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Cytogenetic of chromosomal synteny evaluation: bioinformatic applications towards screening of chromosomal aberrations/ genetic disorder
Title
Cytogenetic of chromosomal synteny evaluation: bioinformatic applications towards screening of chromosomal aberrations/ genetic disorder.
Creator
Sharma, Sandhya, Neelakanta, Perambur S., Florida Atlantic University, College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description
The research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study...
Show moreThe research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study addresses: (i) Cytogenetic framework of syntenic correlation and, (ii) applying information-theoretics to determine entropy-dictated synteny across an exhaustive set of orthologs of the test pairs of species.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00004331, http://purl.flvc.org/fau/fd/FA00004331
Subject Headings
Cytogenetics, Genetic screening, Human chromosome abnormalities, Medical genetics, Molecular biology, Molecular diagnosis, Molecular genetics, Mutation (Biology)
Format
Document (PDF)
Mechanisms of Placental Dysfunction in Pregnancy Malaria
Title
Mechanisms of Placental Dysfunction in Pregnancy Malaria.
Creator
Lybbert, Jared, Oleinikov, Andrew V., Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description
The molecular mechanisms by which pregnancy malaria affects the outcome of fetal development are unknown. Megalin, which has been well studied in kidney, has high expression in the placenta from early stages to term, and is proposed to be an important factor in extensive maternofetal exchange during development of the fetus. Pregnancy malaria (PM) is characterized by inflammation in placenta and is associated with low birthweight (LBW), stillborn birth, and other pathologies. It is...
Show moreThe molecular mechanisms by which pregnancy malaria affects the outcome of fetal development are unknown. Megalin, which has been well studied in kidney, has high expression in the placenta from early stages to term, and is proposed to be an important factor in extensive maternofetal exchange during development of the fetus. Pregnancy malaria (PM) is characterized by inflammation in placenta and is associated with low birthweight (LBW), stillborn birth, and other pathologies. It is hypothesized that PM disturbs megalin function/expression/distribution in the brush boarder of syncytiotrophoblast which, in turn, may contribute significantly to pathology of LBW. Our studies show that the presence of infected erythrocytes in placenta at the time of delivery negatively affects protein abundance for megalin and Dab2. This is the first report associating the abundance of placental megalin system proteins with the birth weight of newborn babies, and associating PM with changes in megalin system protein abundance.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004520, http://purl.flvc.org/fau/fd/FA00004520
Subject Headings
Birth weight, Low, Critical care medicine, Fetus -- Diseases -- Molecular diagnosis, Pregnancy -- Complications, Prenatal diagnosis, Stillbirth
Format
Document (PDF)
cTnI N-Terminal deletion: an agent for rescuing restrictive cardiomyopathy, a disease caused by mutations of Cardiac Troponin I
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)
Mechanism and treatment of restrictive cardiomyopathy
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)
Assessment of anatomical structures and hemodynamic function of cTnI[193His] transgenic mice with micro-echocardiography
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)
Roles of troponin I in heart development and cardiac function
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)
Mechanisms of protection against ischemic damage in the heart
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)