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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Effects of extracellular ATP and ADP on growth and development of Arabidopsis seedlings

Tang, Wen-qiang, Roux, Stanley J. January 2004 (has links) (PDF)
Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Stanley J. Roux. Vita. Includes bibliographical references.
32

Efeitos da abamectina na bioenergética de mitocôndrias isoladas de fígado de rato / Juliana Carla Castanha Zanoli. -

Zanoli, Juliana Carla Castanha. - January 2011 (has links)
Orientador: Fabio Erminio Mingatto / Banca: Flavia Thomaz Verechia Pereira / Banca: Tiago Rodrigues / Resumo: Abamectina é uma lactona macrocíclica pertencente à família das avermectinas, utilizada mundialmente como agente antiparasitário em animais de criação e estimação, além do emprego agrícola como princípio ativo dos inseticidas e nematicidas. Mitocôndrias são responsáveis pela conversão da energia liberada pelo transporte de elétrons e armazenamento como energia de ligação na molécula de ATP, um componente metabólico essencial. Interferências em sua síntese ou utilização caracterizam mecanismos pelos quais os xenobióticos podem expressar toxicidade aguda ou crônica. Neste trabalho, os efeitos da abamectina na bioenergética de mitocôndrias isoladas de fígado de rato foram avaliados. Nas concentrações utilizadas (5 a 25 µM), abamectina causou inibição da cadeia respiratória, sem afetar a atividade das enzimas NADH desidrogenase, succinato desidrogenase e o potencial de membrana, comportando-se de maneira semelhante à oligomicina e ao atractilosídeo. A principal atuação da abamectina foi reduzir o potencial mitocondrial de fosforilação oxidativa, diminuindo os níveis de ATP provavelmente como resultado de sua ação direta sobre a FoF1-ATPase, uma vez que inibiu a atividade desta enzima, e/ou sobre o translocador de ADP/ATP. A inibição mais acentuada da atividade fosfohidrolase em mitocôndrias intactas desacopladas do que em mitocôndrias rompidas juntamente com a inibição da despolarização do potencial de membrana induzida pelo ADP sugerem que a abamectina atuou inibindo mais especificamente o translocador de ADP/ATP do que a FoF1-ATPase / Abstract: Abamectin is a macrocyclic lactone belonging to the avermectin family, used worldwide as antiparasitic agent in farm animals and pets, and agricultural employment as the active ingredient of insecticides and nematicides. Mitochondria are responsible for converting the energy released by electron transport and storage as the binding energy molecule ATP, an essential metabolic component. Interference in its synthesis or utilization characterize mechanisms by which xenobiotics can express acute or chronic toxicity. In this study, the effects of abamectin in the bioenergetics of mitochondria isolated from rat liver were evaluated. At the concentrations used (5-25 mM), abamectin caused inhibition of the respiratory chain without affecting the activity of enzymes NADH dehydrogenase, succinate dehydrogenase and the membrane potential, behaving similarly to oligomycin and Atractyloside. The main activity of abamectin was to reduce the potential of mitochondrial oxidative phosphorylation, decreasing ATP levels probably as a result of its direct action on the Fo-F1 ATPase, since it inhibited the activity of this enzyme, and/or the ADP/ATP translocator. The more pronounced inhibition of the fosfohydrolase activity in intact uncoupled mitochondria than in disrupted mitochondria, in addition to the inhibition of the ADP-stimulated depolarization of mitochondrial membrane potential suggest that abamectin acted more specifically by inhibiting the ADP/ATP translocator than the FoF1-ATPase / Mestre
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33

Ornithine decarboxylase:expression and regulation in rat brain and in transgenic mice

Kilpeläinen, P. (Pekka) 25 March 2002 (has links)
Abstract Ornithine decarboxylase (EC 4.1.1. 17) is the first and the rate-controlling enzyme in polyamine biosynthesis. It decarboxylates L-ornithine to form diamine putrescine. ODC activity in cells is strictly regulated and one of the central elements of ODC regulation is an inhibitory protein called antizyme. Antizyme binds to ODC, inhibits its activity and targets ODC for the proteasomal degradation. Essentiality of polyamines for the normal cell growth and proliferation is well known. Recently their roles in the regulation of several classes of cation channels have been discovered. Some of these channels are expressed abundantly in the brain, which has increased interest in the polyamine metabolism in the central nervous system. In this study guanosine 5'-triphosphate activatable ODC was detected in the rat brain lysates. This activation was more significant after antizyme was separated from ODC. GTP-activatable ODC was more resistant to heat and displayed higher Vmax than kidney ODC. Previously GTP-activatable ODC had been found in mammalian tissues only in some tumors. ODC and antizyme expression in brain was localized by in situ hybridization and immunocytochemistry. Both proteins displayed wide and largely overlapping expression patterns restricted to neurons. The proteins were localized predominantly to cytoplasm at the most brain regions, but antizyme had a main localization in nuclei in some regions of the brain. In addition, the role of one of the most highly conserved regions in eukaryotic ODCs was studied using site-directed mutagenesis. The aspartate-233 to valine mutation was made and detected to increase Km values for the cofactor PLP and the substrate L-ornithine as well as Ki value for the inhibitor DFMO. In another part of this study a transgenic mouse line expressing ODC under the control of viral promotor was generated. The most significant changes in ODC activity were detected in reproductive organs of male mice. The high number of infertile transgenic males supported earlier reports about the importance of balanced polyamine metabolism for spermatogenesis. Infertility of female mice was increased as well, but the involvement of polyamines remained unproven. Transgenic mice were prone to various pathological conditions such as inflammations and tumour formation, which may be due to deregulated polyamine metabolism.
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34

Synthetic, spectrometric and computer modelling studies of novel ATP analogues

Gxoyiya, Babalwa Siliziwe Blossom January 2008 (has links)
This study has been concerned with the design and synthesis of A TP analogues with the potential to act as inhibitors of glutamine synthetase - a novel target for therapeutic intervention in the treatment of tuberculosis. Using a structural -analogy approach, various 3-indolylalkanoic acid, benzimidazole and pyrazolo[3,4-dJpyrimidine derivatives have been prepared and characterized. Alkylation of the heterocyclic bases using 4-(bromomethyl)-2,2-dimethyl-1 ,3-d ioxolane, 2-(bromomethoxy)ethyl acetate and 2-(chloroethoxy)ethanol in the presence of either NaH or BulOK afforded the corresponding N-alkylated derivatives of benzimidazole and 4-aminopyrazolo[3,4-dJpyrimidine (4-APP). Similar reactions with 3-indo lylalkanoic esters resulted in O-alkyl cleavage with the formation of new esters. Alkylation of benzimidazole with allyl bromide, 4-bromobutene and 2-methylbut-2-ene has also been shown to afford the corresponding l-alkenylbenzimidazoles in moderate to excellent yield (43-96%). Subsequent oxidation of these products using CTAP, gave the dihydroxy derivatives in poor to good yields (26-77%). Phosphorylation of various hydroxy derivatives of benzimidazole and 4-APP has been achieved using diethyl chlorophosphate to afford the corresponding monophosphate and 1,2-diphosphate esters. Glycosylation of each of the heterocyclic bases has been successfully achieved using 1,2,3,4,6-penta-O-acetyl-D-glucopyranose and SnCl4 in acetonitri le, while methanolysis of the resulting tetraacetates, using methanolic NaOMe, afforded the hydroxy derivatives in good yield (50-70%). Various 1- and 2-dimensional NMR spectroscopic methods (e.g., IH, 13C, lip, COSY, HSQC and HMBC) have been used to confirm the structures of the synthesized A IP analogues. The application of NMR prediction programmes has been explored, permitting assessment of their agreement with the experimental data and confirmation of assigned structures. High-resolution electron impact (EI) mass spectrometric data have been used to explore the mass fragmentation pathways exhibited by selected derivatives, and certain common fragmentations have been identified. Molecular modelling of selected products as potential glutamine synthetase ligands has been performed on the Accelrys Cerius2 platform, and interactive receptor-ligand docking studies have been conducted using the Ligand-Fit module. These studies have revealed possible hydrogen-boding interactions between the selected analogues and various amino acid residues in the glutamine synthetase active site.
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35

A Framework for Understanding Power Supply and Demand in Presynaptic Nerve Terminals

Unknown Date (has links)
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-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. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection
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36

Cell-free enzymatic preparation of important biochemicals : l-glycerol phosphate, NAD, NADP and ATP

Rios-Mercadillo, Victor Manuel. January 1980 (has links)
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 1980 / Vita. / Includes bibliographical references. / by Victor Manuel Rios-Mercadillo. / Ph. D. / Ph. D. Massachusetts Institute of Technology, Department of Chemistry
37

The Use of Adenosine Triphosphate (ATP) Assays in Describing the Limnology of Moss Reservoir, Texas

Boswell, James T. 05 1900 (has links)
Limnological study of Moss Reservoir from May, 1975 through August, 1976 was conducted to evaluate the use of ATP assay in describing planktonic changes within the water column.
38

The distribution and regulation of ATP citrate lyase in rat liver /

Voss, Anne Coble, January 1984 (has links)
No description available.
39

ATP Citrate Lyase (ACLY) à l'interface des dérégulations métaboliques et épigénétiques dans l'hypertension artérielle pulmonaire

Romanet, Charlotte 17 February 2025 (has links)
L'hypertension artérielle pulmonaire (HTAP) est une maladie complexe, progressive et fatale, définie cliniquement par la présence d'une pression artérielle pulmonaire moyenne supérieure à 20mmHg au repos, résultant d'une vasoconstriction soutenue et d'un remodelage vasculaire pulmonaire important des artères pulmonaires (AP) distales. Les thérapies actuelles spécifiques de l'HTAP ciblent essentiellement la balance vasoconstriction/vasodilatation et ne sont pas curatives, laissant la transplantation pulmonaire comme seule option thérapeutique. Face à ce constat, il est devenu une priorité d'identifier de nouvelles cibles thérapeutiques dans le but de faire régresser le remodelage vasculaire. L'introduction du premier agent « anti-remodelant », le Sotatercept, semble promoteur, néanmoins ses effets secondaires indésirables graves justifient de poursuivre nos études visant à mieux comprendre la physiopathologie de la maladie; un prérequis à l'élaboration de nouveaux outils thérapeutiques. Le remodelage vasculaire est largement attribué à une survie accrue et à une prolifération excessive des cellules musculaires lisses (CML) de l'AP (CMLAP), phénotype ressemblant à celui des cellules cancéreuses. Ce phénotype anormal est entretenu par une dérégulation épigénétique et métabolique (glycolyse et biosynthèse des lipides). L'acétyl-CoA, produit via la glycolyse, occupe une position critique au carrefour du métabolisme et de la dynamique de la chromatine. En effet, l'acétyl-CoA sert de précurseur clé pour dans la biosynthèse lipidique dans le cytoplasme alors que sa disponibilité dans le noyau favorise l'acétylation des histones médiée par les histones acétyltransférases (HAT) et par conséquent l'activation de la transcription génique. L'acétyl-CoA est synthétisé à partir du clivage du citrate par l'enzyme ATP Citrate Lyase (ACLY). Du fait de sa localisation nucléocytoplasmique, ACLY produit l'acétyl-CoA dans ces deux compartiments. Dans divers types de tumeurs, l'activité et l'expression d'ACLY sont anormalement élevées et son inhibition diminue la progression tumorale. Compte tenu du rôle crucial d'ACLY à l'interface du métabolisme et de l'épigénétique et des similitudes entre le cancer et l'HTAP, ***nous avons émis l'hypothèse qu'ACLY contribue au remodelage vasculaire pulmonaire en HTAP en favorisant la prolifération et la résistance à l'apoptose des CMLAP.*** Dans notre étude nous avons démontré une surexpression/activité d'ACLY dans les tissus pulmonaires et dans les CMLAP de patients HTAP ainsi que dans notre modèle expérimentale d'HTAP le Sugen/Hypoxie (Su/Hx). L'inhibition moléculaire (siARN) et pharmacologique (BMS) d'ACLY dans les CMLAP-HTAP a entrainé une diminution de leur prolifération, de leur survie et de leur migration. Ces effets ont été associé à une réduction de la glycolyse et de la biosynthèse des lipides ainsi qu'une diminution de nombreux gènes impliqués dans la progression du cycle cellulaire et de la synthèse de lipides constaté grâce à une approche transcriptomique par séquençage des ARN. Au niveau nucléaire, l'inhibition d'ACLY s'est traduit par une hypoacétylation des histones due à une baisse des niveaux d'acétyl-CoA nucléaire. A l'aide de la littérature et de la bio-informatique, nous sommes parvenus à identifier la HAT GCN5 et le facteur de transcription FOXM1 comme étant des facteurs impliqués dans le contrôle de l'expression génique par ACLY. D'un point de vue translationnel, nous avons montré qu'un inhibiteur pharmacologique d'ACLY (BMS) améliorait les paramètres hémodynamiques et diminuait le remodelage vasculaire pulmonaire dans un modèle de rat Su/Hx mimant la pathologie. En complément, nous avons montré chez la souris que l'inactivation d'*Acly* ciblée aux CML prévenait et corrigeait les anomalies vasculaires pulmonaires provoquées par l'exposition aux Su/Hx. Pour finir, les résultats préliminaires obtenus dans un modèle ex-vivo de culture de tranches de poumon humain semblent confirmer les effets bénéfiques de l'inhibition d'ACLY sur le remodelage pulmonaire. En conclusion, par une approche multidisciplinaire, nous avons démontré qu'ACLY jouait un rôle clé dans le processus de remodelage vasculaire pulmonaire en HTAP et que son inhibition constitue une avenue thérapeutique prometteuse. / Pulmonary arterial hypertension (PAH) is a complex, progressive and fatal disease, clinically defined by the presence of a mean pulmonary arterial pressure greater than 20mmHg at rest, resulting from sustained vasoconstriction and significant pulmonary vascular remodeling of the distal pulmonary arteries (PA). Current specific therapies for PAH mainly target the vasoconstriction/vasodilation balance and are not curative, leaving lung transplantation as the only therapeutic option. Given this observation, it has become a priority to identify new therapeutic targets in order to reverse vascular remodeling. The introduction of the first "anti-remodeling" agent, Sotatercept, seems promising, however its serious adverse side effects justify continuing our studies aimed at better understanding the pathophysiology of the disease, a prerequisite for the development of new therapeutic tools. Vascular remodeling is largely attributed to increased survival and excessive proliferation of PA smooth muscle cells (SMCs) (PASMCs), a phenotype resembling that of cancer cells. This abnormal phenotype is maintained by epigenetic and metabolic (glycolysis and lipid biosynthesis) dysregulation. Acetyl-CoA, produced via glycolysis, occupies a critical position at the crossroads of metabolism and chromatin dynamics. Indeed, acetyl-CoA serves as a key precursor for lipid biosynthesis in the cytoplasm while its availability in the nucleus promotes histone acetylation mediated by histone acetyltransferases (HATs) and consequently activation of gene transcription. Acetyl-CoA is synthesized from the cleavage of citrate by the enzyme ATP Citrate Lyase (ACLY). Due to its nucleocytoplasmic localization, ACLY produces acetyl-CoA in both compartments. In various tumor types, ACLY activity and expression are abnormally elevated, and its inhibition decreases tumor progression. Given the crucial role of ACLY at the interface of metabolism and epigenetics and the similarities between cancer and PAH, ***we hypothesized that ACLY contributes to pulmonary vascular remodeling in PAH by promoting proliferation and resistance to apoptosis of PASMCs.*** In our study, we demonstrated an overexpression/activity of ACLY in lung tissues and PAMSCs of PAH patients as well as in our experimental PAH model, Sugen/Hypoxia (Su/Hx). Molecular (siRNA) and pharmacological (BMS) inhibition of ACLY in PAMSCs-PAH resulted in a decrease in their proliferation, survival, and migration. These effects were associated with a reduction in glycolysis and lipid biosynthesis as well as a decrease in many genes involved in cell cycle progression and lipid synthesis observed using a transcriptomic approach by RNA sequencing. At the nuclear level, ACLY inhibition resulted in histone hypoacetylation due to a decrease in nuclear acetyl-CoA levels. Using literature and bioinformatics, we were able to identify the HAT GCN5 and the transcription factor FOXM1 as factors involved in the control of gene expression by ACLY. From a translational perspective, we showed that a pharmacological inhibitor of ACLY (BMS) improved hemodynamic parameters and decreased pulmonary vascular remodeling in a Su/Hx rat model mimicking the pathology. In addition, we showed in mice that SMC-targeted inactivation of *Acly* prevented and corrected pulmonary vascular abnormalities caused by Su/Hx exposure. Finally, preliminary results obtained in an ex-vivo model of human lung slice culture seem to confirm the beneficial effects of ACLY inhibition on pulmonary remodeling. In conclusion, through a multidisciplinary approach, we demonstrated that ACLY plays a key role in the pulmonary vascular remodeling process in PAH and that its inhibition constitutes a promising therapeutic avenue.
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40

Salivary gland P2 nucleotide receptors structure and function studies /

Landon, Linda A. Neighbors January 1998 (has links)
Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves: 145-165). Also available on the Internet.

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