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Title: Genetic and Neural Mechanisms Regulating the Interaction Between Sleep and Metabolism in Drosophila Melanogaster.
Creator: Yurgel, Maria E., Keene, Alex C., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Dysregulation of sleep and metabolism has enormous health consequences. Sleep loss is linked to increased appetite and insulin insensitivity, and epidemiological studies link chronic sleep deprivation to obesity-related disorders. Interactions between sleep and metabolism involve the integration of signalling from brain regions regulating sleep, feeding, and metabolism, as well as communication between the brain and peripheral organs. In this series of studies, using the fruit fly as a model...
Show moreDysregulation of sleep and metabolism has enormous health consequences. Sleep loss is linked to increased appetite and insulin insensitivity, and epidemiological studies link chronic sleep deprivation to obesity-related disorders. Interactions between sleep and metabolism involve the integration of signalling from brain regions regulating sleep, feeding, and metabolism, as well as communication between the brain and peripheral organs. In this series of studies, using the fruit fly as a model organism, we investigated how feeding information is processed to regulate sleep, and how peripheral tissues regulate sleep through the modulation of energy stores. In order to address these questions, we performed a large RNAi screen to identify novel genetic regulators of sleep and metabolism. We found that, the mRNA/DNA binding protein, Translin (trsn), is necessary for the acute modulation of sleep in accordance with feeding state. Flies mutant for trsn or selective knockdown of trsn in Leucokinin (Lk) neurons abolishes starvation-induced sleep suppression. In addition, genetic silencing of Lk neurons or a mutation in the Lk locus also disrupts the integration between sleep and metabolism, suggesting that Lk neurons are active during starvation. We confirmed this hypothesis by measuring baseline activity during fed and starved states. We found that LHLK neurons, which have axonal projections to sleep and metabolic centers of the brain, are more active during starvation. These findings suggest that LHLK neurons are modulated in accordance with feeding state to regulate sleep. Finally, to address how peripheral tissues regulate sleep, we performed an RNAi screen, selectively knocking down genes in the fat body. We found that knockdown of Phosphoribosylformylglycinamidine synthase (Ade2), a highly conserved gene involved the biosynthesis of purines, regulates sleep and energy stores. Flies heterozygous for two Ade2 mutations are short sleepers and this effect is partially rescued by restoring Ade2 to the fly fat body. These findings suggest Ade2 functions within the fat body to promote both sleep and energy storage, providing a functional link between these processes. Together, the experimental evidence presented here provides an initial model for how the peripheral tissues communicate to the brain to modulate sleep in accordance with metabolic state.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013163
Subject Headings: Drosophila melanogaster, Sleep, Metabolism
Format: Document (PDF)

Title: Neuronal Energetics: Mitochondrial Distribution and The Phosphagen System.
Creator: Riboul, Danielle V., Macleod, Gregory T., Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description: The relationship between neuronal function and energy metabolism is a field of intense inquiry and while bioenergetic per se are well understood, we lack a good understanding of the ways in which these mechanisms overcome the challenges presented by the unique morphology of neurons and their volatile energy demands. Here we examined the extent to which these challenges can be met through strategic mitochondrial placement and the support of a phosphagen system. We examined fluctuations in...
Show moreThe relationship between neuronal function and energy metabolism is a field of intense inquiry and while bioenergetic per se are well understood, we lack a good understanding of the ways in which these mechanisms overcome the challenges presented by the unique morphology of neurons and their volatile energy demands. Here we examined the extent to which these challenges can be met through strategic mitochondrial placement and the support of a phosphagen system. We examined fluctuations in energy demand of Drosophila larval motor neurons utilizing a combination of computational modeling and empirical analysis, and uncovered a neglected aspect of cellular energy metabolism that appears to accommodate the stress of highly volatile energy demands. Our findings highlight a reliance on the phosphagen system to buffer against rapid changes in the rate of ATP consumption induced by burst firing. The knockdown of a key element in the phosphagen system of invertebrates, arginine kinase, revealed a suppression of the mitochondrial proton motive force, and a more rapid decline in the presynaptic ATP/ADP ratio during burst firing. The knock down of arginine kinase also revealed metabolic shifts that indicated a compensatory increase in glycolysis, but, surprisingly, few consequences for either presynaptic Ca2+ handling or neurotransmission. In a final effort to ensure that we were imposing a metabolic load adequate to challenge these motor neurons, we developed an ex vivo calcium clearance assay and in vivo locomotor performance assay – currently in their final stages of validation.
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Date Issued: 2024
PURL: http://purl.flvc.org/fau/fd/FA00014419
Subject Headings: Mitochondria, Neurons, Energy metabolism
Format: Document (PDF)

Title: Energy metabolism and slow skeletal troponin I phosphorylation in cardiac troponin I null mouse heart.
Creator: Jia, Yuanyuan, Florida Atlantic University, Huang, Xupei, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Troponin I (TnI) plays an important role in cardiac muscle contraction. Two TnI genes (cardiac and slow skeletal TnI) are predominantly expressed in the heart. In cTnI knockout mice, myocardial TnI deficiency results in a diastolic dysfunction and a sudden death in homozygous mutants. In the present studies, energy metabolism has been analyzed in myocardial cells from cTnI null hearts. Our results have demonstrated that damaged relaxation and increased Ca2+-independent force production in...
Show moreTroponin I (TnI) plays an important role in cardiac muscle contraction. Two TnI genes (cardiac and slow skeletal TnI) are predominantly expressed in the heart. In cTnI knockout mice, myocardial TnI deficiency results in a diastolic dysfunction and a sudden death in homozygous mutants. In the present studies, energy metabolism has been analyzed in myocardial cells from cTnI null hearts. Our results have demonstrated that damaged relaxation and increased Ca2+-independent force production in cTnI null hearts stimulated myofibril MgATPase activities accompanied by the increase of mitochondria quantity and ATPase activities. In addition, an increase of ssTnI phosphorylation level has been observed in cTnI null hearts. The results indicate that TnI deficiency can cause the disturbance of energy metabolism and some protein overphosphorylation.
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Date Issued: 2003
PURL: http://purl.flvc.org/fcla/dt/12998
Subject Headings: Mice as laboratory animals, Mice--Metabolism, Energy metabolism, Mitochondria
Format: Document (PDF)

Title: A study on glucose metabolism: Computer simulation and modeling.
Creator: Leesirikul, Meta., Florida Atlantic University, Neelakanta, Perambur S., Roth, Zvi S., Morgera, Salvatore D., College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description: Sorensen's model of glucose metabolism and regulation is reconstructed using SimulinkRTM. Most of the existing glucose metabolism models consist of several mass balance equations that interact with each others. Graphical format used by SimulinkRTM provides a visualized perspective of such relations so that it is easier to modify the model on ad hoc basis. Type-I and Type-II diabetes with relevant clinical details are simulated. Further, a control strategy is introduced in order to simulate...
Show moreSorensen's model of glucose metabolism and regulation is reconstructed using SimulinkRTM. Most of the existing glucose metabolism models consist of several mass balance equations that interact with each others. Graphical format used by SimulinkRTM provides a visualized perspective of such relations so that it is easier to modify the model on ad hoc basis. Type-I and Type-II diabetes with relevant clinical details are simulated. Further, a control strategy is introduced in order to simulate the control of exogenous insulin pump. Simulated results are consistent with available clinical data. Living systems in general, exhibit both stochastical and deterministic characteristics. Activities such as glucose metabolism traditionally modeled do not include stochastical properties, nor that they are viewed in the large framework of complex system with explicit interaction details. Currently, a complexity system model is developed to describe the glucose metabolism related activities. The simulation results obtained thereof illustrate the bounding domain of variations in some clinically observed details.
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Date Issued: 2005
PURL: http://purl.flvc.org/fcla/dt/13254
Subject Headings: Glucose--Metabolism, Computer simulation, Diabetes--Metabolism, Computer modeling
Format: Document (PDF)

Title: Role of taurine in the central nervous system.
Creator: Wu, Jang-Yen, Prentice, Howard
Date Issued: 2010-08-24
PURL: http://purl.flvc.org/fau/fd/FADT3327262
Subject Headings: Central Nervous System --metabolism, Glutamic Acid --metabolism, Homeostasis --physiology, Neuroprotective Agents --metabolism, Neurotransmitter Agents --metabolism, Proto-Oncogene Proteins c-bcl-2 --metabolism, Receptors, Neurotransmitter --metabolism, Signal Transduction --physiology, Taurine, Taurine --metabolism, Neuroprotective Agents, Neurotransmitter Agents
Format: Document (PDF)

Title: Identification of a truncated form of methionine sulfoxide reductase a expressed in mouse embryonic stem cells.
Creator: Jia, Pingping, Zhang, Chi, Jia, Yuanyuan, Webster, Keith A., Huang, Xupei, Kochegarov, Andrei A., Lemanski, Sharon L., Lemanski, Larry F.
Date Issued: 2011-06-22
PURL: http://purl.flvc.org/fcla/dt/3327268
Subject Headings: Cell nucleus -- metabolism, Cloning, Molecular, Cytosol --metabolism, Embryonic Stem Cells --metabolism, Methionine --metabolism, Methionine Sulfoxide Reductases, Methionine Sulfoxide Reductases --metabolism, Methionine Sulfoxide Reductases --genetics, Mitochondria --metabolism, Molecular Sequence Data, Oxidation --Reduction, Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Methionine
Format: Document (PDF)

Title: Effect of decompression on mesopelagic gelatinous zooplankton: a comparison of in situ and shipboard measurements of metabolism.
Creator: Bailey, T. G., Torres, Joseph J., Youngbluth, Marsh J., Owen, G. P.
Date Issued: 1994
PURL: http://purl.flvc.org/FCLA/DT/3350872
Subject Headings: Zooplankton, Decompression (Physiology), Metabolism--Measurement
Format: Document (PDF)

Title: Light quality effects on carbon metabolism and allocation in Gracilaria verrucosa.
Creator: Bird, Kimon T., Dawes, Clinton J., Romeo, J. T., Harbor Branch Oceanographic Institute
Date Issued: 1981
PURL: http://purl.flvc.org/FCLA/DT/3176713
Subject Headings: Gracilaria verrucosa, Carbon--Metabolism, Red algae
Format: Document (PDF)

Title: Vertical distribution, behavior, chemical composition and metabolism of Stauroteuthis syrtensis (Octopoda:Cirrata) in the Northwest Atlantic.
Creator: Jacoby, C. A., Youngbluth, Marsh J., Frost, J. R., Flood, P. R., Uiblein, F., Bamstedt, Ulf, Pagès, F., Shale, D.
Date Issued: 2009
PURL: http://purl.flvc.org/FCLA/DT/3350904
Subject Headings: Octopoda, Metabolism, Vertical distribution (Aquatic biology), Biochemistry
Format: Document (PDF)

Title: Chemical composition, metabolic rates and feeding behavior of the midwater ctenophore Bathocyroe fosteri.
Creator: Youngbluth, Marsh J., Kremer, P., Bailey, T. G., Jacoby, C. A.
Date Issued: 1988
PURL: http://purl.flvc.org/FCLA/DT/3333092
Subject Headings: Ctenophora, Feeding Behavior, Biochemistry, Metabolism--Measurement
Format: Document (PDF)

Title: A Study on the Potential Role of Stress Granules and Processing Bodies in Eliminating Oxidatively Damaged RNA.
Creator: Pourkalbassi, Delaram, Li, Zhongwei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Oxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and...
Show moreOxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and processing bodies (PB) in eliminating abasic RNA in situ. We demonstrated that RNA is a major target of oxidative damage, constituting the majority of OS-induced abasic nucleic acids in HeLa cell. Importantly, the level of abasic RNA is strongly correlated with SG abundance. Furthermore, inhibition of SG/PB formation causes accumulation of abasic RNA, suggesting that SG/PB participates in removing oxidized RNA and protects cells under OS, which offers novel targets for therapeutic intervention in age-related diseases.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004702
Subject Headings: Aging -- Physiological aspects., Oxidative stress., RNA -- Metabolism.
Format: Document (PDF)

Title: Associations between mercury and hepatic, renal, endocrine, and hematological parameters in Atlantic bottlenose dolphins (Tursiops truncatus) along the eastern coast of Florida and South Carolina.
Creator: Schaefer, Adam M., Stavros, Hui-Chen W., Bossart, Gregory D., Fair, Patricia A., Goldstein, Juli D., Reif, John S.
Date Issued: 2011
PURL: http://purl.flvc.org/fau/fd/FA00007464
Subject Headings: Florida, South Carolina, Bottlenose dolphin--Atlantic Coast (U.S.), Mercury, Liver--metabolism, Kidney--Metabolism, Endocrine Glands--metabolism, Hematology
Format: Document (PDF)

Title: Climate change impacts on the secondary metabolite production in Caribbean coral reef sponges.
Creator: Vansach, Tifanie, Duckworth, Alan R., Hard, M., Stubler, A., West, Lyndon, Graduate College
Date Issued: 2011-04-08
PURL: http://purl.flvc.org/fcla/dt/3164802
Subject Headings: Climatic changes --Environmental aspects, Metabolism, Sponges --Caribbean Sea
Format: Document (PDF)

Title: Comparison of the metabolic fate of carbaryl-naphthy1-1-¹⁴C in two beetle species(Coleoptera: Scolytidae).
Creator: Zhong, H., Hastings, F. L., Hain, F. P., Dauterman, W. C., Harbor Branch Oceanographic Institute
Date Issued: 1995
PURL: http://purl.flvc.org/fau/fd/FA00007228
Subject Headings: Carbaryl, Coleoptera, Scolytidae, Spruce beetle, Southern pine beetle, Metabolism
Format: Document (PDF)

Title: Uptake and assimilation of 15N-ammonium by the symbiotic sea anemones, Bartholomea annulata and Aiptasia pallida: conservation versus recycling of nitrogen.
Creator: Lipschultz, F, Cook, Clayton B.
Date Issued: 2001
PURL: http://purl.flvc.org/FCLA/DT/2783238
Subject Headings: Dinoflagellates, Nitrification, Nitrates --physiology, Ammonia--metabolism, Coral reef --ecology
Format: Document (PDF)

Title: Construction of mitochondrion-targeted telomerase for analysis in Saccharomyces cerevisiae.
Creator: Martin, Ricardo., Harriet L. Wilkes Honors College
Abstract/Description: Telomerase is associated with telomere production and nDNA protection. However, studies by Santos et al. have demonstrated that human telomerase has a mitochondrial entry sequence and in the presence of hydrogen peroxide it has been found inside the mitochondrion and may cause mitochondrial DNA mutations. Saccharomyces cerevisiae contains telomerase, but it does not have the mitochondrial entry sequence. To determine if the presence of telomerase in the mitochondria can induce mutations an...
Show moreTelomerase is associated with telomere production and nDNA protection. However, studies by Santos et al. have demonstrated that human telomerase has a mitochondrial entry sequence and in the presence of hydrogen peroxide it has been found inside the mitochondrion and may cause mitochondrial DNA mutations. Saccharomyces cerevisiae contains telomerase, but it does not have the mitochondrial entry sequence. To determine if the presence of telomerase in the mitochondria can induce mutations an experiment was developed in which a mitochondrion entry sequence would be fused to the S. cerevisiae telomerase enzyme. This fusion could then be screened in S. cerevisiae with an ade2 mutation for a simple color assay of mitochondrial activity. To date, no successful transformant has been identified. The frequency of incorrect ligations has been recognized and may indicate that the desired fusion is lethal to E. coli cells.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/209994
Subject Headings: Cell membranes, Formation, Mitochondrial DNA, Mutation (Biology), Cell metabolism
Format: Document (PDF)

Title: Optimizing atrazine catabolism in Pseudomonas sp. strain ADP.
Creator: Anderson, Robert., Harriet L. Wilkes Honors College
Abstract/Description: Atrazine is a popular herbicide used in over 80 countries to inhibit the growth of broadleaf and grassy weeds. Atrazine is a common pollutant in soil and groundwater, and high concentrations of atrazine cause developmental defects in fish, amphibians, and birds. The bacteria Pseudomonas sp. strain ADP (P.ADP) uses atrazine as a nitrogen source by transforming atrazine to ammonia through a number of enzymatic reactions. In this project I measured the growth and atrazine degradation of P.ADP in...
Show moreAtrazine is a popular herbicide used in over 80 countries to inhibit the growth of broadleaf and grassy weeds. Atrazine is a common pollutant in soil and groundwater, and high concentrations of atrazine cause developmental defects in fish, amphibians, and birds. The bacteria Pseudomonas sp. strain ADP (P.ADP) uses atrazine as a nitrogen source by transforming atrazine to ammonia through a number of enzymatic reactions. In this project I measured the growth and atrazine degradation of P.ADP in media with atrazine as the sole nitrogen source. A mutant strain isolated after mutagenesis with UV light showed faster growth and reached higher densities than the control strain. A series of mating experiments were performed to determine whether the growth mutation was on the atrazine degrading plasmid or in the chromosome. The limitations and potential of P.ADP for atrazine degradation are discussed.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/3334252
Subject Headings: Plasmids, Genetics, Alginates, Physiological effect, Microbial ecology, Biotransformation (Metabolism)
Format: Document (PDF)

Title: Determination of the acid dissociation constant of cytochrome B5 reductase.
Creator: Chong, Samantha., Harriet L. Wilkes Honors College
Abstract/Description: Most living organisms transduce electron transport chains in order to obtain energy. Flavin adenine dinucleotide (FAD) is a common electron transfer cofactor found in electron transport proteins referred to as flavoproteins. In this study, the different ionization and oxidation states of this cofactor found in cytochrome b5 reductase were identified spectroscopically and quantified as a function of solution potential and pH. The large data sets obtained from these experiments were analyzed...
Show moreMost living organisms transduce electron transport chains in order to obtain energy. Flavin adenine dinucleotide (FAD) is a common electron transfer cofactor found in electron transport proteins referred to as flavoproteins. In this study, the different ionization and oxidation states of this cofactor found in cytochrome b5 reductase were identified spectroscopically and quantified as a function of solution potential and pH. The large data sets obtained from these experiments were analyzed and the acid dissociation constant for reduced cytochrome b5 reductase was determined.
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Date Issued: 2008
PURL: http://purl.flvc.org/FAU/77662
Subject Headings: Cell metabolism, Cellular signal transduction, Chemistry, Statistical methods, Electron spectroscopy
Format: Document (PDF)

$Aggregation kinetics of A\U+fffd\ peptides and the inhibition effects of small molecules on A\U+fffd\ peptide aggregation$

Title: Aggregation kinetics of A\U+fffd\ peptides and the inhibition effects of small molecules on A\U+fffd\ peptide aggregation.
Creator: Hijazi, Ahmad Alex., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: 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: 2012
PURL: http://purl.flvc.org/FAU/3358550
Subject Headings: Amyloid beta-protein, Proteins, Metabolism, Disorders, Prions, Alzheimer's disease
Format: Document (PDF)

Title: A Framework for Understanding Power Supply and Demand in Presynaptic Nerve Terminals.
Creator: Justs, Karlis Anthony, Macleod, Gregory T., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The molecular mechanisms of synaptic function and development have been studied extensively, but little is known about the energy requirements of synapses, or the mechanisms that coordinate their energy production with their metabolic demands. These are oversights, as synapses with high energy demands are more susceptible to degeneration and degrade in the early stages of diseases such as amyotrophic lateral sclerosis, spinal muscle atrophy and Parkinson’s disease. Here, in a structure...
Show moreThe molecular mechanisms of synaptic function and development have been studied extensively, but little is known about the energy requirements of synapses, or the mechanisms that coordinate their energy production with their metabolic demands. These are oversights, as synapses with high energy demands are more susceptible to degeneration and degrade in the early stages of diseases such as amyotrophic lateral sclerosis, spinal muscle atrophy and Parkinson’s disease. Here, in a structure-function study at Drosophila motor neuron terminals, a neurophysiological model was generated to investigate how power (ATP/s) supply is integrated to satisfy the power demand of presynaptic terminals. Power demands were estimated from six nerve terminals through direct measurements of neurotransmitter release and Ca2+ entry, as well as theoretical estimation of Na+ entry and power demands at rest (cost of housekeeping). The data was leveraged with a computational model that simulated the power demands of the terminals during their physiological activity, revealing high volatility in which power demands can increase 15-fold within milliseconds as neurons transition from rest to activity. Another computational model was generated that simulated ATP production scenarios regarding feedback to the power supply machinery (Oxphos and glycolysis) through changes in nucleotide concentrations, showing that feedback from nucleotides alone fail to stimulate power supply to match the power demands of each terminal. Failure of feedback models invokes the need for feed forward mechanisms (such as Ca2+) to stimulate power supply machinery to match power demands. We also quantified mitochondrial volume, density, number and size in each nerve terminal, revealing all four features positively correlate with the terminals power demands. This suggests the terminals enhance their oxidative capacity by increasing mitochondrial content to satisfy their power demands. And lastly, we demonstrate that abolishing an ATP buffering system (the phosphagen system) does not impair neurotransmission in the nerve terminals, suggesting motor nerve terminals are capable of satisfying their power demands without the ATP buffering system.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013323
Subject Headings: Presynaptic Terminals, Adenosine triphosphate, Synapses--metabolism, Bioenergetics
Format: Document (PDF)

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