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Richardson, John Lee. "Structural and kinetic characterization of the leech derived inhibitor haemadin in complex with human [alpha]-thrombin [alpha-thrombin] structural analysis of the tsetse thrombin inhibitor in complex with bovine [alpha]-thrombin [alpha-thrombin] /". [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=965976335.
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Ascolani, Gianluca. "EEG, Alpha Waves and Coherence". Thesis, University of North Texas, 2010. https://digital.library.unt.edu/ark:/67531/metadc28389/.
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This thesis addresses some theoretical issues generated by the results of recent analysis of EEG time series proving the brain dynamics are driven by abrupt changes making them depart from the ordinary Poisson condition. These changes are renewal, unpredictable and non-ergodic. We refer to them as crucial events. How is it possible that this form of randomness be compatible with the generation of waves, for instance alpha waves, whose observation seems to suggest the opposite view the brain is characterized by surprisingly extended coherence? To shed light into this apparently irretrievable contradiction we propose a model based on a generalized form of Langevin equation under the influence of a periodic stimulus. We assume that there exist two different forms of time, a subjective form compatible with Poisson statistical physical and an objective form that is accessible to experimental observation. The transition from the former to the latter form is determined by the brain dynamics interpreted as emerging from the cooperative interaction among many units that, in the absence of cooperation would generate Poisson fluctuations. We call natural time the brain internal time and we make the assumption that in the natural time representation the time evolution of the EEG variable y(t) is determined by a Langevin equation perturbed by a periodic process that in this time representation is hardly distinguishable from an erratic process. We show that the representation of this random process in the experimental time scale is characterized by a surprisingly extended coherence. We show that this model generates a sequence of damped oscillations with a time behavior that is remarkably similar to that derived from the analysis of real EEG's. The main result of this research work is that the existence of crucial events is not incompatible with the alpha wave coherence. In addition to this important result, we find another result that may help our group, or any other research group working on the analysis of brain's dynamics, to prove or to disprove the existence of crucial events. We study the diffusion process generated by fluctuations emerging from the same model after filtering out the alpha coherence, and we study the recursion to the origin. We study the survival probability of this process, namely the probability that up to a given time no re-crossing of the origin occurs. We find that this is an inverse power law with a power that depends on whether or not crucial events exist.
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Niranjan, Adityanarayan C. "Normalization of Complex Mode Shapes by Truncation of the Alpha-Polynomial". University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037029.
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Cingolani, Gino. "Biochemical and crystallographic analysis of the human importin [alpha]/[bêta] complex". Grenoble 1, 1999. http://www.theses.fr/1999GRE10096.
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Le travail presente dans cette these decrit l'analyse structurale du complexe forme par les proteines humaines et importin. Le projet a debute par la caracterisation biochimique des 2 proteines, seules en solution, et du complexe qu'elles forment. Nous avons observe que dans le complexe la proteine importin est resistante a la chymotrypsine. La meme protection a ete observee lorsque la proteine -importin est incubee en presence d'un peptide, synthetise chimiquement, contenant les domaines ibb de la proteine importin. La co-cristallisation de la proteine -importin avec le peptide a donne naissance a 2 formes cristallines dans le groupe d'espace p21, diffractant respectivement a une resolution de 2. 5a et 2. 3a. La structure du complexe a ete resolue dans la premiere forme cristalline par diffusion anomale en utilisant la proteine -importin exprimee en presence de selenio-methionine. La structure a ensuite ete affinee a 2. 5 a de resolution. La deuxieme forme cristalline a ete resolue par remplacement moleculaire et le modele affine jusqu'a 2. 3 a de resolution. Un important changement conformationel a ete observe entre les deux formes cristallines donnant des informations sur la flexibilite interieure de la proteine importin. L'analyse de la structure du complexe ainsi que la comparaison avec les donnees biochimiques obtenues nous ont permis 4 observations majeures : - l'architecture caracteristique des proteines de la superfamille- a ete observe pour la premiere fois. - l'interaction intime entre les proteines et -importin a ete decrite au niveau moleculaire. - le double changement conformationel des proteines et importin observe par les methodes biochimiques a pu etre confirme grace a la structure tridimensionnelle. - une similarite de structure entre le complexe importin : domaines ibb et importin : sequence de localisation nucleaire (nls) a ete observe, confirmant une possible evolution commune de ces proteines.
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Barran, Paul Arthur. "The structure and transcription of a rat RT1 B alpha class II gene". Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26957.
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The major histocompatibility complex of the rat (RT1 complex) encodes two sets of class II molecules referred to as RT1 B and RT1 D. The RT1 Bα gene was isolated from a Sprague-Dawley (RT1b) rat genomic library using a rat RT1 Bα chain cDNA as a hybridization probe. The coding and the majority of the intron DNA sequence was determined. The structure of the RT1 Bα gene is equivalent to that of H-2 and HLA a chain genes. Comparison of the nucleotide and predicted amino acid sequences of the RT1 Bα gene to those of the H-2 and HLA genes revealed a high degree of overall sequence conservation. However, two regions of the first external domain (a1), residues 19-23 and 45-78, exhibit marked sequence variation. Two blocks of conserved nucleotide sequence were identified in the 5' promoter region of the RT1 Bα gene that have been described in all MHC class II genes sequenced to date. These conserved sequences may be involved in the co-ordinate regulation of expression of class II genes. The cloned RT1 Bα gene was efficiently transcribed when transfected into mouse L cells.Medicine, Faculty of
Medical Genetics, Department of
Graduate
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Hurt, Nicholas S. "Electronic detection of DNA polymerase complex formation and dissociation using an alpha-hemolysin nanopore /". Diss., Digital Dissertations Database. Restricted to UC campuses, 2009. http://uclibs.org/PID/11984.
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Sikarwar, Anurag Singh. "Post-translational modifications of thromboxane receptor G-protein alpha q complex in hypoxic PPHN". American Thoracic Society, 2014. http://hdl.handle.net/1993/31664.
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Introduction: Persistent pulmonary hypertension of the newborn (PPHN) is associated with an elevated thromboxane to prostacyclin ratio, pulmonary artery (PA) hyperreactivity and hypersensitivity. Thromboxane receptor (TP), coupling with G-protein Gαq causes pulmonary vasoconstriction; whereas prostacyclin receptor (IP), coupling with Gαs, causes vasodilation and TP phosphorylation via adenylyl cyclase (AC)-cAMP-protein kinase A (PKA), desensitizes TP. Both TP phosphorylation and Gαq palmitoylation play major roles in regulation of signaling through the TP-Gαq complex. We hypothesized that increased Gαq palmitoylation and decreased AC activity could cause hypoxic TP hyperresponsiveness. We studied the impact of hypoxia on selected post-translational modifications of the receptor-G-protein complex, determining TP vasoconstriction: Gαq palmitoylation, TP phosphorylation and upstream AC activity.
Methods: Force responses to thromboxane mimetic U46619, palmitoylation inhibition by 2-bromopalmitate (2-BP) and AC activation (forskolin) were studied by myography in hypoxic PPHN and control newborn swine pulmonary artery. Ca2+ mobilization was studied by fluorescent calcium indicators fura-2AM in pulmonary myocytes (PASMC), and fluo-4NW in HEK293 cells. Effects of hypoxia on Gαq palmitoylation were studied by metabolic labeling. Gαq cysteines and TP serines were mutated to determine sites of post-translational modifications. Protein expression and receptor-G-protein coupling were studied by Western blot and co-immunoprecipitation. PKA activity was assayed; and AC activity quantified.
Results: Hypoxia increases Gαq palmitoylation, without increasing total palmitate uptake. Palmitoylation inhibition decreases U46619-stimulated force generation as well as Ca2+ mobilization in PPHN PA rings and hypoxic PASMC. Mutation of palmitoylable cysteine and palmitoylation inhibition proportionately decrease U46619-mediated Ca2+ mobilization in HEK293 cells. TP serine phosphorylation is decreased by hypoxia due to decreased PKA activity; this causes TP hypersensitivity and hyper-reactivity. Serine 324 of TPα is the target of PKA-mediated desensitization. AC activator-induced relaxation is reduced in PPHN PA. Basal and receptor-stimulated AC activity are decreased in hypoxic PASMC. Decreased AC activity is not due to decreased AC expression, ATP availability nor increased Gαi activation.
Conclusion: Increased Gαq palmitoylation plays a role in TPα hyper-responsiveness in hypoxic PPHN. Hypoxia also reduces responses to agents acting through AC, unleashing TP-mediated vasoconstriction. Reactivation of pulmonary AC might be useful therapeutically to promote vasodilation and TP desensitization.October 2016
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Huart, Anne-Sophie. "Casein kinase 1 alpha-MDM2 complex : phosphorylation and ubiquitination signals converging on p53 pathway". Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17282.
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The tumour suppressor p53 is a key regulatory protein that prevents proliferation of damaged cells. Under unperturbed conditions, the ubiquitin ligase murine double minute 2 (MDM2) mediates p53 ubiquitination and further degradation by the proteasome. In consequence p53 is present at low levels, but becomes rapidly stabilised and activated in response to a variety of stimuli, such as DNA damage or virus infection. P53 responds to these diverse stresses to regulate the expression of many target genes that induce cell cycle arrest, DNA repair, or apoptosis. The attenuation of p53 interaction with MDM2 is maintained by enzymes catalysing p53 post-translational modifications such as phosphorylation. Casein kinase 1 α (CK1α) is one such enzyme; it stimulates p53 after DNA virus infection. Surprisingly depletion of CK1α using small interfering RNA or inhibition using a CK1 kinase inhibitor activated the transcription factor p53, indicating that p53 steady-state level is controlled by CK1α. Disrupting MDM2-p53 interaction using small molecule Nutlin-3 displayed similar pharmacological properties to the CK1 inhibitor on p53, indicating that the MDM2-CK1α complex co-regulates p53 stability. Indeed co-immunoprecipitation of endogenous CK1α with MDM2 occurred in undamaged cells. CK1α was shown in vitro to directly bind to and phosphorylate MDM2. Therefore it appears that CK1α must be recruited into specific complexes under different conditions, which can influence its substrate selectivity and explain its dual role on the p53 pathway. Apart from CK1, there are few other kinases whose action can directly contribute to the inhibition of p53. A novel pyrazolo-pyridine analogue showing dual activity against CK1 and Checkpoint kinase 1 led to increased p53 activation. These data highlighted the potential value of dual kinase inhibitors as therapeutics in cancer. The dominant protein-protein interface that stabilises the MDM2-CK1α complex was mapped using a peptide-based approach. One CK1α peptide bound strongly to MDM2, it specifically disrupted the protein-protein interaction, and its transfection was able to reduce cancer cell growth. A peptide phage display approach was finally combined with Next-Generation Sequencing to define the change in MDM2 binding motifs when the CK1α peptide or Nutlin-3 is bound, compared to ligand-free MDM2, and thus will help to understand protein-protein interaction network re-wirings which led to cell growth inhibition.
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Golub, M. V. "Age features of the power spectrum of alpha-band eeg during complex mental activities". Thesis, Sumy State University, 2017. http://essuir.sumdu.edu.ua/handle/123456789/53943.
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Urgency: Electroencephalographic analysis is one of the most informative methods of study of the systemic organization of integrative processes of the human brain in different functional States, mental activity, attention. Objective: to Study the age peculiarities of the organization of the cerebral cortex in the alpha sub-bands with complex mental activities with verbal and figurative components.
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Romano, Dina Lynn. "Characterization of alpha-cyclodextrin inclusion complexes with trans-cinnamic acid in an acid-based beverage system". Thesis, Virginia Tech, 2008. http://hdl.handle.net/10919/42111.
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In response to a need for a natural antimicrobial to replace sodium benzoate, cinnamic acid was chosen. Due to cinnamic acidâ s solubility issues, α-cyclodextrin was used as a host molecule to form an inclusion complex with the cinnamic acid molecule. The cinnamic acid: α-cyclodextrin inclusion complex was then characterized using phase solubility analysis, proton nuclear magnetic resonance (H-NMR), and solid inclusion. Phase solubility analysis verified the maximum amount of cinnamic acid that α-cyclodextrin was able to host. H-NMR was used to determine the complex association constant, determine the chemical shifts of available protons, and yield a stoichiometry for the complex. The solid inclusion complex allowed for a physical formation of the complex, yielding further information in support of the complex stoichiometry. Microbiological tests were also performed to quantify the antimicrobial abilities of the complex, the guest, and the host against the yeast Saccharomyces cerevisiae and mold Paecilomyces variotii.
Results indicated that approximately 990.29 ppm in aqueous solution was the maximum amount of cinnamic acid in the complex. The 2:1 stoichiometry yields an association constant of 21.7 M-1. Results also indicated that the cinnamic acid readily conformed to fit within the α-cyclodextrin host molecule, which remained a rigid structure. An 8.9% weight to weight of cinnamic acid was calculated for the solid inclusion again reinforcing a 2:1 stoichiometry. Microbiological studies showed little to no inhibition power by the complex at varying concentrations against S. cerevisiae and P. variotii. Free cinnamic acid showed greater antimicrobial activity compared with free α-cyclodextrin and the complex.Master of Science in Life Sciences
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Selezneva, Liudmila V., i Andrei V. Nazarov. "The influence of interstitial impurity atom – vacancy complex on diffusivity of interstitial atom in alpha-iron". Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-193608.
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Selezneva, Liudmila V., i Andrei V. Nazarov. "The influence of interstitial impurity atom – vacancy complex on diffusivity of interstitial atom in alpha-iron". Diffusion fundamentals 6 (2007) 34, S. 1-2, 2007. https://ul.qucosa.de/id/qucosa%3A14210.
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Poisson, Guillaume. "Nouveaux tripodes tris-A,C,E-alpha-Cyclodextrine et leurs complexes Métallo-supramoléculaires". Thesis, Université de Lorraine, 2012. http://www.theses.fr/2012LORR0094/document.
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Ce travail s'articule autour de deux grandes parties : i- la synthèse de nouveaux tripodes tris-A,C,E-alpha-cyclodextrine, et l'étude de leurs complexes de coordination avec les métaux. La fonctionnalisation des bis-hétérocycles est une étape importante dans la préparation de ces tripodes moléculaires. En conséquence, la mise au point d'une nouvelle famille de réactifs, les tétrahalogeno-diarylglycoluriles, a permis une halogénation radicalaire sélective des systèmes hétéro-aromatiques pi-déficients non réactifs et impliqués dans la construction des podants cyclodextriniques. La sélectivité et le mécanisme de la réaction ont pu être expliqués en partie par la formation d'un complexe supramoléculaire [réactif /substrat] et l'existence d'interactions halogène-halogène dans le solide; ii- la mise en évidence d'une haute spéciation des tripodes cyclodextrines vis-à-vis d'un certain nombre de métaux et la formation d'hélices métallo-supramoléculaires chirales induite par l'implantation en position 6,6' des unités hétérocycliques. La configuration absolue des hélicates formés est résolue dans quelques casThis work is structured around two main parts: i- the synthesis of new tris-A,C,E-alpha-cyclodextrin tripods, and studies of their complexes with transition metals. The functionalization of bis-heterocycles is an important step in the preparation of tripods. Therefore, the development of a new family of reagents tetrahalo-diarylglycolurils allowed a selective radical halogenation of heteroaromatic pi-deficient systems, non-reactive and involved in the construction of podants cyclodextrinics. The selectivity and the mechanism of the reaction could be partially explained by the formation of a supramolecular complex [reagent / substrate] and the existence of halogen-halogen interactions in solid state; ii- the highlight of a high speciation tripods cyclodextrins towards a number of metals and formation of supramolecular chiral metallo-helices induced by anchoring in position 6,6' of heterocyclic units. The absolute configuration of helicates formed in some cases is resolved
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Bhatia, Harminder Singh. "Bacterial expression, purification and characterization of human alpha 2 antiplasmin". VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd_retro/170.
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The serpin antiplasmin (APL) is the primary inhibitor of plasmin, a proteinase that digests fibrin, the main component of blood clots. Most serpins are serine protease inhibitors, which undergo dramatic conformational change in forming a tight covalent complex with the target protease. Plasmin has been shown to be angiogenic through its protease activity, but it is also angiostatic, being the source of angiostatin, which inhibits angiogenesis. The main objective of our study is to obtain antiplasmin in large amounts, for crystallization and structure determination of APL and of its complex with plasmin, and for solution studies of the complex. Bacterially expressed APL will not be glycosylated, an advantage in crystallization trials.Bacterial expression of rAPL has been problematic. We have found that it can be greatly enhanced through the use of host E.coli cells that carry extra copies of genes for tRNAs coding for rarely used codons in E.coli that occur in high frequency in eukaryotic genes. Several vectors were screened for rAPL expression (pET19b, pET20b and pET28b). rAPL is expressed in high yield from a pET28b construct in host BL-21 RIPL codon plus cells. rAPL thus expressed accumulates as inclusion bodies, but can be solubilized using N-lauroyl sarcosine at pH11. Refolding and purification of rAPL is achieved by using a sizing column followed by a Nickel His-tag affinity column with an imidazole gradient. rAPL fractions thus obtained are stable at 4°C in the presence of EDTA. However, no inhibitor activity of this rAPL towards trypsin was observed, nor did it form inhibition complex with trypsin. The presence of trace protease and/or failure to fold correctly may be preventing recovery of inhibitory activity. A screen of various refolding buffers failed to yield soluble, stable APL.
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Ghosh, Kakoli. "Molecular characterisation and expression of the E1#alpha# gene of the mitochondrial pyruvate dehydrogenase complex from potato". Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297938.
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Berggren, Olof. "Regulation of Type I Interferon Production in Plasmacytoid Dendritic Cells : Effect of Genetic Factors and Interactions with NK Cells and B Cells". Doctoral thesis, Uppsala universitet, Reumatologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-246526.
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The type I interferon (IFN) system plays a central role in the etiopathogenesis of many autoimmune diseases, e.g. systemic lupus erythematosus (SLE). Activation of the type I IFN system in SLE is promoted by endogenous nucleic acid-containing immune complexes (ICs) which stimulate plasmacytoid dendritic cells (pDCs). This thesis focuses on the regulation of IFN-α production in pDCs, by interactions with B cells and natural killer (NK) cells, and by genetic factors. In Study I, RNA-IC-stimulated CD56dim NK cells were found to be activated via FcγRIIIa and enhanced the IFN-α production by pDCs. The enhancing effect of the NK cells was mediated via both soluble factors, such as the cytokine MIP-1β, and in a cell-cell contact mediated manner via the adhesion molecule LFA-1. In Study II, B cells enhanced the IFN-α production by pDCs via cell-cell contact or soluble factors, depending on the stimuli. The cell-cell contact-mediated enhancement, when the cells were stimulated with RNA-IC, was abolished by blocking the cell adhesion molecule CD31. B cells stimulated with the oligonucleotide ODN2216 enhanced the IFN-α production via soluble factors. In Study III, gene variants related to autoimmune or inflammatory diseases were analyzed for the association to the IFN-α production by pDCs, alone or in coculture with NK or B cells. Depending on cell combination, 18-86 SNPs (p < 0.001) were associated with the IFN-α production. Several of the SNPs showed novel associations to the type I IFN system, while some loci have been described earlier for their association with SLE, e.g. IL10 and PXK. In Study IV, several B cell populations were affected by cocultivation with pDCs and stimulation with RNA-IC. The frequency of CD24hiCD38hi B cells of regulatory character was increased in the pDC-B cell cocultures. However, RNA-IC-stimulation only induced modest levels of IL-10. A remarkably increased frequency of double negative CD27-IgD- B cells was found in the RNA-IC-stimulated cocultures of pDCs and B cells. In conclusion, the findings in the present thesis reveal novel mechanisms behind the regulation of the type I IFN system which could be important targets in autoimmune diseases with constantly activated pDCs.
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Emch, Gregory Simon. "EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT". The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175.
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Simms, Michelle. "Characterization of the TNFa microsatellite's reliability, MHC associations and occurrence in two ethnically different SLE populations". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0004/MQ42446.pdf.
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Attia, Ramy Naguib. "Regulation of pyruvate dehydrogenase kinase 4 by thyroid hormone role of peroxisome proliferator activated receptor gamma coactivator-1 Alpha and CCAAT enhancer binding protein /". View the abstract Download the full-text PDF version, 2009. http://etd.utmem.edu/ABSTRACTS/2009-007-Attia-index.htm.
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Thesis (Ph.D.)--University of Tennessee Health Science Center, 2009.Title from title page screen (viewed on July 22, 2009). Research advisor: Edwards A. Park. Document formatted into pages (xi, 94 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 69-89).
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Baron, Sylvain. "Dialogue entre le récepteur des oestrogènes alpha et le facteur de croissance IGF-I dans l'activation transcriptionnelle des cellules cancéreuses mammaires". Toulouse 3, 2007. http://www.theses.fr/2007TOU30053.
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Le contrôle de la prolifération des cellules cancéreuses mammaires est un phénomène complexe. Les oestrogènes jouent un rôle important dans le contrôle de cette prolifération. L'action des oestrogènes se fait via le récepteur des oestrogènes α (REα), un facteur de transcription qui complexé à l'oestradiol, est capable de moduler la transcription de nombreux gènes impliqués dans la prolifération, l'apoptose ou la différentiation cellulaire. L'utilisation d'anti-hormones qui sont des inhibiteurs compétitifs de l'œstradiol bloquent la prolifération des cellules cancéreuses mammaires. Malheureusement les patientes métastatiques traitées par ce type de molécules développent systématiquement une résistance aux thérapies anti-hormonales. Les facteurs de croissance, tels que l'EGF ou l'IGF-I, qui entraînent une activation du REα de manière ligand indépendante pourraient être responsable de l'apparition de ces phénomènes de résistance. L'étude des voies d'activation du REα par ces facteurs de croissance est donc importante. Le facteur de croissance IGF-I participe au contrôle du développement de la glande mammaire pendant l'embryogenèse et il a une activité œstrogène dans les cellules cancéreuses mammaires. Cette activité oestrogène de l'IGF-I requiert l'expression du récepteur des oestrogènes α (REα), mais on ne connaît pas les mécanismes moléculaires mis en jeu. Nous avons démontré que sur un promoteur complexe tel que le promoteur du gène oestrogéno régulé pS2/TFF1, qui contient un site de liaison au REα et un site de liaison au complexe AP1, l'activation transcriptionnelle de ce gène requiert le REα et le complexe AP1. L'ensemble de ces travaux a permis de mettre en évidence un mécanisme d'action original et non conventionnel du RE, en absence d'hormone. En présence du facteur de croissance IGF-I, le REα est nécessaire mais pas suffisant pour activer la transcription et le complexe AP1 joue un rôle aussi important que le REα dans l'activation transcriptionnelle du gène pS2/TFF1. Ce complexe AP1, ou les voies conduisant à son activation pourrait donc être des cibles thérapeutique de choix pour le traitement du cancer du seinInsulin like growth factor I (IGF-I) displays estrogenic activity in breast cancer cells. This activity is strictly dependent on the presence of estrogen receptor (ER). However the precise molecular mechanisms involved in this process are still unclear. IGF-I treatment induces phosphorylation of the AF1 domain of ERα and activation of estrogen regulated genes. These genes are characterized by important differences in promoter architecture and response element composition. We show that promoter structure is crucial for IGF-I induced transcription activation. We demonstrate that on a complex promoter such as the pS2/TFF1 promoter, which contains binding sites for ERα and for the AP1 complex, transcriptional activation by IGF-I requires both ERα and the AP1 complex. IGF-I is unable to stimulate transcription of an estrogen-regulated gene under the control of a minimal promoter containing only a binding site for ERα. We propose a molecular mechanism with stepwise assembly of the AP1 complex and ERα during transcription activation of pS2/TFF1 by IGF-I. IGF-I stimulation induces rapid phosphorylation and an increase in protein levels of the AP1 complex. Binding of the phosphorylated AP1 complex to the pS2/TFF1 promoter allows recruitment of the chromatin remodeling factor Brg1 followed by binding of ERα, via its interaction with c-Jun
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Coburn, Leslie Ann. "Studies of platelet gpib-alpha and von willebrand factor bond formation under flow". Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/39565.
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Understanding the differential bonding mechanics underlying bleeding disorders is of crucial importance to human health. In this research insight is provided into how four of these bleeding disorders (each with somewhat similar clinical characteristics), work at the molecular bond level. The bleeding diseases studied here can result from defects in the platelet glycoprotein (GP) Ibα the von Willebrand factor (vWF) molecule, or the ADAMTS-13 enzyme. Types 2B and 2M von Willebrand Disease (VWD) result in excess bleeding, yet type 2B has increased binding affinity between platelet GPIbα and vWF, while type 2M has decreased binding affinity between these two molecules. Platelet type VWD (pt-VWD) causes mutations in the GPIbα molecule and has similar characteristics to type 2B VWD. Further, in thrombotic thrombocytopenic purpura, bleeding results when there is a lack of active ADAMTS-13 enzyme. Each disease results in patient bleeding, but due to different mechanisms. This dissertation will explore the bonding mechanics between GPIbα and vWF and how they are altered in each disease state. To observe the GPIbα-vWF bonding mechanics, rolling velocities, transient tethering lifetimes, and tether frequency were determined using a parallel plate flow chamber. Data from these experiments suggest that wt-wt interactions are force dependent and have biphasic catch-slip bonding behavior. The data show that the shear stress at which the maximum mean stop time occurs differs between gain-of-function and loss-of-function mutations. Using similar methods, we study the changes resulting from pt-VWD mutations in GPIbα, and find that the catch bond seen for wt-wt interactions is lost for these mutations. Further, the data suggest that interactions with gain-of-function GPIbα mutations may be transport rather than force dependent. Finally, how the GPIbα-vWF tether bond changes for thrombotic thrombocytopenic purpura was also investigated to show that the bond lifetime in the absence of the enzyme is increased presenting a possible rationale for why bleeding occurs in this disease. Overall, the data show how the bonding mechanics of the GPIbα-vWF tether bond differ in four bleeding diseases. Further, these observations offer potential explanations for how these changes in the bonding mechanism may play a role in the observed patient bleeding.
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Love-Gregory, Latisha Debrett. "Investigation of the origin of the Y393N allele in old order mennonite and non-mennonite maple syrup urine disease patients : analysis of the branched chain [alpha]-keto acid dehydrogenase complex E1[alpha] gene /". free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3012999.
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Mohan, Megha. "Role of VPS35 in the pathogenesis of Parkinson's disease". Thesis, Griffith University, 2017. http://hdl.handle.net/10072/370642.
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Parkinson’s disease (PD) is a heterogeneous and complex neurodegenerative disorder whose
aetiology is not fully understood. Studying familial Parkinson’s disease has identified several
mutations that cause the disease and investigating the functions of these genes has given us
clues to the cellular mechanisms that underlie the neurodegenerative phenotype in the
patients. A clear understanding of these cellular mechanisms is necessary to halt disease
progression. Next generation sequencing of a Swiss kindred with autosomal dominant
Parkinson’s disease has identified a causative D620N mutation in the VPS35 (vacuolar
sorting protein 35) gene. The VPS35 protein is a subunit of a retromer complex, which is a
key element of the endosomal sorting process. Little is known about the effects of this
mutation and this thesis presents our efforts to gain a better understanding of the mechanism
by which mutations in the VPS35 gene influences the pathogenesis of PD. This project also
investigates disease specific differences in organelles along the retromer pathway in sporadic
PD cases.
The first cell model used in the study is a fibroblast model derived from a PD patient carrying
the D620N mutation and healthy “wild-type” controls. It was found that the D620N mutation
did not present any loss of endogenous VPS35 protein levels in the fibroblasts. However, in
the presence of the mutation a redistribution of the endosomes was observed. This was
indicative of altered endolysosomal trafficking within the cell. Further, defective trafficking
of CIMPR, a well-known cargo molecule of the retromer complex was observed in the
presence of the mutation. This trafficking defect resulted in compromised lysosomal function
mainly through the impaired processing of its ligand cathepsin D, a lysosomal enzyme
involved in the degradation of alpha synuclein. In addition to this, high content image
analysis of the cells revealed a disease specific difference in features of organelles involved
in the retromer trafficking pathway. The fibroblasts were also treated with rotenone to
analyse the effects of mitochondrial stress in the presence of the mutation. Treatment with
this pesticide which is also a known complex 1 inhibitor, that causes PD like pathology in
animals, showed disease specific changes in cells with the mutation. The D620N mutation
did not confer increased susceptibility to cell death, but caused disease specific changes in
properties of the early endosome, lysosomal and retromer subunit of the fibroblasts. On treatment with rotenone, cathepsin D processing defects were also exacerbated in the patient
cells with the mutation.
Further, the effect of the D620N mutation on alpha synuclein processing was also
investigated. Uptake of monomeric and fibrillar alpha synuclein forms was shown in the
fibroblasts. Reduced clearance of the alpha synuclein fibrils was observed in the presence of
the D620N mutation. In addition to this, the D620N mutation conferred an increased
sensitivity to alpha synuclein toxicity within these cells. Although increased alpha synuclein
aggregation in the presence of the D620N mutation was hypothesised, the mutation did not
show increased aggregation under the experimental conditions described here.
In order to investigate disease specific differences in sporadic patients, a second cell model
was used in this study, namely the human olfactory neurosphere derived (hONS) model.
Investigation surrounding the retromer functions in hONS cells derived from sporadic PD did
not reveal any alterations in the retromer levels and cathepsin D processing defects relative to
cells derived from healthy donors. However, a nonsignificant trend towards decreased
cathepsin D levels was observed in the patient cells. Analysis of retromer related markers in
these cells did not show any disease specific differences. In contrast to this, inducing
mitochondrial stress using rotenone resulted in disease specific changes in several organelles
within these cells. Treatment with rotenone brought about changes in cellular parameters of
mitochondria, lysosomes and tubulin, indicating disease specific responses to mitochondrial
stress that served as potential biomarkers for the disease.
In conclusion, this study identified retromer trafficking defects and alpha synuclein
processing defects in the presence of the D620N mutation. It is the first report that shows
synuclein processing defects in fibroblasts from PD patients with the D620N mutation. This
study also marks the identification of potential biomarkers for the disease by building on
previously identified disease specific differences identified in hONS cells obtained from sporadic PD patients.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
Full Text
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Love-Gregory, Latisha D. "Investigation of the origin of the Y393N allele in Old Order Mennonite and non-Mennonite maple syrup urine disease patients analysis of the branched chain [alpha]-keto acid dehydrogenase complex E1[alpha] gene : a dissertation ... /". free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3012999.
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Moriceau, Lucille. "Caractérisation de la protéine 140K impliquée dans l’adressage aux chloroplastes des complexes de réplication du virus de la mosaïque jaune du navet (TYMV)". Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS255/document.
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Le virus de la mosaïque jaune du navet (TYMV) possède un génome monopartite constitué d’ARN de polarité positive codant pour trois protéines, dont seule la polyprotéine 206K est indispensable à la réplication virale.Elle subit une maturation protéolytique, générant les protéines 140K et 66K, localisées au niveau de l’enveloppe des chloroplastes, siège de la réplication virale.Adressée aux chloroplastes, la protéine 140K y recrute la 66K et se comporte comme une protéine intégrale membranaire.Le domaine d’adressage aux chloroplastes (DAC) de la protéine 140K a été défini grâce à la transfection et à des protoplastes d’Arabidopsis thaliana par différentes constructions codantpour des versions délétées de la protéine fusionnées à l’EGFP, et à leur observation en microscopie confocale. Le DAC comprend deux hélices alpha amphipathiques dont la présence a été attestée par dichroïsme circulaire. Leur nécessité pour la localisation aux chloroplastes, l’association aux membranes et la réplication virale, a été étudiée. Différents patterns de distribution subcellulaire de la protéine 140K ont été observés. Ils sont corrélés au taux d’expression de la protéine. Sa dimérisation a également été démontrée.L’implication d’autres résidus du DAC dans la localisation subcellulaire, la dimérisation et la réplication virale, a également été recherchéeTurnip yellow mosaic virus (TYMV) is a positive single-stranded RNA virus. Among the three ORFs encoded by the TYMV genome, 206K is the only protein required for viral replication. It is cleaved into 140K and 66K, which are both present at the chloroplast envelope membrane, where viral replication takes place.The 140K protein is targeted to chloroplasts, where it recruits 66K, and behaves as an integral membrane protein. The chloroplast targeting domain (DAC) of the 140K protein was defined using Arabidopsis thaliana protoplasts transfected by various constructs encoding deleted versions of 140Kfused to EGFP and subsequent confocal microscopy. The DAC comprises two amphipathic alpha helices, as confirmed by circular dichroism. Their involvement in chloroplast localisation and membrane association has been assessed, as well as their contribution to viral replication.We observed different subcellular distribution patterns of 140K protein, which correlate with the expression level of the protein. Its capability to dimerize has also been demonstrated.The involvement of other DAC residues in subcellular localisation, dimerization and viral replication has been studied
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Chan, Wing-han, i 陳詠嫻. "Coordination chemistry of the pyridyl, naphthyridyl and [alpha], [omega]-polyether phosphine ligands and x-ray crystal structures andspectroscopic properties of the metal complex derivatives". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31236595.
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Chan, Wing-han. "Coordination chemistry of the pyridyl, naphthyridyl and [alpha], [omega]-polyether phosphine ligands and x-ray crystal structures and spectroscopic properties of the metal complex derivatives /". Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19481640.
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Koontz, John L. "Controlled Release of Natural Antioxidants from Polymer Food Packaging by Molecular Encapsulation with Cyclodextrins". Diss., Virginia Tech, 2008. http://hdl.handle.net/10919/26757.
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Synthetic antioxidants have traditionally been added directly to food products in a single initial dose to protect against oxidation of lipids and generation of free radicals. Natural antioxidants have been shown to undergo loss of activity and become prooxidants at high concentrations; therefore, a need exists to develop active packaging which can gradually deliver antioxidants in a controlled manner. The objectives of this research were to (1) form and characterize cyclodextrin inclusion complexes with the natural antioxidants, alpha-tocopherol and quercetin, (2) incorporate cyclodextrin inclusion complexes of natural antioxidants into linear low density polyethylene (LLDPE), and (3) measure the release kinetics of inclusion complexes of natural antioxidants from LLDPE into a model food system. Cyclodextrin inclusion complexes of alpha-tocopherol and quercetin were formed by the coprecipitation method and characterized in the solid state by NMR, IR spectroscopy, and thermal analyses. Solid inclusion complex products of alpha-tocopherol:beta-cyclodextrin and quercetin:gamma-cyclodextrin had molar ratios of 1.7:1 as determined by UV spectrophotometry, which were equivalent to 18.1% (w/w) alpha-tocopherol and 13.0% (w/w) quercetin. Free and cyclodextrin complexed antioxidant additives were compounded with a twin-screw mixer into two LLDPE resin types followed by compression molding into films. Release of alpha-tocopherol and quercetin from LLDPE films into coconut oil at 30 °C was quantified by HPLC during 4 weeks of storage. The total release of alpha-tocopherol after 4 weeks was 70% from the free form and 8% from the complexed form averaged across both LLDPE resins. The mechanism by which alpha-tocopherol was released was modified due to its encapsulation inside the beta-cyclodextrin cavity within the LLDPE matrix as indicated by its diffusion coefficient decreasing by two orders of magnitude. Molecular encapsulation of natural antioxidants using cyclodextrins may be used as a controlled release mechanism within polymer food packaging to gradually deliver an effective antioxidant concentration to a food product, thereby, limiting oxidation, maintaining nutritional quality, and extending shelf life.Ph. D.
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Bonfitto, Pedro Henrique Leite 1987. "Efeito do fator de necrose tumoral alfa na agregação plaquetária". [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313092.
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Orientador: Sisi Marcondes PaschoalDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: As plaquetas são importantes células na inflamação, entretanto, os trabalhos que estudam as citocinas na reatividade plaquetária são raros. O objetivo do presente trabalho foi estudar os efeitos do fator de necrose tumoral-alfa (TNF-?) em plaquetas. Ensaios de agregação foram realizados incubando-se plaquetas com crescentes concentrações de TNF-? (1 - 3000 pg/ml) por diferentes intervalos de tempo (5 - 60 min), na ausência ou presença do antagonista não seletivo dos receptores TNFR1 e TNFR2, o R7050. Também foi estudado o efeito do TNF-? na viabilidade plaquetária utilizando-se o MTT. O efeito do TNF-? na mobilização de Ca2+ em plaquetas foi investigado através de ensaios de fluorescência utilizando-se o fluo-3-AM; os ensaios de western blotting foram realizados para o estudo da ativação da enzima c-Src e do receptor de fibrinogênio. Finalmente, foram determinados os níveis intraplaquetários de AMPc e GMPc por ELISA. O TNF-? inibiu a agregação plaquetária induzida por ADP ou trombina de forma dependente da concentração da citocina e do tempo de incubação. O efeito inibitório máximo do TNF-? na agregação induzida por ADP (5 ?M) foi obtido com a concentração de 300 pg/ml por um tempo de incubação de 30 min (90 ± 7% de inibição), o qual foi significativamente prevenido pela pré-incubação das plaquetas com o R7050. A viabilidade plaquetária não foi modificada pela incubação por 60 min com o TNF-? (30 e 3000 pg/ml). A incubação de plaquetas com TNF-? (300 pg/ml, 30 min) reduziu em 53% o aumento da concentração de Ca2+ total causado pela adição de trombina (200 mU/ml). A queda da concentração de Ca2+ citosólica plaquetária causada pelo TNF-? foi em decorrência da diminuição em 1,8 e 3,4 vezes da mobilização interna do íon e do influxo do mesmo, respectivamente. O TNF-? reduziu em 60% os níveis de AMPc em plaquetas ativadas com ADP. Por outro lado, o TNF-? aumentou significativamente os níveis de GMPc em plaquetas ativadas por ADP (aumento de 51%). A pré-incubação de plaquetas com o inibidor da guanilil ciclase ODQ não reduziu o efeito inibitório do TNF-? na agregação induzida por ADP. Os ensaios de western blotting mostraram que o TNF-? reduziu significativamente a fosforilação do resíduo de Tyr416 da c-Src em plaquetas ativadas. Da mesma forma, o TNF-? reduziu em 37% a fosforilação do resíduo de Tyr773 da subunidade ?3 da integrina ?IIb?3 (receptor de fibrinogênio) em plaquetas ativadas por ADP. Portanto concluímos que o TNF-? inibe a agregação plaquetária via receptores TNFR1 e/ou TNFR2, sem reduzir a viabilidade das plaquetas. O efeito inibitório do TNF-? na agregação é acompanhado pela redução de Ca2+ citosólico e inibição de c-Src e do receptor de fibrinogênio em plaquetas, sendo estes independentes de AMPc ou GMPc
Abstract: Platelets have been described as important cells in inflammation; however, the effects of cytokines on platelet reactivity are rarely studied. The objective of the present work was to investigate the effects of the tumor necrosis factor-alpha (TNF-?) in platelets. Aggregation assays were carried out incubating platelets with increasing TNF-? concentrations (1 - 3000 pg/ml) for different intervals of times (5 - 60 min), in the absence or in presence of the non-selective antagonist of TNFR1 and TNFR2, R7050. Effect of TNF-? on platelet viability was determined using MTT. The effect of TNF-? on the Ca2+ mobilization in platelets was investigated through fluorescence assays using fluo-3AM and Western blotting assays were carried out to determine the activation of c-Src and the fibrinogen receptor. Finally, the cAMP and cGMP levels in platelets were determined by ELISA. TNF-? dose- and time-dependently inhibited ADP or thrombin-induced platelet aggregation. The inhibitory effect of TNF-? on ADP(5 ?M)-induced platelet aggregation was maximum in a concentration of 300 pg/ml incubated with platelets for 30 min (90 ± 7% of inhibition), which was significantly prevented by the incubation of platelets with R7050. Platelet viability was not modified by TNF-? (30 and 3000 pg/ml) incubated for 5 to 60 min. Incubation of platelets with TNF-? (300 pg/ml, 30 min) reduced the increased total Ca2+ concentration induced by thrombin (200 mU/ml) by 53%. Decreasing Ca2+ internal mobilization (1,8 fold) and decreasing in external Ca2+ influx (3,4 fold) led to a reduction of total cytosolic Ca2+ in TNF-? activated platelets. TNF-? reduced the cAMP levels in ADP-activated platelets by 60%. On the other hand, TNF-? significantly increased cGMP levels in ADP-activated platelets (51% increase). Pre-incubation of platelets with the guanylyl cyclase inhibitor ODQ did not modify the inhibitory effect of TNF-? on ADP-induced platelet aggregation. Western blotting analysis showed that TNF-? significantly reduced phosphorylation on Tyr416 of c-Src in activated platelets. Similarly, TNF-? reduced by 37% the Tyr773 phosphorylation of ?3 subunit of ?IIb?3 integrin (fibrinogen receptor) in ADP-activated platelets. Therefore, our results show that TNF-? inhibits platelet aggregation via TNFR1 and/or TNFR2 receptors, without affecting platelet viability. The inhibitory effect of TNF-? on aggregation is accompanied by a reduction in cytosolic Ca2+ and the inhibition of c-Src and fibrinogen receptor activation, which are cAMP and cGMP-independent effects
Mestrado
Farmacologia
Mestre em Farmacologia
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Mohd, Najib Mohd Idris. "Characterisation of THOC4 response to replicative stress". Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/122562/1/Mohd%20Idris_Mohd%20Najib_Thesis.pdf.
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Human cells are continuously subject to conditions that cause breaks to DNA. This project explored the interaction between molecules involved in repairing this damage, called hSSB1 and THOC4. Novel discoveries were made that expand our understanding of this important process and identified THOC4 as a potential novel therapeutic target in lung and breast cancer.
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Bott, Raymond C. "The Synthesis and Characterisation of Group 15 Coordination Complexes involving a-Hydroxy Carboxylic Acid Ligands". Thesis, Queensland University of Technology, 1993. https://eprints.qut.edu.au/226578/1/T%28S%29%2032_Bott_1993.pdf.
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This thesis investigates the chemistry of the group 15 elements, arsenic(III), antimony(III), and bismuth(III) together with the a-hydroxy carboxylic acids, (2R,3R)-( + )-tartaric acid and citric acid in the formation of stable coordination complexes. Arsenic and antimony form 1:1 dimeric cage anions [Mz(tartrate)z]2-which are subsequently charge stabilised through monovalent cations. The coordination about the arsenic and antimony is pseudo trigonal bipyramidal because of a stereochemically active lone pair of electrons. However, the metallic bismuth member does not form the dimeric cages nor does it display a stereochemically pair of electrons. Instead, it exhibits both eight- and nine-coordinate geometry about bismuth and forms simple polymeric chains. The bismuth stereochemistry is typically mono-face-capped-square arfriprismatic and tri-face-capped-trigonal prismatic. The ionic radius of the monovalent counter metal ions is found to be an important factor in the stabilisation and formation of these complexes. This is shown in the structural similarlity of the silver(I) and sodium hydrogen ( + )-tartrates reported in this work (ionic radius; 1.15 - 1.18A ) and in the isomorphous Groth hydrogen )-tartrate series (ammonium, potassium, rubidium, caesium, and thallium: ionic radius; 1.46 - 1.67 A). The infrared spectra of these complexes and the arsenic(III)
( + )-tartrate complexes also show this through a decrease in frequency of the asymmetric carbonyl vibrational bands. The infrared spectra also indicate the effect that different metals and combinations of metals have on the carbonyl groups through the splitting or suppression of splitting of the characteristic carbonyl vibrational band. The increase in metallic character of the group 15 elements also parallels the ease in formation of their complexes. This is due to the largely covalent character of arsenic compared to the highly ionic character of bismuth. The complete series of group 1 metal antimony(III) citrates have also been isolated and characterised in this work while a number of arsenic(III) ( + )-tartrate complexes were isolated using sodium and silver(!) counter ions (ionic radii 1.15 and 1.18A respectively).
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Pandarakalam, Jency Johnsons [Verfasser]. "Role of protein kinase alpha and microRNA 15a in Endothelin-1 mediated complex formation via estrogen receptors in MCF-cells [ductal breast carcinoma cell line] / Jency Johnsons Pandarakalam". Köln : Deutsche Zentralbibliothek für Medizin, 2016. http://d-nb.info/1104379600/34.
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Lundmark, Richard. "Sorting nexin 9 in clathrin-mediated endocytosis". Doctoral thesis, Umeå : Department of Medical Biochemistry and Biophysics, Umeå University, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-197.
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Simpson, Naomi Rosalind Mary. "The supramolecular photochemistry of precious metal #alpha#,#alpha#'-diimine complexes". Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368205.
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Magalhães, Renata Ferreira 1972. "Polimorfismos dos genes HLA e regiões promotoras do TNF-'alfa'-238 e -308 como fatores de sucetibilidade a psoriase e gravidade da doença". [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310969.
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Orientador: Maria Helena Stangler KraemerTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Psoríase é uma dermatose inflamatória crônica, determinada por desregulação do sistema imune e associada a várias comorbidades. O marcador genético mais associado à psoríase em todas as populações é o HLA-CW06. Polimorfismos na região promotora do TNF-a, especialmente a troca de uma guanina por uma adenina nas posições -238 e -308 estão relacionados à alta produção de TNF-a e risco aumentado para psoríase nas populações caucasóides e não em asiáticos. Com o objetivo de determinar se polimorfismos destes genes podem ser fatores de risco para susceptibilidade ou gravidade da doença em pacientes brasileiros, foi realizado um estudo caso-controle com 69 pacientes com psoríase de início até 40 anos, com acompanhamento por dez anos para caracterização de sua evolução clínica em doença leve (grupo I) e grave (grupo II), e 70 indivíduos sadios. Foi feita a identificação dos alelos HLA classe I e II e SNPs da região promotora do TNF-a -238 e -308. Coletaram-se 10 mL de sangue periférico dos indivíduos e se realizou a extração do DNA através do método salting out. O DNA foi amplificado pela reação em cadeia da polimerase (PCR), com primers sequência-específica. As freqüências alélicas e gênicas foram estimadas por contagem direta e a comparação entre as frequências dos grupos foi efetuada por Teste de Fisher (programa GraphPad InStat 3.05). Dois métodos computacionais foram usados para determinar os haplótipos dos indivíduo: (1) o algoritmo ELB implementado pelo software Arlequin 3.1 e (2) um método de base coalescente implementado pelo software PHASE v2, e as freqüências de cada haplótipo foram comparadas por Teste de Fisher. No grupo II, observou-se maior associação com fatores desencadeantes como estresse, início na adolescência e predominância do sexo masculino. Pode-se sugerir que os alelos HLA-B*37, -Cw*06, -Cw*12 e -DRB1*07 foram associados ao curso mais grave da doença, enquanto - B*57 à doença mais leve. O aielo DRBT04 teve tendência a associação negativa. Ao se comparar o grupo I com o grupo II, o alelo HLA-B*37 pode ser interpretado como fator de mau prognóstico. Não houve diferença estatística entre polimorfismos da região promotora do TNF-a entre pacientes e controles. Este estudo apontou uma alta frequência do genótipo TNF-a -238 G/G {OFt 3,21; Cl:1,06-9,71; p=0,04), assim como do alelo -238 G, no grupo com doença mais grave e, ao contrário, o genótipo -238 G/A com frequência maior no grupo de boa evolução. O haplótipo -238A-308G mostrou frequência reduzida conferindo um efeito protetor. Estes dados não correspondem ao reportado para as populações caucasianas, considerando que a população brasileira é miscigenada. Polimorfismos dos SNPs do TNF-a não parecem ser um fator de susceptibilidade genética mais importante do que o já conhecido HLA-Cw*06 em pacientes brasileiros, mas podem ter relação com as manifestações e evolução da doença.
Abstract: Psoriasis is an erythematous, scaly inflammatory dermatosis with a complex immunologic basis. The strongest genetic marker for psoriasis is HLA-Cw*06. Polymorphisms in the TNF-a promoter region, especially replacement of guanine with adenine in positions -238 and -308 are related to higher TNF-a production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We did a case-control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10-years of follow-up in mild or severe disease and determined HLA class I, II and TNF-a SNPs -238 and -308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians. Peripheral blood (10 ml) was collected. Genomic DNA from both psoriasis patients and controls was isolated using a salting out procedure. Polymorphisms were identified by PCR/SSP. Alleles and genotypes frequencies were compared by Fisher's test (GraphPad InStat 3.05 software). Two computational methods were used to determine the haplotypes of each subject, without taking into account any prior information: (1) the ELB algorithm implemented by the ARLEQUIN 3.1 software and (2) a coalescence based method as implemented by the PHASE v2 software. The haplotype frequencies were compared between group pairs by Fisher's test. Severe disease was found more frequently in male patients, associated with environmental factors and onset at adolescence. It may be suggested that alleles HLA- B*37, -Cw*06, -Cw*12 and -DRB1*07 were associated with severe disease course, while -B"57 with mild disease. No statistical difference was found between the patients and controls regarding polymorphisms frequencies in TNF SNPs. This study pointed to a higher TNF-238 G/G genotype frequency (OR 3,21; Cl:1,06-8,71; p=0,04) in the group with severe disease and -238A-308G haplotype was found in reduced frequencies revealing a protective effect. These data do not correspond to those reported for the Caucasian population, considering that Brazilian population is admixed, and this is the first consideration about TNF-a SNPs in psoriasis in this population. Polymorphisms in the TNF-a SNPs do not seem to be a more important genetic risk factor for psoriasis than the already known Cw*06 in Brazilian patients, but these markers may be related to clinical manifestations.
Doutorado
Clinica Medica
Doutor em Clínica Médica
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Romano, Manuela. "Stage-specific changes in the Krebs cycle network regulate human erythroid differentiation". Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT077.
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Le processus conduisant à la prolifération et différenciation des cellules souches hématopoïétiques (CSH) en cellules de toutes les lignées sanguines s’appelle l’hématopoïèse. Bien que l'engagement des CSH soit régi par les cytokines, les facteurs de transcription, les modificateurs épigénétiques et la niche des CSH, notre groupe a constaté que leur engagement vers la lignée érythroïde dépendait aussi du métabolisme de la glutamine. La glutaminolyse contribue à la biosynthèse des nucléotides de novo ainsi qu’à la production de l'alpha-kétoglutarate (αKG), intermédiaire métabolique du cycle TCA (Oburoglu et al. 2014). Il est cependant important de noter que la différenciation érythroïde est un processus unique, où chaque cellule fille est structurellement et fonctionnellement différente de sa cellule mère. Chaque division définit un stade de différenciation précis avec un dernier cycle de division produisant un réticulocyte énucléé. Ainsi, nous avons émis l'hypothèse que les réseaux métaboliques mobilisés dans les progéniteurs érythroïdes changent en fonction du stade de différenciation et que ces réseaux régulent la transition des progéniteurs d'un stade à l'autre.Au cours de ma thèse, j’ai caractérisé les états métaboliques associés aux différents stades de différenciation des progéniteurs érythroïdes. Nous avons ainsi montré qu'aux stades précoces de différenciation érythroïde, avant la différenciation terminale, les progéniteurs hématopoïétiques présentent une activité métabolique accrue avec un niveau de phosphorylation oxydative (OXPHOS) plus élevé. Ces données sont en corrélation avec l'augmentation de la génération de l’αKG à ces stades de différenciation. De plus, nous avons constaté une augmentation de l’OXPHOS de ces progéniteurs en présence d’αKG exogène. Cependant, la différenciation terminale des précurseurs érythroïdes, caractérisée par la perte de la masse mitochondriale et de leur potentiel membranaire, est associée à une diminution du niveau d'OXPHOS. Ainsi, l'administration exogène d’αKG, a fortement atténué la différenciation érythroïde terminale et l'énucléation, sans affecter la différenciation des pro-érythroblastes. Inversement, un antagoniste de l’αKG (diméthyloxalylglycine, DMOG) n'a pas altéré la différenciation terminale ou l'énucléation, malgré l'abrogation de l'OXPHOS dans les érythroblastes.Ces données suggèrent que la production d’αKG et sa contribution à l’OXPHOS perturbent l'énucléation des globules rouges. C'est pourquoi, dans le but de réduire les niveaux intracellulaires d’αKG, nous avons inhibé l’expression de l'isocitrate déshydrogénase I (IDH1), enzyme cytosolique catalysant la conversion de l'isocitrate en αKG. Cependant, comme IDH1 peut catalyser les réactions dans les deux sens, la diminution de son expression pourrait également augmenter les niveaux d’αKG. En effet, nous avons constaté que le knockdown d'IDH1 entraînait une forte atténuation de la différenciation terminale et de l'énucléation des précurseurs érythroïdes. Cet effet est probablement dû à un déséquilibre de la disponibilité des substrats ; ainsi l’administration ectopique de l’αKG ainsi que du citrate renforce l’altération de la différenciation terminale des précurseurs érythroïdes IDH1-/- ainsi que leur énucléation. Cette étude identifie donc un rôle crucial pour le métabolite αKG dans la régulation de la fonction mitochondriale et de l’OXPHOS, processus qui sont une condition sine qua non pour la différenciation des précurseurs érythroïdes au stade proérythroblaste. Nous montrons en outre que la suppression d’OXPHOS et la catalyse d’intermédiaires du TCA, substrats d’IDH1, sont requis pour les phases terminales de la différenciation érythroïde et l'énucléation.En conclusion, les résultats obtenus au cours de ma thèse mettent en évidence la nature dynamique des réseaux métaboliques qui régulent la progression des précurseurs érythroïdes tout au long des différents stades de la différenciation érythroïdeHematopoiesis is the process whereby hematopoietic stem cells (HSCs) proliferate and differentiate to all blood cell lineages. While HSC commitment is known to be regulated by cytokines, transcription factors, epigenetic modifiers and the HSC niche, our group found that specification of HSCs to the red cell lineage is dependent on glutamine metabolism. Glutaminolysis contributes to de novo nucleotide biosynthesis and to the generation of the alpha-ketoglutarate (αKG) TCA cycle metabolite (Oburoglu et al. 2014). Importantly though, erythroid differentiation is a unique process as each daughter cell is structurally and functionally different from its parent cell. Each division defines a stage of differentiation with the final division cycle resulting in the production of an enucleated reticulocyte which further matures to a biconcave erythrocyte. Thus, we hypothesized that progenitor metabolic networks change as a function of the erythroid differentiation stage and moreover, that they regulate the transition of progenitors from one stage of differentiation to the next.During my PhD, I assessed the metabolic alterations that occur as a function of the erythroid differentiation stage. We showed that at early stages of human red cell development, prior to terminal differentiation, hematopoietic progenitors exhibited an increased metabolic activity with a significantly higher level of oxidative phosphorylation (OXPHOS). This correlated with the increased generation of αKG and indeed, we found that ectopic αKG directly augmented OXPHOS in these progenitors. However, the terminal differentiation of erythroid precursors, characterized by the loss of mitochondrial mass and membrane potential, was associated with a decreased level of OXPHOS. Notably, ectopic αKG, which did not alter pro-erythroblast erythroid differentiation, severely attenuated terminal differentiation and enucleation. Conversely, an αKG antagonist (dimethyloxalyl glycine, DMOG) did not negatively impact on terminal differentiation or enucleation despite abrogating OXPHOS in erythroblasts.These data suggested that the production of αKG and its subsequent contribution to oxidative phosphorylation perturb red cell enucleation. We therefore downregulated isocitrate dehydrogenase I (IDH1), the cytosolic enzyme that catalyzes the conversion of isocitrate to αKG, by an shRNA approach in an attempt to decrease αKG levels. However, because IDH1 can catalyze both the forward and reverse reactions, its downregulation could also increase αKG levels. Indeed, we found that IDH1 knockdown resulted in a severe attenuation of terminal erythroid differentiation and enucleation. This effect was likely due to an imbalance in substrate availability––both ectopic αKG as well as citrate further decreased polychromatic to orthochromatic erythroblast differentiation and the subsequent enucleation of IDH1-knockdown erythroid precursors. Thus, the present study identifies a crucial role for the αKG metabolite in regulating mitochondrial function and oxidative phosphorylation, processes that are a sine qua non for erythroid precursors at the pro-erythroblast stage. We further show that terminal erythroid differentiation and enucleation requires OXPHOS suppression and the IDH1-mediated enzymatic catalysis of its TCA substrates.To conclude, the results generated during my PhD highlight the dynamic nature of the metabolic networks that regulate the progression of erythroid precursors through the distinct stages of erythroid differentiation
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Rurak, Jennifer Mary Elizabeth. "Implications of alpha-dystroglycan glycosylation in the proper assembly of the dystroglycan associated protein complex and the polarized distribution of the inwardly rectifying potassium channel, Kir4.1, and the water permeable channel, AQP4, in perivascular glia". Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/32339.
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The dystroglycan protein complex spans the plasma membrane and provides a link
between the cytoskeleton and the extracellular matrix (ECM). Defective O-linked
glycosylation of α-dystroglycan (α-DG) within the complex severs this link leading to a
subset of muscular dystrophies known as the dystroglycanopathies. These are
characterized by muscle weakness and degeneration as well as by brain and ocular
defects of unknown etiology. In brain and retina, α-DG and ECM molecules are enriched
at astrocytic domains abutting blood vessels where they may be involved in localizing the
inwardly rectifying potassium channel, Kir4.1, and aquaporin channel, AQP4, to
astrocytic endfeet. To investigate the role of ECM ligand-binding to glycosylated sites on
α-DG in the polarized distribution of these channels in vivo, we used the Large [superscript] myd mouse,
an accepted animal model for dystroglycanopathies. We found that Kir4.1 and AQP4 are
lost from astrocytic endfeet in brain while significant labeling for these channels is still
detected at analogous cell domains in retina. Furthermore, while both α- and β₁-
syntrophins are lost from perivascular astrocytes in brain of the Large [superscript] myd mouse, labeling
for β₁-syntrophin is still evident at parallel domains in retina. These findings show that
while ligand-binding to glycosylated sites on α-DG in concert with α- and β₁-syntrophins
is crucial for the polarized distribution of Kir4.1 and AQP4 to functional domains in
brain, distinct mechanisms may contribute to their localization in retina.Medicine, Faculty of
Graduate
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Rath, Emma. "Structural characterisation of BAMLET-like anti-cancer complexes and investigation of their potential for treating mesothelioma". Thesis, The University of Sydney, 2018. https://hdl.handle.net/2123/21797.
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BAMLET and related compounds are a family of protein-oleic acid complexes that are cytotoxic towards a range of cancer cells and some bacteria, and for which no evidence of similar toxicity towards healthy tissue has yet been presented. This thesis determines the structure of BAMLET-like complexes, revealing that they belong to a new type of lipid-binding protein structure family consisting of the distinctive features of protein located on the periphery encapsulating a drop of oleic acid in the centre. This work is the first to reveal these distinctive structural features of what is now called the liprotide family. The oleic acid component of the BAMLET family member is shown to form a 36 Å diameter spheroid with the partially unfolded bovine α-lactalbumin polypeptide component expanded to a diameter of 79 Å. Small angle X-ray and neutron scattering were the principal techniques used and comprehensively elucidate the structure. The anti-cancer mechanism of BAMLET compounds appears to be novel and the novel structure revealed in this thesis provides part of the explanation for how they achieve broad spectrum activity. In an aqueous environment, the BAMLET complex is stable and its oleic acid cargo is thus solubilised, until a cell membrane is encountered, for which the oleic acid could have higher affinity resulting in activity against the cell. This thesis also demonstrates a possible application to the treatment of mesothelioma for BAMLET-like compounds, that negates the disadvantage that blood components disable BAMLET’s anti-cancer activity. Tissue culture and cell death assay techniques were used to show that BAMLET is equally cytotoxic towards mesothelioma cells that have developed increased resistance to the cisplatin or pemetrexed chemotherapy drugs, as towards mesothelioma cells that do not have heightened resistance. These results position BAMLET as a potentially valuable treatment option for this ultimately treatment-resistant cancer.
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Hughes, Clifford. "Studies on improving the predictive markers for the diagnosis of acute pancreatitis after Endoscopic Retrograde Cholangiopancreatography (ERCP)". Thesis, Queensland University of Technology, 1999. https://eprints.qut.edu.au/37065/1/37065_Hughes_1999.pdf.
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Endoscopic Retrograde Cholangiopancreatography (ERCP) is a widely performed gastroenterological procedure often accompanied by the development of acute pancreatitis post-ERCP - the current literature quoting an incidence between 0% and 39.5%. Because acute pancreatitis can be a very serious outcome, sometimes leading to death, a method for predicting poor outcomes post-ERCP would be an advantage to the clinicians and patients. Described below is the development of two algorithms with a strong capacity to predict poor outcomes post-ERCP.
In addition to assessing a battery of common laboratory blood tests, this study also took the opportunity to study a recently described but still research-based analyte, the enzymatic activity of the trypsin bound to the serine protease inhibitor alpha- 2- macroglobulin ( a2M) complex called Macroglobulin-Trypsin complex-Like Substance (MTLS), high levels of MTLS have been identified in patients who developed acute pancreatitis post-ERCP. It was hypothesized that MTLS might be a useful, novel indicator of patients at risk of development of post-ERCP pancreatitis.
Three separate studies were carried out. The first was a retrospective study of 72 patients presenting for ERCP to the collaborating gastroenterologist, and the second was a prospective study involving 29 more patients. The retrospective study involved the analysis of previously collected blood specimens pre-ERCP and post-ERCP. On the pre-ERCP specimens 22 laboratory tests were performed to test the haematological, biochemical and coagulation status of the patients. Lipase, a classical diagnostic marker for acute pancreatitis, was measured on the patient's post-ERCP samples. From this study sophisticated statistical analysis was based on a 2-step process - Factor Analysis with Principal Component Extraction followed by Discriminant Analysis on the key components identified by Factor Analysis - in order to develop a predictive algorithm for poor outcomes post-ERCP.
The objective of the second, prospective, trial was to test algorthms developed by the initial
retrospective study. 29 patients were selected and their clinical outcomes using the system of Cotton (1991) compared in a blind trial with the predictions of the algorithm·. The third study involved developing a methodology for measuring the activity of trypsin in MTLS or associated with a2M. The investigation of the residual protease activity of the MTLS complexes, was based on the hypothesis that patients who develop post-ERCP acute pancreatitis, have abnormally active trypsin associated with MTLS or a2M before the ERCP. This was the least successful part of the research, as the methodology proved to be too insensitive and therefore not a useful marker for poor outcomes.
Two algorithms were derived from the retrospective trial. Algorithm 1 used a combination of gamma glutamyltransferase (GGT) and lipase, measured pre-ERCP, whereas Algorithm 2 used GGT, lipase and alpha - 1 - antitrypsin (AAT). Predictions were then made for the 29 prospective study patients using the two algorithms.
The results were: Algorithm 1, 27 out of 29 cases were predicted successfully with Pearson's correlation of 0.946 and significance p = <0.001 and likewise for Algorithm 2 - 27 out of 29 were successfully predicted with a comparable Pearson's correlation of 0.753 and p = <0.001.
Both algorithms have very strong capacities to predict poor outcomes and require additional clinical trials, Algorithm 2 has a better capacity to grade the predictions for poor outcomes, normal, mild and severe. Additional larger studies will be needed to refine these algorithms and to better appraise their clinical usefulness.
This study provides two very valid outcomes. The first is a method of statistical analysis with the capacity to produce predictive algorithms in a clinical setting and the second the development of two significant algorithms for predicting poor outcomes post-ERCP.
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Meyer, Régis. "Analyse du gène de la Yemanucléine-alpha (yem-alpha) : un nouvel acteur essentiel de la méiose ovocytaire de drosophile". Montpellier 1, 2006. http://www.theses.fr/2006MON1T016.
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Ce travail s'inscrit dans une analyse de la méiose ovocytaire chez Drosophila melanogaster. Notre équipe avait montré que la Yemanucléine-alpha (Yem-alpha) est une protéine spécifique du noyau de l'ovocyte, conservée chez les vertébrés. Nous décrivons la première mutation (yem1) qui affecte un des domaines conservés de Yem-alpha. Elle se traduit par un arrêt de la méiose ovocytaire dans la transition métaphase I-anaphase I, première preuve de l'existence d'un checkpoint à cette étape. Une analyse génétique et cytologique montre que ce blocage répond à un défaut de l'orientation des kinétochores soeurs en métaphase I. En accord avec ces résultats, Yem-alpha est trouvée associée aux centromères des chromosomes méiotiques. La distribution des crossing overs est affectée chez le mutant yem1. La mise en évidence de l'association de Yem-alpha au complexe synaptonémal est en accord avec un effet sur la recombinaison.
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Victoria, Rosemary. "Development of luminescent ruthenium complexes for in-vitro fluorescence imaging of angiogenesis with the RGD peptide". Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/633.
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Herein we report the synthesis of an RGD-ruthenium bipyridine [Ru(Bpy)2(BpyRGD)]2+ complex aimed at the detection of angiogenesis. Angiogenesis plays a critical role in many pathophysiological processes, such as tumor growth. The αv-integrins (αv[beta]3, αv[beta]5) are currently used as molecular targeting sites for anti-angiogenic therapies. The [Ru(Bpy)2(BpyRGD)]2+ complex is an organometallic luminescent probe, which enables noninvasive, in vitro imaging of αv[beta]3 expression. Peptides containing the arginine-glycine-aspartic acid (RGD) sequence have been shown to bind strongly to the αvb3 integrin. The RuBpy probes are soluble in water, display long lifetimes, and are photochemically stable. These properties enable the Ru(tris-bpy) complexes to be useful in numerous applications in biophysical and cell biology. The [Ru(Bpy)2(BpyRGD)]2+ complex was synthesized by combining the succinimidyl ester on the RuBpy complex with the lysine of the c(RGDfK) peptide. The results of the one-photon fluorescence bioimaging showed selective binding of the cyclic RGD to αv[beta]3 integrin, which supports previous literature. The high luminescence intensity, long lifetimes, and low cell toxicity levels of dye [Ru(Bpy)2(BpyRGD)]2+, illustrates the potential usage of this probe for future biological applications.B.S.
Bachelors
Sciences
Biology
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Baxter, Paul N. W. "Substituted #alpha#-diimine complexes of group VI metal carbonyls". Thesis, University of Kent, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279680.
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McGrath, Catherine Mary. "Lanthanide and transition metal complexes of #alpha#-functionalized phosphonate derivatives". Thesis, London Metropolitan University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321712.
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Wijaya, Linda Kurnia. "Inflammation and complex regional pain syndrome: The role of alpha1-adrenoceptors". Thesis, Wijaya, Linda Kurnia (2020) Inflammation and complex regional pain syndrome: The role of alpha1-adrenoceptors. PhD thesis, Murdoch University, 2020. https://researchrepository.murdoch.edu.au/id/eprint/58462/.
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A growing number of studies have investigated novel roles of the alpha1-adrenoceptor (α1-AR; a receptor for sympathetic neurotransmitter catecholamines) in inflammation. Stimulation of 1-AR in immune cells modulates cellular functions, including migration and inflammatory cytokine production. However, whether α1-ARs in the skin play a role in cutaneous inflammation is not well understood. Complex regional pain syndrome (CRPS) is a complex and debilitating type of neuropathic pain. In the acute stage of CRPS, excessive inflammation persists in the affected limb. Moreover, α1-AR expression is heightened in the skin of the affected limb. However, the causes of this upregulation of cutaneous α1-AR expression and whether this upregulation contributes to the persistent inflammation are unknown.
In this study, the role of α1-AR in cutaneous inflammation was explored, in both normal and pathological conditions, utilizing in vitro, in vivo and ex vivo approaches. It was hypothesized that inflammatory mediators produced by keratinocytes, as a response to injury, would up-regulate α1-AR expression in these cells, and that heightened expression of α1-AR would increase α1-AR sensitivity to stimulation, leading to further release of inflammatory mediators from keratinocytes. Moreover, in CRPS, it was hypothesized that this feedback loop would be amplified and the response stronger than in healthy controls.
A positive feedback interaction between α1-AR and inflammatory mediators in keratinocytes was demonstrated. In particular, α1-AR expression increased after exposure to the primary proinflammatory cytokine tumour necrosis factor α (TNF α). Furthermore, activation of α1-AR further induced a pro-inflammatory cytokine, interleukin 6 (IL-6), expression, thereby suggesting a positive feedback loop between α1-AR and IL-6 in keratinocytes. Interestingly, the interaction was stronger in keratinocytes obtained from CRPS patients, particularly those with high baseline levels of α1-AR expression, compared to healthy controls.
In conclusion, this study demonstrated a positive feedback interaction between α1-AR and IL-6 in the skin, which may play an important role in normal cutaneous inflammation. Maintaining homeostasis of this interaction could be crucial to prevent the development of persistent inflammation underlying pathophysiology in chronic diseases, such as CRPS.
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Chrisman, Mark A. "Non-Fe Metal Complexes with a Siderophore Inspired Chelate". University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1490702494736234.
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Achi, Sabah Samira. "Nouvelle voie d'acces aux acides alpha -amines, par catalyse homogene a l'aide de complexes de metaux de transition, synthese de nouveaux complexes phosphores chiraux du tungstene pentacarbonyle". Paris 6, 1987. http://www.theses.fr/1987PA066227.
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Rosa, Patrick. "Utilisation de complexes de zirconium(iv) pour la synthèse de phosphinines alpha, alpha-fonctionnalisees et de 2,2-biphosphinines. Chimie de coordination des 2,2-biphosphinines". Palaiseau, Ecole polytechnique, 2000. http://www.theses.fr/2000EPXX0035.
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Les phosphinines sont les analogues phosphores des pyridines. Au cours du premier chapitre, nous faisons quelques rappels importants sur la structure électronique, les synthèses et la réactivité des phosphinines. Ce chapitre est conclu par un passage en revue de l'utilisation de ce type de ligand à base de phosphore SP 2 en chimie de coordination. Les halogenophosphinines sont des précurseurs importants. Une des méthodes développées pour leur fonctionnalisation repose sur l'utilisation de métallocènes du groupe 4, en particulier du zirconium, méthode qui est développée dans le deuxième chapitre : - synthèse de complexes de phosphabenzyne-zirconocenes, dont la réaction avec divers substrats (alcynes, cétones, aldehydes, etc) permet d'obtenir des phosphinines fonctionnalisées en position alpha ; - réaction de métathèse zirconium-phosphore ou zirconium-nickel donnant accès a des 1,4-diphosphaindenes ou des 2,2-biphosphinines. Cette nouvelle méthode de synthèse des 2,2-biphosphinines a été mise à profit pour développer l'utilisation de ce ligand pour la stabilisation de complexes métalliques à des états d'oxydation formels très bas (ZR(-II) et ZR(-I), RU(-II), CO(-I),). Le troisième chapitre décrit dans un premier temps l'étude en réduction du ligand, les espèces réduites étant caractérisées par des méthodes spectroscopiques couplées à une étude théorique, et par diffraction de rayons X. Dans un deuxième temps des complexes métalliques réduits sont décrits dans l'ordre des groupes du tableau périodique. Des structures, parfois inattendues, ont été obtenues par diffraction de rayons X. Ces structures servent alors de point de départ pour discuter de l'état de réduction des ligands et du transfert électronique entre métal et ligands, et de la cause des anomalies structurales observées. Pour des motifs de comparaison, la structure de quelques complexes analogues de 2,2-bipyridine a été établie.
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Elshewy, Ahmed. "Alpha hydroxy acid-containing chelates and their homo and hetero metallic complexes". University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1563876435270199.
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Farrell, Ian Robert. "Charge transfer photochemistry of group six and seven #alpha#-diimine complexes". Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393715.
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Landais, Didier. "Analyse moleculaire des sites fonctionnels de la chaine a alpha du complexe majeur d'histocompatibilite murin". Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR13215.
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