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Title: EFFECTIVENESS OF CARDIAC REHABILITATION: SECONDARY PREVENTION INCREASES FUNCTIONAL CAPACITY IN POST-MYOCARDIAL INFARCTION PATIENTS.
Creator: Badillo, Kristin, Fisher, Thomas, University of Central Florida
Abstract / Description: The purpose of this study was to discern the effectiveness of Cardiac Rehabilitation/ Secondary Prevention Programs (CR/ SPPs) by evaluating increased functional capacity in the form of MET (metabolic equivalent) scores post-myocardial infarction (MI) or heart attack. The Duke Activity Status Index (DASI) survey is administered as part of the Standard Operating Procedure (SOP) for participation in the Secondary Prevention Program. Criterion for the research included patients 65 and older,...
Show moreThe purpose of this study was to discern the effectiveness of Cardiac Rehabilitation/ Secondary Prevention Programs (CR/ SPPs) by evaluating increased functional capacity in the form of MET (metabolic equivalent) scores post-myocardial infarction (MI) or heart attack. The Duke Activity Status Index (DASI) survey is administered as part of the Standard Operating Procedure (SOP) for participation in the Secondary Prevention Program. Criterion for the research included patients 65 and older, with a history of one myocardial infarction, and had completed all 36 sessions of CR. The scores from 11 SPP surveys were analyzed and compared in three time increments from sessions 1-18 (initial, or"pre"), sessions 19-36 ("pan"), and sessions 1-36 ("post"). A total of 11 (n=11) surveys were collected and analyzed at The Computing and Statistical Technology Laboratory in Education (CASTLE) in the Teaching Academy on UCF Main Campus. Results from the data showed mean MET scores of 6.21 at session 1, 7.59 at session 18, and 8.15 at session 36. The mean changes over time represented in METs were 1.38 (1), .56 (18), and 1.93 (36). Percent changes over time were 27% (1), 8% (18), and 36% (36). This study showed increased functional capacity over time and will improve program design in terms of frequency and duration.
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Date Issued: 2015
Identifier: CFH0004770, ucf:45339
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004770

Title: DEVELOPMENT OF AN ALKALINE PHOSPHATASE REPORTER SYSTEM FOR USE IN THE LYME DISEASE SPIROCHETE BORRELIA BURGDORFERI.
Creator: Sutchu, Selina, Jewett, Mollie, University of Central Florida
Abstract / Description: The use of the periplasmic alkaline phosphatase (PhoA) reporter protein from E. coli has been critical for definition of the topology of transmembrane proteins of multiple bacterial species. This report demonstrates development of a PhoA reporter system in B. burgdorferi. Codon usage of the E. coli phoA in B. burgdorferi was analyzed and an optimized version of the gene was obtained. In order to assess the differential activity of the reporter system, two optimized PhoA-fusion construct using...
Show moreThe use of the periplasmic alkaline phosphatase (PhoA) reporter protein from E. coli has been critical for definition of the topology of transmembrane proteins of multiple bacterial species. This report demonstrates development of a PhoA reporter system in B. burgdorferi. Codon usage of the E. coli phoA in B. burgdorferi was analyzed and an optimized version of the gene was obtained. In order to assess the differential activity of the reporter system, two optimized PhoA-fusion construct using B. burgdorferi proteins were engineered: one using the periplasmic protein OppAIV and one using the cytoplasmic protein PncA. The activity of PhoA requires periplasmic localization. The periplasmic OppAIV-PhoA fusion as well as the cytoplasmic PncA-PhoA fusion produced detectable PhoA protein in E. coli and in B. burgdorferi. The periplasmic fusion construct, but not the cytoplasmic fusion construct, resulted in functional alkaline phosphatase (AP) activity in E. coli, as observed by blue colonies on agar plates containing a chromogenic substrate for AP. In contrast, both of the fusion constructs produced limited detectable levels of functional alkaline phosphatase activity in B. burgdorferi, as observed by yellow color change in liquid protein lysate containing a chromogenic substrate for AP. Development of a PhoA fusion reporter system for use in B. burgdorferi will provide a new molecular genetics tool for analyzing the topology of B. burgdorferi transmembrane proteins. These types of studies are critical for understanding the function of B. burgdorferi transport systems and may identify novel molecular approaches for the treatment of Lyme disease.
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Date Issued: 2013
Identifier: CFH0004343, ucf:44985
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004343

Title: Brief Behavioral Health Intervention Program for Patients with Stable Coronary Artery Disease.
Creator: Wiener, Chelsea, Cassisi, Jeffrey, Gupta, Rema, Paulson, Daniel, University of Central Florida
Abstract / Description: Healthy eating, physical activity, stress management, and smoking cessation are widely recognized as essential for preventing and treating coronary artery disease (CAD). Research on lifestyle programs for patients with CAD has largely focused on long-term interventions (e.g., several months to one-year in duration). Further, many studies have recruited patients immediately post-cardiac event. By contrast, evaluation of brief lifestyle interventions for stable patients treated in outpatient...
Show moreHealthy eating, physical activity, stress management, and smoking cessation are widely recognized as essential for preventing and treating coronary artery disease (CAD). Research on lifestyle programs for patients with CAD has largely focused on long-term interventions (e.g., several months to one-year in duration). Further, many studies have recruited patients immediately post-cardiac event. By contrast, evaluation of brief lifestyle interventions for stable patients treated in outpatient cardiology is lacking. The present study evaluated the feasibility, acceptability, and efficacy of a 3-session behavioral health lifestyle program for patients with stable CAD being treated in an outpatient cardiology clinic. Thirty-three patients were randomized to the Intervention Group (IG) or to Treatment as Usual (TAU). Outcome measures were assessed at Post-treatment (two-weeks after Baseline) and at 30-day Follow-up. Reliable change and parametric analyses were used to evaluate study outcomes. Results indicated that the program was both feasible and acceptable to patients, as determined by a priori criteria: over 60 percent of referred and eligible patients agreed to participate, over 75 percent of consented IG participants completed the program through 30-day Follow-up, and over 80 percent of participants reported that they would recommend the program to other patients. With regard to treatment outcomes, data from 28 participants were available. Reliable change analyses revealed that at both Post-treatment and 30-day Follow-up, significantly more IG than TAU participants exhibited an increase in self-efficacy as compared with Baseline. There were no observed between-group differences on other study measures, though repeated-measures ANOVAs were underpowered. Overall, results support the feasibility and acceptability of brief lifestyle interventions in outpatient cardiology care and highlight the role of behavioral health providers on integrated cardiology care teams in helping to increase patient self-efficacy in managing chronic disease.
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Date Issued: 2019
Identifier: CFE0007876, ucf:52770
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007876

Title: Neuromuscular junction defects in a mouse model of Charcot-Marie-Tooth disease type 2O.
Creator: Sabblah, Thywill, Kim, Yoon-Seong, King, Stephen, Bossy-Wetzel, Ella, Altomare, Deborah, University of Central Florida
Abstract / Description: Charcot Marie Tooth disease (CMT) represents the most common inheritable peripheral group of motor and sensory disorders; affecting 1 in 2500 people worldwide. Individuals with CMT experience slow progressing weakness of the muscle, atrophy, mild loss of motor coordination and in some cases loss of sensory function in the hands and feet which could ultimately affect mobility. Dynein is an essential molecular motor that functions to transport cargos in all cells. A point mutation in the dynein...
Show moreCharcot Marie Tooth disease (CMT) represents the most common inheritable peripheral group of motor and sensory disorders; affecting 1 in 2500 people worldwide. Individuals with CMT experience slow progressing weakness of the muscle, atrophy, mild loss of motor coordination and in some cases loss of sensory function in the hands and feet which could ultimately affect mobility. Dynein is an essential molecular motor that functions to transport cargos in all cells. A point mutation in the dynein heavy chain was discovered to cause CMT disease in humans, specifically CMT type 2O. We generated a knock-in mouse model bearing the same mutation(H304R) in the dynein heavy chain to study the disease. We utilized behavioral assays to determine whether our mutant mice had a phenotype linked to CMT disease. The mutant mice had motor coordination defects and reduced muscle strength compared to normal mice. To better understand the disease pathway, we obtained homozygous mutants from a heterozygous cross, and the homozygotes show even more severe deficits compared to heterozygotes. They also developed an abnormal gait which separates them from heterozygous mice. In view of the locomotor deficits observed in mutants, we examined the neuromuscular junction (NMJ) for possible impairments. We identified defects in innervation at the later stages of the study and abnormal NMJ architecture in the muscle as well. The dysmorphology of the NMJ was again worse in the homozygous mutants with reduced complexity and denervation at all the timepoints assessed. Our homozygous dynein mutants can live up to two years and therefore make the design of longitudinal studies possible. Altogether, this mouse model provides dynein researchers an opportunity to work towards establishing the link between dynein mutations, dynein dysfunction and the onset and progression of disease.
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Date Issued: 2018
Identifier: CFE0007088, ucf:51956
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007088

Title: Development and Characterization of Solid-Contact Paper-Based and Micro Ion-Selective Electrodes for Environmental Analysis.
Creator: Armas, Stephanie, Chumbimuni Torres, Karin, Beazley, Melanie, Santra, Swadeshmukul, University of Central Florida
Abstract / Description: Ion-selective electrodes (ISEs) have extensively been used for food analysis, as medical diagnostic tools, and for some environmental applications. However, ISEs are hindered by the need of a bulky reference electrode and the pre-conditioning step of the sensor, which can often be lengthy. This work will discuss how the direct addition of target analyte into the cocktail sensing membrane can circumvent the pre-conditioning step. Furthermore, the work is presented in an optimized ready-to-use...
Show moreIon-selective electrodes (ISEs) have extensively been used for food analysis, as medical diagnostic tools, and for some environmental applications. However, ISEs are hindered by the need of a bulky reference electrode and the pre-conditioning step of the sensor, which can often be lengthy. This work will discuss how the direct addition of target analyte into the cocktail sensing membrane can circumvent the pre-conditioning step. Furthermore, the work is presented in an optimized ready-to-use single strip design, where the bulky glass reference electrode (RE) is no longer needed. The bulky RE was replaced by drop casting a simple two-component mixture consisting of the co-polymer methyl methacrylate-co-decyl methacrylate and the ionic liquid 1-Ethyl-3-methylimidazolium bis (trifluoromethane sulfonyl) amide. Furthermore, this work will also highlight the benefits of solid-contact ISEs, specifically focusing on two solid- contact platforms: 1) paper-based and 2) a micro-electrode platform. Paper-based based sensors were designed to be used as a possible diagnostic tool to be implemented in undeveloped countries to monitor low levels of potassium and iodide, as model ions. The micro((&)#181;) ISEs were applied for the in-situ analysis of zinc in citrus plants as a mean to monitor and assess disease progression or therapy.
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Date Issued: 2018
Identifier: CFE0007152, ucf:52316
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007152

Title: Modeling Disease Impact of Vibrio-Phage Interactions.
Creator: Botelho, Christopher, Shuai, Zhisheng, Nevai, A, Zhang, Teng, Teter, Kenneth, University of Central Florida
Abstract / Description: Since the work of John Snow, scientists and medical professionals have understood that individuals develop cholera by means of consuming contaminated water. Despite the knowledge(&)nbsp;of cholera's route of infection, many countries have experienced and still experience endemic cholera. Cholera is caused by the Vibrio cholerae (V. cholerae) bacterium and presents with acute diarrhea and vomiting. If untreated, infected individuals may die due to dehydration. Cholera is a disease that most...
Show moreSince the work of John Snow, scientists and medical professionals have understood that individuals develop cholera by means of consuming contaminated water. Despite the knowledge(&)nbsp;of cholera's route of infection, many countries have experienced and still experience endemic cholera. Cholera is caused by the Vibrio cholerae (V. cholerae) bacterium and presents with acute diarrhea and vomiting. If untreated, infected individuals may die due to dehydration. Cholera is a disease that most commonly affects countries with poor infrastructure and water sanitation. Despite efforts to control cholera in such countries, the disease persists. One such example is Haiti which has been experiencing a cholera outbreak since 2010. While there has been much research in the field of microbiology to understand V. cholerae, there has been comparably less research in the field of mathematical biology to understand the dynamics of V. cholerae in the environment. A mathematical model of V. cholerae incorporating a phage population is coupled with a SIRS disease model to examine the impact of vibrio and phage interaction. It is shown that there might exist two endemic equilibria, besides the disease free equilibrium: one in which phage persist in the environment and one in which the phage fail to persist. Existence and stability of these equilibria are established. Disease control strategies based on vibrio and phage interactions are discussed.
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Date Issued: 2019
Identifier: CFE0007604, ucf:52544
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007604

Title: AMELIORATION OF AMYLOID BURDEN IN ADVANCED HUMAN AND MOUSE ALZHEIMER'S DISEASE BRAINS BY ORAL DELIVERY OF MYELIN BASIC PROTEIN BIOENCAPSULATED IN PLANT CELLS.
Creator: Kohli, Neha, Daniell, Henry, Kim, Yoon-Seong, Cheng, Zixi, University of Central Florida
Abstract / Description: One of the pathological hallmarks of Alzheimer's disease (AD) is the amyloid plaque deposition in aging brains by aggregation of amyloid-? (A?) peptides. In this study, the effect of chloroplast derived myelin basic protein (MBP) fused with cholera toxin subunit B (CTB) was investigated in advanced diseased stage of human and mouse AD brains. The CTB-fusion protein in chloroplasts facilitates transmucosal delivery in the gut by the natural binding ability of CTB pentameric form with GM1...
Show moreOne of the pathological hallmarks of Alzheimer's disease (AD) is the amyloid plaque deposition in aging brains by aggregation of amyloid-? (A?) peptides. In this study, the effect of chloroplast derived myelin basic protein (MBP) fused with cholera toxin subunit B (CTB) was investigated in advanced diseased stage of human and mouse AD brains. The CTB-fusion protein in chloroplasts facilitates transmucosal delivery in the gut by the natural binding ability of CTB pentameric form with GM1 receptors on the intestinal epithelium. Further, bioencapsulation of the MBP within plant cells confers protection from enzymes and acids in the digestive system. Here, 12-14 months old triple transgenic AD mice were fed with CTB-MBP bioencapsulated in the plant cells for 3 months. A reduction of 67.3% and 33.3% amyloid levels in hippocampal and cortical regions, respectively were observed by immunostaining of brain sections with anti- A? antibody. Similarly, 70% decrease in plaque number and 40% reduction of plaque intensity was observed through thioflavin S (ThS) staining that specifically stains amyloid in the AD brain. Furthermore, ex vivo 3xTg AD mice brain sections showed up to 45% reduction of ThS stained amyloid levels when incubated with enriched CTB-MBP in a concentration dependent manner. Similarly, incubation of enriched CTB-MBP with ex vivo postmortem human brain tissue sections with advanced stage of AD resulted up to 47% decrease of ThS stained amyloid plaque intensity. Lastly, lyophilization of plant material facilitates dehydration and long term storage of capsules at room temperature, in addition to increasing CTB-MBP concentration by 17 fold. These observations offer a low cost solution for treatment of even advanced stages of the AD by facilitating delivery of therapeutic proteins to central nervous system to address other neurodegenerative disease.
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Date Issued: 2012
Identifier: CFE0004564, ucf:49237
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004564

Title: Evolutionary Relationships Among Staphylococci and the Prevention of Staphylococcus aureus Nasal Colonization.
Creator: Lamers, Ryan, Cole, Alexander, Parkinson, Christopher, Chai, Xinqing, Moore, Sean, University of Central Florida
Abstract / Description: Staphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of...
Show moreStaphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of this bacterium is a known risk factor for autoinfection. The predisposition to infection by nasal carriers of S. aureus, and the ease with which strains are transferred between individuals, suggests that nasal carriage is a major vector for the transmission of virulent strains throughout the community. This hypothesis, however, has not been assessed in any great detail to identify the genetic relationships between clinical isolates of S. aureus and those strains being carried asymptomatically throughout the community. Also lacking within this field is a unified and robust estimate of phylogeny among species of Staphylococcus.Here, we report on a highly unified species phylogeny for Staphylococcus that has been derived using multilocus nucleotide data under multiple Bayesian and maximum likelihood approaches. Our findings are in general agreement with previous reports of the staphylococcal phylogeny, although we identify multiple previously unreported relationships. Regardless of methodology, strong nodal support and high topological agreement was observed with only minor variations in results between methods. Based on our phylogenetic estimates, we propose that Staphylococcus species can be evolutionarily clustered into 15 groups, and six species groups. In addition, our more defined phylogenetic analyses of S. aureus revealed strong genetic associations between both nasal carriage strains and clinical isolates. Genetic analyses of hypervariable regions from virulence genes revealed that not only do clinically relevant strains belong to identical genetic lineages as the nasal carriage isolates, but they also exhibited 100% sequence similarity within these regions. Our findings indicate that strains of S. aureus being carried asymptomatically throughout the community via nasal colonization are genetically related to those responsible for high levels of infection and mortality.Due to nasal carriage of S. aureus being a risk factor for autoinfection, standardized preoperative decolonization has become a major consideration for the prevention of nosocomial infection. Toward this end, we have identified the macrocyclic ?-defensin analogue RC-101 as a promising anti-S. aureus agent for nasal decolonization. RC-101 exhibited bactericidal effects against S. aureus in both epithelium-free systems, and ex vivo models containing human airway epithelia. Importantly, RC-101 exhibited potent anti-S. aureus activities against all strains tested, including USA300. Moreover, RC-101 significantly reduced the adherence, survival, and proliferation of S. aureus on human airway epithelia without any noted cellular toxicity or the induction of a proinflammatory response. Collectively, our findings identify RC-101 as a potential preventative of S. aureus nasal colonization.
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Date Issued: 2011
Identifier: CFE0004124, ucf:49092
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004124

Title: Psychological Responses of Fathers and Mothers to Amniocentesis.
Creator: Williamson, Nancy D., Blau, Burton I., Arts and Sciences
Abstract / Description: University of Central Florida College of Arts and Sciences Thesis; Amniocentesis is one of the most widely used prenatal diagnostic techniques for congenital disorders. It was hypothesized that the spychological responses of mothers and fathers to amniocenthesis during high-rish pregnancies would be positively correlated on scales of Symptomatology (Anxiety, Depression, Anger, and Somatic Complaints) and Well-Being (Relaxed, Contented, Friendliness, and Somatic Well-Being). It was also...
Show moreUniversity of Central Florida College of Arts and Sciences Thesis; Amniocentesis is one of the most widely used prenatal diagnostic techniques for congenital disorders. It was hypothesized that the spychological responses of mothers and fathers to amniocenthesis during high-rish pregnancies would be positively correlated on scales of Symptomatology (Anxiety, Depression, Anger, and Somatic Complaints) and Well-Being (Relaxed, Contented, Friendliness, and Somatic Well-Being). It was also hypothesized that Symptomatology would be negatively correlated with Well-Being. Nineteen couples, who were referred by their physicians, voluntarily participated in the study. Each partner completed the Symptom Questionnaire (Kellner, 1983), a self-rating scale of Symptomatology and Well-Being, in addition to the Pre-Amniocentesis and Post-Amniocentesis Questionnaires (original questionnaires developed for this study) at intervals prior to and following the procedure, while awaiting results. A Pearson product-moment correlation of the total scores revealed a positive correlation (p < 0.5) between the scores of fathers and mothers on the Symptomatology Scale, both pre- and post-amniocentesis (r = .47 and .47). In addition, there was a significant negative correlation (p < .05) between Symptomatolgy and Well-Being scores for both mothers (r = -.55 and -.60) and fathers (r = -.48 and -.74) at the pre- and post-amniocentesis periods, respectively. The hypothesis cannot be completely accepted because the positive correlation does not exist at the post-amniocentesis level. Mothers appear to experience more Symptomatology and less Well-Being than fathers at the post-amniocentesis level. The results are interpreted to suggest that fathers and mothers may both benefit from pre- and post-amniocentesis supportive intervention.
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Date Issued: 1985
Identifier: CFR0008164, ucf:53074
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFR0008164

Title: Behavioral and disease ecology of Gopher Tortoises (Gopherus polyphemus) post exclusion and relocation with a novel approach to homing determination.
Creator: Napier, Johnathan, Savage, Anna, Moore, Sean, Vonkalm, Laurence, Fedorka, Kenneth, University of Central Florida
Abstract / Description: In the wake of human expansion, relocations and the loss of habitat can be stressful to an organism, plausibly leading to population declines. The gopher tortoise (Gopherus polyphemus) is a keystone species that constructs burrows it shares with 362 commensal species. Frequent exclusions and relocations and long generation times have contributed to G. polyphemus being State-designated as Threatened in Florida. Prior studies have indicated that G. polyphemus may possess homing behavior and...
Show moreIn the wake of human expansion, relocations and the loss of habitat can be stressful to an organism, plausibly leading to population declines. The gopher tortoise (Gopherus polyphemus) is a keystone species that constructs burrows it shares with 362 commensal species. Frequent exclusions and relocations and long generation times have contributed to G. polyphemus being State-designated as Threatened in Florida. Prior studies have indicated that G. polyphemus may possess homing behavior and thus be able to counteract stressors due to relocation and exclusion. I radiotracked a cohort of G. polyphemus for 11 months following excavation, relocation, and exclusion due to a pipeline construction project. In conjunction with analyzing G. polyphemus movement patterns post-release, I developed novel statistical methodologies with broad application for movement analysis and compared them to traditional analyses. I evaluated habitat usage, burrowing behavior, movements, growth, and disease signs among control versus relocated and excluded individuals and among sexes and size classes, forming predictors for behavior and disease risk. I found statistical support that my new methodology is superior to previous statistical tests for movement analyses. I also found that G. polyphemus engages in homing behavior, but only in males. Behavioral differences were also found between the sexes with respect to burrowing behavior. Overall health, disease prevalence, and immune response were unaffected by relocation and exclusion, nor were they statistically correlated. Signs were unreliable as etiological agents, outperformed by serological detection. I determined that the Sabal Trail pipeline as a potential stressor did not affect movement behavior, homing, nor the disease/immune profile of G. polyphemus in this study.
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Date Issued: 2018
Identifier: CFE0007581, ucf:52581
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007581

Title: Analysis and Simulation for Homogeneous and Heterogeneous SIR Models.
Creator: Wilda, Joseph, Shuai, Zhisheng, Brennan, Joseph, Nevai, A, University of Central Florida
Abstract / Description: In mathematical epidemiology, disease transmission is commonly assumed to behave in accordance with the law of mass action; however, other disease incidence terms also exist in the literature. A homogeneous Susceptible-Infectious-Removed (SIR) model with a generalized incidence term is presented along with analytic and numerical results concerning effects of the generalization on the global disease dynamics. The spatial heterogeneity of the metapopulation with nonrandom directed movement...
Show moreIn mathematical epidemiology, disease transmission is commonly assumed to behave in accordance with the law of mass action; however, other disease incidence terms also exist in the literature. A homogeneous Susceptible-Infectious-Removed (SIR) model with a generalized incidence term is presented along with analytic and numerical results concerning effects of the generalization on the global disease dynamics. The spatial heterogeneity of the metapopulation with nonrandom directed movement between populations is incorporated into a heterogeneous SIR model with nonlinear incidence. The analysis of the combined effects of the spatial heterogeneity and nonlinear incidence on the disease dynamics of our model is presented along with supporting simulations. New global stability results are established for the heterogeneous model utilizing a graph-theoretic approach and Lyapunov functions. Numerical simulations confirm nonlinear incidence gives raise to rich dynamics such as synchronization and phase-lock oscillations.
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Date Issued: 2015
Identifier: CFE0005906, ucf:50872
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005906

Title: Evaluation of Intestinal Microbial Diversity and a New Antibiotic Regimen in Crohn's Disease Patients.
Creator: Alcedo, Karel, Naser, Saleh, Cheng, Zixi, Siddiqi, Shadab, University of Central Florida
Abstract / Description: Crohn's disease (CD) is a chronic granulomatous inflammatory bowel disease involving Mycobacterium avium subspecies paratuberculosis (MAP). Other microorganisms such as adherent-invasive Escherichia coli (AIEC) have also been proposed in CD association. To date, only one study investigated both MAP and AIEC simultaneously using peripheral blood but not in affected intestinal tissues. A standardized and effective antibiotic therapy against MAP and/or AIEC is needed for better treatment. Three...
Show moreCrohn's disease (CD) is a chronic granulomatous inflammatory bowel disease involving Mycobacterium avium subspecies paratuberculosis (MAP). Other microorganisms such as adherent-invasive Escherichia coli (AIEC) have also been proposed in CD association. To date, only one study investigated both MAP and AIEC simultaneously using peripheral blood but not in affected intestinal tissues. A standardized and effective antibiotic therapy against MAP and/or AIEC is needed for better treatment. Three antibiotic drugs (-) Clarithromycin (CLA), Rifabutin (RIF), and Clofazimine (CLO) have been used to treat CD patients suspected with MAP infection. However, the outcome has been controversial. The treatment dosage is high, the duration is long, and the reported drug side effects resulted in patient non-compliance; therefore, a lower and effective drug dosage is needed. In this study, we developed two aims 1) to evaluate RHB 104, a drug formula comprised of low dosages of CLA, RIF, and CLO, against clinical MAP strains in-vitro using fluorescence quenching method, and 2) to develop a fluorescence in-situ hybridization method to detect both MAP and AIEC simultaneously in intestinal tissues of CD patients. A total of 16 clinical MAP strains and 19 non-MAP strains were tested against varied concentrations of RHB 104, CLA, RIF, and CLO. Although the MIC for all drugs ranged between 0.5-20 ?g/ml, the MIC for RHB 104 was significantly lower against most MAP strains. The effect of RHB 104 against MAP was bactericidal. Unlike RHB-104 formula, CLA, CLO, and RIF dosage similar to those in RHB-104 did not inhibit MAP growth when trialed individually and in dual-drug combinations. The data illustrated the presence of synergistic anti-MAP activity of low dosage of the three antibiotics in RHB-104. We also developed a rapid and sensitive multicolor in-situ hybridization technique that can detect MAP and AIEC using tagged-oligonucleotide probes. Non-pathogenic Escherichia coli (npEC) was used as a control for the study. Specifically, cultured MAP and npEC were fixed and hybridized with MAP488 and EC647 probes, respectively. Confocal laser scanning microscope (CLSM) revealed specific signals at 488nm for MAP and 647nm for npEC, indicating probe binding to each bacteria. This was confirmed with hybridization of MAP with EC647 and npEC with MAP488 resulting in absence of signals. Intestinal tissue samples from 9 CD patients were then analyzed using our technique. Preliminary data indicated positive results in 6/6 samples for MAP, 6/6 for npEC, 3/3 for AIEC, and 2/2 for both MAP and AIEC with MAP being more dominant. This protocol shortened the FISH procedure from multiple days to short-hours. The protocol allows the investigation of more than one pathogen simultaneously in the same clinical sample. A quantitative measurement of the signals is needed.
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Date Issued: 2015
Identifier: CFE0005917, ucf:50831
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005917

Title: Prehabilitation (Prehab): Prevention in Motion.
Creator: Russell, Billie, Sole, Mary Lou, Chase, Susan, Damato-Kubiet, Leslee, Gammonley, Denise, University of Central Florida
Abstract / Description: ABSTRACTCardiovascular disease is the leading cause of death for U.S. adults. It adds greater than $100 billion to U.S. health care costs annually. Rates of morbidity, mortality, and economic burden of the disease could be dramatically reduced with improvements in sedentary behaviors among adults with coronary artery disease (CAD). A regular commitment to moderate physical activity can reduce ischemic heart events up to 50%. Although the benefits of physical activity are well-known for...
Show moreABSTRACTCardiovascular disease is the leading cause of death for U.S. adults. It adds greater than $100 billion to U.S. health care costs annually. Rates of morbidity, mortality, and economic burden of the disease could be dramatically reduced with improvements in sedentary behaviors among adults with coronary artery disease (CAD). A regular commitment to moderate physical activity can reduce ischemic heart events up to 50%. Although the benefits of physical activity are well-known for individuals with coronary artery disease, an estimated 70% of this population remains relatively sedentary. Hospital-based cardiac rehabilitation programs are the single secondary prevention option offered to improve physical activity habits in persons with CAD. Although effective, cardiac rehabilitation is inaccessible for the majority of CAD sufferers and is offered only after an acute cardiac event. Different from rehabilitation, prehabilitation (prehab) programs use physical activity as a means to deter a worsening condition or prevent injury before an acute event occurs. These programs have proved successful in other areas of medicine but there are currently no such secondary prevention programs available for stable persons with CAD in the U.S. A home-based prehab program could help adults with CAD establish improved physical activity habits and circumvent many of the barriers associated with admission and attendance of a hospital-based cardiac rehabilitation program. Researchers have indicated that self-efficacy is key to initiation and sustentation of a regular physical activity habit, regardless of the physical activity program that one attends. These habits are more likely to last when participants receive self-efficacy based support for an average of 66 days. The purpose of this study was to determine if a nurse-practitioner-led, home-based, prehab program could assist adults with CAD to improve and maintain increased physical activity habits and levels of self-efficacy for physical activity. The five primary facilitators of self-efficacy were used to devise a 10-week prehab program. A convenience sample of 54 adults with diagnosed CAD was recruited from cardiology practices in St. Johns County, Florida. The research population was 68.5% (n=37) male, 88.9% (n=48) Caucasian, and 74% (n=40) married with a mean age of 68.57 years. Participants attended a 90-minute prehab class which offered health education and group discussion of barriers and goals for regular physical activity. Following the class, participants were contacted weekly for 10-weeks to discuss goal progress, assist in circumventing barriers, and revise physical activity goals as needed. After the 10-week call period, participants were contacted 30-days later to assess for physical activity habit maintenance and any sustained benefit in self-efficacy for physical activity. Self-efficacy for exercise was measured before the prehab class, after the prehab class, and after the 10-week intervention period using the Short Self-Efficacy Expectations scale (SSEE), Multidimensional Outcomes Expectations for Exercise Scale (MOEES), and the Barriers Self-Efficacy Scale (BARSE). All baseline measures of self-efficacy (MOEES, BARSE, SSEE) improved significantly immediately following the prehab class. Baseline physical outcome expectations of the MOEES (m=21.87, sd=4.67), self-evaluative outcome expectations of the MOEES (m=16.70, sd=4.15) and SSEE (m=12.75, sd=4.02) remained significantly improved after the 10-week intervention period (p(<).05). At the 10-week assessment, mean significant self-efficacy scores were 24.39 (sd=1.26, p(<).01) for physical outcome expectations, 18.39 (sd=2.27, p(<).02) for self-evaluative outcome expectations, and 15.06, (sd=3.25, p(<).001) for SSEE. The SSEE was reassessed 30-days after the study and remained significantly improved compared to baseline (m=15.65, sd=3.42, p(<).01). Qualitative data collection coincided with the quantitative self-efficacy findings. Participants reported satisfaction with physical activity goal attainment and increased confidence to continue with a regular physical activity plan. The Godin Leisure-Time Exercise Questionnaire (GLTEQ) was used to assess activity levels at baseline, during each weekly phone call, at the end of 10-weeks, and 30-days after the study. Repeated-measures ANOVA (F (2,90) = 21.86, p(<).001) revealed that participant's baseline physical activity volume measured by GLTEQ (m=18.39, sd= 16.93) improved significantly after 10 weeks in the prehab study (m=41.10, sd=24.11, p(<).001) and remained significantly improved when re-measured 30-days after the study (m=39.02, sd=21.87, p(<).001). Qualitative data concurred with quantitative data with participants reporting physical activity habit formation and maintenance of self-regulatory skills. Qualitative data also demonstrated that participants in prehab experienced very similar facilitators and barriers compared to other adults with CAD attempting an exercise program. In summary, the prehab study findings coincided with other research findings in this area. Self-efficacy based support can assist individuals with CAD to improve and maintain physical activity habits. The ease of the intervention likely contributed to lower cost and attrition rates (7%) compared to hospital-based cardiac rehabilitation programs. Although more research is needed, study findings suggest that a nurse-practitioner-led, home-based program could be a viable secondary prevention strategy for stable adults with CAD. This should be considered for the future given that even modest improvements in physical activity can substantially reduce all-cause mortality in this population.
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Date Issued: 2016
Identifier: CFE0006384, ucf:51530
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006384

Title: Geolocation of Diseased Leaves in Strawberry Orchards for a Custom-Designed Octorotor.
Creator: Garcia, Christian, Xu, Yunjun, Lin, Kuo-Chi, Kauffman, Jeffrey, University of Central Florida
Abstract / Description: In recent years, technological advances have shown a strive for more automated processes in agriculture, as seem with the use of unmanned aerial vehicles (UAVs) with onboard sensors in many applications, including disease detection and yield prediction. In this thesis, an octorotor UAV is presented that was designed, built, and flight tested, with features that are custom-designed for strawberry orchard disease detection. To further automate the disease scouting operation, geolocation, or the...
Show moreIn recent years, technological advances have shown a strive for more automated processes in agriculture, as seem with the use of unmanned aerial vehicles (UAVs) with onboard sensors in many applications, including disease detection and yield prediction. In this thesis, an octorotor UAV is presented that was designed, built, and flight tested, with features that are custom-designed for strawberry orchard disease detection. To further automate the disease scouting operation, geolocation, or the process of determining global position coordinates of identified diseased regions based on images taken, is investigated. A Kalman filter is designed, based on a linear measurement model derived from an orthographic projection method, to estimate the target position. Simulation, as well as an ad-hoc experiment using flight data, is performed to compare this filter to the extended Kalman filter (EKF), which is based on the commonly used perspective projection method. The filter is embedded onto a CPU board for real-time use aboard the octorotor UAV, and the algorithm structure for this process is presented. In the later part of the thesis, a probabilistic data association method is used, jointly with a proposed logic-based measurement-to-target correlation method, to analyze measurements of different target sources and is incorporated into the Kalman filter. A simulation and an ad-hoc experiment, using video and flight data acquired aboard the octorotor UAV with a gimballed camera in hover flight, are performed to demonstrate the effectiveness of the algorithm and UAV platform.
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Date Issued: 2016
Identifier: CFE0006305, ucf:51597
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006305

Title: Implication of alpha-synuclein transcriptional regulation and mutagenesis in the pathogenesis of sporadic Parkinson's disease.
Creator: Basu, Sambuddha, Kim, Yoon-Seong, King, Stephen, Estevez, Alvaro, Altomare, Deborah, University of Central Florida
Abstract / Description: Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by selective loss of dopaminergic neurons (DA neurons) from the substantia nigra (SN) of the mid-brain. PD is classically associated with cytoplasmic inclusion of aggregated proteins called Lewy bodies. alpha-synuclein (?-SYN) coded by the gene SNCA, is one of the major components of Lewy body and neurite along with several other proteins like ubiquitin, neurofilament to name a few. PD is broadly categorized...
Show moreParkinson's disease (PD) is an age-related neurodegenerative disorder characterized by selective loss of dopaminergic neurons (DA neurons) from the substantia nigra (SN) of the mid-brain. PD is classically associated with cytoplasmic inclusion of aggregated proteins called Lewy bodies. alpha-synuclein (?-SYN) coded by the gene SNCA, is one of the major components of Lewy body and neurite along with several other proteins like ubiquitin, neurofilament to name a few. PD is broadly categorized into two groups based on their incidence of occurrence. First is the familial form that occurs due to known genetic aberrations like mutation, gene duplication/triplication in important PD associated gene like SNCA which in turn leads to early-onset PD (EOPD). Second is the late-onset idiopathic or sporadic form, whose origin of occurrence is often unknown. Interestingly, more than 90%-95% of reported PD cases belong to the latter category. Although, the familial and the idiopathic form of PD are different in their respective cause of occurrence, aggregation of ?-SYN into Lewy body is a common pathologic hallmark seen in both. Aggregation of ?-SYN in turn is strongly implicated by the transcriptional upregulation of the gene as seen in both familial forms as well as idiopathic forms. In this thesis, we first describe the designing and functioning of a novel tool to monitor real-time SNCA transcription in Human Embryonic Kidney (HEK) 293T cells. In the next part, we shed light into a novel transcriptional deregulation phenomenon called transcriptional mutagenesis, which leads to accelerated aggregation of ?-SYN as seen in sporadic PD. In brief, the focus of this work is to highlight the importance of transcriptional regulation of SNCA gene, through development of a tool and a mechanism affecting the fidelity of transcription under pathologic condition. In the first study, we developed a stable cell line in HEK293T cells in which ?-SYN was tagged with Nanoluc luciferase reporter using CRISPR/Cas9-mediated genome editing. Nanoluc is a small stable reporter of 19KDa size, which is 150 fold brighter compared to firefly and Renilla luciferase, thus making it a very good candidate for endogenous monitoring of gene regulations. We successfully integrated the Nanoluc at the 3'end of the SNCA before the stop codon. Successful integration of the Nanoluc was demonstrated by the fusion ?-SYN protein containing the Nanoluc. This allowed efficient monitoring of ?-SYN transcription keeping its native epigenetic landscape unperturbed which was otherwise difficult using exogenous luciferase reporter assays. The Nanoluc activity monitored by a simple two-step assay faithfully reflected the endogenous deregulation of SNCA following treatment with different drugs including epigenetic modulators and dopamine which were already known to up-regulate SNCA transcription. Interestingly, use of exogenous promoter-reporter assays (firefly luciferase assays) failed to reproduce the similar outcomes. In fact, exogenous system showed contradictory results in terms of the ?-SYN regulation which aroused from spurious effects of the drug on the reporter system. To our knowledge, this is the first report showing endogenous monitoring of ?-SYN transcription, thus making it an efficient drug screening tool that can be very effectively used for therapeutic intervention in PD. In the next study, we investigated the effect of oxidative DNA damage in the form of 8-hydroxy-2-deoxyguanosine (8-oxodG, oxidized guanine) on aggregation of ?-SYN through a novel phenomenon called transcriptional mutagenesis. It is already known that 8-oxodG is repaired by a specific component of the base excision repair machinery of the cell called 8-oxodG-DNA glycosylase 1 (OGG1). If left unrepaired, 8-oxodG can lead to misincorporation of adenine instead of cytosine (C?A transversion) in the synthesized mRNA during transcription for post-mitotic cells like neurons. This phenomenon is called transcriptional mutagenesis (TM) and can generate novel mutant variants of any functional protein. ?-SYN, which is implicated very strongly in the pathogenesis of PD, has been shown to become aggregation prone by specific point mutation. Previous studies have shown that certain point mutations can make ?-SYN more prone to aggregation and can affect the aggregation of the parental protein as a template directed misfolding mechanism. We used SNCA as a model gene and predicted the generation of forty-three different positions that can be mutated by the TM event. We investigated the generation of three out of the forty-three possible TM mutants from the SN of post-mortem PD and age-matched control brain cohorts based on their potential to aggregate as predicted by aggregation prediction software TANGO. The three mutants were Serine42Tyrosine (S42Y), Alanine53Glutamate (A53E) and Serine129Tyrosine (S129Y). We confirmed the presence of all the three mutant ?-SYN (S42Y, A53E and S129Y) in SNCA mRNA from the SN of human post-mortem PD brain using a PCR-based detection technique. As expected, analysis of the overall distribution of the three mutants showed a higher rate of occurance in the PD cohort compared to the age-matched controls. Sequencing genomic DNA of the same PD sample from the same region of ?-SYN revealed no mutations at the genomic DNA level, thus implying its generation during transcription. Although we could detect the presence of S42Y, A53E and S129Y ?-SYN in the cohort of PD patients, we focused to analyse the contribution of S42Y towards the aggregation of wild-type (WT) ?-SYN parental protein based on its higher potential to aggregate. By using cell-based biochemical and recombinant protein assays, we saw that S42Y-?-SYN can accelerate the aggregation process involving the WT protein even when present in significantly lower proportion (100 times less compared to the WT). Importantly, we developed antibody to specifically detect the S42Y ?-SYN in human PD cohort. Immunohistochemical analysis of serial post-mortem PD brain sections with Hematoxylin and Eosin staining (H(&)E), anti-ubiquitin staining and anti-S42Y ?-SYN staining, showed Lewy bodies that stained positively with S42Y ? -SYN. To our knowledge, this is the first report about TM related mutations of ?-SYN in Parkinson's disease and their role in the pathogenesis.
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Date Issued: 2017
Identifier: CFE0006719, ucf:51882
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006719

Title: Cerium oxide nanoparticles act as a unique catalyst and scavenge nitric oxide and peroxynitrite and decrease RNS in vitro and in vivo.
Creator: Dowding, Janet, Self, William, Bossy-Wetzel, Ella, Zervos, Antonis, Seal, Sudipta, Santra, Swadeshmukul, University of Central Florida
Abstract / Description: Cerium oxide nanoparticles (CeO2 NPs)(nanoceria) have been shown to possess a substantial oxygen storage capacity via the interchangeable surface reduction and oxidation of cerium atoms, cycling between the Ce4+ and Ce3+ redox states. Reduction of Ce4+ to Ce3+ causes oxygen vacancies or defects on the surface of the crystalline lattice structure of the particles, generating a cage for redox reactions to occur. The study of the chemical and biological properties of CeO2 NPs has expanded...
Show moreCerium oxide nanoparticles (CeO2 NPs)(nanoceria) have been shown to possess a substantial oxygen storage capacity via the interchangeable surface reduction and oxidation of cerium atoms, cycling between the Ce4+ and Ce3+ redox states. Reduction of Ce4+ to Ce3+ causes oxygen vacancies or defects on the surface of the crystalline lattice structure of the particles, generating a cage for redox reactions to occur. The study of the chemical and biological properties of CeO2 NPs has expanded recently, and the methods used to synthesize these materials are also quite diverse. This has led to a plethora of studies describing various preparations of CeO2 NPs for potential use in both industry and for biomedical research. Our own work has centered on studies that measure the ability of water-based CeO2 NPs materials to reduce reactive oxygen and nitrogen species in biological systems, and correlating changes in surface chemistry and charge to the catalytic nature of the particles. The application in experimental and biomedical research of CeO2 NPs began with the discovery that water-based cerium oxide nanoparticles could act as superoxide dismutase mimetics followed by their ability to reduce hydrogen dioxide similar to catalase. While their ROS scavenging ability was well established, their ability to interact with specific RNS species, specifically nitric oxide (NO) or peroxynitrite (ONOO-) was not known. The studies described in this dissertation focus on the study of RNS and cerium oxide nanoparticles.Our in vitro work revealed that CeO2 NPs that have higher levels of reduced cerium sites (3+) at the surface (which are effective SOD mimetics) are also capable of accelerating the decay of peroxynitrite in vitro. In contrast, CeO2 NPs that have fewer reduced cerium sites at the particle surface (which also exhibit better catalase mimetic activity) have NO scavenging capabilities as well as some reactivity with peroxynitrite. Our studies and many others have shown cerium oxide nanoparticles can reduce ROS and RNS in cell culture or animal models. The accumulation of ROS and RNS is a common feature of many diseases including Alzheimer's disease (AD). Testing our CeO2 NPS in cortical neurons, we used addition of A? peptide as an AD model system. CeO2 NPs delayed A?-induced mitochondrial fragmentation and neuronal cell death. When mitochondrial ROS levels are increased, mitochondrial fission is activated by DRP1 S616 phosphorylation. Specifically, our studies showed the reduction of phosphorylated DRP1 S616 in the presence of CeO2 NPs. Results from our studies have begun to unravel the molecule mechanism behind the catalytic nature of how CeO2 NPs reduce ROS/RNS in biological systems and represents an important step forward to test the potential neuroprotective effects of CeO2 NPs in model systems of AD.A plethora of studies describing various preparations of CeO2 NPs for potential use in both industry and for biomedical research have been described in the past five years. It has become apparent that the outcomes of CeO2 NPs exposure can vary as much as the synthesis methods and cell types tested. In an effort to understand the disparity in reports describing the toxicity or protective effects of exposure to CeO2 NPs, we compared CeO2 NPs synthesized by three different methods; H2O2 (CNP1), NH4OH (CNP2) or hexamethylenetetramine (HMT-CNP1). Exposure to HMT-CNP1 led to reduced metabolic activity (MTT) at a 10-fold lower concentration than CNP1 or CNP2 and surprisingly, exposure to HMT-CNP1 led to substantial decreases in the ATP levels. Mechanistic studies revealed that HMT-CNP1 and CNP2 exhibited robust ATPase (phosphatase) activity, whereas CNP1 lacked ATPase activity. HMT-CNP1 were taken up into HUVECs far more efficiently than the other preparations of CeO2 NPs. Taken together, these results suggest the combination of increased uptake and ATPase activity of HMT-CNP1 may underlie the mechanism of the toxicity of this preparation of CeO2 NPs, and may suggest ATPase activity should be considered when synthesizing CeO2 NPs for use in biomedical applications. Overall the studies have uncovered two new catalytic activities for water-based CeO2 NPs (NO scavenging and accelerated decay of peroxynitrite), demonstrated their ability to reduce RNS in an AD cell culture model as well as identifying a catalytic activity (phosphatase) that may underlie the observed toxicity of CeO2 NPs reported in other studies.
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Date Issued: 2012
Identifier: CFE0004782, ucf:49783
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004782

Title: Host and Bacterial Determinants of Staphylococcus aureus Nasal Colonization in Humans.
Creator: Muthukrishnan, Gowrishankar, Cole, Alexander, Moore, Sean, Self, William, Parkinson, Christopher, University of Central Florida
Abstract / Description: Staphylococcus aureus (SA), an opportunistic pathogen colonizing the anterior nares in approximately 30% of the human population, causes severe hospital-associated and community-acquired infections. SA nasal carriage plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage...
Show moreStaphylococcus aureus (SA), an opportunistic pathogen colonizing the anterior nares in approximately 30% of the human population, causes severe hospital-associated and community-acquired infections. SA nasal carriage plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage dynamics among a diverse population and determining factors responsible for SA nasal carriage have become major imperatives.Here, we report on an extensive longitudinal monitoring of SA nasal carriage in 109 healthy individuals over a period of up to three years to assess nasal carriage dynamics. Phylogenetic analyses of SA housekeeping genes and hypervariable virulence genes revealed that not only were SA strains colonizing intermittent and persistent nasal carriers genetically similar, but no preferential colonization of specific SA strains in these carriers was observed over time. These results indicated that other non-SA factors could be involved in determining specific carriage states. Therefore, to elucidate host responses during SA nasal carriage, we performed human SA nasal recolonization in a subset of SA nasal carriers within our cohort. In these studies, SA colonization levels were determined, and nasal secretions were collected and analyzed for host immune factors responsible for SA nasal carriage. Interestingly, we observed that stimulation of host immune responses lead to clearance of SA while sustained SA colonization was observed in hosts that did not mount a response during carriage. Further, analysis of nasal secretions from hosts revealed that proinflammatory cytokines and chemokines were significantly induced during SA nasal clearance suggesting that innate immune effectors influence carriage.SA utilizes a repertoire of surface and secreted proteins to evade host immune response and successfully colonize the nose. Analysis of the most abundant immunoevasive proteins in the exoproteome of SA nasal carrier strains revealed that expression levels of Staphylococcal protein A (SPA) produced by SA nasal carrier strains in vitro corresponded to the level of persistence of SA in the human nose. To determine if SPA is involved in modulating the host's response to SA colonization, a subset of participants in our cohort was nasally recolonized with equal concentrations of both wild-type (WT) and spa-disrupted (?spa) autologous strains of SA. Interestingly, ?spa strains were eliminated from the nares significantly faster than WT when the host mounted an immune response, suggesting that the immunoevasive role of SPA is a determinant of carriage persistence. Collectively, this report augments our understanding of SA nasal carriage dynamics, in addition to identifying important host and microbial determinants that influence SA nasal colonization in humans. Better understanding of this phenomenon can lead to improved preventative strategies to thwart carriage-associated SA infections.
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Date Issued: 2014
Identifier: CFE0005673, ucf:50173
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005673

Title: In Vitro Characterization of Unmodified and Pyroglutamylated Alzheimer's Amyloid beta peptide.
Creator: Matos, Jason, Tatulian, Suren, Teter, Kenneth, Davidson, Victor, University of Central Florida
Abstract / Description: Plaques of amyloid ? peptide (A?) are a hallmark trait of Alzheimer's disease (AD). However, the precise role of A? aggregates is not well understood. Recent studies have identified that naturally occurring N-terminal truncation and pyroglutamylation of A? significantly increases its neurotoxicity by an unknown mechanism. Content of pyroglutamylated A? (pE-A?) in AD brains has been shown to reach up to 50% of total A?. Modified pE-A? co-aggregates with A? by a seeding mechanism and forms...
Show morePlaques of amyloid ? peptide (A?) are a hallmark trait of Alzheimer's disease (AD). However, the precise role of A? aggregates is not well understood. Recent studies have identified that naturally occurring N-terminal truncation and pyroglutamylation of A? significantly increases its neurotoxicity by an unknown mechanism. Content of pyroglutamylated A? (pE-A?) in AD brains has been shown to reach up to 50% of total A?. Modified pE-A? co-aggregates with A? by a seeding mechanism and forms structurally distinct and highly toxic oligomers. We studied structural transitions of the full-length A?1-42, its pyroglutamylated form A?pE3-42, their 9:1 (A?1-42/A?pE3-42) and 1:1 molar combinations. Transmission electron microscopy was used to directly visualize the fibrils of the samples in a buffer mimicking physiological environment. Atomic force microscopy measurements were done to determine rate of second nucleation events in fibrils. Thioflavin-T fluorescence indicated that low ionic strength suppressed the aggregation of A?pE3-42 but promoted that of A?1-42, suggesting different paths of fibrillogenesis of unmodified A? and pE-A?. Interestingly, A?pE3-42 at only 10% significantly facilitated the fibrillization of A?1-42 at near physiological ionic strength but had little effect at low salt. Circular dichroism and Fourier transform infrared (FTIR) spectroscopy were used to characterize the structural transitions during fibrillogenesis. In aqueous buffer, both unmodified A? and pE-A? peptides adopted parallel intermolecular ?-structure. Interestingly, A?pE3-42 contained lower ?-sheet content than 13C-A?1-42, while retaining significantly larger fractions of ?-helical and turn structures. Structural details of A? and pE-A? combinations were unveiled by isotope-edited FTIR spectroscopy, using 13C-labeled A?1-42 and unlabeled A?pE3-42. When exposed to environmental humidity, A?pE3-42 not only maintained an increased fraction of ?-helix but also was able to reverse 13C-A?1-42 ?-sheet structure. These data provide a novel structural mechanism for pE-A? hypertoxicity; pE-A? undergoes fasternucleation due to its increased hydrophobicity, thus promoting formation of smaller, hypertoxic oligomers of partial ?-helical structure.
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Date Issued: 2014
Identifier: CFE0005378, ucf:50465
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005378

Title: Genetic and biochemical characterization of the roles of two putative purine transporters in the infectious cycle of Borrelia burgdorferi.
Creator: Jain, Sunny, Jewett, Mollie, Naser, Saleh, Self, William, Vonkalm, Laurence, University of Central Florida
Abstract / Description: Lyme disease, the most common tick borne disease in United States, is caused by the bacterial pathogen Borrelia burgdorferi. In nature, B. burgdorferi exists in an enzootic infectious cycle between an arthropod vector and mammalian hosts. Identification and characterization of the genes essential for B. burgdorferi survival throughout its infectious cycle is an important step toward understanding the molecular mechanisms involved in B. burgdorferi pathogenesis. B. burgdorferi contains a small...
Show moreLyme disease, the most common tick borne disease in United States, is caused by the bacterial pathogen Borrelia burgdorferi. In nature, B. burgdorferi exists in an enzootic infectious cycle between an arthropod vector and mammalian hosts. Identification and characterization of the genes essential for B. burgdorferi survival throughout its infectious cycle is an important step toward understanding the molecular mechanisms involved in B. burgdorferi pathogenesis. B. burgdorferi contains a small genome, which lacks the genes encoding for the enzymes required for de novo synthesis of amino acids, fatty acids and nucleic acid precursors. Therefore, the spirochete is dependent upon the host environment for the uptake of these essential nutrients. Purines are required for the synthesis of nucleotides for the biosynthesis of DNA and RNA. Due to the lack of de novo purine synthesis, the ability of B. burgdorferi to salvage purines from its host environments is essential to its survival. While the enzymes critical for the B. burgdorferi purine salvage pathway are known, the transporters involved in the uptake of purines from the host environments are not. The work in this thesis is focused on identification of the genes encoding purine permeases in B. burgdorferi and genetic and biochemical characterization of their functions in the infectious cycle of B. burgdorferi. Here, we demonstrate that homologous genes bbb22 and bbb23 present on circular plasmid 26 encode for purine permeases, which are important for transport of hypoxanthine, adenine and guanine. Furthermore, genes bbb22-23 together were essential for B. burgdorferi infection in mice. BBB22 and BBB23 share 78% amino acid identify. And although, individually both BBB22 and BBB23 were found to be capable of purine transport, BBB22 has higher affinity for hypoxanthine and adenine compared to BBB23. Moreover, the bbb22 gene alone was sufficient to restore mouse infectivity to spirochetes lacking both bbb22 and bbb23, whereas, bbb23 was not. Nonetheless, the spirochete loads in the tissues of mice infected with B. burgdorferi carrying bbb22 alone were significantly reduced compared to B. burgdorferi carrying both bbb22 and bbb23, demonstrating the importance of the two genes together for the spirochetes to achieve wild type levels of infection. In ticks, genes bbb22 and bbb23 were dispensable for spirochete survival but contributed to spirochete replication in fed larvae. The replication of spirochetes lacking bbb22-23 in larval ticks was restored to wild type levels by the reintroduction of the low affinity purine transporter encoded by bbb23 alone. Overall, we have identified a purine transport system in B. burgdorferi, which is essential for spirochete survival in the mammalian host and contributes to spirochete replication in the tick vector. As B. burgdorferi lacks typical virulence factors and toxins, these studies highlight the critical role of physiological functions in the virulence of this pathogen. Moreover, the BBB22-23 in vivo essential transport system may represent a novel therapeutic target to deliver antimicrobial drugs to treat Lyme disease.
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Date Issued: 2014
Identifier: CFE0005511, ucf:50303
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005511

Title: A mathematical model for feral cat ecology with application to disease.
Creator: Sharpe, Jeff, Nevai, A, Shuai, Zhisheng, Qi, Yuanwei, Quintana-Ascencio, Pedro, University of Central Florida
Abstract / Description: We formulate and analyze a mathematical model for feral cats living in an isolated colony. The model contains compartments for kittens, adult females and adult males. Kittens are born at a rate proportional to the population of adult females and mature at equal rates into adult females and adult males. Adults compete with each other in a manner analogous to Lotka-Volterra competition. This competition comes in four forms, classified by gender. Native house cats, and their effects are also...
Show moreWe formulate and analyze a mathematical model for feral cats living in an isolated colony. The model contains compartments for kittens, adult females and adult males. Kittens are born at a rate proportional to the population of adult females and mature at equal rates into adult females and adult males. Adults compete with each other in a manner analogous to Lotka-Volterra competition. This competition comes in four forms, classified by gender. Native house cats, and their effects are also considered, including additional competition and abandonment into the feral population. Control measures are also modeled in the form of per-capita removal rates. We compute the net reproduction number (R_0) for the colony and consider its influence. In the absence of abandonment, if R_0(>)1, the population always persists at a positive equilibrium and if R_0 (<)= 1, the population always tends toward local extinction. This work will be referred to as the core model.The model is then expanded to include a set of colonies (patches) such as those in the core model (this time neglecting the effect of abandonment). Adult females and kittens remain in their native patch while adult males spend a fixed proportion of their time in each patch. Adult females experience competition from both the adult females living in the same patch as well as the visiting adult males. The proportion of adult males in patch j suffer competition from both adult females resident to that patch as well the proportion of adult males also in the patch. We formulate a net reproduction number for each patch (a patch reproduction number) R_j. If R_j(>)1 for at least one patch, then the collective population always persists at some nontrivial (but possibly semitrivial) steady state. We consider the number of possible steady states and their properties. This work will be referred to as the patch model.Finally, the core model is expanded to include the introduction of the feline leukemia virus. Since this disease has many modes of transmission, each of which depends on the host's gender and life-stage, we regard this as a model disease. A basic reproduction number R_0 for the disease is defined and analyzed. Vaccination terms are included and their role in disease propagation is analyzed. Necessary and sufficient conditions are given under which the disease-free equilibrium is stable.
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Date Issued: 2016
Identifier: CFE0006502, ucf:51389
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006502

Crohn's Disease (6)	+ -
Crohn's disease (6)	+ -
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Alzheimer's disease (4)	+ -
Lyme disease (4)	+ -

MAP (4)	+ -
Borrelia burgdorferi (3)	+ -
Infectious disease (3)	+ -
Parkinson's disease (3)	+ -
Alpha-Synuclein (2)	+ -
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Paleopathology (2)	+ -
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cardiovascular disease (2)	+ -
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dialysis (2)	+ -
disease (2)	+ -
heart disease (2)	+ -
infectious diseases (2)	+ -
network (2)	+ -
ordinary differential equations (2)	+ -
secondary prevention (2)	+ -
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University of Central Florida (74)	+ -
Naser, Saleh (13)	+ -
Moore, Sean (7)	+ -
Shuai, Zhisheng (6)	+ -
Kim, Yoon-Seong (5)	+ -

Self, William (5)	+ -
Altomare, Deborah (4)	+ -
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