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- Title
- POSSIBLE USE OF P20 ANTIGEN IN SERODIAGNOSIS OF INFLAMMATORY BOWEL DISEASE.
- Creator
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Yang, ShinChieh, Naser, Saleh, University of Central Florida
- Abstract / Description
-
Crohn's disease (CD) is an idiopathic, chronic, relapsing inflammatory disorder, which is most commonly involved terminal ileum and colon. The incidence and prevalence of CD has dramatically increased during the last 50 years; however, the etiology and mechanism of this disorder remain unveiled. Besides genetic susceptibility, recent integrated researches investigated the role of environmental triggers such as microflora, measles viruses and mycobacteria in the pathogenesis of CD. The...
Show moreCrohn's disease (CD) is an idiopathic, chronic, relapsing inflammatory disorder, which is most commonly involved terminal ileum and colon. The incidence and prevalence of CD has dramatically increased during the last 50 years; however, the etiology and mechanism of this disorder remain unveiled. Besides genetic susceptibility, recent integrated researches investigated the role of environmental triggers such as microflora, measles viruses and mycobacteria in the pathogenesis of CD. The association between M. avium subsp paratuberculosis (MAP) and CD has been heightened because of clinical resemblance to Johne's disease (JD), a granulomatous enteritis in ruminants caused by MAP. Isolation of MAP from tissue and milk samples from CD patients and from commercial pasteurized milk and dairy products from JD-infected animals implies a possible re-classification of CD as zoonotic disorder. Clinical signs and symptoms of CD are often non-specific and a challenge to distinguish it from other disorders. Current methods for inflammatory bowel disease diagnosis, especially for CD are highly invasive, distressing and expensive. In this study, the recombinant clone pB11 containing 1.1 kb insert, identified from a MAP genomic library constructed in E. coli, expressed a 20 kDa (p20) antigen encoded on 549 bp partial MAP gene with an ORF cloned in frame within pBAD/His cloning vector. Immunoreactivity of p20 was confirmed by Immunoblot. Purified p20 antigen was then used in the development of an enzyme-linked immunosorbent assay (ELISA) for possible serodiagnosis of Inflammatory Bowel Disease (IBD) associated with MAP infection. All variables associated with ELISA test with regard to concentrations, washes and incubations were optimized using hyper immune rabbit t-anti-MAP polyclonal IgG antibodies and sera from CD and non-CD subjects. The cut-off value for positive response was established as 0.3 following the analysis of statistically formulated samples from normal and non-CD subjects. The developed ELISA test was then used to test a blindly coded 2 17 clinical sera. All sera samples were tested in duplicates and in both p20-coated and uncoated micro titer plates. Consequently, 116/134 (87%) CD sera were positive compared to 24/83 (33%) non-CD sera (P<0.05). Specifically anti-MAP IgG was detected in 8/22 (36%) Ulcerative colitis and 16/61 (26%) non-IBD sera. p20-ORF encoding sequence was recloned (pB11/B6) and the expressed protein reactivity remained consistent. Moreover, the full length of the cloned gene was also identified through blast and alignment analysis and predicted to encode 346 amino acids with unknown function and no identity with other known proteins. The latter supports the clinical data, which reflect on the unique characteristics of this antigen. The result so far suggests that the recombinant clone and its subclone derivative may have potential role in serodiagnosis of CD.
Show less - Date Issued
- 2004
- Identifier
- CFE0000089, ucf:46148
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0000089
- Title
- Defective Dynamics of Mitochondria in Amyotrophic Lateral Sclerosis and Huntington's Disease.
- Creator
-
Song, Wenjun, Bossy-Wetzel, Ella, Fernandez-Valle, Cristina, Cheng, Zixi, Self, William, University of Central Florida
- Abstract / Description
-
Mitochondria play important roles in neuronal function and survival, including ATP production, Ca2+ buffering, and apoptosis. Mitochondrial dysfunction is a common event in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD); however, what causes the mitochondrial dysfunction remains unclear. Mitochondrial fission is mediated by dynamin-related protein 1 (DRP1) and fusion by mitofusin 1/2 (MFN1/2) and optic atrophy 1 (OPA1),...
Show moreMitochondria play important roles in neuronal function and survival, including ATP production, Ca2+ buffering, and apoptosis. Mitochondrial dysfunction is a common event in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD); however, what causes the mitochondrial dysfunction remains unclear. Mitochondrial fission is mediated by dynamin-related protein 1 (DRP1) and fusion by mitofusin 1/2 (MFN1/2) and optic atrophy 1 (OPA1), which are essential for mitochondrial function. Mutations in the mitochondrial fission and fusion machinery lead to neurodegeneration. Thus, whether defective mitochondrial dynamics participates in ALS and HD requires further investigation.ALS is a fatal neurodegenerative disease characterized by upper and lower motor neuron loss. Mutations in Cu/Zn superoxide dismutase (SOD1) cause the most common familiar form of ALS by mechanisms not fully understood. Here, a new motor neuron-astrocyte co-culture system was created and live-cell imaging was used to evaluate mitochondrial dynamics. Excessive mitochondrial fission was observed in mutant SOD1G93A motor neurons, correlating with impaired axonal transport and neuronal cell death. Inhibition of mitochondrial fission restored mitochondrial dynamics and protected neurons against SOD1G93A-induced mitochondrial fragmentation and neuronal cell death, implicating defects in mitochondrial dynamics in ALS pathogenesis.HD is an inherited neurodegenerative disorder caused by glutamine (Q) expansion in the polyQ region of the huntingtin (HTT) protein. In the current work, mutant HTT caused mitochondrial fragmentation in a polyQ-dependent manner in both primary cortical neurons and fibroblasts from human patients. An abnormal interaction between DRP1 and HTT was observed in mutant HTT mice and inhibition of mitochondrial fission or promotion of mitochondrial fusion restored mitochondrial dynamics and protected neurons against mutant HTT-induced cell death. Thus, mutant HTT may increase mitochondrial fission by elevating DRP1 GTPase activity, suggesting that mitochondrial dynamics plays a causal role in HD.In summary, rebalanced mitochondrial fission and fusion rescues neuronal cell death in ALS and HD, suggesting that mitochondrial dynamics could be the molecular mechanism underlying these diseases. Furthermore, DRP1 might be a therapeutic target to delay or prevent neurodegeneration.
Show less - Date Issued
- 2012
- Identifier
- CFE0004444, ucf:49356
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004444
- Title
- SURVIVAL OF MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS IN THE POLYMORPHONUCLEAR LEUKOCYTES OF A CROHN'S DISEASE PATIENT.
- Creator
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Rumsey, John, Naser, Saleh, University of Central Florida
- Abstract / Description
-
Mycobacterium avium subspecies paratuberculosis (map) is an intracellular pathogen that is known to parasitize macrophages and monocytes. Map infiltrates gastrointestinal tract host tissue where it is the known etiological agent of johne's disease in ruminants and implicated in the etiology of crohn's disease in humans. Map's ability to survive within macrophages enables it to disseminate throughout the rest of the host, possibly infecting other circulating blood leukocytes. In this study,...
Show moreMycobacterium avium subspecies paratuberculosis (map) is an intracellular pathogen that is known to parasitize macrophages and monocytes. Map infiltrates gastrointestinal tract host tissue where it is the known etiological agent of johne's disease in ruminants and implicated in the etiology of crohn's disease in humans. Map's ability to survive within macrophages enables it to disseminate throughout the rest of the host, possibly infecting other circulating blood leukocytes. In this study, the survival and fate of map strain atcc 43015 (human isolate) following phagocytosis was determined using in vitro murine macrophage cell line j774a.1 and polymorphonuclear cells (pmnc's) from five crohn's disease patients. Pmnc's from three healthy individuals and two ulcerative colitis patients, as well as escherichia coli (atcc 11303) and mycobacterium tuberculosis strain h37ra (atcc 25177), were included as controls (moi 10:1). Maturation of the phagosome was determined by evaluating the presence of stage specific markers on the surface of the phagosomal membrane. The endosomal protein, transferrin receptor, and the lysosomal marker, lamp-1, were then immunostained with cy-5 conjugated secondary antibodies, and colocalization of bacteria with each marker was evaluated separately using confocal scanning laser microscopy (cslm). In both tissue models, colocalization of viable map and m. Tuberculosis with the early endosomal marker, transferrin receptor occurred with an estimated five fold higher frequency than did association with the late lysosomal marker, lamp-1, as compared to live e. Coli, and all dead bacterial species. Using differential live/dead staining and fluorescent microscopy, survival of m. Tuberculosis and map was estimated at 85% and 79%, respectively compared to only 14% for e. Coli. The outcome was similar for both tissue culture and pmncs from all patients tested, suggesting that map and m. Tuberculosis can survive readily in both cell types, and regardless of the disease state of the host or the killing power of the cell. Map's survival appears to mimic m. Tuberculosis', suggesting the ability to resist phagolysosome fusion, by maintaining association with the early endosomes. Overall, the data confirms map virulence in host human blood leukocytes.
Show less - Date Issued
- 2004
- Identifier
- CFE0000184, ucf:52838
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0000184
- Title
- Immunological studies of the host parasite relationship of Dirofilaria immitis in domestic canines.
- Creator
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Qualls, Douglas Felton, Sweeney, Michael J., Natural Sciences
- Abstract / Description
-
Florida Technological University College of Natural Sciences Thesis; Canine immunoglobulins of the IgG group were shown to be intimately associated with the cuticle of circulating non-infection Dirofilaria immitis microfilaria. The significance of these immunoglobulins in blocking a complete immune response in the definitive host is discussed. Immunodiffusion, immunoelectrophoresis and fluorescent inhibition techniques are described and their applicability to the study of host-parasite...
Show moreFlorida Technological University College of Natural Sciences Thesis; Canine immunoglobulins of the IgG group were shown to be intimately associated with the cuticle of circulating non-infection Dirofilaria immitis microfilaria. The significance of these immunoglobulins in blocking a complete immune response in the definitive host is discussed. Immunodiffusion, immunoelectrophoresis and fluorescent inhibition techniques are described and their applicability to the study of host-parasite relationships are evaluated. A rapid reproducible method for the production of specifically labeled anti-D. immitis microfilaria globulins is presented.
Show less - Date Issued
- 1975
- Identifier
- CFR0003520, ucf:52993
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFR0003520
- Title
- Antibodies to milk antigens in human coronary heart disease.
- Creator
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Spinos, Efstathios, Sweeney, Michael J., Natural Sciences
- Abstract / Description
-
Florida Technological University College of Natural Sciences Thesis; Milk protein has been implicated as a factor in the development of atherosclerosis. Significantly higher titers of antibodies (P
Show moreFlorida Technological University College of Natural Sciences Thesis; Milk protein has been implicated as a factor in the development of atherosclerosis. Significantly higher titers of antibodies (P < 0.0002) toward milk antigens were observed in patients suffering from coronary heart disease as compared to age matched controls. These hemagglutination titers were not sex related but may have been related to age. Specificity of the antigen-antibody reaction was demonstrated by a hemagglutination inhibition test. The complement fixation test was evaluated and was less sensitive than the tanned hemaggIutination test. Treatment with 2-mercapto-ethanol resulted in reduced hemagglutination titers, indicating that significant antibody activity may be due to IgM. A special application of the Combs test detected specific antibodies on the surface of tanned and coated RBC which did not otherwise produce detectable agglutination.
Show less - Date Issued
- 1977
- Identifier
- CFR0003521, ucf:52985
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFR0003521
- Title
- A correlation study on the chronic obstructive pulmonary diseases.
- Creator
-
Capraun, Lynn Walter, Washington, David W., Natural Sciences
- Abstract / Description
-
Florida Technological University College of Natural Sciences Thesis; Data were extracted from medical records of 202 former patients of a well established central Florida general hospital. Records were selected so as to include an equal number of disease catagories dispersed equally over the two years. One hundred records were dated 1973 and 102 were dated 1976. Emphysema, chronic bronchitis, and asthma had been diagnosed in 67, 67, and 68 of the cases respectively. The age, sex, race,...
Show moreFlorida Technological University College of Natural Sciences Thesis; Data were extracted from medical records of 202 former patients of a well established central Florida general hospital. Records were selected so as to include an equal number of disease catagories dispersed equally over the two years. One hundred records were dated 1973 and 102 were dated 1976. Emphysema, chronic bronchitis, and asthma had been diagnosed in 67, 67, and 68 of the cases respectively. The age, sex, race, smoking habits, and occupations of the patients were recorded and crosstabulated with the diagnostic tests and subsequent treatment ordered by the various physicians. Most of the emphysematous patients were males over 50, the asthmatics were females under 30, and the bronchitics were older than 50 with an even sex distribution. Most of the emphysematous and bronchitic patients had smoked over 25 years, while only 13% of the asthmatics smoked. A majority of the chronic obstructive pulmonary disease patients complained of shortness of breath, were hospitalized ten days or less, treated four times a day with intermittent positive pressure breathing had little or no pulmonary rehabilitation, and survived. Respiratory care appeared to improve over the three-year period as judged by an increase in the frequency of blood gas monitoring and a reduction in the required ventilator times with improved techniques.
Show less - Date Issued
- 1978
- Identifier
- CFR0003461, ucf:53025
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFR0003461
- Title
- INVESTIGATING THE ROLE OF THE GUT MICROBIOME IN HUNTINGTON DISEASE.
- Creator
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Hart, Casey G, Southwell, Amber, University of Central Florida
- Abstract / Description
-
Huntington disease (HD) is an inherited neurodegenerative disease caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene. Metabolic dysfunction is a feature of HD that is recapitulated in HD mouse models. Our lab has shown that circadian feeding rhythms are disrupted in humanized HD mice and restored by suppression of brain HTT. Furthermore, when circadian feeding rhythm is artificially restored, in addition to normalization of metabolic function, liver and striatal HTT is...
Show moreHuntington disease (HD) is an inherited neurodegenerative disease caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene. Metabolic dysfunction is a feature of HD that is recapitulated in HD mouse models. Our lab has shown that circadian feeding rhythms are disrupted in humanized HD mice and restored by suppression of brain HTT. Furthermore, when circadian feeding rhythm is artificially restored, in addition to normalization of metabolic function, liver and striatal HTT is temporarily reduced, demonstrating that HTT is involved in gut-brain feedback. The gut microbiome, which can regulate gut-brain feedback, has been implicated in the pathogenesis of other central nervous system disorders and we hypothesize it also plays a role in HD. The objective of this study is to investigate alterations in relative abundance of HD gut microbiota using existing plasma metabolomics data to identify candidate bacteria. If distinct microbiota profiles are demonstrated, this would provide the basis for future unbiased studies to investigate the complete HD microbiome.
Show less - Date Issued
- 2018
- Identifier
- CFH2000418, ucf:45814
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000418
- Title
- STUDY AND ANALYSIS OF UPPER GASTROINTESTINAL SYMPTOMS AMONG STUDENTS AT THE UNIVERSITY OF CENTRAL FLORIDA.
- Creator
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Anzueto, Deberly M, Saleh, Suha, University of Central Florida
- Abstract / Description
-
Upper gastrointestinal symptoms can be caused by many different diseases and can present themselves in many different forms and range in intensity depending on the person. In previous research, upper gastrointestinal symptoms have been correlated with stress, smoking, alcohol intake, and nonsteroidal anti-inflammatory drugs (NSAIDs), among others. The purpose of this study will be focusing on finding any association between these risk factors mention and symptoms of upper gastrointestinal...
Show moreUpper gastrointestinal symptoms can be caused by many different diseases and can present themselves in many different forms and range in intensity depending on the person. In previous research, upper gastrointestinal symptoms have been correlated with stress, smoking, alcohol intake, and nonsteroidal anti-inflammatory drugs (NSAIDs), among others. The purpose of this study will be focusing on finding any association between these risk factors mention and symptoms of upper gastrointestinal disease among college students. The study will utilize an Izumo scale questionnaire for the assessment of abdominal symptoms and Quality of Life (QOL). The questionnaire was built using Survey Monkey and distributed via email to students at the University of Central Florida (UCF). The main hypothesis was that the more the student's advancement in their college career, stress load, alcohol consumption, smoking, poor diet and a high consumption of some over the counter medication (specifically Non-Steroidal Anti Inflammatory Drugs), the more prone the students will be to present symptoms of upper gastrointestinal disease. The results were analyzed using Statistical Package for the Social Science (SPSS), and Analysis of Variance (ANOVA) were used to find any associations. The One-Way ANOVA tests showed an association between gender, ethnicity, student status, major, cigarette smoking habits, alcohol consumption, binge drinking, diet, stress, sleeping, and overall health. The results of this study present clear evidence that among college students, their demographics as well as lifestyle and school choices have significant associations to the amount of gastrointestinal symptoms they present with.
Show less - Date Issued
- 2016
- Identifier
- CFH2000132, ucf:45949
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000132
- Title
- RIGOROUS ANALYSIS OF AN EDGE-BASED NETWORK DISEASE MODEL.
- Creator
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Mai, Sabrina, Shuai, Zhisheng, University of Central Florida
- Abstract / Description
-
Edge-based network disease models, in comparison to classic compartmental epidemiological models, better capture social factors affecting disease spread such as contact duration and social heterogeneity. We reason that there should exist infinitely many equilibria rather than only an endemic equilibrium and a disease-free equilibrium for the edge-based network disease model commonly used in the literature, as there do not exist any changes in demographic in the model. We modify the commonly...
Show moreEdge-based network disease models, in comparison to classic compartmental epidemiological models, better capture social factors affecting disease spread such as contact duration and social heterogeneity. We reason that there should exist infinitely many equilibria rather than only an endemic equilibrium and a disease-free equilibrium for the edge-based network disease model commonly used in the literature, as there do not exist any changes in demographic in the model. We modify the commonly used network model by relaxing some assumed conditions and factor in a dependency on initial conditions. We find that this modification still accounts for realistic dynamics of disease spread (such as the probability of contracting a disease based off your neighbors' susceptibility to the disease) based on the basic reproduction number. Specifically, if the basic reproduction number is below 1, then the infection dies out; while if the basic reproduction number is above 1, then there is possibility of an epidemic.
Show less - Date Issued
- 2019
- Identifier
- CFH2000537, ucf:45651
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000537
- Title
- Investigation of a Self-powered Fontan Concept Using a Multiscale Computational Fluid-Structure Interaction Model.
- Creator
-
Beggs, Kyle, Kassab, Alain, Steward, Robert, Mansy, Hansen, DeCampli, William, University of Central Florida
- Abstract / Description
-
Congenital Heart Disease (CHD) occurs in about 1\% (40,000) of newborn babies each year in the United States alone. About 10.9\% (960) of whom suffer from Hypoplastic Left Heart Syndrome (HLHS) - a subset of CHD where children are born with a single-ventricle (SV). A series of three surgeries are carried out to correct HLHS culminating in the Fontan procedure where venous flow returns passively to the lungs. The current configuration for the Fontan results in elevated Central Venous Pressure ...
Show moreCongenital Heart Disease (CHD) occurs in about 1\% (40,000) of newborn babies each year in the United States alone. About 10.9\% (960) of whom suffer from Hypoplastic Left Heart Syndrome (HLHS) - a subset of CHD where children are born with a single-ventricle (SV). A series of three surgeries are carried out to correct HLHS culminating in the Fontan procedure where venous flow returns passively to the lungs. The current configuration for the Fontan results in elevated Central Venous Pressure (CVP), inadequate ventricular preload, and elevated Pulmonary Vascular Resistance (PVR) leading to a barrage of disease. To alleviate these complications, a `self-powered' Fontan is suggested where an Injection Jet Shunt (IJS) emanating from the aorta is anastomosed to each pulmonary artery. The IJS attempts to reduce the central venous pressure, increase preload, and aid in pulmonary arterial growth by entraining the flow with a high energy source provided by the aorta. Previous computational studies on this concept with rigid vessel walls show mild success, but not enough to be clinically relevant. It is hypothesized that vessel wall deformation may play an important role in enhancing the jet effect to provide a larger exit area for the flow to diffuse while also being more physiologically accurate. A multiscale 0D-3D tightly coupled Computational Fluid Dynamics (CFD) with Fluid-Structure Interaction (FSI) model is developed to investigate the efficacy of the proposed `self-powered' Fontan modification. Several runs are made varying the PVR to investigate the sensitivity of IVC pressure on PVR. IVC pressure decreased by 2.41 mmHg while the rigid wall study decreased the IVC pressure by 2.88 mmHg. It is shown that IVC pressure is highly sensitive to changes in PVR and modifications to the Fontan procedure should target aiding pulmonary arterial growth as it is the main indicator of Fontan success.
Show less - Date Issued
- 2018
- Identifier
- CFE0007311, ucf:52107
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0007311
- Title
- The Evolution of Shared Responsibility and Instructional Risk Communication in Brazil's Campaign against the Zika Virus.
- Creator
-
Mauricio Soares, Rodrigo Augusto, Sellnow, Timothy, Sellnow, Deanna, Littlefield, Robert, University of Central Florida
- Abstract / Description
-
This study provides an evaluation of instructional risk communication practices in Brazil's response to the Zika virus during the 2016/2017 campaign. The communication was instructionally focused, explaining the way the disease is transmitted, what to do if the person is infected, and characteristics of the mosquito. The authorities also tried to convince the publics that, because the mosquito breeds in everyone's houses and apartments, everyone could be part of the solution. The social,...
Show moreThis study provides an evaluation of instructional risk communication practices in Brazil's response to the Zika virus during the 2016/2017 campaign. The communication was instructionally focused, explaining the way the disease is transmitted, what to do if the person is infected, and characteristics of the mosquito. The authorities also tried to convince the publics that, because the mosquito breeds in everyone's houses and apartments, everyone could be part of the solution. The social, economic and cultural characteristics of the country, the population's low levels of health literacy, and a long-lasting government credibility problem in the country make Brazil's fight against these types of diseases considerably difficult. The IDEA model (T. Sellnow (&) D. Sellnow, 2013) was used as the theoretical grounding for the analysis. This study presents the concepts of collective efficacy and shared responsibility and recommendations for risk and crisis communication practitioners as well as government agencies with regard to engaging the population in managing this type of disease outbreak. Knowledge about how to generate and share strategic communication of this nature is increasingly important as the spread of novel diseases is increasing in frequency and intensity (Kilpatrick (&) Randolph, 2012).
Show less - Date Issued
- 2018
- Identifier
- CFE0007050, ucf:51974
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0007050
- Title
- A Paleopathological Assessment of Osteoarthritis in the Lower Appendicular Joints of Individuals from the Kellis 2 Cemetery in the Dakhleh Oasis, Egypt.
- Creator
-
Robin, Joshua, Dupras, Tosha, Schultz, John, Mcintyre, Matthew, University of Central Florida
- Abstract / Description
-
Osteoarthritis (OA) is a degenerative pathological condition of the appendicular joints which affects the cartilage and underlying bone. OA is relatively common in both the archaeological and clinical context, and a significant amount of research has been conducted on this osteological condition. The purpose of this thesis is to assess the incidence, demographic prevalence, and general severity of hip and knee OA in a Roman-Christian period (50 A.D (-) 450 A.D) population sample from the...
Show moreOsteoarthritis (OA) is a degenerative pathological condition of the appendicular joints which affects the cartilage and underlying bone. OA is relatively common in both the archaeological and clinical context, and a significant amount of research has been conducted on this osteological condition. The purpose of this thesis is to assess the incidence, demographic prevalence, and general severity of hip and knee OA in a Roman-Christian period (50 A.D (-) 450 A.D) population sample from the Dakhleh Oasis, Egypt. The bioarchaeological sample originates from the Kellis 2 cemetery which is associated with the ancient town of Kellis. The town of Kellis is believed to have been a prosperous economic hub in Egypt, located in the Western Sahara Desert approximately 250 kilometers west of the Nile. The skeletal samples (n=135, 83 females and 51 males) was visually assessed for the osteological characteristics of OA in the hips and the knees. Joint surfaces of the hip include the acetabulum and femoral head. Joint surfaces of the knee include lateral/medial tibio-femoral compartments and the patellofemoral compartment. The ages of the individuals assessed in this study range from 19-72 years, and have been divided into five age categories which were then cross-tabulated with sex and OA incidence in order to determine demographic prevalence of OA. Findings indicate that age is a significant etiological factor of OA prevalence for both males and females. Males are afflicted by the disease significantly more than females in the hips (F: [L] 3.6%, [R] 5.9% and M: [L] 13.7%,[R] 13.7%) and also slightly more affected in the knees(F: [L] 17.5%,[R] 18.3% and M: [L] 22.9%,[R]21.3%). The acetabulum tends to be more arthritic than the femoral head for both males and females. Femoral condyles tend to be more arthritic than tibial condyles for both males and females. The patello-femoral compartment tends to be the most arthritic part of the knee while the medial condyles of both tibiae exhibit virtually no OA (with the exception of one individual). The joint surface observed with the highest OA prevalence is the femoral surface of the patella (F: [L] 17.5%,[R] 15.9% and M: [L] 21.3%,[R] 21.3%). The highest prevalence of OA by joint complex is observed on the left knee in males (22.9%), and the lowest prevalence of OA is observed on the left hip of females (3.6%). Both hip and knee joints have higher prevalence of unilateral OA manifestation than bilateral. Isotopic and archaeological evidence indicates that the individuals at Kellis maintained an agricultural subsistence regime, and that the males within the population may have been highly mobile migrating to and from the Dakhleh Oasis. Subsistence agriculture has its necessary physical demands which may have been a contributory factor to OA rates. Males show higher OA rates than females throughout the joints of the legs. Sexual dimorphism of OA for the hips is suggestive of sexual divisions of labor. OA of the knees lacks sexual dimorphism therefore the knee joint complex of males and females were likely subjected to similar levels of mechanical loading. It can be concluded based on the OA data that males and females exhibit similar activity, or biomechanical stress levels in the knee joint complexes. Males exhibit significantly higher pathological manifestation of OA in the hip joint complexes, indicative of higher levels of mechanical loading in the hip joint complex which can theoretically be attributed to sexual divisions of labor or perhaps terrestrial mobility.
Show less - Date Issued
- 2011
- Identifier
- CFE0004162, ucf:49066
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004162
- Title
- AWARENESS OF INCREASED RISK FOR HEART DISEASE AND CARDIOVASCULAR RISK FACTORS IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS.
- Creator
-
Weinstein, Patricia, Dennis, Karen, University of Central Florida
- Abstract / Description
-
Women with systemic lupus erythematosus (SLE) develop cardiovascular disease (CVD) earlier and at a more accelerated rate compared to women without SLE. Many women with SLE are unaware of their increased risk despite years spent in the health care system, thus giving the atherogenic process time to accrue damage. Research has not explained fully why women with SLE are unaware of their increased risk for CVD or why awareness does not correspond to risk-educing behaviors. Stage theories of...
Show moreWomen with systemic lupus erythematosus (SLE) develop cardiovascular disease (CVD) earlier and at a more accelerated rate compared to women without SLE. Many women with SLE are unaware of their increased risk despite years spent in the health care system, thus giving the atherogenic process time to accrue damage. Research has not explained fully why women with SLE are unaware of their increased risk for CVD or why awareness does not correspond to risk-educing behaviors. Stage theories of behavior like the Precaution Adoption Process Model (PAPM) propose that health behavior change proceeds through qualitatively different stages, and people at one stage face similar barriers before they can progress to the next. The Common Sense Model (CSM), a self-regulatory model of health behavior, explains the emotional and cognitive processes involved in progression from one stage to the next and the formation of a personal risk/illness representation. Combining the PAPM and CSM helps understand the relationship between risk perception and adoption of risk reducing behaviors. The specific aims of this study were to assess in women with SLE: (1) general knowledge of heart disease compared to women without SLE; (2) awareness of increased CVD risk and CVD risk factors; and (3) personal and healthcare system factors that influence awareness of increased CVD risk and adoption of risk reducing behaviors. Sixty women with SLE, 18 years of age or older, were recruited to participate in this descriptive study. Data included demographic information, self-report questionnaires (perceived CVD risk, CVD risk factors, depression, physical activity), body measures (height, weight, waist circumference, blood pressure), and blood samples for physiologic markers of traditional and novel CVD risk factors (glucose, insulin, lipoprotein lipids, creatinine, C-reactive protein, homocysteine, antiphospholipid antibodies). The Beck Depression Inventory-Primary Care and the Physical Activity Disability Survey were used to determine depression and activity level respectively. General knowledge of heart disease was assessed using the American Heart Association (AHA) National Survey on women's awareness of heart disease. Logistic regression was used to categorize participants into subgroups according to perceived risk and identify important factors that influenced their PAPM stage categorization. Women with SLE in this study were more aware of women's leading cause of death than United States women who responded to the 2006 AHA survey (73% v 57%), but fewer than 25% perceived themselves at increased CVD risk. Age was a significant predictor (p=0.05) for awareness of increased risk; younger age correlated with increased awareness. Most women received information about heart disease from public media. On average, women had 4 CVD risk factors, but they perceived they had only 2. The number of perceived risk factors predicted adoption of risk reducing behaviors (p=0.03). Women in this study with SLE underestimated their CVD risk factors and did not personalize their increased CVD risk. Healthcare providers' identification and discussion of CVD risk factors in women with SLE may enhance their risk awareness and the adoption of risk reducing behaviors. This information may contribute to the development of stage-matched interventions, a potentially more effective and efficient approach than a generic program of risk-reduction, especially in individuals with SLE who face the additional burden of a chronic illness.
Show less - Date Issued
- 2009
- Identifier
- CFE0002755, ucf:48138
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0002755
- Title
- Pebbles and Shards.
- Creator
-
Kindle, Edith, Bartkevicius, Jocelyn, Uttich, Laurie, Rushin, Patrick, University of Central Florida
- Abstract / Description
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Pebbles and Shards is a collection of personal essays based on family relationships that focus upon motherhood, responsibility, and the complexity of love and loss. The essays explore how people cope with the inevitability of loss and how they move beyond that loss to find something meaningful, perhaps even beautiful. They reflect upon success and failure in the face of loss and how, either way, life goes on, heedless of people's desires and plans.The essays in Pebbles and Shards, while meant...
Show morePebbles and Shards is a collection of personal essays based on family relationships that focus upon motherhood, responsibility, and the complexity of love and loss. The essays explore how people cope with the inevitability of loss and how they move beyond that loss to find something meaningful, perhaps even beautiful. They reflect upon success and failure in the face of loss and how, either way, life goes on, heedless of people's desires and plans.The essays in Pebbles and Shards, while meant to stand alone, are thematically connected so that, read together, each story resonates with the others. In (")Promises,(") I explore the fear of watching my mother die of Alzheimer's disease. In related essays (")Frame by Frame(") and (")In Darkness,(") I focus on my mother's efforts to struggle with Alzheimer's and how, as an adopted daughter, I underwent a role-reversal and became the mother figure. Other essays, such as (")Heart of a Deadhead(") and (")Circus,(") consider the mothering impulse, especially the guilt and conflict that so often accompany my desire to nurture others. In attempting to support and strengthen those who seem (")weak,(") I have sometimes found that my own actions and thoughts underscore a deeper weakness in myself.As a collection, Pebbles and Shards contemplates the suffering and joy that is a family.
Show less - Date Issued
- 2013
- Identifier
- CFE0004704, ucf:49813
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004704
- Title
- Dangerous jobs.
- Creator
-
Burnham, Grace Martha
- Date Issued
- 1933
- Identifier
- 363418, CFDT363418, ucf:5313
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/FCLA/DT/363418
- Title
- TARGETED DELIVERY OF A THERAPEUTIC PROTEIN FOR THE TREATMENT OF ALZHEIMER'S DISEASE.
- Creator
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Holman, Heather, Sugaya, Kiminobu, University of Central Florida
- Abstract / Description
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Neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are linked to mitochondrial dysfunction and the underexpression of TOM40, a protein with chaperone-like qualities that is responsible for transporting precursor proteins into the mitochondria. Overexpression of TOM40 is reported to partially restore mitochondrial dysfunction and decrease the accumulation of neurotoxic aggregates of ?-synuclein. Our goal is to develop an effective method for delivery of TOM40...
Show moreNeurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are linked to mitochondrial dysfunction and the underexpression of TOM40, a protein with chaperone-like qualities that is responsible for transporting precursor proteins into the mitochondria. Overexpression of TOM40 is reported to partially restore mitochondrial dysfunction and decrease the accumulation of neurotoxic aggregates of ?-synuclein. Our goal is to develop an effective method for delivery of TOM40 protein to the brain. Previous studies have used lentiviruses to carry TOM40 into the hippocampus of ?-synuclein transgenic mice. The disadvantage of lentiviral transfection is the random insertions of the target gene into the host genome, which could cause toxic effects. Synthetic phospholipid vesicles containing TOM40 were considered as an alternative delivery method, but these "liposomes" elicit not only toxicity, but also an immune response. Thus, development of a safer delivery method of TOM40 protein is needed. We investigated exosomes, which are extracellular vesicles originating from multivesicular endosomes filled with protein, lipid, or RNA cargoes for cell-cell communication. Since exosomes are created from host cells, they are non-immunogenic and may be a more desirable method. Expression constructs have been made for the production of TOM40 protein within or on the surface of exosomes. In order to target the delivery of TOM40 to the brain, we attached peptides to the surface of the exosomes, which specifically interact with receptors on neural cells. We attempted to confirm the functionality of the expression constructs through immunocytochemistry followed by flow cytometry and Western blotting.
Show less - Date Issued
- 2018
- Identifier
- CFH2000328, ucf:45803
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000328
- Title
- STUDIES ON THE NOVEL FUNCTION OF AMYLOID PRECURSOR PROTEIN IN GLIAL DIFFERENTIATION OF NEURAL STEM CELLS.
- Creator
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Kwak, Young-Don, Sugaya, Kiminobu, University of Central Florida
- Abstract / Description
-
Although amyloid beta (A beta) deposition has been a hallmark of Alzheimer's disease (AD), the physiological function of amyloid precursor protein (APP) is not clear. Our results suggested that high concentration of APP induces glial differentiation while physiological level of APP promotes migration and differentiation of neural stem cell (HNSC). HNSCs were mainly differentiated into astrocytes when they are transplanted into APP transgenic mouse brain or treated with a high...
Show moreAlthough amyloid beta (A beta) deposition has been a hallmark of Alzheimer's disease (AD), the physiological function of amyloid precursor protein (APP) is not clear. Our results suggested that high concentration of APP induces glial differentiation while physiological level of APP promotes migration and differentiation of neural stem cell (HNSC). HNSCs were mainly differentiated into astrocytes when they are transplanted into APP transgenic mouse brain or treated with a high concentration of secreted-type APP (sAPP) in culture. Staurosporine (STS) induced a distinctive astrocytic morphology in NT-2/D1 neural progenitor cells with expressions of APP and astrocyte-specific markers, glial fibrillary acidic protein (GFAP), aspartate transporter, and glutamate transporter-1. Expression of APP is correlated with GFAP expression in both mRNA and protein level in this experiment. Inhibition of APP expression by RNA interference (RNAi) or treatment with MEK1 inhibitor (PD098059), which reduces APP expression by suppressing ERK phosphorylation, abolished GFAP expression. These results indicate that STS induces glial differentiation of neuronal progenitor cells by increasing APP levels through activation of ERK pathway. We also found that APP-induced glial differentiation of neural progenitor NT-2/D1 cells is mediated by activation of IL-6/gp130 and notch signaling pathway. Treatment of APP activated IL-6/gp130 signal pathway via protein-protein interaction between APP and gp130 and it increased the gene expressions of CNTF, gp130 and JAK1, and phosphorylation of STAT3 while gene silencing of CNTF, JAK1 or STAT3 by RNAi, or treatment the cells with antibodies recognizing gp130 suppressed GFAP expression, indicating these molecules are crucial for APP-induced glial differentiation. Thus treatment of sAPP may promote glial differentiation of neural progenitor cells by activation of IL-6/gp130 signaling cascade. Treatment of sAPP increased the generation of notch intracellular domain as well as gene expression of Hes1 but did not change expression levels of notch or its ligands. We also found protein-protein interaction of APP and notch using immunoprecipitation suggesting that glial differentiation of NT-2/D1 cells is mediated by the physical interaction between APP and notch. N-terminal domain of APP (1-205 a.a.) alone can bind to notch and activate these signaling cascade in NT-2/D1 cells. Thus, APP may induce glial differentiation through activation of IL-6/gp130 and notch signal cascade by binding with its N-terminal domain. Taken together, our results suggest that APP regulates neural stem cell (NSC) differentiation through IL-6/gp130 and notch signaling pathway. Furthermore, the activation of both glial differentiation mechanisms may be necessary to potentiate APP-induced glial differentiation of NSC. Altered APP metabolism in Down syndrome and Alzheimer's disease may accelerate premature glial differentiation of NSCs, resulting in gliosis found in these diseases. Although it is not clear that how adult neurogenesis contributes to maintain normal brain function, destruction of neuroreplacement mechanism by NSCs may pose a problem. We may also have to consider effect of APP on the stem cell therapy for these diseases, since HNSCs may not properly differentiate into neurons under these pathological conditions.
Show less - Date Issued
- 2006
- Identifier
- CFE0001375, ucf:46980
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0001375
- Title
- CELLULAR IMMUNE RESPONSE AND GENE EXPRESSION PROFILING IN CROHN'S DISEASE PATIENTS ASSOCIATED WITH MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS.
- Creator
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Romero, Claudia, Naser, Saleh A., University of Central Florida
- Abstract / Description
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Despite the chronic debate in the etiology of crohn's disease (cd), a debilitating inflammatory bowel disease (ibd) closely related to ulcerative colitis (uc), an emerging interest in a possible mycobacterial role has been marked. Granuloma and pathologic manifestations in cd resemble aspects found in tuberculosis, leprosy and paratuberculosis. The latter, a chronic enteritis in cattle, goat, sheep and primates, which is similar to human enteritis, also known as cd, is caused by a fastidious,...
Show moreDespite the chronic debate in the etiology of crohn's disease (cd), a debilitating inflammatory bowel disease (ibd) closely related to ulcerative colitis (uc), an emerging interest in a possible mycobacterial role has been marked. Granuloma and pathologic manifestations in cd resemble aspects found in tuberculosis, leprosy and paratuberculosis. The latter, a chronic enteritis in cattle, goat, sheep and primates, which is similar to human enteritis, also known as cd, is caused by a fastidious, slow growing mycobacterium avium subspecies paratuberculosis (map). Due to the similarities between cd and paratuberculosis, a mycobacterial cause in cd has been proposed. Recent discovery of a possible association between nod2/card15 mutations and risk of cd added support to microorganism-host interactions. In this study, a possible mycobacterial role in cd etiology has been evaluated by investigating the presence of map dna, the state of the cellular immune response and microarray gene expression profiling in peripheral blood and surgical tissue from cd, uc and healthy control subjects. Nested pcr detected map dna in tissue from 10/12(83%) cd patients compared to 1/6(17%) non-ibd subjects. Fluorescence in situ hybridization (fish) with the aid of confocal scanning laser microscopy (cslm) detected map dna in 8/12(67%) cd subjects compared to 0/6(0%) in non-ibd subjects. The detection of map dna by either technique in tissue from cd subjects is significant compared to non-ibd subjects (p < 0.05). Map dna was also detected in both inflamed and non-inflamed tissue from patients with cd suggesting map infiltration in human tissue. Correlation of possible map presence and the function of polymorphonuclear leukocytes (pmn) and peripheral blood mononuclear cells (pbmc) in 19 cd patients and 12 controls have been evaluated. Pmn phagocytosis of viable fitc-map was suppressed in 13/19(68%) cd patients compared to 0/12(0%) in healthy controls (p<0.05). Pbmc phagocytosis of viable fitc-map was suppressed in 5/19(26%) of cd patients compared to 0/12(0%) of healthy controls (p<0.05). The proliferative response of pbmc with t-cell majority from cd and controls subjects was evaluated against pha, candida albicans, pwm and map ppd. Dysfunctional proliferative response against pha was found in 8/19(42%) cd patients compared to 1/12(8.3%) in controls suggesting possible t-cell anergy. Pbmc from 11 cd subjects reacted normally to pha, 7/11(64%) reacted strongly to map ppd suggesting previous exposure to mycobacteria, and 3/11(27%) did not react with map ppd suggesting lack of pre-exposure to mycobacteria. From the seven mycobacterial pre-exposed samples, 6/7(86%) showed a normal ability to recall antigens by activated macrophages when exposed to c. Albicans, and all 7 samples had a normal pwm response. Finally, microarray-chip technology was employed to identify the expression profile of genes that have a role in the immune response of cd patients. Rna was isolated from fresh buffy coats from 8 healthy controls, 2 cd, and 1 uc patients. Chips with an estimated of 30,000 human genes were hybridized to cdna from these samples. We found that 17% of the total number of genes was differentially expressed. Over 200 genes were involved in the immune response, 7 genes where common to both forms of ibd (uc and cd), and 8 genes were found to be either downregulated in cd and upregulated in uc or viceversa. The ifngr1 gene, which encodes the ligand-binding chain of the ifn-gamma receptor, was found to be downregulated in 2/2(100%) of cd patients, but not in uc patients. It is known that defects in ifngr1 are a cause of atypical mycobacterial infection and bcg infection. Patients suffering from this deficiency have an immunologic defect predisposing them to infection with mycobacteria. This correlates with the proposed theory as map being the causative agent of cd. Furthermore, the results indicate a host susceptibility requirement for the establishment of mycobacterial infection in cd patients. Further characterization of ifngr1 using real-time pcr is underway. Collectively, detection of map dna in the majority of cd tissue and the alteration in pmn and pbmc to respond efficiently to map may be related to the fact that mycobacterial pathogens infect phagocytic cells of susceptible hosts and consequently the immune response is dysregulated. Furthermore, the fact that a gene linked to mycobacterial susceptibility was found to be downregulated in cd patients only, strengthens the mycobacterial etiology of cd. In general, the data suggest a possible role for a bacterial pathogen in cd pathogenesis.
Show less - Date Issued
- 2004
- Identifier
- CFE0000170, ucf:46170
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0000170
- Title
- CORRELATION OF RPOB GENE MUTATION WITH CLINICAL RIFABUTIN AND RIFAMPICIN RESISTANCE FOR TREATMENT OF CROHN'S DISEASE.
- Creator
-
Beckler, Daniel, Naser, Saleh, University of Central Florida
- Abstract / Description
-
Emerging rise in microbial drug resistance and the slow-growing characteristic of some intracellular pathogens such as MAP (Mycobacterium avium subspecies paratuberculosis) strongly urges the need for an effective approach for unconventional drug susceptibility testing. We designed a molecular-based PCR method for the evaluation of rifabutin (RFB) and rifampicin (RIF) resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located...
Show moreEmerging rise in microbial drug resistance and the slow-growing characteristic of some intracellular pathogens such as MAP (Mycobacterium avium subspecies paratuberculosis) strongly urges the need for an effective approach for unconventional drug susceptibility testing. We designed a molecular-based PCR method for the evaluation of rifabutin (RFB) and rifampicin (RIF) resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration (MIC) for RIF was also determined against 10 MAP isolates in attempt to seek correlation with rpoB sequences. We determined that MAP strain 18 had an MIC > 30 ug/ml and > 5 ug/ml for RIF and RFB respectively, and a significant rpoB mutation C1367T, compared to an MIC of < 1.0 ug/ml for both drugs in the wild type MAP. The 30-fold increase in the MIC was a direct result of the rpoB mutation C1367T, which caused an amino acid change Thr456 to Ile456 in the drug's binding site; the beta subunit of RNA polymerase. Our in vitro induced mutation in MAP strain UCF5 resulted in the generation of a new resistant strain (UCF5-RIF16r) that possessed T1442C rpoB mutation and an MIC > 30 ug/ml and > 10 ug/ml for RIF and RFB respectively. The T1442C mutation resulted in a Leu481 to Pro481 amino acid change, consequently altering the beta subunit sequence. Sequencing the entire 3.5 kb rpoB in strains 18 and UCF5-RIF16r revealed no additional expressed nucleotide mutation. Of the 10 MAP strains analyzed, an additional one strain (UCF4) exhibited a slight increase in the MIC against RIF and RFB compared to the wild-type. Nucleotide sequencing of the rpoB gene revealed an A2284C mutation in strain UCF4 that occurred further downstream of the expected probable rpoB region and resulted in an amino acid alteration Asn762 to His762. The location of this mutation outside the binding site and its correlation with the minor increase in MIC suggests a possible secondary interaction between the drug and the beta subunit. We have provided three dimensional images through the utilization of PyMol Molecular-based Graphics to display a clear comparison of the mutations observed in the beta subunit for MAP strains 18, UCF5-RIF16r, and UCF4. We propose that these alterations may have caused a less stable interaction between RIF and the beta subunit, resulting in the observed increased in MIC. Furthermore, the change in amino acid sequence did not affect the viability for our RIF resistant strains. The data clearly illustrates that clinical and in vitro-induced MAP mutants with rpoB mutations result in resistance to RIF and RFB. Consequently, unconventional drug susceptibility testing such as our molecular approach will be beneficial for evaluation of antibiotic effectiveness. This molecular approach may also serve as a model for other drugs used for treatment of MAP infections.
Show less - Date Issued
- 2007
- Identifier
- CFE0001729, ucf:47310
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0001729
- Title
- ALPHA-SYNUCLEIN: INSIGHT INTO THE HALLMARK OF PARKINSON'S DISEASE AS A TARGET FOR QUANTITATIVE MOLECULAR DIAGNOSTICS AND THERAPEUTICS.
- Creator
-
Evangelista, Baggio A, Kim, Yoon-Seong, University of Central Florida
- Abstract / Description
-
Parkinson's disease (PD) is the second-most common neurodegenerative disease after Alzheimer's disease. With 500,000 individuals currently living with Parkinson's and nearly 60,000 new cases diagnosed each year, this disease causes significant financial burden on the healthcare system - amassing to annual expenditures totaling 200 billion dollars; predicted to increase through 2050. The disease phenotype is characterized by a combination of a resting tremor, bradykinesia, muscular rigidity,...
Show moreParkinson's disease (PD) is the second-most common neurodegenerative disease after Alzheimer's disease. With 500,000 individuals currently living with Parkinson's and nearly 60,000 new cases diagnosed each year, this disease causes significant financial burden on the healthcare system - amassing to annual expenditures totaling 200 billion dollars; predicted to increase through 2050. The disease phenotype is characterized by a combination of a resting tremor, bradykinesia, muscular rigidity, and depression due to dopaminergic neuronal death in the midbrain. The cause of the neurotoxicity has been largely discussed, with strong evidence suggesting that the protein, alpha-Synuclein, is a key factor. Under native conditions, alpha-Synuclein can be found localized at synaptic terminals where it is hypothesized to be involved in vesicle trafficking and recycling. However, its biochemical profile reveals a hydrophobic region that, once subjected to insult, initiates an aggregation cascade. Oligomeric species-products of the aggregation cascade-demonstrate marked neurotoxicity in dopaminergic neurons and illustrate migratory potential to neighboring healthy neurons, thereby contributing to progressive neurodegeneration. The current golden standard for PD diagnostics is a highly qualitative system involving a process-by-elimination with accuracy that is contingent upon physician experience. This, and a lack of standardized clinical testing procedures, lends to a 25% misdiagnosis rate. Even under circumstances of an accurate PD diagnosis, the only treatment options are pharmacologics that have a wide range of adverse side effects and ultimately contribute to systemic metabolic dysfunction. Thus, the research presented in this thesis seeks to overcome these current challenges by providing (1) a quantitative diagnostic platform and (2) a biomolecular therapeutic, towards oligomeric alpha-Synuclein. Aim 1: serves as a proof-of-concept for the use of catalytic nucleic acid moieties, deoxyribozymes and aptamers, to quantify alpha-Synuclein in a novel manner and explore the ability to detect oligomeric cytotoxic species. The cost-effective nature of these sensors allows for continued optimization. Aim 2: serves to establish a potential therapy that can abrogate alpha-synuclein oligomerization and toxicity through use of a modified Protein Disulfide Isomerase (PDI) peptide when introduced to live cells treated to simulate pre-parkinsonian pathology.
Show less - Date Issued
- 2017
- Identifier
- CFH2000188, ucf:46024
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000188
