microfluidic Electrical Impedance Spectroscopy for Blood Analysis.
Creator: Rikhtehgaran, Samaneh, Wille, Luc T., Du, E., Florida Atlantic University, Department of Physics, Charles E. Schmidt College of Science
Abstract/Description: The study of the electrical properties of red blood cells (RBCs) plays a crucial role in advancing our understanding of human health. As RBCs age, they undergo changes that affect hemorheology and blood microcirculation, which have far-reaching implications for disease research. Furthermore, the shortage of RBC storage units can be a major issue for patients, underscoring the importance of characterizing RBC aging with respect to cell densities. In individuals with abnormal hemoglobin disease...
Show moreThe study of the electrical properties of red blood cells (RBCs) plays a crucial role in advancing our understanding of human health. As RBCs age, they undergo changes that affect hemorheology and blood microcirculation, which have far-reaching implications for disease research. Furthermore, the shortage of RBC storage units can be a major issue for patients, underscoring the importance of characterizing RBC aging with respect to cell densities. In individuals with abnormal hemoglobin disease, alterations in hemoglobin and its functionality can modify the volume and density of RBCs, making their study even more crucial. To this end, our aim is to investigate the impedance alterations of RBCs after distributing them into different layers based on their densities. We have developed a novel method for non-invasive, rapid, and real-time single-cell analysis of RBCs. Our approach involves the use of electrical impedance spectroscopy (EIS) to study the cells after performing cell fractionation. Our studies indicate an increasing trend for RBC resistance and a decreasing trend for the cell membrane as the density of the layer increases. Additionally, we have developed a method for extracting hemoglobin with high purity from fresh samples of RBCs. By passing lysed RBCs through ultrafiltration devices and removing debris and membranes, we were able to isolate hemoglobin. Using the EIS technique, we studied the alterations of impedance over a frequency range, obtaining valuable insight into the electrical properties of hemoglobin.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014223
Subject Headings: Blood--Analysis, Erythrocytes--Aging, Hemorheology, Electrical impedance spectroscopy, Microfluidics
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: INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128).
Creator: Regmi, Deepika, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: The misfolding of native, cellular prion protein (PrPc) to a conformationally altered pathogenic isoform, designated scrapie PrPsc, is the main molecular process involved in the pathogenesis of prion diseases. Prion diseases are marked by the accumulation of conformationally modified forms of cellular prion protein. An N-terminal portion of the prion protein, PrP (106-128), is a 23-residue peptide fragment and is characterized by an amphipathic structure with two domains: a hydrophilic N...
Show moreThe misfolding of native, cellular prion protein (PrPc) to a conformationally altered pathogenic isoform, designated scrapie PrPsc, is the main molecular process involved in the pathogenesis of prion diseases. Prion diseases are marked by the accumulation of conformationally modified forms of cellular prion protein. An N-terminal portion of the prion protein, PrP (106-128), is a 23-residue peptide fragment and is characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. In this study, the aggregation characteristics of the PrP (106-128) peptide were investigated using a combination of biophysical approaches. We investigated the effect of different factors including concentrations, pH, and metal ions, on the aggregation of the peptide. Our results demonstrated that the peptide steadily aggregates at concentrations higher than 25 M. The aggregation propensity and fibril formation is higher at pH 7.4 and pH 8.1, and the aggregation is inhibited at pH lower than 6. Furthermore, our results indicate that the Cu2+ has much less effect on the peptide amyloidogenesis, while Zn2+ has a significant influence on the PrP (106-128) amyloidogenesis. We further presented a systematic analysis of the impact of phospholipid liposomes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1’-racglycerol) (POPG) in the absence or presence of cholesterol, on the amyloidogenesis of PrP (106-128). The results showed that POPC vesicles does not significantly influence the aggregation kinetics of the peptide. However, the anionic lipid POPG delays the aggregation in a concentration-dependent manner, whereas the addition of POPG with the cholesterol shows fast kinetics of fibrillization, thus reducing the lag time of the aggregation kinetics. We also monitored the effect of cholesterol and its derivatives including cholesterol-SO4 and DC-cholesterol on PrP (106-128) amyloidogenesis. Our results showed that the cholesterol inhibits the peptide aggregation and delays the formation of fibrils in a concentration-dependent manner. Cholesterol-SO4 dramatically facilitates the aggregation at high concentrations but has the potential to slow down the fibrillization at low concentrations, whereas cationic DC-cholesterol vesicles can effectively inhibit peptide fibril formation at high concentrations.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013565
Subject Headings: Prion Diseases, Prions--pathogenicity, Amyloid, Peptides, Prions
Format: Document (PDF)

Title: HUMAN CALCITONIN: AN INVESTIGATION OF AMYLOID FORMATION AND INHIBITION.
Creator: Lantz, Richard, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Human calcitonin (hCT) is a peptide hormone that is produced by the thyroid gland where it regulates blood calcium and stimulates bone formation. However, increased concentrations can cause hCT to aggregate into amyloid fibrils where they can cause cellular toxicity. In this dissertation, we investigated the role of the N-terminal intramolecular disulfide bond, the effects cholesterol derivatives, the inhibitory effects of a group of polyphenolic molecules, and membrane interactions on hCT...
Show moreHuman calcitonin (hCT) is a peptide hormone that is produced by the thyroid gland where it regulates blood calcium and stimulates bone formation. However, increased concentrations can cause hCT to aggregate into amyloid fibrils where they can cause cellular toxicity. In this dissertation, we investigated the role of the N-terminal intramolecular disulfide bond, the effects cholesterol derivatives, the inhibitory effects of a group of polyphenolic molecules, and membrane interactions on hCT amyloid formation. To better understand hCT amyloid formation, we investigated the role of the N-terminal intramolecular disulfide bond has on the aggregation kinetics of hCT. Our results demonstrated that the presence of the disulfide bond is key to the formation of the oligomeric nucleus that is needed for amyloid formation. We also investigated the role of cholesterol, cholesterol sulfate, and 3β-[N-(dimethylaminoethane)carbamoyl]-cholesterol (DC-cholesterol) in moderating hCT fibril formation. We showed that cholesterol does not significantly affect hCT fibrillization while high concentrations of cholesterol sulfate has a moderate inhibiting effect. However, DC-cholesterol strongly inhibits hCT fibril formation in a concentration-dependent manner suggesting the role of electrostatic and hydrogen bonding interactions have in moderating the interactivity between hCT and the surface of DC-cholesterol vesicles. We also probed the inhibitory effects of a group of polyphenolic molecules on hCT fibril formation. Our results showed that molecules containing vicinal hydroxyl groups on the phenyl ring effectively inhibits hCT fibril formation though a plausible covalent linkage between the oxidized polyphenol and hCT.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013514
Subject Headings: Calcitonin, Amyloid
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: Role of the N-Terminal Hydrophilic Region of Amyloid Beta Peptide in Amyloidogenesis, Membrane Interaction and Toxicity Associated with Alzheimer’s Disease.
Creator: Morris, Clifford M., Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Alzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain...
Show moreAlzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain understanding on the electrostatic and hydrophobic constituents of the mechanism. This was achieved by substituting specific charged residues located in the NTR of Aβ40 and investigating their effects through a variety of techniques. We also investigated the role of NTR charged residues in their interaction with supported phospholipid bilayer membranes through the use of Quartz Crystal Microbalance with Dissipation (QCM-D) monitoring to gain insight on the mechanistic details of the interaction. To further understand the implications of substituting charged NTR residues on membrane interaction, pore formation and damage, we utilized a carboxyfluorescein dye leakage assay to quantify the membrane damage caused by Aβ40 and the NTR mutants. We also performed neurotoxicity assay with SH-SY5Y neuroblastoma cells to shed light on the effects of NTR substitutions on cellular toxicity. Finally, we synthesized a polymer, trimethyl chitosan (TMC), and utilized it as a polyelectrolyte monitor of electrostatic interactions occurring between TMC and the NTR of Aβ40. Our results demonstrate that the NTR charged residues of Aβ40 contribute significantly to the aggregation process, amyloidogenesis, and phospholipid membrane interaction and perturbation by means of electrostatic, thermodynamic and hydrophobic forces.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013246
Subject Headings: Alzheimer's disease, Amyloid beta-Peptides, Amyloid
Format: Document (PDF)

Title: Studying the Effects of Lipid Membranes and Polysaccharides on the Amyloidogenicity of Fragments of Amyloid Beta.
Creator: Petersen, Katherine, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: The amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely...
Show moreThe amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely resulting in the etiology of AD. In this study, two fragments are used, the 23-residue N-terminal fragment, Aβ23 and the 30-residue C-terminal fragment, Aβ11-40, to better understand the role of the N and C-terminus in the aggregation of Aβ peptide. Aβ11-40 has also been found in the brains of AD patients, playing a biological role in the disease. This study used analytical and biophysical techniques to systematically synthesize, purify, characterize, and study these fragments' aggregation in different conditions. We investigated the effects of lipid membranes on the aggregation of Aβ23 and Aβ11-40 and the activities of these peptides in inducing membrane damage. The results show that the aggregation of Aβ23 was increased in the presence of lipid membranes, likely due to favorable electrostatic interactions. However, the aggregation of Aβ11-40 was not influenced by lipid membranes. A dye leakage study was carried out to study the membrane damage occurring as a result of fragments' interaction with lipid membranes. The results showed that neither fragment had a profound effect on membrane destruction, although the charge of the lipid head seemed to play a role. This work's second study focused on the effect of three specific polysaccharides, heparin, chitosan (CHT), and trimethyl chitosan (TMC), on the aggregation of Aβ23 and Aβ11-40. The results showed that for Aβ23, heparin increased aggregation, while both CHT and TMC decreased aggregation. However, for Aβ11-40, both heparin and CHT did not affect aggregation, while TMC decreased aggregation.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014294
Subject Headings: Amyloid beta-Peptides, Alzheimer's disease
Format: Document (PDF)

Title: PRION FRAGMENT 106-128: AN INVESTIGATION OF AMYLOID FORMATION AND INHIBITION.
Creator: Regmi, Deepika, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Misfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a...
Show moreMisfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a concentration-dependent manner in an aqueous solution and that the aggregation is sensitive to pH and the preformed amyloid seeds.Furthermore, we show that the zwitterionic POPC liposomes moderately inhibit the aggregation of PrP(106–128), whereas POPC/cholesterol (8:2) vesicles facilitate peptide aggregation likely due to the increase of the lipid packing order and membrane rigidity in the presence of cholesterol. In addition, anionic lipid vesicles of POPG and POPG/cholesterol above a certain concentration accelerate the aggregation of the peptide remarkably. The strong electrostatic interactions between the N-terminal region of the peptide and POPG may constrain the conformational plasticity of the peptide, preventing insertion of the peptide into the inner side of the membrane and thus promoting fibrillation on the membrane surface. The results suggest that the charge properties of the membrane, the composition of the liposomes, and the rigidity of lipid packing are critical in determining peptide adsorption on the membrane surface and the efficiency of the membrane in catalyzing peptide oligomeric nucleation and amyloid formation.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014356
Subject Headings: Prion Proteins, Prion diseases, Epigallocatechin gallate, Amyloid
Format: Document (PDF)

Title: DISSECTING THE MECHANISTIC ROLES OF REGULATORS IN MEDIATING AMYLOID-BETA AMYLOIDOGENESIS.
Creator: Shen, Fengyun, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Alzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and...
Show moreAlzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and carnosine, phospholipids, and β-hairpins on Aβ aggregation to dissect their mechanistic roles in the amyloidogenesis of Aβ. We first systematically studied the kinetic impact of Zn2+ on the aggregation of Aβ40 and Aβ40-M. Our results show that the presence of Zn2+ transforms the Aβ40 aggregation kinetics from a single sigmoidal to a biphasic process, while the aggregation of Aβ40-M is significantly suppressed by Zn2+. We also found that a nature dipeptide, carnosine, remarkably decreases the activity of Zn2+ on modulating Aβ aggregation, although it has a weak direct effect on the peptide aggregation kinetics. Second, we investigated the activities of Aβ40 and Aβ42 in inducing membrane damage and the effects of lipid membranes on the aggregation of these peptides using liposome models containing mitochondrial-specific phospholipid–cardiolipin (CL).
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014314
Subject Headings: Alzheimer's disease, Amyloid beta-Peptides, Neurodegenerative Diseases
Format: Document (PDF)

Title: AMYLOIDOGENICITY OF THE PEPTIDE FRAGMENT IN MICROTUBULE BINDING REPEAT DOMAIN OF TAU.
Creator: Islam, Majedul, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Tau, a microtubule-associated protein, is involved in more than 20 different tauopathic disorders characterized by aberrant intracellular aggregation of tau in the brain. However, it is still unclear how this highly soluble tau protein aggregates inside the brain. Thus, understanding the mechanistic details of tau aggregation is critical for unraveling the underlying pathology of tauopathies and developing effective strategies to inhibit tau aggregation. Herein, we investigated the...
Show moreTau, a microtubule-associated protein, is involved in more than 20 different tauopathic disorders characterized by aberrant intracellular aggregation of tau in the brain. However, it is still unclear how this highly soluble tau protein aggregates inside the brain. Thus, understanding the mechanistic details of tau aggregation is critical for unraveling the underlying pathology of tauopathies and developing effective strategies to inhibit tau aggregation. Herein, we investigated the aggregation of a novel 20-residue model peptide, tau₂₉₈₋₃₁₇, derived from the key microtubule-binding domain of the full sequence tau. Our study demonstrates that tau₂₉₈₋₃₁₇ highly mimics full-length tau's physical and aggregation properties. The fibrillation of the peptide is strongly dependent on external factors. The presence of polyanionic heparin (Hep) significantly promotes the aggregation of this peptide to form amyloid fibrils. The Hep-induced aggregation is sensitive to the ionic strength of the solution, suggesting an important role of electrostatic interactions in the mechanism of Hep-mediated aggregation. In addition, two positively charged polysaccharides, chitosan (CHT) and its quaternary derivative N-trimethyl chitosan (TMC), effectively inhibit Hep-induced aggregation of tau₂₉₈₋₃₁₇ in a concentration-dependent manner. Attractive electrostatic interactions between the positively charged moieties in CHT/TMC and the negatively charged residues of Hep play a critical role in inhibiting Hep–peptide interactions and suppressing peptide aggregation.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014211
Subject Headings: tau Proteins, Tauopathies, Amyloidogenic Proteins
Format: Document (PDF)

Title: ELECTRICAL IMPEDANCE SENSING OF ERYTHROCYTES AND CYTOADHESION.
Creator: Liu, Jia, Du, Sarah E., Florida Atlantic University, Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science
Abstract/Description: Electrical impedance of cells is a sensitive indicator of changes in cellular structure and biophysical characteristics. Integration of electrical impedance sensing in microfluidics can be a useful tool for characterization of blood cells for their disease state, such as sickle cell disease and malaria. The first part of this dissertation presents application of a microfluidics-based electrical impedance sensor for the study of sickle cell disease. Dynamic cell sickling-unsickling process of...
Show moreElectrical impedance of cells is a sensitive indicator of changes in cellular structure and biophysical characteristics. Integration of electrical impedance sensing in microfluidics can be a useful tool for characterization of blood cells for their disease state, such as sickle cell disease and malaria. The first part of this dissertation presents application of a microfluidics-based electrical impedance sensor for the study of sickle cell disease. Dynamic cell sickling-unsickling process of blood cells in response to cyclic hypoxia was measured. Strong correlation was found between the electrical impedance data and patients’ hematological parameters such as levels of sickle hemoglobin and fetal hemoglobin. In addition, application of electrical impedance spectroscopy in narrow microfluidic channel was used for label-free flow cytometry and non-invasive assay of single sickle cells under controlled oxygen level. We demonstrate the capability of this new technique in differentiating normal red blood cells from sickle cells, as well as sickled cells from unsickled cells, using normoxic and hypoxic conditions. The second part of this dissertation reports an application of electrical impedance sensing for the study of placental malaria. Testing conditions were optimized so that electrical impedance can be used for real time monitoring of different cellular and molecular level variations in this in vitro model of placental malaria. Impedance characteristics of cell proliferation, syncytial fusion and long-term response of BeWo cells to adhesion of infected erythrocytes were obtained and related to the immunostaining results and inflammatory cytokines measurements. Comparing to the conventional optical microscope-based methods, electrical impedance sensing technique can provide a label-free, real-time monitoring tool to study erythrocytes and cytoadhesion, and can further be extended to other disease models and cell types.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013389
Subject Headings: Microfluidics, Erythrocytes, Electric Impedance, Sickle cell disease, Malaria, Cell Adhesion
Format: Document (PDF)

Title: Modeling and Experimental Study of Evaporation and Diffusion of Water Droplets on Foam Substrates.
Creator: Tian, Yining, Du, Sarah E., Florida Atlantic University, College of Engineering and Computer Science, Department of Ocean and Mechanical Engineering
Abstract/Description: The objective of this thesis is to develop a new experimental method to characterize the diffusion of water in polymer resins, based on the evolution in the volume of water droplets as a function of time. A finite element model is established to model the mass transport of water droplet through evaporation and diffusion processes. Diffusivity of water into polymer resins is then extracted by matching the volume variation of the simulated water droplet to the experimental results. Capability...
Show moreThe objective of this thesis is to develop a new experimental method to characterize the diffusion of water in polymer resins, based on the evolution in the volume of water droplets as a function of time. A finite element model is established to model the mass transport of water droplet through evaporation and diffusion processes. Diffusivity of water into polymer resins is then extracted by matching the volume variation of the simulated water droplet to the experimental results. Capability of this method is demonstrated by determining the diffusivity of water into void-free epoxy and epoxy samples with voids. Diffusion coefficient value obtained from this method agrees with data from conventional water immersion method. The significantly small scale of the water droplet (less than 10 microliter) allows rapid characterization of diffusivity in hours instead of months as typically required by the conventional immersion method. The method developed here provides a useful tool for rapid and effective characterization of diffusivity of water in polymer substrates and can be extended to other substances as well.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013270
Subject Headings: Polymers, Resins, Diffusion, Water, Evaporation--Experiments
Format: Document (PDF)

Title: MULTIPHYSICS SIMULATION OF DIELECTROPHORESIS ENRICHMENT FOR DETECTION OF LOW PARASITEMIA PLASMODIUM FALCIPARUM IN HUMAN BLOOD.
Creator: Oladokun, Oladiran, Du, E., Florida Atlantic University, Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science
Abstract/Description: Malaria is an ancient lethargic disease that remains a global burden. It has been difficult to end the scourge of P. falciparum malaria because of the parasites’ drug resistance so early diagnosis of malaria is crucial. Microscopy remains the gold standard but has limited reliability in detecting malaria parasites. This study proffered a method towards detection of low parasitemia P. falciparum infected RBCs (Pf-RBCs) based on dielectrophoresis (DEP). A microfluidic device was designed for...
Show moreMalaria is an ancient lethargic disease that remains a global burden. It has been difficult to end the scourge of P. falciparum malaria because of the parasites’ drug resistance so early diagnosis of malaria is crucial. Microscopy remains the gold standard but has limited reliability in detecting malaria parasites. This study proffered a method towards detection of low parasitemia P. falciparum infected RBCs (Pf-RBCs) based on dielectrophoresis (DEP). A microfluidic device was designed for label-free cell sorting of Pf-RBCs from other whole blood in a continuous manner, based on the intrinsic electrical signatures of the cells. The design was validated by a finite element simulation using COMSOL Multiphysics. Simulations show the feasibility of the separation in a 9-mm long microfluidic channel under laminar flow conditions, using a low voltage supply of +/-10 V at 50 kHz.
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Date Issued: 2024
PURL: http://purl.flvc.org/fau/fd/FA00014415
Subject Headings: Plasmodium falciparum, Microfluidic devices, Dielectrophoresis, Biomedical engineering, Point-of-care testing
Format: Document (PDF)

Title: INFLUENCE OF DEFORMATION CONSTRAINTS OF HONEYCOMB CORE CELLS ON THE BENDING STIFFNESS OF SINGLE-FACE SANDWICH.
Creator: Ayanoglu, Mustafa Oguzhan, Carlsson, Leif A., Du, E, Florida Atlantic University, Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science
Abstract/Description: This research focuses on deformation constraints of honeycomb core cells in a sandwich imposed by bonds to the face sheets. Specifically, the influence of one-sided core constraints on the bending stiffness of a single-face honeycomb core sandwich is examined. To characterize the unconstrained in-plane compressive response of honeycomb core, a range of honeycomb cores was experimentally examined. Cores with a thin cell wall displayed extensive bending deformation of inclined cell walls while...
Show moreThis research focuses on deformation constraints of honeycomb core cells in a sandwich imposed by bonds to the face sheets. Specifically, the influence of one-sided core constraints on the bending stiffness of a single-face honeycomb core sandwich is examined. To characterize the unconstrained in-plane compressive response of honeycomb core, a range of honeycomb cores was experimentally examined. Cores with a thin cell wall displayed extensive bending deformation of inclined cell walls while cores with thicker walls failed by a shear-type instability of the cells indicated by tilting of vertical cell wall segments. The modulus and compressive strength of the core were compared to the predictions from unit cell models. The results show that geometrical imperfections such as deviation from the intended cell wall angle cause in-plane anisotropy and have strong influence on modulus and strength of the core. Modulus and strength were in reasonable agreement with predictions from unit cell models for cell wall modulus and strength between 5-12 GPa and 72-171 MPa for the set of cores examined.
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Date Issued: 2024
PURL: http://purl.flvc.org/fau/fd/FA00014438
Subject Headings: Honeycomb structures, Materials--Compression testing, Sandwich construction
Format: Document (PDF)

Title: An experimental survey of the transition between two-state and downhill protein folding scenarios.
Creator: Liu, Feng, Du, Deguo, Fuller, Amelia A., Davoren, Jennifer E., Wipf, Peter, Kelly, Jeffery W., Gruebele, Martin
Date Issued: 2008-02-19
PURL: http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1073_pnas.0711908105_1647975037
Format: Document (PDF)

Title: Evaluating β-turn mimics as β-sheet folding nucleators.
Creator: Fuller, Amelia A., Du, Deguo, Liu, Feng, Davoren, Jennifer E., Bhabha, Gira, Kroon, Gerard, Case, David A., Dyson, H. Jane, Powers, Evan T., Wipf, Peter, Gruebele, Martin, Kelly, Jeffery W.
Date Issued: 2009-07-07
PURL: http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1073_pnas.0813012106_1648043559
Format: Document (PDF)

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