Current Search: info:fedora/islandora:personCModel (x) » info:fedora/fau:legacyETDs (x) » Electronic Thesis or Dissertation (x) » Charles E. Schmidt College of Medicine (x)
View All Items
Pages
- Title
- A review of corporate-based wellness programs for general health promotion and prevention of type II diabetes mellitus.
- Creator
- Hemmings, Jodian R., Blanks, Robert H., Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
This research focuses on obesity and other major risk factors for chronic diseases such as Type II Diabetes Mellitus, Heart Disease, and Stroke. Worksite wellness programs have been successful in this realm of health promotion and disease prevention for heart disease and stroke, but their effectiveness in treating diabetes has been uncertain partially due to poor patient compliance, lack of stress reduction strategies, poor diet and lack of persuasive health education on the risk of being...
Show moreThis research focuses on obesity and other major risk factors for chronic diseases such as Type II Diabetes Mellitus, Heart Disease, and Stroke. Worksite wellness programs have been successful in this realm of health promotion and disease prevention for heart disease and stroke, but their effectiveness in treating diabetes has been uncertain partially due to poor patient compliance, lack of stress reduction strategies, poor diet and lack of persuasive health education on the risk of being obese. Published peer-reviewed articles were reviewed, coded and analyzed to determine best practices, using a modified systematic review approach. The findings from these studies yield results that were used to develop a new employer-sponsored wellness program that is in accordance with the recently passed Affordable Care Act.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004201, http://purl.flvc.org/fau/fd/FA00004201
- Subject Headings
- Behavior modification, Employee assistance programs, Health promotion, Medicine, Preventive, Non insulin dependent diabetes -- Prevention, obesity -- Risk factors, Preventive health services, Psychology, Industrial, Social responsibility of business, United States -- Patient Protection and Affordable Care Act
- Format
- Document (PDF)
- Title
- A Study on the Potential Role of Stress Granules and Processing Bodies in Eliminating Oxidatively Damaged RNA.
- Creator
- Pourkalbassi, Delaram, Li, Zhongwei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Oxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and...
Show moreOxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and processing bodies (PB) in eliminating abasic RNA in situ. We demonstrated that RNA is a major target of oxidative damage, constituting the majority of OS-induced abasic nucleic acids in HeLa cell. Importantly, the level of abasic RNA is strongly correlated with SG abundance. Furthermore, inhibition of SG/PB formation causes accumulation of abasic RNA, suggesting that SG/PB participates in removing oxidized RNA and protects cells under OS, which offers novel targets for therapeutic intervention in age-related diseases.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00004702
- Subject Headings
- Aging -- Physiological aspects., Oxidative stress., RNA -- Metabolism.
- Format
- Document (PDF)
- Title
- Amyloid Cascade Hypothesis Perspective on Alzheimer's Disease.
- Creator
- Elsouri, Kawther, Kantorow, Marc, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Alzheimer’s disease (AD) has been defined as a type of dementia that causes problems with memory, thinking, and behavior. AD is characterized by tau tangles and Aβ plaques in and around neurons, respectively. The impact this disease has on its victims’ health, both physically and mentally, is unimaginable and the rate of progression is not expected to decrease any time soon. This threat to our minds encourages the importance of understanding AD. Amongst the theories as to what bio mechanisms...
Show moreAlzheimer’s disease (AD) has been defined as a type of dementia that causes problems with memory, thinking, and behavior. AD is characterized by tau tangles and Aβ plaques in and around neurons, respectively. The impact this disease has on its victims’ health, both physically and mentally, is unimaginable and the rate of progression is not expected to decrease any time soon. This threat to our minds encourages the importance of understanding AD. Amongst the theories as to what bio mechanisms cause the brain to intertwine is the amyloid cascade hypothesis. The purpose of this thesis is to review the amyloid cascade hypothesis and discuss treatments which utilize this model. We also wish to examine social aspects such as loneliness and socioeconomic factors which are associated with the progression of AD. Research presented provides evidence that targeting the accumulation of Aβ in the brain will prevent further biochemical responses to form neurodegenerative pathology. From the collected data, we observe that therapies targeting the amyloidogenic pathway have received positive feedback in the medical community. Amongst them, an Aβ synthetic peptide vaccine which made history in vaccine development due to their responder rate. The impact of social factors such as loneliness in the advancement of AD is also supported by research. While it is acknowledged that any neurodegenerative disease is far too complex to narrow its cause specifically, this thesis provides an association with multiple aspects that can be understood and applied to future research in this field.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00005986
- Subject Headings
- Alzheimer Disease--etiology, Amyloid, Amyloid beta-protein
- Format
- Document (PDF)
- Title
- Analyses of neuronal replacement in the neuron-depleted olfactory systems in adult mice.
- Creator
- Liu, Huan, Charles E. Schmidt College of Medicine
- Abstract/Description
-
New neurons are continuously generated in the olfactory system of adult mice, including olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) and interneurons, produced in the subventricular zone (SVZ) and migrated toward olfactory bulb (OB) along rostral migratory stream (RMS). The present study observed the effects of target neuron loss on the life-span and maturation of adult-born OSNs in the OE and on the proliferation, migration and differentiation of SVZ stem cells in the...
Show moreNew neurons are continuously generated in the olfactory system of adult mice, including olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) and interneurons, produced in the subventricular zone (SVZ) and migrated toward olfactory bulb (OB) along rostral migratory stream (RMS). The present study observed the effects of target neuron loss on the life-span and maturation of adult-born OSNs in the OE and on the proliferation, migration and differentiation of SVZ stem cells in the forebrain after eliminating bulb neurons. We found the life-span of newborn neurons in the absence of synaptic targets was shortened, but the timing of maturation was not delayed. In addition, SVZ cells continued to divide and migrate to the damaged bulb, and the migration of newborn cells in the RMS on the contralateral side was delayed at 2 weeks post-BrdU. Also, the proliferation of cells in dentate gyrus of the hippocampus was not affected by OB damage at 3 weeks post-lesion, though lesion affects occurred in the adult SVZ/RMS.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/fcla/dt/172671
- Subject Headings
- Mice as laboratory animals, Neurotransmitter receptors, Sensory neurons, Testing, Cellular control mechanisms
- Format
- Document (PDF)
- Title
- Approaches for raising the level of FOXO3a in animal cells.
- Creator
- Navarro, Diana., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
The turtle is a unique model of anoxic survival. The turtle's brain can tolerate total oxygen deprivation for hours to days as well as prevent high levels of mitochondrial-derived free radicals upon re-oxygenation. Because of its ability to prevent elevated free radical generation, the turtle has also become recognized as a model of exceptional longevity. We are employing the turtle model for an investigation into the regulation of a key antioxidant enzyme system - methionine sulfoxide...
Show moreThe turtle is a unique model of anoxic survival. The turtle's brain can tolerate total oxygen deprivation for hours to days as well as prevent high levels of mitochondrial-derived free radicals upon re-oxygenation. Because of its ability to prevent elevated free radical generation, the turtle has also become recognized as a model of exceptional longevity. We are employing the turtle model for an investigation into the regulation of a key antioxidant enzyme system - methionine sulfoxide reductases (Msrs), primarily MsrA and MsrB. The Msr system is capable of reversing oxidation of methionines in proteins and Msr subtypes have been implicated in protecting tissues against oxidative stress, as well as, enhancing the longevity of organisms from yeast to mammals. Preliminary data, unpublished results, indicate that MsrA protein and transcripts are elevated by anoxia. A recent study on Caenorhabditis elegans demonstrated that FOXO is involved in activation of the MsrA promoter. Using the turtle MsrA promoter sequence we worked to determine which regions in the promoter are necessary for activation by anoxia. The results of the present study were 1) to prepare a TAT-FOXO3a fusion protein which could penetrate animal cells and 2) to construct a FOXO3a expression vector for transcription studies on MsrA expression.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3342243
- Subject Headings
- Cellular signal transduction, Cell proliferation, Oxidative stress, Prevention, Adaptation (Physiology)
- 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.
Show less - 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
- CHARACTERIZATION OF BAZ1B, A TARGET PROTEIN OF CHEMOTHERAPEUTIC RESISTANCE IN CANCER.
- Creator
- Toussaint, Mohamed-Tamar, Grant, Patrick, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Epigenetic dysregulation has been implicated in oncogenesis, with post-translational histone modifications being linked to cancer progression. WSTF/BAZ1B forms chromatin-remodeling complexes with other proteins and lowers cancer survival outcomes. Treatment resistance causes >90 % of all cancer deaths. In particular, cancers develop tolerance to cisplatin-induced genotoxicity. It is hypothesized that the BAZ1B bromodomain, PHD finger, and DDT domain recognize epigenetic modifications,...
Show moreEpigenetic dysregulation has been implicated in oncogenesis, with post-translational histone modifications being linked to cancer progression. WSTF/BAZ1B forms chromatin-remodeling complexes with other proteins and lowers cancer survival outcomes. Treatment resistance causes >90 % of all cancer deaths. In particular, cancers develop tolerance to cisplatin-induced genotoxicity. It is hypothesized that the BAZ1B bromodomain, PHD finger, and DDT domain recognize epigenetic modifications, contributing to cisplatin resistance in cancers. To test this, the domains were expressed in Rosetta 2 BL21(DE3) and Rosetta 2 BL21(DE3) PLysS Escherichia coli strains. Soluble proteins were extracted, purified, and then analyzed using pulldown assays and modified histone peptide arrays. The DDT and PHD finger domains were found to bind to specific histone modifications with the DDT domain also displayed DNA-binding properties. Some of the identified histone modifications have known roles/correlations in normal and cancer cells, implicating BAZ1B as an agent in oncogenesis, treatment resistance, and as a therapeutic target.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014296
- Subject Headings
- Cancer, Epigenetics, Histones
- Format
- Document (PDF)
- Title
- CHARACTERIZATION OF DIFFERENTIATED HUMAN NEUROBLASTOMA SH-SY5Y CELLS IN CULTURE.
- Creator
- Condikey, Siri, Prentice, Howard, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases affecting an estimated 20 million worldwide. The primary pathology of AD is the progressive loss of basal forebrain cholinergic neurons, which is responsible for the cognitive decline experienced by AD patients. The mechanisms underlying this selective vulnerability have not been fully elucidated. Furthermore, oxidative stress is a key factor behind the pathology of AD leading to this neuronal loss. The current...
Show moreAlzheimer’s disease (AD) is one of the most common neurodegenerative diseases affecting an estimated 20 million worldwide. The primary pathology of AD is the progressive loss of basal forebrain cholinergic neurons, which is responsible for the cognitive decline experienced by AD patients. The mechanisms underlying this selective vulnerability have not been fully elucidated. Furthermore, oxidative stress is a key factor behind the pathology of AD leading to this neuronal loss. The current literature suggests that there are limited in-vitro models available to accurately simulate the hallmark symptoms of Alzheimer's disease (AD). The SH-SY5Y cell line has been used extensively to study neuronal stress responses but the undifferentiated cell type has been predominantly used. Undifferentiated SH-SY5Y versus differentiated SH-SY5Y have been shown to have different interaction, expression and localization with AD hallmark, amyloid-b -42. This project sought to use differentiated cholinergic cells from the line SH-SY5Y to further isolate and elucidate, in-vitro, the mechanisms behind the oxidative stress response, a key stressor in the pathology of AD. Building upon previous studies, a protocol to differentiate SH-SY5Y cells with retinoic acid (RA) and neurotrophin (BDNF) to mature neurons of the cholinergic phenotype was optimized and implemented. The results showed successful differentiation into the cholinergic phenotype as evidenced via immunofluorescence imaging of choline acetyl transferase (ChAT) expression and mature neurite morphology. To simulate oxidative stress, we exposed both undifferentiated and differentiated SH-SY5Y cells to hypoxic conditions. Results indicated a stress response to mild hypoxic conditions with higher sensitivity in cholinergic differentiated SH-SY5Y. Understanding these hallmark mechanisms behind oxidative stress is crucial to developing mechanism-based therapeutics for AD.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014347
- Subject Headings
- Alzheimer Disease, Cholinergic Neurons, Alzheimer Disease--pathology
- Format
- Document (PDF)
- Title
- Characterization of RNase in Mycoplasma genitalium and study of its possible role in tRNA processing.
- Creator
- Lalonde, Maureen S., Florida Atlantic University, Li, Zhongwei, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Exoribonucleases degrade RNA and are important in RNA metabolism and gene expression. Mycoplasma genitalium, a bacterium with the smallest genome known, has only one identified exoribonuclease, RNase R (MgR). In this work RNA degradation properties of purified MgR were examined. As observed in Escherichia coli RNase R (EcR) studies, MgR degrades poly(A), rRNA, and oligoribonucleotides in 3'--->5' direction, though its substrate specificity and optimal activity requirements vary. Interestingly...
Show moreExoribonucleases degrade RNA and are important in RNA metabolism and gene expression. Mycoplasma genitalium, a bacterium with the smallest genome known, has only one identified exoribonuclease, RNase R (MgR). In this work RNA degradation properties of purified MgR were examined. As observed in Escherichia coli RNase R (EcR) studies, MgR degrades poly(A), rRNA, and oligoribonucleotides in 3'--->5' direction, though its substrate specificity and optimal activity requirements vary. Interestingly, MgR is sensitive to 2-O-methylation stopping downstream of such modifications in native rRNA and synthetic oligoribonucleotides. MgR removes the 3' trailer sequence from a tRNA precursor of M. genitalium and generates products equal to the mature tRNA, demonstrating a role of MgR in tRNA maturation. The 3' terminal CCA sequence and the acceptor stem of tRNA play a role in determining the formation of such products by MgR. These results suggest multiple functions of RNase R in RNA metabolism in Mycoplasma.
Show less - Date Issued
- 2006
- PURL
- http://purl.flvc.org/fcla/dt/13317
- Subject Headings
- Gene expression, RNA-protein interactions, Cellular control mechanisms, Ribonucleases--Analysis, Cell membranes
- Format
- Document (PDF)
- Title
- Chitin Microparticles (CMPs) Induce M1 Macrophage Activation via Intracellular TLR2 Signaling Mechanism.
- Creator
- Davis, Spring, Shibata, Yoshimi, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biological Sciences
- Abstract/Description
-
Chitin Microparticles (CMPs, 1-10um), a special form of the ubiquitous and nontoxic polysaccharide Chitin (GlcNAc), is capable of inducing a switch in macrophages from the wound-healing M2 phenotype to the classically activated pro-inflammatory M1 phenotype; which has therapeutic implications in allergy and cancer. We hypothesized that TLR2 forms a complex with CMPs and Chitin-Binding Proteins (CBPs) at the surface of peritoneal macrophages and remains with that complex after internalization...
Show moreChitin Microparticles (CMPs, 1-10um), a special form of the ubiquitous and nontoxic polysaccharide Chitin (GlcNAc), is capable of inducing a switch in macrophages from the wound-healing M2 phenotype to the classically activated pro-inflammatory M1 phenotype; which has therapeutic implications in allergy and cancer. We hypothesized that TLR2 forms a complex with CMPs and Chitin-Binding Proteins (CBPs) at the surface of peritoneal macrophages and remains with that complex after internalization to initiate downstream signaling events, leading to the production of the M1 cytokine, TNFalpha. Our results from experiments performed in RAW 264.7 cells show that TLR2 and TLR1, but not TLR6, are associated with the CMP binding fraction, and that both TLR1 and TLR2 might be important for M1 activation as a result of CMP phagocytosis. This project sheds light on CMP as a potential therapeutic agent and provides more evidence for a phagocytosis-dependent TLR2 signaling pathway.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00004762, http://purl.flvc.org/fau/fd/FA00004762
- Subject Headings
- Biopharmaceutics., Macrophages., Cell receptors., Ligands (Biochemistry), High performance processors.
- Format
- Document (PDF)
- Title
- Chronic variable stress affects hippocampal neurotrophic factor gene expression in the novelty-seeking phenotype: epigenetic regulation.
- Creator
- Oztan, Ozge., Charles E. Schmidt College of Medicine
- Abstract/Description
-
Experimentally naive rats exhibit varying degrees of novelty exploration. Some rats display high rates of locomotor reactivity to novelty (high responders; HR), and others display low rates (low responders; LR). The novelty-seeking phenotype (LRHR) is introduced as a model of stress responsiveness. In this thesis I examined effects of chronic variable physical and social stress or control handling on the levels of various neurotrophins in the hippocampus, and changes in mossy fibre terminal...
Show moreExperimentally naive rats exhibit varying degrees of novelty exploration. Some rats display high rates of locomotor reactivity to novelty (high responders; HR), and others display low rates (low responders; LR). The novelty-seeking phenotype (LRHR) is introduced as a model of stress responsiveness. In this thesis I examined effects of chronic variable physical and social stress or control handling on the levels of various neurotrophins in the hippocampus, and changes in mossy fibre terminal fields in LRHR rats. A positive correlation is seen between histone deacetylase 2 and brain-derived neurotrophic factor (BDNF) levels both of which are oppositely regulated in LRHR CA3 fields in response to chronic social stress. Increase in BDNF levels in CA3 field accompanied increase in supra-pyramidal mossy fibre terminal field size (SP-MF) in HRs, and decrease in BDNF levels accompanied decrease in SP-MF volume in LRs. Epigenetic regulation of neurotrophic support underlying these structural changes is discussed.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/215290
- Subject Headings
- Rats as laboratory animals, Cellular signal transduction, Gene expression, Hippocampus (Brain), Physiology, Neural transmission, Genetic regulation
- Format
- Document (PDF)
- Title
- Control of Mitochondrial αB-crystallin Function by Phosphorylation.
- Creator
- Posada, Angie, Kantorow, Marc, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
αB-crystallin is a small heat-shock chaperone protein (sHSP) required for the homeostasis of multiple tissues including eye lens, retina, heart and brain. Correspondingly, mutation or altered levels of αB-crystallin are associated with multiple degenerative diseases including cataract, retinal degeneration, cardiomyopathy and Lewy body disease. Based on its wide-ranging importance understanding the protective and homeostatic properties of α B-crystallin is critical for understanding...
Show moreαB-crystallin is a small heat-shock chaperone protein (sHSP) required for the homeostasis of multiple tissues including eye lens, retina, heart and brain. Correspondingly, mutation or altered levels of αB-crystallin are associated with multiple degenerative diseases including cataract, retinal degeneration, cardiomyopathy and Lewy body disease. Based on its wide-ranging importance understanding the protective and homeostatic properties of α B-crystallin is critical for understanding degenerative diseases and could lead to the development of therapies to treat these diseases. αB-crystallin is localized to the mitochondria suggesting a direct effect on mitochondrial function. My thesis work has examined those molecular pathways required for translocation of αB-crystallin to the mitochondria and to identify the downstream pathways controlled by mitochondrial translocation of αB-crystallin that could be important for cellular protection and differentiation. My results point to a novel role of αB-crystallin in regulation of key apoptotic pathways that mediate the balance between cell survival and differentiation.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013166
- Subject Headings
- alpha-Crystallin B Chain, Mitochondria, Phosphorylation, Degenerative diseases
- 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.
Show less - 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
- Determining the subcellular localization of a group II p21-activated kinase - PAK6.
- Creator
- John, Ciny, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
p-21-activated kinase 6 (PAK6) is a serine-threonine protein kinase originally identified as an Androgen Receptor (AR) interacting protein. In current study, we determined the subcellular localization of PAK6 through mutational analysis. We have found that the N-terminal CRIB domain is partly responsible for plasma membrane targeting, the region between amino acid residues #292 to #368 is functionally relevant to plasma membrane localization and that amino acid residues #119 through #190 are...
Show morep-21-activated kinase 6 (PAK6) is a serine-threonine protein kinase originally identified as an Androgen Receptor (AR) interacting protein. In current study, we determined the subcellular localization of PAK6 through mutational analysis. We have found that the N-terminal CRIB domain is partly responsible for plasma membrane targeting, the region between amino acid residues #292 to #368 is functionally relevant to plasma membrane localization and that amino acid residues #119 through #190 are responsible for nuclear targeting of PAK6, in addition to a stretch of positively charged N-terminal residues (#2-#11) since mutants lacking this sequence mis-localizes to cytoplasm. In junction forming epithelial cells, PAK6 is demonstrated to co-localize with B-catenin at adherens junctions, suggesting that PAK6 is an activation-dependent event and that PAK6 translocates from plasma membrane to the cytoplasm in response activation via the PKA signal pathway.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3355569
- Subject Headings
- Cellular signal transduction, Serine proteinases, Phosphorylation, Protein kinases, Pathophysiology, Phosphoroproteins, Metabolism
- Format
- Document (PDF)
- Title
- DEVELOPMENT OF A HIFI-Α LENS SPECIFIC KNOCKOUT MOUSE AS A MODEL FOR HYPOXIA DRIVEN LENS DIFFERENTIATION.
- Creator
- Adele, Adedamola, Kantorow, Marc, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
During eye lens development the lens receives oxygen from a network of capillaries that comprise of the tunica vasculosa lentis and the anterior pupillary membrane. In development there is regression of this capillaries with the vitreous and aqueous humor, which is the lens only source of oxygen, leaving the lens in low oxygen state. The lens contains a decreasing oxygen gradient from the surface to the core that parallels the differentiation of immature surface epithelial cells into mature...
Show moreDuring eye lens development the lens receives oxygen from a network of capillaries that comprise of the tunica vasculosa lentis and the anterior pupillary membrane. In development there is regression of this capillaries with the vitreous and aqueous humor, which is the lens only source of oxygen, leaving the lens in low oxygen state. The lens contains a decreasing oxygen gradient from the surface to the core that parallels the differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia and the master regulator of the hypoxic response, hypoxia-inducible transcription factor 1 alpha (HIF1a), in the regulation of genes required for lens fiber cell differentiation, structure, and transparency. Previous studies by our lab discovered the HIF1a-dependent gene expression patterns of lens genes by utilizing a Multiomics approach that integrated analysis from CUT&RUN, RNA-seq, and ATACseq. Additionally, our lab also established a hypoxia and HIF1a-dependent mechanism for the non-nuclear organelle degradation process required to form mature transparent fiber cells.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014167
- Subject Headings
- Cell differentiation, Lens, Crystalline, Eye lens
- Format
- Document (PDF)
- Title
- DISCOVERY OF GENES AND MOLECULAR PROCESSES THAT ARE IMPORTANT FOR THE PATHOGENESIS OF ALZHEIMER’S DISEASE.
- Creator
- Kwakye, Alexander, Li, Zhongwei, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Alzheimer’s Disease (AD) is a complex brain disorder that affects at least one in every ten persons aged 65 and above worldwide. The pathogenesis of this disorder remains elusive. In this work, we utilized a rich set of publicly available gene expression data to elucidate the genes and molecular processes that may underlie its pathogenesis. We developed a new ranking score to prioritize molecular pathways enriched in differentially expressed genes during AD. After applying our new ranking...
Show moreAlzheimer’s Disease (AD) is a complex brain disorder that affects at least one in every ten persons aged 65 and above worldwide. The pathogenesis of this disorder remains elusive. In this work, we utilized a rich set of publicly available gene expression data to elucidate the genes and molecular processes that may underlie its pathogenesis. We developed a new ranking score to prioritize molecular pathways enriched in differentially expressed genes during AD. After applying our new ranking score, GO categories such as cotranslational protein targeting to membrane, SRP-dependent cotranslational protein targeting to membrane, and spliceosomal snRNP assembly were found to be significantly associated with AD. We also confirm the protein-protein interaction between APP, NPAS4 and ARNT2 and explain that this interaction could be implicated in AD. This interaction could serve as a theoretical framework for further analyses into the role of NPAS4 and other immediate-early genes in AD pathogenesis.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013541
- Subject Headings
- Alzheimer's disease, Alzheimer's disease--Genetic aspects, Alzheimer's disease--Molecular aspects, Alzheimer's disease--Pathogenesis
- Format
- Document (PDF)
- Title
- DNAJC25 Pro90Leu J-domain mutation demonstrates decreased chaperone activity in vitro.
- Creator
- Chauss, Daniel C., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Molecular chaperones guide peptide fold conformation throughout the lifetime of the peptide. One network of chaperone proteins involved in this activity, Heat shock protein 70s (Hsp70s), are well characterized at restoring peptide fold, utilizing J-domain containing protein chaperone cofactors to activate Hsp70 activity. DnaJ (Hsp40) homolog, subfamily C, member 25 (DNAJC25) is a class III transmembrane J-domain containing protein that to date is underrepresented in the literature. Recently,...
Show moreMolecular chaperones guide peptide fold conformation throughout the lifetime of the peptide. One network of chaperone proteins involved in this activity, Heat shock protein 70s (Hsp70s), are well characterized at restoring peptide fold, utilizing J-domain containing protein chaperone cofactors to activate Hsp70 activity. DnaJ (Hsp40) homolog, subfamily C, member 25 (DNAJC25) is a class III transmembrane J-domain containing protein that to date is underrepresented in the literature. Recently, Hejtmancik et al. 2012. (unpublished data) have revealed that missense mutation to DNACJ25 at Pro90Leu (P90L) is strongly correlated with inherited Closed-Angle Glaucoma. Inherited mutations are well characterized for Open-Angle Glaucoma, however, prior to this finding, were unknown for Closed-Angle Glaucoma. In this report, analysis of the in vitro chaperone activity of DNAJC25 w+ and P90L is assessed utilizing an Hsp70 mediated Glucose-6-Phosphate Dehydrogenase refolding system, SWISS-MODEL predictions are performed for the J-domain structure of DNAJC25 w+ and P90L with consequent analysis of DNAJC25 Pro90 conservation relative to other type I, II, and III J-domain containing proteins. DNAJC25 P90L demonstrated decreased chaperone activity in vitro compared to w+ DNAJC25.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3342040
- Subject Headings
- Cell physiology, Methodology, Molecular chaperones, Physiological effect, Cellular signal transduction, Proteolytic enzymes
- Format
- Document (PDF)
- Title
- EEG Topographic Changes in Opioid Use Disorder.
- Creator
- Minnerly, Christopher, Tao, Rui, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
The present study aimed at quantifying the topographic distribution of spectral power as measured with electroencephalogram (EEG) in patients with opioid use disorder (OUD) across five broad band frequencies (δ, θ, α, β, and γ). Through comparative groups of healthy controls, patients with methamphetamine use disorder, and patients with alcohol use disorder, it was determined that OUD EEG spectral power was globally increased in the δ frequency, and more region-specific in others (frontal...
Show moreThe present study aimed at quantifying the topographic distribution of spectral power as measured with electroencephalogram (EEG) in patients with opioid use disorder (OUD) across five broad band frequencies (δ, θ, α, β, and γ). Through comparative groups of healthy controls, patients with methamphetamine use disorder, and patients with alcohol use disorder, it was determined that OUD EEG spectral power was globally increased in the δ frequency, and more region-specific in others (frontal lobes in θ and β frequencies). α frequency was reduced in occipital lobes in OUD. The observed changes are discussed in terms of the microcircuit-level changes in the cortex. Based on these findings, EEG may prove to be a valuable tool for diagnostic and prognostic evaluation of OUD.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013488
- Subject Headings
- Opioid-Related Disorders, Electroencephalography, Brain Mapping
- Format
- Document (PDF)
- Title
- The effect of ambient temperature on serotonin syndrome.
- Creator
- Krishnamoorthy, Swapna., Charles E. Schmidt College of Medicine
- Abstract/Description
-
Serotonin syndrome (SS) is a drug-induced toxicity caused by an excess of serotonin (5-HT) in the central nervous system (CNS). The symptoms of the disorder range from mild to severe, with the severe state evoking life-threatening hyperthermia. Autonomic dysfunction is controlled in part by serotonin receptors, with the 5-HT2A receptor responsible for increasing core body temperature (Tcor). Our results show that the 5-HT2A receptors on the preoptic/anterior hypothalamus (PO/AH) and...
Show moreSerotonin syndrome (SS) is a drug-induced toxicity caused by an excess of serotonin (5-HT) in the central nervous system (CNS). The symptoms of the disorder range from mild to severe, with the severe state evoking life-threatening hyperthermia. Autonomic dysfunction is controlled in part by serotonin receptors, with the 5-HT2A receptor responsible for increasing core body temperature (Tcor). Our results show that the 5-HT2A receptors on the preoptic/anterior hypothalamus (PO/AH) and prefrontal cortex (PFC), in particular, are sensitive to changes in ambient temperature (Tamb). The toxic increase of 5-HT is postulated to occur due to the temperature-dependent activation of these receptors that promotes a positive feedback mechanism. Our results suggest that changes in Tamb can either exacerbate or alleviate the symptom and that this is mediated by the 5-HT2A receptors. Understanding the mechanism involved in elevating Tcor is imperative in treating and preventing the disorder.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/FAU/186297
- Subject Headings
- Serotoninergic mechanisms, Central nervous system, Physiology, Body temperature, Regulation, Neurotransmitter receptors, Serotonin, Physiological effect
- Format
- Document (PDF)
- Title
- Effect of amyloid beta on nutrient uptake and ATP in the brain cells.
- Creator
- To, William, Tao, Rui, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Unintentional weight loss in older adults often precedes Alzheimer’s disease (AD). Positron emission tomography (PET) scan reveals that AD patients exhibit reduced uptake of fluorodeoxyglucose into brain cells, defined as ‘hypometabolism’. However, cellular mechanisms underlying weight loss and hypometabolism have not received much attention. The primary goal of the study was to test the hypothesis that cells become starved in confrontation with amyloid beta proteins (Aβ), which are...
Show moreUnintentional weight loss in older adults often precedes Alzheimer’s disease (AD). Positron emission tomography (PET) scan reveals that AD patients exhibit reduced uptake of fluorodeoxyglucose into brain cells, defined as ‘hypometabolism’. However, cellular mechanisms underlying weight loss and hypometabolism have not received much attention. The primary goal of the study was to test the hypothesis that cells become starved in confrontation with amyloid beta proteins (Aβ), which are increasingly aggregated in the AD brain. Cellular ATP is known as a biomarker indicating for cell starvation. We found that Aβ caused a dose-dependent reduction in ATP of astrocytes. This effect was similar to those of cells being deprived from nutrients (i.e., glucose, pyruvate and glutamine). Together, the data of the present study support the hypothesis that cell starvation is likely associated with weight loss and hypometabolism in AD patients.
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FA00013941
- Subject Headings
- Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Adenosine Triphosphate
- Format
- Document (PDF)