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Title: Study of Cell Penetrating Peptide Uptake and Cancer Cell Discrimination with Raman Spectroscopy and Microscopy.
Creator: Cosme, Patrick Jason, Terentis, Andrew C., Florida Atlantic University, Charles E Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cell penetrating peptides (CPPs) are short sequences of amino acids that excel in crossing the cellular membrane without inducing cytotoxicity Interest in these peptides stem from their ability to be attached, and grant their penetrating properties to, a variety of cargo In this work we have combined the application of Confocal Raman Microscopy (CRM) and Atomic Force Microscopy for the first time to examine the interactions of unlabeled Transportan (TP), one of the most well studied CPPs,...
Show moreCell penetrating peptides (CPPs) are short sequences of amino acids that excel in crossing the cellular membrane without inducing cytotoxicity Interest in these peptides stem from their ability to be attached, and grant their penetrating properties to, a variety of cargo In this work we have combined the application of Confocal Raman Microscopy (CRM) and Atomic Force Microscopy for the first time to examine the interactions of unlabeled Transportan (TP), one of the most well studied CPPs, with mammalian cells CRM’s capability to discriminate control and treated cell groups was verified by principal component analysis (PCA) and linear discriminant analysis (LDA) and was 93-100% accurate We’ve determined that at a concentration of 20 μM TP enters cells through a non-endocytotic mechanism, has a high affinity for the cytoplasm and membranes, and results in a significant increase in cellular stiffness Our work provides the first direct evidence of this cell-stiffening phenomenon SFTI-1, the smallest member of a bicyclic, cysteine rich class of CPPs, was examined by CRM to determine the potential role of cyclic structure on cellular uptake The peptide, along with monocyclic and linear analogs was heavy isotope labeled and incubated with mammalian cells at numerous concentrations and timespans Our work is the first SFTI-1 uptake study forgoing the use of fluorophore conjugates, which have been linked to artificial cellular uptake We demonstrate herein the absence of any CRM detectable uptake, providing the first evidence that SFTI-1 may not be a CPP Finally, CRM was applied to the discrimination of normal and basal cell carcinoma cells obtained from the same donor The use of patient matched cells avoids the normal biochemical variations that exist among individuals, ensuring that discrimination is based solely on the cell’s diseased state CRM spectra, analyzed by PCA and LDA, were capable of spectral discrimination with 100% accuracy Major differences in the cancerous cells were an increase in lipids and nucleic acids, and an overall decrease in protein We also demonstrate an enhancement in Raman signal through the use of an aluminum foil substrate, providing a practical approach for measuring cells with thin morphologies
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004756
Subject Headings: Peptides--Analysis, Peptides--Therapeutic use, Peptides--Physiological transport, Cellular signal transduction, Raman spectroscopy, Infrared spectroscopy
Format: Document (PDF)

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

Title: Regulation of rapid signaling at the cone ribbon synapse via distinct pre- and postsynaptic mechanisms.
Creator: Rowan, Matthew JM., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Background: Light-adaptation is a multifaceted process in the retina that helps adjust the visual system to changing illumination levels. Many studies are focused on the photochemical mechanism of light-adaptation. Neural network adaptation mechanisms at the photoreceptor synapse are largely unknown. We find that large, spontaneous Excitatory Amino Acid Transporter (EAATs) activity in cone terminals may contribute to cone synaptic adaptation, specifically with respect to how these signals...
Show moreBackground: Light-adaptation is a multifaceted process in the retina that helps adjust the visual system to changing illumination levels. Many studies are focused on the photochemical mechanism of light-adaptation. Neural network adaptation mechanisms at the photoreceptor synapse are largely unknown. We find that large, spontaneous Excitatory Amino Acid Transporter (EAATs) activity in cone terminals may contribute to cone synaptic adaptation, specifically with respect to how these signals change in differing conditions of light. EAATs in neurons quickly transport glutamate from the synaptic cleft, and also elicit large thermodynamically uncoupled Cl- currents when activated. We recorded synaptic EAAT currents from cones to study glutamate-uptake events elicited by glutamate release from the local cone, and from adjacent photoreceptors. We find that cones are synaptically connected via EAATs in dark ; this synaptic connection is diminished in light-adapted cones. Methods: Whole-cell patch-clamp was performed on dark- and transiently light-adapted tiger salamander cones. Endogenous EAAT currents were recorded in cones with a short depolarization to -10mV/2ms, while spontaneous transporter currents from network cones were observed while a local cone holding at -70mV constantly. DHKA, a specific transporter inhibitor, was used to identify EAAT2 currents in the cone terminals, while TBOA identified other EAAT subtypes. GABAergic and glycinergic network inputs were always blocked with picrotoxin and strychnine. Results: Spontaneous EAAT currents were observed in cones held constantly at -70mV in dark, indicating that the cones received glutamate inputs from adjacent photoreceptors. These spontaneous EAAT currents disappeared in presence of a strong light, possibly because the light suppressed glutamate releases from the adjacent photoreceptors. The spontaneous EAAT currents were blocked with TBOA, but not DHKA, an inhibitor for EAAT2 subtype, suggesting that a, non-EAAT 2 subtype may reside in a basal or perisynaptic area of cones, with a specialized ability to bind exocytosed glutamate from adjacent cones in dark. Furthermore, these results could be artificially replicated by dual-electrode recordings from two adjacent cones. When glutamate release was elicited from one cone, the TBOA-sensitive EAAT currents were observed from the other cone. Conclusions: Cones appear to act like a meshwork, synaptically connected via glutamate transporters. Light attenuates glutamate release and diminishes the cone-cone synaptic connections. This process may act as an important network mechanism for cone light adaptation.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3337186
Subject Headings: Synapses, Neural transmission, VIsual perception, Presynaptic receptors, Molecular neurobiology, Glutamic acid, Neural receptors, Cellular signal transduction, Retina, Cytology
Format: Document (PDF)

Title: Purification and characterization of two members of the protein tyrosine phosphatase family: dual specificity phosphatase PVP and low molecular weight phosphatase WZB.
Creator: Livingston, Paula A., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Two protein tyrosine phosphatases, dual specificity phosphatase PVP and low molecular weight phosphatase WZB were purified and characterized. PVP was expressed as inclusion bodies and a suitable purification and refolding method was devised. Enzyme kinetics revealed that p-nitrophenylphosphate and (Sb(B-naphthyl phosphate were substrates with KM of 4.0mM and 8.1mM respectively. PVP showed no reactivity towards phosphoserine. Kinetic characterization of WZB showed that only...
Show moreTwo protein tyrosine phosphatases, dual specificity phosphatase PVP and low molecular weight phosphatase WZB were purified and characterized. PVP was expressed as inclusion bodies and a suitable purification and refolding method was devised. Enzyme kinetics revealed that p-nitrophenylphosphate and (Sb(B-naphthyl phosphate were substrates with KM of 4.0mM and 8.1mM respectively. PVP showed no reactivity towards phosphoserine. Kinetic characterization of WZB showed that only pnitrophenylphosphate was a substrate with no affinity for Ç-naphthyl phosphate and phosphoserine. Optimal conditions for activity with PNPP were found at a pH of 5 with a KM of 1.1mM, kcat of 35.4s-1 and kcat/KM of 32.2s-1mM-1. Inhibition studies showed that phosphate, fluoride, and molybdate were competitive inhibitors with Ki of 3.2mM, 71.7mM, and 50.4(So(BM respectively and hydrogen peroxide abolished activity. Active site mutants of WZB Cys9Ser and Asp115Asn showed no activity.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/332911
Subject Headings: Protein-tyrosine phosphatase, Cellular signal transduction, Cell cycle, Regulation, Membrane proteins, Structure-activity relationships, Protein kinases
Format: Document (PDF)

Title: Role of methionine sulfoxide reductase in thermal-induced spreading depression coma in Drosophila melanogaster.
Creator: Schey, Karin., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Drosophila melanogaster encounter periods of increased temperature or decreased oxygen in its native environment. One consequence of these environmental stresses is increased production of reactive oxygen species that damage major molecules within cells. Another consequence is that flies fall into a protective coma where biological functions are minimized to conserve energy expenditures. This biological phenomenon is called spreading depression. The overarching aim of this project is to...
Show moreDrosophila melanogaster encounter periods of increased temperature or decreased oxygen in its native environment. One consequence of these environmental stresses is increased production of reactive oxygen species that damage major molecules within cells. Another consequence is that flies fall into a protective coma where biological functions are minimized to conserve energy expenditures. This biological phenomenon is called spreading depression. The overarching aim of this project is to determine if methionine sulfoxide reductases affect entrance or exit from the protective coma induced by acute thermal stress. The data revealed that complete deficiency of Msr in young flies causes a faster induction of the coma. In both young and old flies, Msr does not affect average recovery time but does affect the pattern of recovery from coma. Entrance into the coma is age dependent with young flies maintaining activity longer than before entering into the coma as compared to old flies.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3355873
Subject Headings: Cellular signal transduction, Proteins, Chemical modification, Spreading cortical depression, Oxidation-reduction reaction, Aging, Molecular aspects, Mutation (Biology)
Format: Document (PDF)

Title: Mitochondrial regulation pathways in the lens: pink1/parkin- and bnip3l-mediated mechanisms.
Creator: Aktan, Kerem, Kantorow, Marc, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: The mitochondrion is the powerhouse of the cell. Therefore, it is critical to the homeostasis of the cell that populations of mitochondria that are damaged or in excess are degraded. The process of targeted elimination of damaged or excess mitochondria by autophagy is called mitophagy. In this report, analysis of the mitophagy regulators PINK1/PARKIN and BNIP3L and their roles are assessed in the lens. PARKIN, an E3 ubiquitin ligase, has been shown to play a role in directing damaged...
Show moreThe mitochondrion is the powerhouse of the cell. Therefore, it is critical to the homeostasis of the cell that populations of mitochondria that are damaged or in excess are degraded. The process of targeted elimination of damaged or excess mitochondria by autophagy is called mitophagy. In this report, analysis of the mitophagy regulators PINK1/PARKIN and BNIP3L and their roles are assessed in the lens. PARKIN, an E3 ubiquitin ligase, has been shown to play a role in directing damaged mitochondria for degradation. While BNIP3L, an outer mitochondrial membrane protein, increases in expression in response to excess mitochondria and organelle degradation during cellular differentiation. We have shown that PARKIN is both induced and translocates from the cytoplasm to the mitochondria in human epithelial lens cells upon oxidative stress exposure. In addition, our findings also show that overexpression of BNIP3L causes premature clearance of mitochondria and other organelles, while loss of BNIP3L results in lack of clearance. Prior to this work, PARKIN mediated mitophagy had not been shown to act as a protective cellular response to oxidative stress in the lens. This project also resulted in the novel finding that BNIP3L-mediated mitophagy mechanisms are required for targeted organelle degradation in the lens.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004427, http://purl.flvc.org/fau/fd/FA00004427
Subject Headings: Cellular signal transduction, Eye -- Diseases -- Etiology, Mitochondrial pathology, Mitophagy, Molecular chaperones, Oxidative stress -- Prevention, Protein folding
Format: Document (PDF)

Title: Polyglutamine aggregates stimulate ER stress and trigger apoptosis by activating BH-3 only protein Bim.
Creator: Bhagavatula, Nithya, Wei, Jianning, Florida Atlantic University
Abstract/Description: Huntington's disease (HD) is an inherited neurological disorder characterized by a selective loss of neurons in the striatum and cortex leading to involuntary movement, dementia and eventually cell death. HD is caused by an expanded polyglutamine (PolyQ) repeat in Huntingtin (Htt) protein. It is well known that misfolded mutant Htt could form intracellular aggregates, trigger ER stress and ultimately lead to apoptosis. However, the molecular link between ER stress and apoptosis in...
Show moreHuntington's disease (HD) is an inherited neurological disorder characterized by a selective loss of neurons in the striatum and cortex leading to involuntary movement, dementia and eventually cell death. HD is caused by an expanded polyglutamine (PolyQ) repeat in Huntingtin (Htt) protein. It is well known that misfolded mutant Htt could form intracellular aggregates, trigger ER stress and ultimately lead to apoptosis. However, the molecular link between ER stress and apoptosis in mitochondria is poorly understood. In the present study, we identified Bim (Bcl-2 interacting mediator of cell death) as the essential protein. We first established a cellular model of HD by over expressing the Nterminus of wild type and mutant Htt into HEK293 cell lines. We showed that the accumulation and aggregation of misfolded mutant Htt protein triggers ER stress and apoptosis. The Bim protein expression level was greatly increased in mutant Htt transfected cells and this increase was partially due to up-regulation of Bim mRNA as analyzed using quantitative RT-PCR. We further showed that Bim phosphorylation also played an important role in regulating Bim expression. Moreover, up-regulation of Bim facilitates the translocation of Bax to mitochondrial membrane, which lead to cytochrome c release and apoptosis. We also silenced Bim using siRNA to further investigate the essential role of Bim in mutant Htt induced ER stress and apoptosis. Identifying the Bim pathway that is altered in response to the mutant Htt protein is important for understanding the cellular processes impacted by the disease.
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Date Issued: 2008
PURL: http://purl.flvc.org/fau/fd/FA00000726
Subject Headings: Nervous system--Degeneration--Molecular aspects, Apoptosis, Cellular signal transduction, Huntington's disease--Genetic aspects, Huntington's disease--Pathophysiology
Format: Document (PDF)

Title: Methionine sulfoxide reductase (MSR) modulates lifespan andLocomotion in drosophila melanogaster.
Creator: Bruce, Lindsay, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Oxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in...
Show moreOxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in proteins back to methionine. This study, using Drosophila melanogaster, decribes the first animal system lacking both MsrA and MsrB. The loss of either MsrA or MsrB had no effect on lifespan in Drosophila, but loss of MsrB results in a slight decrease in locomotor activity from middle age onward. Double mutants lacking both forms of Msr have a significantly decreased lifespan and decreased locomotor activity at all ages examined. The double Msr mutants had no detectable increase in protein oxidation or decrease in mitochondrial function and were not more sensitive to oxidative stress. These results suggested that other cellular antioxidant systems were protecting the flies against oxidative damage and the decreased life span observed in the double knockouts was not due to widespread oxidative damage. However, one cannot exclude limited oxidative damage to a specific locus or cell type. In this regard, it was observed that older animals, lacking both MsrA and MsrB, have significantly reduced levels of dopamine, suggesting there might be oxidative damage to the dopaminergic neurons. Preliminary results also suggest that the ratio of F to G actin is skewed towards G actin in all mutants. The present results could have relevance to the loss of dopaminergic neurons in Parkinson’s disease.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004431, http://purl.flvc.org/fau/fd/FA00004431
Subject Headings: Aging -- Molecular aspects, Cellular signal transduction, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Mutation (Biology), Oxidative stress, Proteins -- Chemical modification
Format: Document (PDF)

Title: Novel molecular targets for genistein in prostate cancer cells.
Creator: Merchant, Kendra T., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Prostate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and...
Show moreProstate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and apoptosis pathways to induce cell death, with little or no toxic side effects to the patient. In this study we investigated the effect of genistein on expression levels of genes involved in these pathways. Genistein is a (4 , 5 , 7-trihydroxyisoflavone) is a major isoflavone constituent of soy that has been shown to inhibit growth proliferation and induce apoptosis in cancer cells. The mechanism of genistein-induced cell death and potential molecular targets for genistein in LNCaP prostate cancer c ells was investigated using several techniques. The chemosensitivity of genistein towards the prostate cancer cells was investigated using the ATP and MTS assays and apoptosis induction was determined using apoptosis and caspase assays. Several molecular targets were also identified using cDNA microarray and RT-PCR analysis. Our results revealed that genistein induces cell death in a time and dose-dependent manner and regulates expression levels of several genes involved in carcinogenesis and immunogenicity. Several cell cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin dependent kinases, indicating that genistein is able to halt cell cycle progression through the regulation of genes involved in this process., Several members of the Bcl-2 family which are involved in apoptosis were also affected and a number of genes involved in immunogenicity were up-regulated including the DefB1 and HLA membrane receptors. The results of this study provide evidence of genistein's ability to inhibit growth proliferation and induce apoptosis and indicates its potential as an adjuvant in chemotherapy and immunotherapy.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/192986
Subject Headings: Prostate, Cancer, Adjuvant treatment, Prostate, Cancer, Molecular aspects, Apoptosis, Molecular aspects, Phytochemicals, Physiological effect, Cellular signal transduction
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.
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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: Hippocampal CA1 activation during object memory encoding in the novel object recognition task.
Creator: Cinalli, David A., Stackman, Robert W., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Psychology
Abstract/Description: Transcription and translation of proteins are required for the consolidation of episodic memory. Arc, an effector immediate early gene, has been linked to synaptic plasticity following learning and memory. It is well established that the rodent hippocampus is essential for processing spatial memory, but its role in processing object memory is a point of contention. Using immunohistochemical techniques, hippocampal sections were stained for arc proteins in the CA1 region of the dorsal...
Show moreTranscription and translation of proteins are required for the consolidation of episodic memory. Arc, an effector immediate early gene, has been linked to synaptic plasticity following learning and memory. It is well established that the rodent hippocampus is essential for processing spatial memory, but its role in processing object memory is a point of contention. Using immunohistochemical techniques, hippocampal sections were stained for arc proteins in the CA1 region of the dorsal hippocampus in mice following two variations of the novel object recognition (NOR) task. Results suggest mice that acquired strong object memory showed significant hippocampal activation. In mice that acquired weak object memory, hippocampal activation was not significantly different from controls. Arc expression was also examined in other hippocampal sub-regions, as well as in the perirhinal cortex. These results suggest that the mice must acquire a threshold amount of object information before the hippocampal CA1 region is engaged.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004436, http://purl.flvc.org/fau/fd/FA00004436
Subject Headings: Association of ideas, Cellular control mechanisms, Cellular signal transduction, Episodic memory, Hippocampus (Brain) -- Physiology, Human information processing, Mice as laboratory animals
Format: Document (PDF)

Title: Of Mice, Men and Memories: The Role of the Rodent Hippocampus in Object Recognition.
Creator: Cohen, Sarah J., Stackman, Robert W., Florida Atlantic University, Charles E. Schmidt College of Science, Center for Complex Systems and Brain Sciences
Abstract/Description: Establishing appropriate animal models for the study of human memory is paramount to the development of memory disorder treatments. Damage to the hippocampus, a medial temporal lobe brain structure, has been implicated in the memory loss associated with Alzheimer’s disease and other dementias. In humans, the role of the hippocampus is largely defined; yet, its role in rodents is much less clear due to conflicting findings. To investigate these discrepancies, an extensive review of the rodent...
Show moreEstablishing appropriate animal models for the study of human memory is paramount to the development of memory disorder treatments. Damage to the hippocampus, a medial temporal lobe brain structure, has been implicated in the memory loss associated with Alzheimer’s disease and other dementias. In humans, the role of the hippocampus is largely defined; yet, its role in rodents is much less clear due to conflicting findings. To investigate these discrepancies, an extensive review of the rodent literature was conducted, with a focus on studies that used the Novel Object Recognition (NOR) paradigm for testing. The total amount of time the objects were explored during training and the delay imposed between training and testing seemed to determine hippocampal recruitment in rodents. Male C57BL/6J mice were implanted with bilateral dorsal CA1 guide cannulae to allow for the inactivation of the hippocampus at discrete time points in the task. The results suggest that the rodent hippocampus is crucial to the encoding, consolidation and retrieval of object memory. Next, it was determined that there is a delay-dependent involvement of the hippocampus in object memory, implying that other structures may be supporting the memory prior to the recruitment of hippocampus. In addition, when the context memory and object memory could be further dissociated, by altering the task design, the results imply a necessary role for the hippocampus in the object memory, irrespective of context. Also, making the task more perceptually demanding, by requiring the mice to perform a two-dimensional to three-dimensional association between stimuli, engaged the hippocampus. Then, in the traditional NOR task, long and short training exploration times were imposed to determine brain region activity for weak and strong object memory. The inactivation and immunohistochemistry findings imply weak object memory is perirhinal cortex dependent, while strong object memory is hippocampal-dependent. Taken together, the findings suggest that mice, like humans, process object memory on a continuum from weak to strong, recruiting the hippocampus conditionally for strong familiarity. Confirming this functional similarity between the rodent and human object memory systems could be beneficial for future studies investigating memory disorders.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004580
Subject Headings: Memory--Research., Mice as laboratory animals., Hippocampus (Brain)--Physiology., Episodic memory., Neurotransmitter receptors., Cellular control mechanisms., Cellular signal transduction., Human information processing.
Format: Document (PDF)

Title: Characterization of receptor protein tyrosine phosphatase PTP69D in the giant fiber circuit.
Creator: Lee, LaTasha Hoskins, Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: PTP69D is a receptor protein tyrosine phosphatase (RPTP) with two intracellular catalytic domains (Cat1 and Cat2), which has been shown to play a role in axon outgrowth and guidance of embryonic motorneurons, as well as targeting of photoreceptor neurons in the visual system of Drosophila melanogaster. Here, we characterized the developmental role of PTP69D in the giant fiber (GF) neurons; two interneurons in the central nervous system (CNS) that control the escape response of the fly. In...
Show morePTP69D is a receptor protein tyrosine phosphatase (RPTP) with two intracellular catalytic domains (Cat1 and Cat2), which has been shown to play a role in axon outgrowth and guidance of embryonic motorneurons, as well as targeting of photoreceptor neurons in the visual system of Drosophila melanogaster. Here, we characterized the developmental role of PTP69D in the giant fiber (GF) neurons; two interneurons in the central nervous system (CNS) that control the escape response of the fly. In addition to guidance and targeting functions, our studies reveal an additional role for PTP69D in synaptic terminal growth in the CNS. We found that inhibition of phosphatase activity in catalytic domain (Cat1) proximal to the transmembrane domain did not affect axon guidance or targeting but resulted in stunted terminal growth of the GFs. Cell autonomous rescue and knockdown experiments demonstrated a function for PTP69D in the GFs, but not its postsynaptic target neurons. In addition,complementation studies and structure-function analyses revealed that for GF terminal growth, Cat1 function of PTP69D requires the immunoglobulin and the Cat2 domain but not the fibronectin type III repeats nor the membrane proximal region. In contrast, the fibronectin type III repeats, but not the immunoglobulin domains, were previously shown to be essential for axon targeting of photoreceptor neurons. Thus, our studies uncover a novel role for PTP69D in synaptic terminal growth in the CNS that is mechanistically distinct from its function during earlier developmental processes.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004301, http://purl.flvc.org/fau/fd/FA00004301
Subject Headings: Drosophila melanogaster., Protein-tyrosine phosphatase--Metabolism., Protein-tyrosine kinase., Protein kinases--Inhibitors., Phosphoprotein phosphatases., Transcription factors., Cell receptors., Cellular signal transduction.
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: 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.
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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: Impact of Vitamin C on Genistein-Induced Apoptosis in Prostate Cancer.
Creator: Famuyiwa, Toluleke, Kumi-Diaka, James, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: This study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) >...
Show moreThis study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) > 10uM genistein > 70uM genistein. The chi-square test for comparing necrosis, apoptosis and life cells showed that Vitamin C could impact genistein-induced apoptosis in LNCaP cells (p = 0.0003). This study forms the basis for in vivo studies of the impact of vitamin C on genistein-induced apoptosis in LNCaP prostate cancer cells.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004497, http://purl.flvc.org/fau/fd/FA00004497
Subject Headings: Apoptosis -- Molecular aspects, Cellular signal transduction, Genistein -- Therapeutic use, Phytochemicals -- Physiological effect, Phytochemicals -- Therapeutic use, Prostate -- Cancer -- Adjuvant treatment, Prostate -- Cancer -- Molecular aspects, Vitamin C -- Therapeutic use
Format: Document (PDF)

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

Title: Reduced Reproductivity and Larval Locomotion in the Absence of Methionine Sulfoxide Reductase in Drosophila.
Creator: Singkornrat, Diana, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The inevitable aging process can be partially attributed to the accumulation of oxidative damage that results from the action of free radicals. Methionine sulfoxide reductases (Msr) are a class of enzymes that repair oxidized methionine residues. The two known forms of Msr are MsrA and MsrB which reduce the R- and S- enantiomers of methionine sulfoxide, respectively. Our lab has created the first genetic animal model that is fully deficient for any Msr activity. Previously our lab showed that...
Show moreThe inevitable aging process can be partially attributed to the accumulation of oxidative damage that results from the action of free radicals. Methionine sulfoxide reductases (Msr) are a class of enzymes that repair oxidized methionine residues. The two known forms of Msr are MsrA and MsrB which reduce the R- and S- enantiomers of methionine sulfoxide, respectively. Our lab has created the first genetic animal model that is fully deficient for any Msr activity. Previously our lab showed that these animals exhibit a 20 hour delay in development of the third instar larvae (unpublished data). My studies have further shown that the prolonged third-instar stage is due to a reduced growth rate associated with slower food intake and a markedly slower motility. These Msr-deficient animals also exhibit decreased egg-laying that can be attributed to a lack of female receptivity to mating.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004777, http://purl.flvc.org/fau/fd/FA00004777
Subject Headings: Proteins--Chemical modification., Oxidative stress., Oxidation-reduction reaction., Drosophila melanogaster--Genetics., Mitochondrial pathology., Cellular signal transduction., Mutation (Biology), Aging--Molecular aspects.
Format: Document (PDF)

Title: Presynaptic Determinants of Synaptic Strength and Energy Efficiency at Drosophila Neuromuscular Junctions.
Creator: Lu, Zhongmin, Macleod, Gregory, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Changes in synaptic strength underlie synaptic plasticity, the cellular substrate for learning and memory. Disruptions in the mechanisms that regulate synaptic strength closely link to many developmental, neurodegenerative and neurological disorders. Release site probability (PAZ) and active zone number (N) are two important presynaptic determinants of synaptic strength; yet, little is known about the processes that establish the balance between N and PAZ at any synapse. Furthermore, it is...
Show moreChanges in synaptic strength underlie synaptic plasticity, the cellular substrate for learning and memory. Disruptions in the mechanisms that regulate synaptic strength closely link to many developmental, neurodegenerative and neurological disorders. Release site probability (PAZ) and active zone number (N) are two important presynaptic determinants of synaptic strength; yet, little is known about the processes that establish the balance between N and PAZ at any synapse. Furthermore, it is not known how PAZ and N are rebalanced during synaptic homeostasis to accomplish circuit stability. To address this knowledge gap, we adapted a neurophysiological experimental system consisting of two functionally differentiated glutamatergic motor neurons (MNs) innervating the same target. Average PAZ varied between nerve terminals, motivating us to explore benefits for high and low PAZ, respectively. We speculated that high PAZ confers high-energy efficiency. To test the hypothesis, electrophysiological and ultrastructural measurements were made. The terminal with the highest PAZ released more neurotransmitter but it did so with the least total energetic cost. An analytical model was built to further explore functional and structural aspects in optimizing energy efficiency. The model supported that energy efficiency optimization requires high PAZ. However, terminals with low PAZ were better able to sustain neurotransmitter release. We suggest that tension between energy efficiency and stamina sets PAZ and thus determines synaptic strength. To test the hypothesis that nerve terminals regulate PAZ rather than N to maintain synaptic strength, we induced sustained synaptic homeostasis at the nerve terminals. Ca2+ imaging revealed that terminals of the MN innervating only one muscle fiber utilized greater Ca2+ influx to achieve compensatory neurotransmitter release. In contrast, morphological measurements revealed that terminals of the MN inner vating multiple postsynaptic targets utilized an increase in N to achieve compensatory neurotransmitter release, but this only occurred at the terminal of the affected postsynaptic target. In conclusion, this dissertation provides several novel insights into a prominent question in neuroscience: how is synaptic strength established and maintained. The work indicates that tension exists between energy efficiency and stamina in neurotransmitter release likely influences PAZ. Furthermore, PAZ and N are rebalanced differently between terminals during synaptic homeostasis.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004519, http://purl.flvc.org/fau/fd/FA00004519
Subject Headings: Drosophila melanogaster--Nervous system., Drosophila melanogaster--Cytogenetics., Fruit-flies--Development., Fruit-flies--Nervous system., Genetic transcription., Transcription factors., Cellular signal transduction., Cellular control mechanisms., Myoneural junction.
Format: Document (PDF)

Title: Analysis of the Role of Autophagy in Dauer Formation and Dauer Recovery Regulated by TGF-β Signaling Pathway in Caenorhabditis elegans.
Creator: Ritter, Portia, Jia, Kailiang, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Caenorhabditis elegans optionally enter into a dauer diapause phase that results in a prolonged life in a semi-dormant state. Entry into and recovery from dauer diapause includes many physical changes in body structure, physiology, and gene expression. Entry into dauer diapause is regulated by several signaling pathways including transforming growth factor (TGF-β). Autophagy plays an important role in dauer formation and recover. During dauer transformation autophagy is up-regulated and may...
Show moreCaenorhabditis elegans optionally enter into a dauer diapause phase that results in a prolonged life in a semi-dormant state. Entry into and recovery from dauer diapause includes many physical changes in body structure, physiology, and gene expression. Entry into dauer diapause is regulated by several signaling pathways including transforming growth factor (TGF-β). Autophagy plays an important role in dauer formation and recover. During dauer transformation autophagy is up-regulated and may play a role in remodeling the molecular structure for long term survival during dauer diapause. This research helps determine the role of autophagy in dauer development and recovery mediated through the TGF-β signaling pathway. This research also determines in which tissue autophagy is necessary for dauer formation and recovery through TGF-β signaling. This research is shedding light on the function of autophagy in the TGF-β signaling pathway, both processes of which have been linked to tumorigenesis, heart disease and cancer.
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Date Issued: 2017
PURL: http://purl.flvc.org/fau/fd/FA00004921, http://purl.flvc.org/fau/fd/FA00004921
Subject Headings: Aging--Molecular aspects., Aging--Physiological aspects., Caenorhabditis elegans--Molecular genetics., Autophagic vacuoles., Gene expression., Apoptosis., Cellular signal transduction., DNA-binding proteins., Transforming growth factors-beta--Receptors.
Format: Document (PDF)

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Cellular signal transduction (67)	+ -
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