Current Search: Proteins (x)
Pages
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Title
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AMYLOIDOGENICITY OF THE PEPTIDE FRAGMENT IN MICROTUBULE BINDING REPEAT DOMAIN OF TAU.
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Creator
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Islam, Majedul, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
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Abstract/Description
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Tau, a microtubule-associated protein, is involved in more than 20 different tauopathic disorders characterized by aberrant intracellular aggregation of tau in the brain. However, it is still unclear how this highly soluble tau protein aggregates inside the brain. Thus, understanding the mechanistic details of tau aggregation is critical for unraveling the underlying pathology of tauopathies and developing effective strategies to inhibit tau aggregation. Herein, we investigated the...
Show moreTau, a microtubule-associated protein, is involved in more than 20 different tauopathic disorders characterized by aberrant intracellular aggregation of tau in the brain. However, it is still unclear how this highly soluble tau protein aggregates inside the brain. Thus, understanding the mechanistic details of tau aggregation is critical for unraveling the underlying pathology of tauopathies and developing effective strategies to inhibit tau aggregation. Herein, we investigated the aggregation of a novel 20-residue model peptide, tau₂₉₈₋₃₁₇, derived from the key microtubule-binding domain of the full sequence tau. Our study demonstrates that tau₂₉₈₋₃₁₇ highly mimics full-length tau's physical and aggregation properties. The fibrillation of the peptide is strongly dependent on external factors. The presence of polyanionic heparin (Hep) significantly promotes the aggregation of this peptide to form amyloid fibrils. The Hep-induced aggregation is sensitive to the ionic strength of the solution, suggesting an important role of electrostatic interactions in the mechanism of Hep-mediated aggregation. In addition, two positively charged polysaccharides, chitosan (CHT) and its quaternary derivative N-trimethyl chitosan (TMC), effectively inhibit Hep-induced aggregation of tau₂₉₈₋₃₁₇ in a concentration-dependent manner. Attractive electrostatic interactions between the positively charged moieties in CHT/TMC and the negatively charged residues of Hep play a critical role in inhibiting Hep–peptide interactions and suppressing peptide aggregation.
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Date Issued
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2023
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PURL
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http://purl.flvc.org/fau/fd/FA00014211
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Subject Headings
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tau Proteins, Tauopathies, Amyloidogenic Proteins
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Format
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Document (PDF)
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Title
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Characterization and distribution of parvalbumin from selected fish species.
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Creator
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Ross, Cliff Ian., Florida Atlantic University, Hartmann, James X., Mari, Frank
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Abstract/Description
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Parvalbumins are acidic calcium-binding proteins found in large quantities in the white muscle fibers of cold-blooded vertebrates. Fish display two to seven parvalbumin isotypes that are species specific and thus constitute a valuable tool in the study of phylogenetic relationships, and as a specific biomarker for fish identification. Parvalbumins were isolated from a selected sample of marine teleosts and elasmobranchs. Purified isotypes were characterized via HPLC (gel filtration, and ion...
Show moreParvalbumins are acidic calcium-binding proteins found in large quantities in the white muscle fibers of cold-blooded vertebrates. Fish display two to seven parvalbumin isotypes that are species specific and thus constitute a valuable tool in the study of phylogenetic relationships, and as a specific biomarker for fish identification. Parvalbumins were isolated from a selected sample of marine teleosts and elasmobranchs. Purified isotypes were characterized via HPLC (gel filtration, and ion exchange), and electrophoresis (IEF, and SDS-PAGE). An indirect immunoassay was developed for the parvalbumin isotypes using monoclonal antibodies directed against the highly conserved calcium-binding site. Parvalbumins from selected fish species are compared and contrasted by standard biochemical and immunological methods.
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Date Issued
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1998
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PURL
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http://purl.flvc.org/fcla/dt/15536
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Subject Headings
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Fishes, Calcium-binding proteins, Globular proteins
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Format
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Document (PDF)
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Title
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Aggregation kinetics of A\U+fffd\ peptides and the inhibition effects of small molecules on A\U+fffd\ peptide aggregation.
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Creator
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Hijazi, Ahmad Alex., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
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Abstract/Description
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The pathology of Alzheimer's disease (AD) remains elusive. Competing evidence links amylois \U+fffd\-peptide (A\U+fffd\) amyloid formation to the phenotype of AD (1). The mechanism of amyloid fibril formation has been an ongoing investigation for many years. A\U+fffd\10-23 peptide, a fragment of A\U+fffd\1-42 peptide, contained crucial hydrophobic core residues (2). In this study, an investigation was launched to study the aggreagation process of A\U+fffd\1023 peptide and its ability to form...
Show moreThe pathology of Alzheimer's disease (AD) remains elusive. Competing evidence links amylois \U+fffd\-peptide (A\U+fffd\) amyloid formation to the phenotype of AD (1). The mechanism of amyloid fibril formation has been an ongoing investigation for many years. A\U+fffd\10-23 peptide, a fragment of A\U+fffd\1-42 peptide, contained crucial hydrophobic core residues (2). In this study, an investigation was launched to study the aggreagation process of A\U+fffd\1023 peptide and its ability to form amyloid fibrils. Furthermore, the presence of its hydrophobic core showed importance for its ability to aggregate and form amyloid fibrils. Thereafter, the inhibition of A\U+fffd\1-42 peptide aggregation was studied by using pyrimidine-based compounds. A\U+fffd\1-42 peptides, known to be neurotoxic, aggregate to form amyloid fibrils (3). This investigation may provide insight into the development of novel small molecular candidates to treat AD.
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Date Issued
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2012
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PURL
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http://purl.flvc.org/FAU/3358550
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Subject Headings
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Amyloid beta-protein, Proteins, Metabolism, Disorders, Prions, Alzheimer's disease
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Format
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Document (PDF)
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Title
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Synthesis and Biological Evaluation of β-hairpin Peptides as Covalent Inhibitors of the PD-1/PD-L1 Immune Checkpoint.
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Creator
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Naylon, Sarah, Roche, Stephane, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
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Abstract/Description
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Protein─protein interactions (PPIs) are essential for cell─cell interactions and cellular signal transduction, which play a crucial role in various human diseases. PPIs involved in cancer immunology pathways, known as immune checkpoints, have been intensely studied, leading to a new approach to cancer therapy. The PD1:PDL1 interaction is one of the most essential immune checkpoints. Studies on PD1:PDL1 showed over ten clinical monoclonal antibodies (mAb) used to treat cancer patients....
Show moreProtein─protein interactions (PPIs) are essential for cell─cell interactions and cellular signal transduction, which play a crucial role in various human diseases. PPIs involved in cancer immunology pathways, known as immune checkpoints, have been intensely studied, leading to a new approach to cancer therapy. The PD1:PDL1 interaction is one of the most essential immune checkpoints. Studies on PD1:PDL1 showed over ten clinical monoclonal antibodies (mAb) used to treat cancer patients. Unfortunately, antibodies do not penetrate the tumor microenvironment well, and clearance from the body is slow, leading to unwanted side effects. There is a significant gap in the drug market between the typical Rule of 5 (Ro5) small-molecule drugs (MW<0.5 kDa, SASA ~150 Å) and large antibodies with molecular weights greater than 40 kDa (SASA >2,000 Å). PPIs remain challenging to modulate by small molecules due to their large, shallow, often dynamic, and water-exposed surfaces lacking well-defined binding pockets. Thus, our lab was drawn to work on large β-hairpin peptides (2-3 kDa) that can potentially mimic the CDR-H3 loops of some of the most potent and clinical anti-PD1 antibodies. Exploration of these β-hairpin peptides provided valuable insights into their folding stability, conformational flexibility, passive membrane permeability, and protein-protein interaction (PPI) blocking activities. Additionally, the rational design of TCIs against PD1, specifically targeting a lysine residue, emerged as a strategy to irreversibly obstruct the PD1:PDL1 protein-protein interaction enhancing potency of the non-covalent inhibitors by taking advantage of their specificity. Meticulous structural analysis, peptide synthesis, and biological evaluations are presented contributing comprehensions into covalent inhibitor development of drugs fbRo5.
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Date Issued
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2023
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PURL
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http://purl.flvc.org/fau/fd/FA00014353
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Subject Headings
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Cancer--Immunological aspects, Protein-protein interactions, Antibodies, Monoclonal
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Format
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Document (PDF)
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Title
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Dietary nitrogen availability in macroalgae enhances growth of the sea hare Aplysia californica (Opisthobranchia: Anaspidea).
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Creator
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Barile, Peter J., Lapointe, Brian E., Capo, Thomas R.
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Date Issued
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2004
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PURL
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http://purl.flvc.org/FCLA/DT/2848319
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Subject Headings
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Nitrogen, Algae, Aplysiidae, Nitrogen, Proteins
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Format
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Document (PDF)
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Title
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Purification and characterization of two members of the protein tyrosine phosphatase family: dual specificity phosphatase PVP and low molecular weight phosphatase WZB.
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Creator
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Livingston, Paula A., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
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Abstract/Description
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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
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2009
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PURL
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http://purl.flvc.org/FAU/332911
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Subject Headings
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Protein-tyrosine phosphatase, Cellular signal transduction, Cell cycle, Regulation, Membrane proteins, Structure-activity relationships, Protein kinases
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Format
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Document (PDF)
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Title
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Seasonal variation in protein: carbohydrate ratios in a subtropical estuarine alga, Gracilaria verrucosa, and the determination of nitrogen limitation status using these ratios.
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Creator
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Bird, Kimon T., Harbor Branch Oceanographic Institute
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Date Issued
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1984
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PURL
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http://purl.flvc.org/fau/fd/FA00007018
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Subject Headings
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Gracilaria verrucosa, Alga, Protein, Carbohydrates, Growth
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Format
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Document (PDF)
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Title
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Proximate composition of eggs andlarvae of the sand dollar Encope michelini (Agassiz): the advantage of higher investment inplankotrophic eggs.
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Creator
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George, Sophie B., Young, Craig M., Fenaux, Lucienne, Harbor Branch Oceanographic Institute
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Date Issued
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1997
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PURL
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http://purl.flvc.org/fau/fd/FA00007268
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Subject Headings
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Sand dollars, Eggs, Larvae, Protein, Lipids
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Format
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Document (PDF)
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Title
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A rapid colorimetric microassay to detect agonists/antagonists of protein kinase C based on adherence of EL-4.IL-2 cells.
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Creator
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Longley, Ross E., Harmody, Dedra K., Harbor Branch Oceanographic Institute
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Date Issued
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1991
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PURL
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http://purl.flvc.org/FCLA/DT/3351944
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Subject Headings
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Protein kinase C, Colorimetric analysis, Diglycerides
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Format
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Document (PDF)
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Title
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Rapid neuroprotection from acute oxidative stress.
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Creator
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Caplan, Stacee Lee, Dawson-Scully, Ken, Milton, Sarah L., Graduate College
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Date Issued
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2011-04-08
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PURL
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http://purl.flvc.org/fcla/dt/3164512
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Subject Headings
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Stress --physiology, Protein kinases, Neuroprotective agents
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Format
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Document (PDF)
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Title
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A cembranolide diterpene farnesyl protein transferase inhibitor from the marine soft coral Lobophytum cristagalli.
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Creator
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Coval, S. J., Patton, R. W., Petrin, J. M., James, L., Rothofsky, M. L., Lin, S. L., Patel, Mahesh, Reed, John K., McPhail, A. T., Bishop, W. R.
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Date Issued
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1996
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PURL
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http://purl.flvc.org/FCLA/DT/3331913
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Subject Headings
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Corals, Alcyoniidae, Ras proteins, Diterpenes, Antineoplastic agents
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Format
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Document (PDF)
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Title
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The role of methionine sulfoxide reductase in thermal stress response.
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Creator
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Martin, James, Bruce, Lindsay, Schey, Karin, Binninger, David
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Date Issued
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2013-04-05
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PURL
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http://purl.flvc.org/fcla/dt/3361149
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Subject Headings
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Hyperthermia, Heat shock proteins, Methionine, Oxidative stress
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Format
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Document (PDF)
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Title
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Characterization of the spinster gene ortholog C13C4.5 in Caenorhabditis elegans.
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Creator
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Zahornacky, Darrin., Harriet L. Wilkes Honors College
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Abstract/Description
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The dauer larva is an alternate larval stage which allows the nematode C. elegans to survive environmestress during development. Dauer formation requires autophagy, a cellular process responsible for degrading and recycling cytoplasmic components. I investigated the role of a spinster orthiolog, C13C4.5, by examining the effects of C13C4.5 loss-of-function and by generating a transgenic strain which expressed a C13C4.5::GFP fusion protein. Under normal conditions C13C4.5::GFP is expressed...
Show moreThe dauer larva is an alternate larval stage which allows the nematode C. elegans to survive environmestress during development. Dauer formation requires autophagy, a cellular process responsible for degrading and recycling cytoplasmic components. I investigated the role of a spinster orthiolog, C13C4.5, by examining the effects of C13C4.5 loss-of-function and by generating a transgenic strain which expressed a C13C4.5::GFP fusion protein. Under normal conditions C13C4.5::GFP is expressed diffusely in the intestine, but under autophagy-promoting conditions the expression pattern becomes more punctate. This is consistent with localization of C13C4.5 to autophagolysomoes during autophagy, as has been shown for spinster in D. melanogaster. Loss of C13C4.5 function in a dauer-constitutive mutant resulted in a reduction in the proportion of animals entering into the dauer stage. Together these data suggest that C13C4.5 is involved in dauer formation and the autophagy pathway.
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Date Issued
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2012
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PURL
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http://purl.flvc.org/FAU/3359320
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Subject Headings
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Gene expression, Apoptosis, Caenorhabditis elegans, Proteins, Analysis
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Format
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Document (PDF)
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Title
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INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men.
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Creator
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Orkunoglu-Suer, Funda E., Gordish-Dressman, Heather, Clarkson, Priscilla M., Thompson, Paul D., Angelopoulos, Theodore J., Gordon, Paul M., Moyna, Niall M., Pescatello, Linda S., Visich, Paul S., Zoeller, Robert F., Harmon, Brennan, Seip, Richard L., Hoffman, Eric P., Devaney, Joseph M.
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Date Issued
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2008-12-23
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PURL
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http://purl.flvc.org/fcla/dt/3327172
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Subject Headings
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Adiposity --genetics, Alleles, Gene Frequency, Intracellular Signaling Peptides and Proteins, Resistance Training, Subcutaneous Fat, INSIG2 protein, Obesity, Genotype, Membrane Proteins, Membrane Proteins --Genetics
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Format
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Document (PDF)
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Title
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Evaluation of alumina-based stationary phases for the separations of proteins and peptides by high performance liquid chromatography.
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Creator
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Raghani, Anil Ratilal., Florida Atlantic University, Haky, Jerome E.
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Abstract/Description
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Alumina-based stationary phases are evaluated for the separations of proteins and peptides by reversed phase high performance liquid chromatography. Separations are compared to those obtained on a widely-used octadecylsilane (ODS) phase. The separations of peptides on alumina-based stationary phases are found to be superior while separations of proteins are inferior as compared to those found on ODS phase. The superior performance of peptide separations on alumina-based columns is attributed...
Show moreAlumina-based stationary phases are evaluated for the separations of proteins and peptides by reversed phase high performance liquid chromatography. Separations are compared to those obtained on a widely-used octadecylsilane (ODS) phase. The separations of peptides on alumina-based stationary phases are found to be superior while separations of proteins are inferior as compared to those found on ODS phase. The superior performance of peptide separations on alumina-based columns is attributed to lower pore size and uniquely-shaped particles of the alumina. The retentions of peptides and proteins on both alumina and silica-based stationary phases are shown to be governed by hydrophobic interaction mechanisms.
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Date Issued
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1991
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PURL
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http://purl.flvc.org/fcla/dt/14719
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Subject Headings
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Proteins--Separation, High performance liquid chromatography
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Format
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Document (PDF)
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Title
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PRION FRAGMENT 106-128: AN INVESTIGATION OF AMYLOID FORMATION AND INHIBITION.
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Creator
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Regmi, Deepika, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
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Abstract/Description
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Misfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a...
Show moreMisfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a concentration-dependent manner in an aqueous solution and that the aggregation is sensitive to pH and the preformed amyloid seeds.Furthermore, we show that the zwitterionic POPC liposomes moderately inhibit the aggregation of PrP(106–128), whereas POPC/cholesterol (8:2) vesicles facilitate peptide aggregation likely due to the increase of the lipid packing order and membrane rigidity in the presence of cholesterol. In addition, anionic lipid vesicles of POPG and POPG/cholesterol above a certain concentration accelerate the aggregation of the peptide remarkably. The strong electrostatic interactions between the N-terminal region of the peptide and POPG may constrain the conformational plasticity of the peptide, preventing insertion of the peptide into the inner side of the membrane and thus promoting fibrillation on the membrane surface. The results suggest that the charge properties of the membrane, the composition of the liposomes, and the rigidity of lipid packing are critical in determining peptide adsorption on the membrane surface and the efficiency of the membrane in catalyzing peptide oligomeric nucleation and amyloid formation.
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Date Issued
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2023
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PURL
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http://purl.flvc.org/fau/fd/FA00014356
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Subject Headings
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Prion Proteins, Prion diseases, Epigallocatechin gallate, Amyloid
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Format
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Document (PDF)
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Title
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Aggregation Inhibition and Detection of Alzheimer’s Amyloidogenic and Oligomeric Peptides.
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Creator
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Elbassal, Esmail A. E., Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
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Abstract/Description
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Protein aggregation, oligomer and fibril formation is one of the dominant characteristics in the pathogenesis of a number of neurodegenerative diseases, such as Alzheimer’s disease (AD). Inhibition of toxic oligomer and fibril formation is one of the approaches to find potential drug candidates for AD. Additionally, early diagnosis of these amyloid species can provide mechanistic understanding of protein aggregation and thus can pave the way for preventing the onset of AD. The aim of this...
Show moreProtein aggregation, oligomer and fibril formation is one of the dominant characteristics in the pathogenesis of a number of neurodegenerative diseases, such as Alzheimer’s disease (AD). Inhibition of toxic oligomer and fibril formation is one of the approaches to find potential drug candidates for AD. Additionally, early diagnosis of these amyloid species can provide mechanistic understanding of protein aggregation and thus can pave the way for preventing the onset of AD. The aim of this dissertation was 1) to explore the effects of charged cholesterol derivatives on the aggregation kinetic behavior of Amyloid-β40 (Aβ40), 2) to probe Aβ40 oligomer and amyloid formation in vitro using gold nanoparticles (AuNPs), and 3) to monitor the kinetic effect of various natural product molecules on Aβ40 aggregation in vitro. In the first chapter, a general introduction about AD as an amyloidogenic disease, amyloid cascade hypothesis, and the manipulation of Aβ peptides aggregation kinetics using different approaches was presented. In the second chapter, we studied the effects of oppositely charged cholesterol derivatives on the aggregation kinetics of Aβ. In the third chapter, we developed a gold nanoparticles (AuNPs) assay to probe Aβ40 oligomers and amyloid formation. In chapter IV, we monitored the effects of various small molecules on the aggregation kinetics of Aβ40. In chapter V, we discussed the methods and experimental details.
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Date Issued
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2018
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PURL
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http://purl.flvc.org/fau/fd/FA00013009
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Subject Headings
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Alzheimer's disease, Amyloid beta-protein, Oligomers, Protein Aggregates, Neurodegenerative Diseases
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Format
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Document (PDF)
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Title
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Neuroprotection during acute hyperthermic stress: Role of the PKG pathway in neurons and glia in the protection of neural function in Drosophila melanogaster.
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Creator
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Krill, Jennifer L., Dawson-Scully, Ken, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
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Abstract/Description
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The human brain functions within a narrow range of temperatures and variations outside of this range incur cellular damage and death and, ultimately, death of the organism. Other organisms, like the poikilotherm Drosophila melanogaster, have adapted mechanisms to maintain brain function over wide ranges in temperature and, if exposed to high temperatures where brain function is no longer supported, these animals enter a protective coma to promote survival of the organism once the acute...
Show moreThe human brain functions within a narrow range of temperatures and variations outside of this range incur cellular damage and death and, ultimately, death of the organism. Other organisms, like the poikilotherm Drosophila melanogaster, have adapted mechanisms to maintain brain function over wide ranges in temperature and, if exposed to high temperatures where brain function is no longer supported, these animals enter a protective coma to promote survival of the organism once the acute temperature stress is alleviated. This research characterized the role of different neuronal cell types, including glia, in the protection of brain function during acute hyperthermia, specifically looking at two protective pathways: the heat shock protein (HSP) pathway and the cGMP-dependent protein kinase G (PKG) pathway. Whole animal behavioral assays were used in combination with tissue-specific genetic manipulation of protective pathways to determine the specific cell types sufficient to confer protection of neuronal function during acute hyperthermia. Using the neuromuscular junction (NMJ) preparation, calcium imaging techniques were combined with pharmacological and genetic manipulations to test the hypothesis that alterations in ion channel conductance via endogenous mechanisms regulating the cellular response to high temperature stress alter neuronal function. Expression of foraging RNAi to inhibit PKG expression in neurons or glia demonstrated protection of function during acute hyperthermia measured behaviorally through the extension of locomotor function. This extension of function with the tissue-specific inhibition of PKG was also confirmed at the cellular level using the genetically encoded calcium indicator (GECI), GCaMP3, to image calcium dynamics at the NMJ, where preparations expressing foraging RNAi could continue to elicit changes in calcium dynamics in response to stimulation. Over the course of this study, the mechanism underlying a novel glial calcium wave in the peripheral nervous system was characterized in order to elucidate glia’s role in the protection of neuronal function during acute hyperthermia.
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Date Issued
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2018
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PURL
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http://purl.flvc.org/fau/fd/FA00013026
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Subject Headings
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Cyclic GMP-Dependent Protein Kinases, Neuroprotection, Hyperthermia, Heat shock proteins, Drosophila melanogaster
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Format
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Document (PDF)
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Title
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Neuroprotection During Acute Oxidative Stress: Role of the PKG Pathway and Identification of Novel Neuromodulatory Agents Using Drosophila Melanogaster.
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Creator
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Caplan, Stacee Lee, Dawson-Scully, Ken, Milton, Sarah L., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
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Abstract/Description
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Oxidant stress and injury is inherent in many human diseases such as ischemic vascular and respiratory diseases, heart failure, myocardial infarction, stroke, perinatal and placental insufficiencies, diabetes, cancer, and numerous psychiatric and neurodegenerative disorders. Finding novel therapeutics to combat the deleterious effects of oxidative stress is critical to create better therapeutic strategies for many conditions that have few treatment options. This study used the anoxia-tolerant...
Show moreOxidant stress and injury is inherent in many human diseases such as ischemic vascular and respiratory diseases, heart failure, myocardial infarction, stroke, perinatal and placental insufficiencies, diabetes, cancer, and numerous psychiatric and neurodegenerative disorders. Finding novel therapeutics to combat the deleterious effects of oxidative stress is critical to create better therapeutic strategies for many conditions that have few treatment options. This study used the anoxia-tolerant fruit fly, Drosophila melanogaster, to investigate endogenous cellular protection mechanisms and potential interactions to determine their ability to regulate synaptic functional tolerance and cell survival during acute oxidative stress. The Drosophila larval neuromuscular junction (NMJ) was used to analyze synaptic transmission and specific motor axon contributions. Drosophila Schneider 2 (S2) cells were used to assess viability. Acute oxidative stress was induced using p harmacological paradigms that generate physiologically relevant oxidant species: mitochondrial superoxide production induced by sodium azide (NaN3) and hydroxyl radical formation via hydrogen peroxide (H2O2). A combination of genetic and pharmacological approaches were used to explore the hypothesis that endogenous protection mechanisms control cellular responses to stress by manipulating ion channel conductance and neurotransmission. Furthermore, this study analyzed a group of marine natural products, pseudopterosins, to identify compounds capable of modulating synaptic transmission during acute oxidative stress and potential novel neuromodulatory agents.
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Date Issued
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2015
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PURL
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http://purl.flvc.org/fau/fd/FA00004487, http://purl.flvc.org/fau/fd/FA00004487
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Subject Headings
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Drosophila melanogaster -- Life cycles, Oxidative stress -- Ecophysiology, Oxidative stress -- Prevention, Protein kinases, Proteins -- Chemical modification
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Format
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Document (PDF)
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Title
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Characterization of receptor protein tyrosine phosphatase PTP69D in the giant fiber circuit.
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Creator
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Lee, LaTasha Hoskins, Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
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Abstract/Description
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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
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2014
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PURL
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http://purl.flvc.org/fau/fd/FA00004301, http://purl.flvc.org/fau/fd/FA00004301
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Subject Headings
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Drosophila melanogaster., Protein-tyrosine phosphatase--Metabolism., Protein-tyrosine kinase., Protein kinases--Inhibitors., Phosphoprotein phosphatases., Transcription factors., Cell receptors., Cellular signal transduction.
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Format
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Document (PDF)
Pages