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Title: Identification of MicroRNA biomarkers for cancer by combining multiple feature selection techniques.
Creator: Kotlarchyk, Alex J., College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description: MicroRNAs (miRNAs) may serve as diagnostic and predictive biomarkers for cancer. The aim of this study was to identify novel cancer biomarkers from miRNA datasets, in addition to those already known. Three published miRNA cancer datasets (liver, breast, and brain) were evaluated, and the performance of the entire feature set was compared to the performance of individual feature filters, an ensemble of those filters, and a support vector machine (SVM) wrapper. In addition to confirming many...
Show moreMicroRNAs (miRNAs) may serve as diagnostic and predictive biomarkers for cancer. The aim of this study was to identify novel cancer biomarkers from miRNA datasets, in addition to those already known. Three published miRNA cancer datasets (liver, breast, and brain) were evaluated, and the performance of the entire feature set was compared to the performance of individual feature filters, an ensemble of those filters, and a support vector machine (SVM) wrapper. In addition to confirming many known biomarkers, the main contribution of this study is that seven miRNAs have been newly identified by our ensemble methodology as possible important biomarkers for hepatocellular carcinoma or breast cancer, pending wet lab confirmation. These biomarkers were identified from miRNA expression datasets by combining multiple feature selection techniques (i.e., creating an ensemble) or by the SVM-wrapper, and then classified by different learners. Generally speaking, creating a subset of features by selecting only the highest ranking features (miRNAs) improved upon results generated when using all the miRNAs, and the ensemble and SVM-wrapper approaches outperformed individual feature selection methods. Finally, an algorithm to determine the number of top-ranked features to include in the creation of feature subsets was developed. This algorithm takes into account the performance improvement gained by adding additional features compared to the cost of adding those features.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3332260
Subject Headings: Gene silencing, Biochemical markers, Cancer, Diagnosis, Data processing, Cancer, Diagnosis, Research, Gene expression, Tumor markers, Diagnostic use
Format: Document (PDF)

Title: Assessment of anatomical structures and hemodynamic function of cTnI[193His] transgenic mice with micro-echocardiography.
Creator: Gobara, Nariman., Charles E. Schmidt College of Medicine
Abstract/Description: Transgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart. My study's objective was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function was monitored in cTnI193His mice and wild-type littermates for a period of 12 months. It progressed gradually from abnormal relaxation to diastolic dysfunction...
Show moreTransgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart. My study's objective was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function was monitored in cTnI193His mice and wild-type littermates for a period of 12 months. It progressed gradually from abnormal relaxation to diastolic dysfunction characterized with micro- echocardiography by a reversed E/A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. The negative impact of cTnI193His on cardiac function was further demonstrated in isolated mouse working heart preparations. Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO. The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation characterized morphologically by enlarged atria and restricted ventricle and functionally by diastolic dysfunction.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186680
Subject Headings: Mice as laboratory animals, Biochemical markers, Diagnostic use, Cardiovascular system, Pathophysiology, Coronary heart disease, Molecular diagnosis
Format: Document (PDF)

Title: Exploring the endocrine profile of a geriatric female chimpanzee (Pan troglodytes).
Creator: Cloutier, Christina T., Dorothy F. Schmidt College of Arts and Letters, Department of Anthropology
Abstract/Description: In light of exceptionally delayed reproductive senescence exhibited by a 64 year old female chimpanzee (Pan troglodytes) housed in Florida, endocrinal analyses meant to determine the state of her current reproductive viability were conducted. Urine was collected from the study subject for a period of 88 days spaced within an interim of roughly 6 months and the specimens were sent to the Hominoid Reproductive Ecology Laboratory for assessment. Additional data was collected from three control...
Show moreIn light of exceptionally delayed reproductive senescence exhibited by a 64 year old female chimpanzee (Pan troglodytes) housed in Florida, endocrinal analyses meant to determine the state of her current reproductive viability were conducted. Urine was collected from the study subject for a period of 88 days spaced within an interim of roughly 6 months and the specimens were sent to the Hominoid Reproductive Ecology Laboratory for assessment. Additional data was collected from three control females in order to provide a basis of comparison against the hormonal markers present in the geriatric study animal. Results indicate that the geriatric female does not presently appear to be cycling, but nor does she exhibit signs of complete reproductive cessation. This could signify that Pan troglodytes adheres to a pattern of reproductive aging not necessarily shared by Homo sapiens, which has further implications for the evolutionary trajectory of menopause in the human female.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2100580
Subject Headings: Aging, Physiological aspects, Primates, Physiology, Primates, Reproduction, Encocrine aspects, Biochemical markers, Menopause, Physiological aspects
Format: Document (PDF)

Title: Genetic differentiation among populations of bald eagles, Haliaeetus leucocephalus.
Creator: Helmick, Ericka Elizabeth., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The bald eagle, Haliaeetus leucocephalus, population declined dramatically in the early 20th century reducing the population from tens of thousands of birds within the lower 48 states, to
Show moreThe bald eagle, Haliaeetus leucocephalus, population declined dramatically in the early 20th century reducing the population from tens of thousands of birds within the lower 48 states, to <450 pairs of birds, effectively inducing a population bottleneck. The overall population has recovered and was removed from the endangered species list in 2007. This study investigates whether such overall population statistics are appropriate descriptors for this widespread species. I investigated the genetic differentiation between three populations of bald eagles from Alaska, North Florida and Florida Bay using both mitochondrial and nuclear DNA loci to determine whether discrete subpopulations comprise the broad range. Significant FST values, for both mtDNA and microsatellites, were found between both Florida populations and Alaska, but not within Florida populations. Results indicate that there is strong population structure, rejecting the null hypothesis of a panmictic population. Future conservation efforts should focus on subpopulations rather than the overall population.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3171395
Subject Headings: Wildlife conservation, Birds, Molecular genetics, Gene targeting, Developmental biology, Biochemical markers
Format: Document (PDF)

Title: The effect of acute moderate-intensity continuous and high intensity interval exercise on serum brain-derived neurotrophic factor in recreationally trained males.
Creator: Mock, Thomas J., Whitehurst, Michael, Florida Atlantic University, College of Education, Department of Exercise Science and Health Promotion
Abstract/Description: BDNF is a neurotrophin that enhances neural health and is increased by exercise. PURPOSE: To compare moderate continuous (MCE) and high-intensity interval exercise (HIE) effects on serum BDNF levels, and examine the relationship between BDNF and lactate. METHODS: Seven males completed a VO2peak test and two protocols on separate days, (MCE) 28 min at 60% Workrate max (WRmax) and (HIE) 28 min of intervals at 90%WRmax (10- 1 min intervals separated by 2 min of rest). Serum BDNF and lactate were...
Show moreBDNF is a neurotrophin that enhances neural health and is increased by exercise. PURPOSE: To compare moderate continuous (MCE) and high-intensity interval exercise (HIE) effects on serum BDNF levels, and examine the relationship between BDNF and lactate. METHODS: Seven males completed a VO2peak test and two protocols on separate days, (MCE) 28 min at 60% Workrate max (WRmax) and (HIE) 28 min of intervals at 90%WRmax (10- 1 min intervals separated by 2 min of rest). Serum BDNF and lactate were determined prior, during, and following both protocols. RESULTS: BDNF levels (pg/mL) increased from baseline during HIE and MCE (p<.05). The BDNF response to HIE correlated with lactate for area under the curve (AUC) (r=0.901; P<0.05). CONCLUSION: HIE is an effective alternative to MCE at increasing BDNF. Additionally, lactate may act as a measure of intensity or a mediator of the BDNF response to exercise.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004219, http://purl.flvc.org/fau/fd/FA00004219
Subject Headings: Biochemical markers., Neurons--Physiology., Cell aging--Physiology., Neurotrophic function., Metabolic syndrome--Pathophysiology.
Format: Document (PDF)

Title: The Effect of Maximal Aerobic Exercise on Plasma BDNF and BDNF Expression in PBMCs in Obese and Non-Obese Individuals.
Creator: Maharaj, Arun, Whitehurst, Michael, Florida Atlantic University, College of Education, Department of Exercise Science and Health Promotion
Abstract/Description: The purpose of this study was to determine if maximal aerobic exercise promotes BDNF expression in obese individuals. Plasma levels and the expression of BDNF in PBMCs were examined. 22 participants (10 obese, 12 non-obese) completed a V02max treadmill test and blood was obtained pre, post, and 1 and 2 hours into exercise recovery. Plasma and PBMCs were isolated and analyzed for BDNF via ELISA and Western blot techniques. A significant effect for time was observed for plasma BDNF (P=
Show moreThe purpose of this study was to determine if maximal aerobic exercise promotes BDNF expression in obese individuals. Plasma levels and the expression of BDNF in PBMCs were examined. 22 participants (10 obese, 12 non-obese) completed a V02max treadmill test and blood was obtained pre, post, and 1 and 2 hours into exercise recovery. Plasma and PBMCs were isolated and analyzed for BDNF via ELISA and Western blot techniques. A significant effect for time was observed for plasma BDNF (P= <0.00 1 ). Additionally, A significant group-by-time interaction was found from pre-to-RIH for BDNF expression in PBMCs (P= 0.046). Further, significant correlations were found between BMI and waist circumference (r= .91, P< 0.001), WHR (r= .51, P= 0.002) and Pre-to-RlH ratio (r=0.58, P=0.008). Young obese subject's BDNF response to maximal exercise was consistent with previous studies. Post-exercise BDNF expressed in PBMCs were significantly higher than rest suggesting immunological-neuroprotective interactions in the CNS.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004664, http://purl.flvc.org/fau/fd/FA00004664
Subject Headings: Biochemical markers, Blood lipoproteins, Blood plasma -- Physiology, Exercise -- Physiological aspects, Obesity -- Exercise therapy
Format: Document (PDF)

Title: The chemistry of Briareum asbestinum.
Creator: Rondeau, Melody D., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Briareum asbestinum, a soft coral, is a rich source of diterpenoid natural products. The secondary metabolites of B. asbestinum fall into four classes : asbestinins, briarellins, briareolate esters, and briaranes. Briareolate esters have been shown to possess biological activity and were previously only reported from Tobago. Our group recently isolated briareolate esters from a specimen collected off the coast of Boca Raton, Florida. To determine whether location has an impact on the...
Show moreBriareum asbestinum, a soft coral, is a rich source of diterpenoid natural products. The secondary metabolites of B. asbestinum fall into four classes : asbestinins, briarellins, briareolate esters, and briaranes. Briareolate esters have been shown to possess biological activity and were previously only reported from Tobago. Our group recently isolated briareolate esters from a specimen collected off the coast of Boca Raton, Florida. To determine whether location has an impact on the chemistry produced by the organism, a method to discern between chemotypes was sought. Several techniques including thin layer chromatography (TLC), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and sclerite analysis were employed, with NMR being the most successful method. By utilizing both 1H and COSY NMR experiments, it is possible to differentiate between the chemotypes of B. asbestinum. Application of this method allowed analysis of chemical variability with respect to location.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3355882
Subject Headings: Heterocyclic compounds, Synthesis, Coral reef ecology, Marine organisms, Environmental aspects, Biochemical markers
Format: Document (PDF)

Title: Protective mechanism of Sulindac against animal model of ischemic stroke.
Creator: Modi, Jigar P., Charles E. Schmidt College of Medicine, Department of Biological Sciences
Abstract/Description: The Effect of Sulindac was studied on an animal model of ischemic stroke. Sulindac, a non steroid anti inflammatory drug (NSAID) could protect cell death due to hypoxia/reoxygenation. This drug was given 2 days before and 24 hrs after ischemia until animals were sacrificed on 3rd or 11th day. Infarct size was measured for these animals. Sulindac induced Hsp 27 in ischemic penumbra and core on Day 3 & 11 with uncoated nylon suture which shows its cell-survival and anti-apoptotic activity. Also...
Show moreThe Effect of Sulindac was studied on an animal model of ischemic stroke. Sulindac, a non steroid anti inflammatory drug (NSAID) could protect cell death due to hypoxia/reoxygenation. This drug was given 2 days before and 24 hrs after ischemia until animals were sacrificed on 3rd or 11th day. Infarct size was measured for these animals. Sulindac induced Hsp 27 in ischemic penumbra and core on Day 3 & 11 with uncoated nylon suture which shows its cell-survival and anti-apoptotic activity. Also, it increased expression of cell survival markers such as Akt, Bcl2 & Grp 78 in ischemic penumbra and core. With silicon suture it reduced expression of Hsp 27 in ischemic penumbra and core, alleviating cell stress and having pro-survival and anti-stress effects. In conclusion sulindac may have excellent potential as neuro protective agent against oxidative stress in cerebral ischemia.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3333056
Subject Headings: Apoptosis, Biochemical markers, Diagnostic use, Oxidation reduction reaction, Cerebral ischemia, Prevention
Format: Document (PDF)

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

Title: Methionine sulfoxide reductases: studies on the reducing requirements and role in the metabolism of sulindac.
Creator: Brunell, David J., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is...
Show moreThe methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is thioredoxin (Trx), although high levels of dithiothreitol (DTT) can be used as the reductant in vitro. In contrast, certain MsrB enzymes show less than 10% of the activity with Trx as compared to DTT. This raises the possibility that in animal cells Trx may not be the direct hydrogen donor for the MsrB enzymes. Studies with bovine liver extracts have shown that thionein, the apoprotein of metallothionein, can function as a reductant for the Msr proteins. Certain selenium compounds such as selenocystamine and selenocystine can also serve as potent reducing agents for the Msr enzymes. Since an increased activity of Msr enzymes can reduce the level of oxidative damage in tissues, compounds that could activate Msr may have therapeutic potential. A high-throughput screening assay has been developed to screen large chemical libraries to find activators of MsrA, as well as specific inhibitors that could be useful research tools. This study will be done in collaboration with The Scripps Florida Research Institute. Sulindac was originally developed as a non-steroidal anti-inflammatory drug but has also shown efficacy in the treatment of certain cancers. The S epimer of sulindac is known to be reduced by MsrA, but the enzymes responsible for reduction of the R epimer are not known., An activity has been purified from rat liver which is capable of reducing the R epimers of sulindac, free Met(O) and a dabsylated Met(O) substrate, the latter suggesting that this enzyme may have properties similar t o the MsrB enzymes. The oxidation of the epimers of sulindac to sulindac sulfone has also been characterized, and the members of the cytochrome P450 family involved in the oxidation have been identified.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/227979
Subject Headings: Cellular signal transduction, Proteins, Chemical modification, Biochemical markers, Oxidation-reduction reaction
Format: Document (PDF)

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

Title: Studies on the mechanism by which sulindac sensitizes cancer cells to oxidative stress.
Creator: Kreymerman, Alexander, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Sulindac is a known NSAID that has also been shown to have anti-cancer activity that is not related to its ability to inhibit COX 1 and 2. During the past 15 years there have been a large number of studies attempting to elucidate its mechanism of action. Our laboratory has shown that sulindac can both protect normal cells and enhance the killing of cancer cells under oxidative stress from H2O2 and TBHP. However, except for mitochondrial dysfunction and ROS production, the mechanism by which...
Show moreSulindac is a known NSAID that has also been shown to have anti-cancer activity that is not related to its ability to inhibit COX 1 and 2. During the past 15 years there have been a large number of studies attempting to elucidate its mechanism of action. Our laboratory has shown that sulindac can both protect normal cells and enhance the killing of cancer cells under oxidative stress from H2O2 and TBHP. However, except for mitochondrial dysfunction and ROS production, the mechanism by which sulindac sensitized the cancer cells to oxidative stress remains unknown. Results of this research project suggest that the effect of sulindac and oxidative stress not only involves mitochondrial ROS production, but also aspects of the preconditioning response. In normal cells this leads to survival by a preconditioning pathway, likely involving PKCε. . However, cancer cells react by initiating a pathway leading to apoptosis involving PKCδ.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3183124
Subject Headings: Proteins, Chemical modification, Cellular signal transduction, Biochemical markers, Diagnostic use, Drug resistance in cancer cells, Oxidation-reduction reaction
Format: Document (PDF)

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

Title: Mechanism of neuroprotection in stroke-related models.
Creator: Pan, Chunliu., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Stroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three...
Show moreStroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three stroke-related models : hypoxia, excessive glutamtate and oxidative stress. In the first part of this dissertation, we studied the neuroprotection of taurine against oxidative stress induced by H2O2 in PC12 cells. Our results show that extracellular taurine exerts a neuroprotective function by restoring the expression of Bcl-2 and downregulation of the three Endoplasmic Reticulum (ER) stress markers : GRP78, Bim and CHOP/GADD153, suggesting that ER stress can be provoked by oxidative stress and can be suppressed by taurine. In the second part, glutamate excitotoxicity-induced ER stress was studied with dose and time as variables in primary cortical neurons. The results demonstrate that glutamate excitotoxicity leads to the activation of three ER stress pathways (PERK, ATF6 and IRE1) by initiating PERK first, ATF6 second and IRE1 pathway last. The third part of this dissertation studied the robust and beneficial protection of taurine in cortical neurons under hypoxia/reoxygenation or glutamate toxicity condition. We found that taurine suppresses the up-regulation of GRP778, Bim, caspase-12 and GADD153/CHOP induced by excessive glutamate or hypoxia/reoxygenation, suggesting that taurine may exert a protective function against hypoxia/regeneration by reducing the ER stress., Moreover, taurine can down-regulate the ratio of cleaved ATF6 and full length ATF6, and p-IRE1 expresssion, indicating that taurine inhibits the ER stress induced by hypoxia/reoxygenation or glutamate through suppressing ATF6 and IRE1 pathways. In the fourth part, the synergistic benefits of the combination of taurine and G-CSF, and the neuroprotective effects of G-CSF, sulindac or DETC-MeSO are studied in cortical neurons. Our results show that G-CSF, sulindac or DETC-MeSO can highly increase the neuron visibility by inhibiting ER stress induced by hypoxia/reoxygenation or glutamate toxicity. Furthermore, we proved that G-CSF or sulindac can significantly inhibit the activation of ATF6 or IRE1 pathway stimulated by hypoxia/reoxygenation, and DETC-MeSO can suppress the activation of both PERK and IRE1 pathways in primary neuron cultures. These findings provide promising and rational strategies for stroke therapy.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3352284
Subject Headings: Sulindac, Physiological effect, Taurine, Physiological effect, Cerebral ischemia, Prevention, Biochemical markers, Diagnostic use, Apoptosis, Oxidation reduction reaction
Format: Document (PDF)

Title: Phenotypic and behavioral effects of methionine sulfoxide reductase deficiency and oxidative stress in Drosophila melanogaster.
Creator: Mulholland, Kori., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Harman's theory of aging proposes that a buildup of damaging reactive oxygen species (ROS) is one of the primary causes of the deleterious symptoms attributed to aging. Cellular defenses in the form of antioxidants have evolved to combat ROS and reverse damage; one such group is the methionine sulfoxide reductases (Msr), which function to reduce oxidized methionine. MsrA reduces the S enantiomer of methionine sulfoxide, Met-S-(o), while MsrB reduces the R enantiomer, Met-R-(o). The focus of...
Show moreHarman's theory of aging proposes that a buildup of damaging reactive oxygen species (ROS) is one of the primary causes of the deleterious symptoms attributed to aging. Cellular defenses in the form of antioxidants have evolved to combat ROS and reverse damage; one such group is the methionine sulfoxide reductases (Msr), which function to reduce oxidized methionine. MsrA reduces the S enantiomer of methionine sulfoxide, Met-S-(o), while MsrB reduces the R enantiomer, Met-R-(o). The focus of this study was to investigate how the absence of one or both forms of Msr affects locomotion in Drosophila using both traditional genetic mutants and more recently developed RNA interference (RNAi) strains. Results indicate that lack of MsrA does not affect locomotion. However, lack of MsrB drastically reduces rates of locomotion in all age classes. Furthermore, creation of an RNAi line capable of knocking down both MsrA and MsrB in progeny was completed.
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Date Issued: 2013
PURL: http://purl.flvc.org/fcla/dt/3362558
Subject Headings: Drosophila melanogaster, Genetics, Aging, Molecular aspects, Oxidative stress, Mitochondrial pathology, Cellular signal transduction, Oxidation-reduction reaction, Biochemical markers, Mutation (Biology)
Format: Document (PDF)

Title: Mechanisms of protection against ischemic damage in the heart.
Creator: Moench, Ian, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Heart disease including ischemic heart disease is the highest contributor to death and morbidity in the western world. The studies presented were conducted to determine possible pathways of protection of the heart against ischemia/reperfusion. We employed adenovirus mediated over-expression of Methionine sulfoxide reductase A (MsrA) in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation. Cells transfected with MsrA encoding...
Show moreHeart disease including ischemic heart disease is the highest contributor to death and morbidity in the western world. The studies presented were conducted to determine possible pathways of protection of the heart against ischemia/reperfusion. We employed adenovirus mediated over-expression of Methionine sulfoxide reductase A (MsrA) in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation. Cells transfected with MsrA encoding adenovirus and subjected to hypoxia/reoxygenation exhibited a 45% decrease in apoptosis as compared to controls. Likewise total cell death as determined by levels of Lactate Dehydrogenase (LDH) release was dramatically decreased by MsrA overexpression. The initial hypothesis that led to our testing sulindac was based on the fact that the S epimer of sulindac was a substrate for MsrA and that this compound might function as a catalytic anti-oxidant based on a reaction cycle that involved reductio n to sulindac sulfide followed by oxidation back to sulindac. To test this we examined the protective effect of sulindac in hypoxia re-oxygenation in both cardiac myocytes in culture and using a Langendorff model of myocardial ischemia. Using this model of myocardial ischemia we showed that pre-incubation of hearts with sulindac, or the S and R epimers of sulindac resulted in protection against cell death. We present several lines of evidence that the protective effect of sulindac is not dependent on the Msr enzyme system nor does it involve the well established role of sulindac as a Cyclooxygenase (COX) inhibitor. Numerous signaling pathways have been implicated in myocardial protective mechanisms, many of which require fluctuations in ROS levels as initiators or mediators., Sulindac shows very good potential as a preconditioning agent that could induce tissue protection against oxidative damage.Blocking of preconditioning pathways by administration of the PKC blocker chelerythine abrogated the ischemic protection afforded by sulindac. Secondly, an end-effector of preconditioning, inducible nitric oxide synthase (iNOS),was found to be induced by greater than 5 fold after 48 h prior feeding sulindac.
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Date Issued: 2008
PURL: http://purl.flvc.org/FAU/186291
Subject Headings: Biochemical markers, Diagnostic use, Cardiovascular system, Diseases, Diagnosis, Heart, Diseases, Molecular aspects, Medical care, Quality control, Coronary heart disease, Prevention, Apoptosis, Myocardial infarction, Prevention
Format: Document (PDF)

Biochemical markers (13)	+ -
Diagnostic use (7)	+ -
Mice as laboratory animals (4)	+ -
Apoptosis (3)	+ -
Cardiovascular system (3)	+ -

Cellular signal transduction (3)	+ -
Oxidation-reduction reaction (3)	+ -
Prevention (3)	+ -
Aging (2)	+ -
Biochemical markers -- Diagnostic use (2)	+ -
Cardiovascular system -- Pathophysiology (2)	+ -
Cerebral ischemia (2)	+ -
Chemical modification (2)	+ -
Coronary heart disease (2)	+ -
Coronary heart disease -- Molecular diagnosis (2)	+ -
Diagnosis (2)	+ -
Diseases (2)	+ -
Heart (2)	+ -
Molecular aspects (2)	+ -
Molecular biology (2)	+ -
Molecular diagnosis (2)	+ -
Oxidation reduction reaction (2)	+ -
Pathophysiology (2)	+ -
Proteins (2)	+ -
Biochemical markers. (1)	+ -
Birds (1)	+ -
Blood lipoproteins (1)	+ -
Blood plasma -- Physiology (1)	+ -
Cancer (1)	+ -
Cell aging--Physiology. (1)	+ -

Charles E. Schmidt College of Science (8)	+ -
Department of Biological Sciences (7)	+ -
Charles E. Schmidt College of Medicine (4)	+ -
Florida Atlantic University (3)	+ -
College of Education (2)	+ -

Department of Biomedical Science (2)	+ -
Department of Chemistry and Biochemistry (2)	+ -
Department of Exercise Science and Health Promotion (2)	+ -
Whitehurst, Michael (2)	+ -
Brunell, David J. (1)	+ -
Cloutier, Christina T. (1)	+ -
College of Engineering and Computer Science (1)	+ -
Department of Anthropology (1)	+ -
Department of Computer and Electrical Engineering and Computer Science (1)	+ -
Dorothy F. Schmidt College of Arts and Letters (1)	+ -
Du, Jianfeng. (1)	+ -
Getfield, Cecile A. (1)	+ -
Gobara, Nariman. (1)	+ -
Helmick, Ericka Elizabeth. (1)	+ -
Huang, Xupei (1)	+ -
Jean-Charles, Pierre-Yves (1)	+ -
Kotlarchyk, Alex J. (1)	+ -
Kreymerman, Alexander (1)	+ -
Maharaj, Arun (1)	+ -
Mock, Thomas J. (1)	+ -
Modi, Jigar P. (1)	+ -
Moench, Ian (1)	+ -
Mulholland, Kori. (1)	+ -
Pan, Chunliu. (1)	+ -
Rondeau, Melody D. (1)	+ -

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