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- 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
- 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
- CELLULAR REQUIREMENTS FOR MBLAC1 EXPRESSION AS ASSESSED IN MBLAC1-/- MOUSE EMBRYONIC FIBROBLASTS.
- Creator
- McGovern, Samantha, Blakely, Randy, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Science
- Abstract/Description
-
The majority of research on drug addiction centers on dopamine (DA)- driven synaptic plasticities and how these changes ultimately lead to compulsive drug seeking. However, growing evidence supports a role of glial factors in various steps that lead to drug abuse and addiction. In this regard, significant evidence implicates glial glutamate (Glu) transporters (GLT-1) and cystine/Glu exchangers (xCT) in determining synaptic and extrasynaptic levels of Glu that support the acute and chronic...
Show moreThe majority of research on drug addiction centers on dopamine (DA)- driven synaptic plasticities and how these changes ultimately lead to compulsive drug seeking. However, growing evidence supports a role of glial factors in various steps that lead to drug abuse and addiction. In this regard, significant evidence implicates glial glutamate (Glu) transporters (GLT-1) and cystine/Glu exchangers (xCT) in determining synaptic and extrasynaptic levels of Glu that support the acute and chronic actions of drugs of abuse. -lactam antibiotics have been found in rodent models to upregulate CNS GLT-1 and xCT and thereby contribute to reinstatement after chronic drug exposure and withdrawal. Previously, the Blakely lab identified a glial expressing gene, swip-10, in Caenorhabditis elegans, whose deletion results in the hyperdominergic phenotype Swimming-Induced Paralysis (Swip), supported by Glu signalingdependent DA neuron hyperexcitability that ultimately drives oxidative stress and DA neuron degeneration. Both SWIP-10 and its putative mammalian ortholog MBLAC1 possess a highly conserved metallo -lactamase domain, and MBLAC1 has been found to bind the Glu modulating, b-lactam antibiotic ceftriaxone (Cef). Indeed, immunodepletion studies indicate that MBLAC1 may be the major highaffinity Cef-binding protein in the brain, leading to the hypothesis that MBLAC1 has a Glu modulatory role(s). Recently a functional role of MBLAC1 been proposed, involving activity as a 3’ exonuclease that processes polyA- mRNAs, including RNAs encoding cell replication-dependent histones. How this role, or others, may support the actions of MBLAC1 in the brain and the non-microbial actions of Cef to extracellular Glu homeostasis, is unclear. Recently, the Blakely lab generated Mblac1-/- mice as a tool to investigate these issues. The following work investigated the requirements of MBLAC1 in growth and the actions of Cef in mouse embryonic fibroblasts (MEFs) cultured from either Mblac1+/+ and Mblac1-/- mice. The presented data suggested that Mblac1-/- MEFs display attenuated growth and cell proliferation relative to Mblac1+/+ MEFs. For the first time, the in vitro protective actions of Cef against oxidative stress is shown to be dependent on MBLAC1. The following studies presented contribute to a definition of the role of MBLAC1 and as a Cef binding protein in native preparations, with findings that can drive models for the role of MBLAC1 in the CNS.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013395
- Subject Headings
- Drug addiction--Research, Amino Acid Transport System X-AG, Mice, Fibroblasts
- 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
- 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
- Developmental and Protective Mechanisms of the Ocular Lens.
- Creator
- Chauss, Daniel C., Kantorow, Marc, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biomedical Science
- Abstract/Description
-
The vertebrate eye lens functions to focus light onto the retina to produce vision. The lens is composed of an anterior monolayer of cuboidal epithelial cells that overlie a core of organelle free fiber cells. The lens develops and grows throughout life by the successive layering of lens fiber cells via their differentiation from lens epithelial cells. Lens developmental defect and damage to the lens are associated with cataract formation, an opacity of the lens that is a leading cause of...
Show moreThe vertebrate eye lens functions to focus light onto the retina to produce vision. The lens is composed of an anterior monolayer of cuboidal epithelial cells that overlie a core of organelle free fiber cells. The lens develops and grows throughout life by the successive layering of lens fiber cells via their differentiation from lens epithelial cells. Lens developmental defect and damage to the lens are associated with cataract formation, an opacity of the lens that is a leading cause of visual impairment worldwide. The only treatment to date for cataract is by surgery. Elucidating those molecules and mechanisms that regulate the development and lifelong protection of the lens is critical toward the development of future therapies to prevent or treat cataract. To determine those molecules and mechanisms that may be important for these lens requirements we employed high-throughput RNA sequencing of microdissected differentiation statespecific lens cells to identify an extensive range of transcripts encoding proteins expressed by these functionally distinct cell types. Using this data, we identified differentiation state-specific molecules that regulate mitochondrial populations between lens epithelial cells that require the maintenance of a functional population of mitochondria and lens fiber cells that must eliminate their mitochondria for their maturation. In addition, we discovered a novel mechanism for how lens epithelial cells clear apoptotic cell debris that could arise from damage to the lens and found that UVlight likely compromises this system. Moreover, the data herein provide a framework to determine novel lens cell differentiation state-specific mechanisms. Future studies are required to determine the requirements of the identified molecules and mechanisms during lens development, lens defense against damage, and cataract formation.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00004577
- Subject Headings
- Eye--Diseases--Etiology., Cell differentiation., Cellular signal transduction., Protein folding., Mitochondrial pathology., Cellular control mechanisms., Apoptosis., Oxidative stress--Prevention.
- 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
- 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
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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)
- Title
- EFFECT OF G-CSF GENE THERAPY IN A MICROGLIA MODEL OF STROKE.
- Creator
- Velasquez Saldarriaga, Esteban, Wu, Jang-Yen, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
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Cerebrovascular events (stroke) are a significant cause of morbidity and mortality worldwide. Ischemic stroke accounts for ~85% of all strokes and is caused by the blockade of blood flow to a certain area of the brain, resulting in oxygen and nutrient deprivation and ultimately cell death. Cerebral ischemia induces a strong neuroinflammatory response that contributes to tissue damage and is driven by changes in the gene expression profile and phenotype of brain cells including neurons,...
Show moreCerebrovascular events (stroke) are a significant cause of morbidity and mortality worldwide. Ischemic stroke accounts for ~85% of all strokes and is caused by the blockade of blood flow to a certain area of the brain, resulting in oxygen and nutrient deprivation and ultimately cell death. Cerebral ischemia induces a strong neuroinflammatory response that contributes to tissue damage and is driven by changes in the gene expression profile and phenotype of brain cells including neurons, astrocytes, and microglia. Microglia are the resident immune and phagocytic cells of the central nervous system. They rapidly respond to ischemia by migrating to the site of injury and modulating the inflammatory response there. Although microglia may play a deleterious role in the acute phase of stroke, evidence suggests that they play an important role in the reduction of excitotoxic injury as well as in neurogenesis during the tissue regeneration phase. Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that has shown beneficial effects in models of ischemic stroke. G-CSF exerts its neuroprotective effects through different mechanisms including mobilization of haemopoietic stem cells, angiogenesis, neurogenesis, anti-inflammation, and anti-apoptosis. However, its effect on microglia is not well understood yet. The main objective of this project was to evaluate the protective and anti-inflammatory effect of G-CSF gene therapy against glutamate cytotoxicity in the human microglial clone 3 cell line (HMC3). Our results show that although G-CSF gene therapy did not significantly protect HMC3 cells against glutamate induced cell death, it reduced the expression levels of pro-inflammatory proteins NF-κB p65, IL-1β and IL-6, while increasing the phosphorylation of Akt, a regulator of cell survival and proliferation.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013821
- Subject Headings
- Stroke, Granulocyte Colony-Stimulating Factor, Cerebrovascular disease, Microglia
- Format
- Document (PDF)
- Title
- Effects of adolescent stress on depressive- and anxiety-like behaviors and hippocampal mossy fibre-CA3 remodeling in the novelty-seeking phenotype: implications for epigenetic regulation of the BDNF gene.
- Creator
- Oztan, Ozge., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
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Experimentally naive rats show variance in their locomotor reactivity to novelty, some displaying higher (HR) while others displaying lower (LR) reactivity, associated with vulnerability to stress. LRHR phenotype is proposed as an antecedent to the development of stress hyper responsiveness. Results presented here show emergence of antidepressive-like behavior following peripubertal-juvenile exposure to chronic variable physical (CVP) and chronic variable social stress (CVS) in HR rats, and...
Show moreExperimentally naive rats show variance in their locomotor reactivity to novelty, some displaying higher (HR) while others displaying lower (LR) reactivity, associated with vulnerability to stress. LRHR phenotype is proposed as an antecedent to the development of stress hyper responsiveness. Results presented here show emergence of antidepressive-like behavior following peripubertal-juvenile exposure to chronic variable physical (CVP) and chronic variable social stress (CVS) in HR rats, and depressive-like behavior following CVP in the LRs. The antidepressive-like behavior in HR rats was accompanied by increased levels of acetylated Histone3 (acH3) and acetylated Histone4 (acH4) at the hippocampal brain-derived neurotrophic factor (BDNF) P2 and P4 promoters respectively. This effect may mediate increased mossy fibre (MF) terminal field size, particularly the suprapyramidal mossy fibre projection volume (SP-MF), in the HR animals following both stress regimens. These findings show that chronic variable stress during adolescence induces individual differences in molecular, neuromorphological and behavioral parameters between LRs and HRs, which provides further evidence that individual differences in stress responsiveness is an important factor in resistance or vulnerability to stress-induced depression and/or anxiety.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3360950
- Subject Headings
- Rats as laboratory animals, Anxiety in adolescence, Depression in adolescence, Stress (Psychology), Cellular signal transduction, Hippocampus (Brain), Physiology, Genetic regulation, Gene expression
- Format
- Document (PDF)
- Title
- EFFECTS OF SPECIFIC PfEMP1 LIGATION INTERACTIONS WITH ICAM-1, INTEGRIN αVβ3, AND CD36 ON MONOCYTES IN AN IN VITRO MALARIANAÏVE HOST MODEL.
- Creator
- Merritt, Jordan, Oleinikov, Andrew, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Science
- Abstract/Description
-
Malaria is a severe global health problem that causes approximately 435,000 deaths per year. Any non-immune individual traveling to malaria endemic regions can be affected too, including humanitarian volunteers, travelers, and US troops. Under physiological conditions, damaged or malaria-infected RBCs would be removed within the spleen, but Plasmodium falciparum infected RBCs (iRBCs) sequester to microvascular endothelial cells to avoid entering the spleen. Adhesion interactions and parasite...
Show moreMalaria is a severe global health problem that causes approximately 435,000 deaths per year. Any non-immune individual traveling to malaria endemic regions can be affected too, including humanitarian volunteers, travelers, and US troops. Under physiological conditions, damaged or malaria-infected RBCs would be removed within the spleen, but Plasmodium falciparum infected RBCs (iRBCs) sequester to microvascular endothelial cells to avoid entering the spleen. Adhesion interactions and parasite sequestration to endothelial cells are mediated by Plasmodium falciparum erythrocyte membrane protein 1 family (PfEMP1) proteins expressed on the iRBC’s surface. The PfEMP1 proteins bind to existing endothelial cell surface receptors that already serve primary functions, including ICAM-1, integrin αVβ3, and CD36. Traditionally, these receptors are explored in the context of endothelial cell sequestration, but this project examines the consequence of receptor::PfEMP1 interaction on immune cells, namely monocyte-like THP-1 cells.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013398
- Subject Headings
- Malaria, Plasmodium falciparum, Integrins, Monocytes, Intercellular Adhesion Molecule-1, CD36 Antigens, Adhesiveness
- Format
- Document (PDF)