Current Search: Charles E. Schmidt College of Medicine (x)
View All Items
Pages
- Title
- UP-regulation of inflammatory cytokines in the lacrimal glands of a predisposed mouse model of Sjèogren's syndrome (SS): the influence of sex hormones and a newly proposed mechanism for SS.
- Creator
- Czerwinski, Stefanie P.C., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Sjèogren's Syndrome (SS) is a chronic, inflammatory autoimmune disease affecting mostly the exocrine cells of lacrimal and salivary glands, leading to diminished secretory function and resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease). Despite several decades of studies focusing on autoimmune diseases and dry eye diseases, the exact etiology and mechanisms of SS remain unknown. Besides the fact that SS is often unreported, unrecognized and...
Show moreSjèogren's Syndrome (SS) is a chronic, inflammatory autoimmune disease affecting mostly the exocrine cells of lacrimal and salivary glands, leading to diminished secretory function and resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease). Despite several decades of studies focusing on autoimmune diseases and dry eye diseases, the exact etiology and mechanisms of SS remain unknown. Besides the fact that SS is often unreported, unrecognized and untreated, today's therapies rely exclusively on treating the symptoms after disease progression; there exists neither prevention therapy nor cure for SS. In addition, SS has been diagnosed predominantly in post-menopausal women with the female to male ratio reaching 9:1, suggesting a role of ovarian sex hormones in the pathogenesis of SS. However, not all postmenopausal women develop SS, indicating the contribution of other factors such as a genetic background to the onset of SS. In the present study, ovariectomized (OVX) NOD.B10.H2b mice provide a model of menopause with a genetic predisposition to SS, as compared to non-predisposed C57BL/10 mice. Both strands of mice were either sham operated, OVX, OVX and treated with 17(Sb (Bestradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected 3, 7, 21, and 30 days after surgery and processed for RNA analysis by rt-qPCR and protein assays by ELISA to evaluate cytokine expression and concentrations of IL- 1\U+fffd\, TNF-a, IFN-(Sd(B, IL-10, and IL-4 on a timeline. Overall, our results showed a significant increase in IL-1\U+fffd\ TNF-a, IL-10, and IL-4 expression and levels in the lacrimal glands of OVX NOD.B10.H2b mice as compared to sham operated animals, and treatment with E2 or DHT at time of OVX prevented the increase in cytokine expression and levels.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/FAU/3360770
- Subject Headings
- Cytokines, Mice as laboratory animals, Dry eye syndromes, Immunological aspects, Sjèogren's syndrome, Immunological aspects, Medical genetics, Molecular immunology
- Format
- Document (PDF)
- Title
- Unraveling the mysteries of Sjogren's syndrome: a closer look at the effects of hormones and genetics over time using the NOD.B10.H2b mouse model.
- Creator
- Seamon, Vanessa., Charles E. Schmidt College of Medicine, Department of Integrated Medical Science
- Abstract/Description
-
Sjogren's Syndrome (SS) is characterized by lymphocytic infiltration, destruction and dysfunction of the lacrimal and salivary glands and the presence of serum autoantibodies. Although, approximately 0.5% of the population suffers from SS, there is a female predominance of 9:1 compared with males. Most women with SS are postmenopausal; however, not all women who are post-menopausal develop SS. Therefore, we postulate that a decrease in the circulating levels of hormones creates an environment...
Show moreSjogren's Syndrome (SS) is characterized by lymphocytic infiltration, destruction and dysfunction of the lacrimal and salivary glands and the presence of serum autoantibodies. Although, approximately 0.5% of the population suffers from SS, there is a female predominance of 9:1 compared with males. Most women with SS are postmenopausal; however, not all women who are post-menopausal develop SS. Therefore, we postulate that a decrease in the circulating levels of hormones creates an environment favorable to the development of SS in a predisposed genetic background. In order to carry out our studies, we used the NOD.B10.H2b mouse model of SS, and ovariectomized (OVX) them as a model for the post-menopausal condition. We removed the lacrimal glands and measured the gene expression and protein levels of several cytokines and chemokines known to be upregulated in patients with SS such as : lL-1B, IL-10, INF-y, TNFa, CCL9 and CXCL13., We also stained for markers of B cells (B220+) and T cells (CD4+ and CD8+), and counted positively stained cleaved caspase-3 cells as an indication of apoptosis. These experiments were done 3, 7 and 21 days post-OVX and compared to sham operated animals. In order to determine whether the changes observed with OVX were triggered mainly by a genetic pre-disposition, a non-prediposed OVX and sham operated mouse (C57BL/10) was used as control. We found that gene expression of IL-1B, IL-10 and IF-y were upregulated in the lacrimal glands of the OVX NOD.B10.H2b mice at 3 days post-OVX compared with sham operated animals. Gene expression of IL-1B, IL-10, IFN-y, TNF-a, CCL9 and CXCL13, and protein levels of IL-1B, IL-10 and CCL9 were upregulated in the OVX NOD.B10.H2b mice at 7 days post-OVX compared to sham operated animals., Also, at 7 days, an increase in B220+ B cells and an increase in cleaved caspase-3 were also observed in the OVX NOD.B10.H2b mice lacrimal glands compared to sham operated animals. At 21 days, protein levels of IL-10 were also highly upregulated in the OVX NOD.B10.H2b mice, together with an increase of B220+ B cells, a slight increase in the CD4/CD8 ratio and an increase on the number of caspase-3 positive cells. No changes were observed in any of the above parameters measured in the OVX C57BL/10 mice compared to the sham operated group, supporting our hypothesis that both, genetics and a decrease in the levels of hormones are necessary for SS to occur.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/215292
- Subject Headings
- Sjèogren's syndrome, Immunological aspects, Sjèogren's syndrome, Animal models, Mice as laboratory animals, Gene expression, Salivary glands, Diseases, Histopathology
- Format
- Document (PDF)
- Title
- Evaluation of cardiac function in cTnI(R192H) transgenic mice and cTni knockout mice with High-Resolution Ultrasound Imaging and Doppler Echocardiography.
- Creator
- Liu, Jing, Huang, Xupei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Troponin I is a contractile protein and plays an important role in cardiac function. We have generated cTnl knockout and cTnI(R192H) transgenic mouse models. All of cTnl knockout homozygous mice die at 17-18 days after birth. Some of cTnI(R192H) transgenic mice die at early life stages, some mice develop heart failure at late stages. High-resolution ultrasound imaging and Doppler echocardiography have been used to evaluate cardiac function on cTnl deficient mice and cTnl(R192H) transgenic...
Show moreTroponin I is a contractile protein and plays an important role in cardiac function. We have generated cTnl knockout and cTnI(R192H) transgenic mouse models. All of cTnl knockout homozygous mice die at 17-18 days after birth. Some of cTnI(R192H) transgenic mice die at early life stages, some mice develop heart failure at late stages. High-resolution ultrasound imaging and Doppler echocardiography have been used to evaluate cardiac function on cTnl deficient mice and cTnl(R192H) transgenic mice. cTnI mice have damaged relaxation with gradually decreased E/A ratio(E/A<1). FS and cardiac output dramatically decrease on 17-day-o1d cTnI mice indicating severe cardiac dysfunction. We find that the damaged heart function is correspondent with the Tnl expression level decline. 6-8 weeks transgenic mice have shown that the dimension of left and right atria increase. In 15-month-old transgenic mice, the E/A ratio shows a pseudonormal pattern indicating a diastolic dysfunction. This study demonstrate that damaged heart function is tightly associated with Tnl levels in the heart.
Show less - Date Issued
- 2006
- PURL
- http://purl.flvc.org/fau/fd/FA00000789
- Subject Headings
- Transgenic mice, Mice as laboratory animals, Coronary heart disease--Seriodiagnosis, Congestive heart failure--Pathophysiology
- Format
- Document (PDF)
- Title
- Energy metabolism and slow skeletal troponin I phosphorylation in cardiac troponin I null mouse heart.
- Creator
- Jia, Yuanyuan, Florida Atlantic University, Huang, Xupei, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Troponin I (TnI) plays an important role in cardiac muscle contraction. Two TnI genes (cardiac and slow skeletal TnI) are predominantly expressed in the heart. In cTnI knockout mice, myocardial TnI deficiency results in a diastolic dysfunction and a sudden death in homozygous mutants. In the present studies, energy metabolism has been analyzed in myocardial cells from cTnI null hearts. Our results have demonstrated that damaged relaxation and increased Ca2+-independent force production in...
Show moreTroponin I (TnI) plays an important role in cardiac muscle contraction. Two TnI genes (cardiac and slow skeletal TnI) are predominantly expressed in the heart. In cTnI knockout mice, myocardial TnI deficiency results in a diastolic dysfunction and a sudden death in homozygous mutants. In the present studies, energy metabolism has been analyzed in myocardial cells from cTnI null hearts. Our results have demonstrated that damaged relaxation and increased Ca2+-independent force production in cTnI null hearts stimulated myofibril MgATPase activities accompanied by the increase of mitochondria quantity and ATPase activities. In addition, an increase of ssTnI phosphorylation level has been observed in cTnI null hearts. The results indicate that TnI deficiency can cause the disturbance of energy metabolism and some protein overphosphorylation.
Show less - Date Issued
- 2003
- PURL
- http://purl.flvc.org/fcla/dt/12998
- Subject Headings
- Mice as laboratory animals, Mice--Metabolism, Energy metabolism, Mitochondria
- Format
- Document (PDF)
- Title
- Study on the Role oftmRNA in Protecting Escherichia coli Cell Under Oxidative stress.
- Creator
- Kollipara, Gayatri, Li, Zhongwei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
tmRNA is a small stable RNA present in Eubacteria. Through a mechanism called trans-translation, tmRNA mediates ribosome rescue and quality control of proteins and mRNA. In this study, the Escherichia coli (E. coli) mutant lacking tmRNA was demonstrated hypersensitive to oxidative stress. The role of tmRNA-mediated surveillance mechanism in protecting E. coli cell under oxidative stress condition was examined. The tmRNA-mediated tagged protein levels were elevated in cells under oxidative...
Show moretmRNA is a small stable RNA present in Eubacteria. Through a mechanism called trans-translation, tmRNA mediates ribosome rescue and quality control of proteins and mRNA. In this study, the Escherichia coli (E. coli) mutant lacking tmRNA was demonstrated hypersensitive to oxidative stress. The role of tmRNA-mediated surveillance mechanism in protecting E. coli cell under oxidative stress condition was examined. The tmRNA-mediated tagged protein levels were elevated in cells under oxidative stress condition, demonstrating the enhanced need for tmRNA under such condition. Our results suggest that mRNA damage by oxidative stress may cause reduced cell viability, and that tmRNA is required to rescue cells under such condition. Furthermore, our observations showed that tmRNA is required for the optimal growth of E. coli under normal aeration but not under anaerobic condition, suggesting that oxidation ofmRNA is the major reason for requirement oftmRNA during normal aeration.
Show less - Date Issued
- 2007
- PURL
- http://purl.flvc.org/fau/fd/FA00000782
- Subject Headings
- Proteins--Synthesis, Bacterial genetics, Escherichia coli infections, Cells--Evolution
- Format
- Document (PDF)
- Title
- Protection of taurine and granulocyte colony-stimulating factor against excitotoxicity induced by glutamate in primary cortical neurons.
- Creator
- Pan, Chunliu, Gupta, Amit, Prentice, Howard, Wu, Jang-Yen
- Date Issued
- 2010-08-24
- PURL
- http://purl.flvc.org/fcla/dt/3329093
- Format
- Document (PDF)
- Title
- Engineering of tissue inhibitor of metalloproteinases mutants as potential therapeutics.
- Creator
- Nagase, Hideaki, Brew, Keith
- Abstract/Description
-
Matrix metalloproteinases (MMPs) play a central role in many biological processes such as development, morphogenesis and wound healing, but their unbalanced activities are implicated innumerous disease processes such as arthritis, cancer metastasis, atherosclerosis, nephritis and fibrosis. One of the key mechanisms to control MMP activities is inhibition by endogenous inhibitors called tissue inhibitors of metalloproteinases (TIMPs). This review highlights the structures and inhibition...
Show moreMatrix metalloproteinases (MMPs) play a central role in many biological processes such as development, morphogenesis and wound healing, but their unbalanced activities are implicated innumerous disease processes such as arthritis, cancer metastasis, atherosclerosis, nephritis and fibrosis. One of the key mechanisms to control MMP activities is inhibition by endogenous inhibitors called tissue inhibitors of metalloproteinases (TIMPs). This review highlights the structures and inhibition mechanism of TIMPs, the biological activities of TIMPs, the unique properties of TIMP-3, and the altered specificity towards MMPs achieved by mutagenesis. A potential therapeutic use of TIMP variants is discussed.
Show less - Date Issued
- 2002-04-02
- PURL
- http://purl.flvc.org/fcla/dt/3327266
- Subject Headings
- Gene Therapy --Methods, Genetic Engineering --methods, Protein Structure, Tertiary, Rheumatic Diseases --therapy, Tissue Inhibitor of Metalloproteinases, Wound Healing --physiology, Metalloproteinases --Inhibitors --Therapeutic use
- Format
- Document (PDF)
- Title
- Reciprocal regulation between taurine and glutamate response via Ca2+ - dependent pathways in retinal third-order neurons.
- Creator
- Bulley, Simon, Shen, Wen
- Date Issued
- 2010-08-24
- PURL
- http://purl.flvc.org/fcla/dt/3327274
- Subject Headings
- Amacrine Cells*/cytology, Amacrine Cells*/drug effects, Amacrine Cells*/metabolism, Ambystoma, Calcium/metabolism, Calcium Channels/metabolism, Cells, Cultured, Enzyme Inhibitors/metabolism, Excitatory Amino Acid Agonists/pharmacology, GABA Antagonists/pharmacology, Glutamic Acid/metabolism, Glycine Agents/pharmacology, Kainic Acid/pharmacology, Membrane Glycoproteins, Membrane Potentials, Neurotransmitter Agents, Retinal Ganglion Cells, Signal Transduction, Synaptic Transmission
- Format
- Document (PDF)
- Title
- Treatment of Kleine-Levin Syndrome With Intranasal Photobiomodulation and Methylene Blue.
- Creator
- Michael Hamper, Paolo Cassano, Jay Lombard
- Abstract/Description
-
Kleine-Levin syndrome (KLS) is a rare neuropsychiatric disorder, characterized by recurrent episodes of idiopathic hypersomnia, and cognitive and behavioral abnormalities, such as memory loss and child-like language. There is no definitive etiology for KLS; however, there are hypotheses of genetic predisposition, autoimmune mechanisms, and abnormal thalamic and hypothalamic functioning. Similarly, there is no definitive treatment for KLS as one method may be beneficial for one patient and not...
Show moreKleine-Levin syndrome (KLS) is a rare neuropsychiatric disorder, characterized by recurrent episodes of idiopathic hypersomnia, and cognitive and behavioral abnormalities, such as memory loss and child-like language. There is no definitive etiology for KLS; however, there are hypotheses of genetic predisposition, autoimmune mechanisms, and abnormal thalamic and hypothalamic functioning. Similarly, there is no definitive treatment for KLS as one method may be beneficial for one patient and not for another. We present a case of KLS in a patient who has no clinical improvement in symptoms with a variety of treatments. The parents of the patient agreed to attempt a trial of intranasal photobiomodulation (i-PBM) with red light, in combination with methylene blue (MB). The patient showed remission of the KLS episode following treatment with no further KLS episodes reported after treatment.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000507
- Format
- Document (PDF)
- Title
- New in-situ hybridization method measuring serotonin 2A (5-HT2A) receptor mRNA levels in rats exposed to MDMA.
- Creator
- Sousa, John, Shokry, Ibrahim M., Callanan, John J., Tao, Rui, Charles E. Schmidt College of Medicine
- Abstract/Description
-
This study aimed to identify changes in the expression of serotonin (5-hydroxytryptamine; 5-HT) receptor 5-HT2a mRNA in paraformaldehyde prefixed rat brain tissue after exposure to 3, 4 methylenedioxymethamphetamine (MDMA). Rather than use traditional, time-consuming methods that were highly prone to error, such as the use of radioactive riboprobes, we used recent advancements in the development of rapid in-situ hybridization to our advantage. The use of rapid in-situ hybridization (such as...
Show moreThis study aimed to identify changes in the expression of serotonin (5-hydroxytryptamine; 5-HT) receptor 5-HT2a mRNA in paraformaldehyde prefixed rat brain tissue after exposure to 3, 4 methylenedioxymethamphetamine (MDMA). Rather than use traditional, time-consuming methods that were highly prone to error, such as the use of radioactive riboprobes, we used recent advancements in the development of rapid in-situ hybridization to our advantage. The use of rapid in-situ hybridization (such as the RNAscope assay) has allowed us to use paraformaldehyde prefixed brain tissue sections, which are more widely available and easier to use, instead of fresh frozen tissue. Here we describe the results from the use of the RNAscope assay to measure the amount of dapB (a bacterial gene), ppiB (a eukaryotic housekeeping gene), and htr2a (a eukaryotic gene coding for 5-HT2A receptors) mRNA.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00005211
- Subject Headings
- College students --Research --United States.
- 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
- 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
- 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
- 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
- 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
- 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
- G-CSF GENE THERAPY FOR BRAIN DISEASES AND/OR SICKLE CELL ANEMIA.
- Creator
- Basilio, Stefan, Prentice, Howard, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
Ischemic stroke is defined as a blockage or reduced flow of blood to select areas of brain tissue due to either plaque formation or buildup of blood clots in the small blood vessels. A characteristic of sickle cell anemic patients is the potential for them to experience a similar type of blockage due to the sticky nature of the sickled red blood cells as well as defective oxygen delivery to the brain. Because of this similarity, sickle cell anemia may represent a good animal research model...
Show moreIschemic stroke is defined as a blockage or reduced flow of blood to select areas of brain tissue due to either plaque formation or buildup of blood clots in the small blood vessels. A characteristic of sickle cell anemic patients is the potential for them to experience a similar type of blockage due to the sticky nature of the sickled red blood cells as well as defective oxygen delivery to the brain. Because of this similarity, sickle cell anemia may represent a good animal research model for therapeutic intervention based on stroke models. In recent studies, Granulocyte-Colony Stimulating Factor (GCSF), has been shown to exhibit a robust range of neuroprotective properties against neurological disorders including ischemic stroke through preservation of the endoplasmic reticulum (ER) by modulating various ER stress pathways. Through cognitive deficit analysis in the form of behavioral and locomotor experiments in addition to in situ biomarker analysis by way of western blotting and immunohistochemistry, we found that G-CSF gene therapy exhibited neurogenic and neuroprotective effects in ischemic mouse models and could possibly serve as a good therapy for other diseases that share similar pathology to stroke.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013787
- Subject Headings
- Sickle cell anemia, Stroke, Granulocyte Colony-Stimulating Factor, Gene therapy
- Format
- Document (PDF)
- 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
- GCSF GENE THERAPY FOR PARKINSON’S DISEASE.
- Creator
- Lee, Zachary, Wu, Jang-Yen, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
-
The kynurenine pathway plays a critical role in regulating immunological homeostasis in the brain. Evidence supporting the hypothesis that kynurenine pathway dysfunction may exacerbate progression of neurodegenerative diseases like Parkinson’s is growing. First, we investigate the effects of Interferon-γ, Lipopolysaccharide, and Interleukin-4 on several key kynurenine pathway metabolites using high performance liquid chromatography. We found that Interferon-γ had significant effects on the...
Show moreThe kynurenine pathway plays a critical role in regulating immunological homeostasis in the brain. Evidence supporting the hypothesis that kynurenine pathway dysfunction may exacerbate progression of neurodegenerative diseases like Parkinson’s is growing. First, we investigate the effects of Interferon-γ, Lipopolysaccharide, and Interleukin-4 on several key kynurenine pathway metabolites using high performance liquid chromatography. We found that Interferon-γ had significant effects on the extracellular concentration of kynurenine metabolites in astrocytes, microglia, and macrophage. GCSF gene therapy is previously demonstrated to exert neuroprotective effects on models of Parkinson’s and Alzheimer’s disease. Seven days after receiving GCSF gene therapy, A53T Parkinson’s mice were found to have increased levels of GCSF and tyrosine hydroxylase positive neurons. A concurrent increase in expression of the kynurenine pathway enzyme kynurenine aminotransferase 2 was observed. GCSF gene therapy may exhibit neuroprotective effects in a Parkinson’s disease mouse model by restoring this key kynurenine pathway enzyme.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013773
- Subject Headings
- Parkinson Disease, Gene therapy, Kynurenine
- Format
- Document (PDF)
- Title
- Thermodynamic Origins of Selectivity in the Interactions of N- TIMP Variants and Metalloproteinases Catalytic Domains.
- Creator
- Zou, Haiyin, Brew, Keith, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
Matrix metalloproteinases (MMPs) constitute the major class of enzymes capable of degrading all protein components of extracellular matrix (ECM) and have important roles in normal physiologic processes of maintaining tissue integrity and remodeling. However, excess MMP activities are associated with many diseases including rheumatoid arthritis and osteoarthritis, cardiomyopathy, and macular degeneration. The activity of MMPs is regulated by their endogenous protein inhibitors, the tissue...
Show moreMatrix metalloproteinases (MMPs) constitute the major class of enzymes capable of degrading all protein components of extracellular matrix (ECM) and have important roles in normal physiologic processes of maintaining tissue integrity and remodeling. However, excess MMP activities are associated with many diseases including rheumatoid arthritis and osteoarthritis, cardiomyopathy, and macular degeneration. The activity of MMPs is regulated by their endogenous protein inhibitors, the tissue inhibitors of metalloproteinases (TIMPs) which are avid broad-spectrum inhibitors of numerous human matrixins (MMPs and ADAMs). Uncontrolled matrix degradation occurs when the balance between TIMPs and MMPs is disrupted, resulting in serious diseases such as cancer, arthritis and chronic tissue ulcers. Thus, the engineering of TIMPs to produce highly selective and efficacious inhibitors of individual MMPs may be utilized for future treatment of diseases. Such engineering requires detailed analysis for the structural and biophysical information of MMP-TIMP interaction. Changes in the dynamics of proteins and solvent that accompany their associations with different binding partners, influence the specificity of binding through entropic effects. From the current studies it appears that the interactions of the inhibitory domains of TIMPs-1 and -2 (N-TIMPs) with MT1-MMP are driven by entropy increases that are partitioned between solvent and conformational entropy (ΔSsolv and ΔSconf), and a large conformational entropy penalty is responsible for the weak inhibition of MT1-MMP by NT1.We investigated how mutations that modify N-TIMP selectivity affect the thermodynamics of interactions with MMP1, MMP3 and MT1-MMP. The weak inhibition of MT1-MMP by N-TIMP-1 is enhanced by mutation of threonine 98, on the edge of the binding ridge, to leucine. This mutation increases the large ΔSconf cost for binding to MT1-MMP but this is offset by a greater increase in ΔSsolv. In contrast, this mutation enhances binding to MMP3 by increasing ΔSconf for the interaction. ΔSsolv and ΔSconf show mutual compensation for all interactions, with characteristic ranges for each MMP. Distinct electrostatic and dynamic features of MMPs are key factors in their selective inhibition.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00004643
- Subject Headings
- Metalloproteinases -- Inhibitors., Proteolytic enzymes., Extracellular matrix proteins., Apoptosis.
- Format
- Document (PDF)