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1
Gurung, Sarah Prava. "Biophysical & crystallographic studies of DNA i-motifs". Thesis, University of Reading, 2018. http://centaur.reading.ac.uk/77642/.
Testo completoAbstract (sommario):
Intramolecular i-motifs of the form C3L3-8C3L3-8C3L3-8C3, where C3 denotes the cytosine stretch and L3-8 are “loop” regions containing any DNA base (L) including cytosine, were studied to understand the effects of loop length on i-motif stability. It contrast to the previously held notion that long-looped i-motifs are more stable, it was found that i-motif structures with short loops exhibit higher thermal stabilities and transitional pH values. The stability of long-looped i-motifs are then shown to increase with the addition of [Ru(phen)2dppz]2+ (phen = 1,10-phenanthroline, dppz = dipyrido [3,2-a:2',3'-c] phenazine); a polypyridyl complex that has a potential for photodynamic therapy. Addition of the complex enhances the stability of d(C3T838)3C3 but not that of d(C3T383)3C3, implying that loop lengths are important in defining i-motif-ligand interactions. The effects of loop base composition on the stability of i-motifs have also been presented. It is shown that when d(C3XYZ)3C3 sequences are used (where X and Z are adenine, thymine and guanine, and Y is any of the four DNA bases), pyrimidine-rich sequences form more stable i-motif structures. However, when guanine is X, only two out of 12 d(C3XYG)3C3 sequences were able to form i-motifs. Change in sequence direction also resulted in different thermal and pH stabilities; emphasising the role of loop base composition on not only the i-motif’s stability but also in its formation. X-ray crystallography was used to further understand the effects of loop bases on i-motif structures. The study focuses on four tetramolecular i-motifs; two of which were solved in the mid1990’s; (d(C4)4 and d(C3T)4 but have now been re-examined using improved experimental approaches. Two novel i-motif structures of d(C3A)4 and [d(C3A) + d(C3T)] are presented. Following the X-ray diffraction of d(C3T)4 crystals to 0.68 Å resolution (previously reported at 1.4 Å) at beamline I02 (Diamond Light Source Ltd.), a novel neutron diffraction study on the particular i-motif was conducted. Single crystal neutron diffraction was carried out at MaNDi beamline (Spallation Neutron Source) to find the distribution of the proton between the hemiprotonated cytosine+·cytosine base pairs and to understand the role that H-bonded water can play in stabilising the i-motif structure.
2
Mir, Morro Bartomeu. "Studies on the formation of i-motif structures at neutral pH. Use of cytidine analogues and importance of minor groove tetrads on mini i-motifs stabilization". Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668126.
Testo completoAbstract (sommario):
Given the increasing interest in i-motif structures, obtaining such structures as well as detailed structural information under physiological conditions have become hot topics in the structural biology field. In this context, the main objectives of this thesis are focused on the design and detailed characterization of several oligonucleotide sequences that may form stable i-motif structures at neutral pH. The starting point is the mini i-motif structure, extensively studied in the research group that exhibits unusual high pH and thermal stability. These are dimeric structures stabilized by the formation of two hemiprotonated C:C+ base pairs capped at both ends by minor groove G:T:G:T tetrads. With the aim of getting deeper insights in this type of structures and enhance their stability at physiological conditions, different approaches were followed.
A first strategy consisted in the incorporation of a neutral analogue of protonated cytidine (pseudoisocytidine, psC) occupying specific positions of the motif. The 3H-tautomer of psC, thanks to the extra hydrogen-bond donor, can form neutral base pairs completely isomorphic to hemiprotonated C:C+ pairs. psC was incorporated in different positions of dimeric mini i-motifs and in the telomeric sequence (HT0). The effect of the incorporation of psC depends on its position in the structure, being in most cases destabilizing. Neutral psC:C base pairs stabilize i-motifs at neutral pH, but the stabilization only occurs when psC:C base pairs are located at the ends of intercalated C:C+ stacks. Structural and stability data on the incorporation of pseudocytidine in i-motifs suggest that positively charged base pairs in the core of the structure are necessary to stabilize this non-canonical DNA structure.
A second approach focused on exploring the compatibility of i-motif structures with other reported minor groove tetrads. The effect of different minor groove tetrads in i-motifs was studied in the context of short linear and cyclic oligonucleotides, affording dimeric mini i-motifs, but also in longer sequences that may form monomeric mini i-motif structures. The results show that the mini i-motif is compatible with different type of minor groove tetrads and a stability ranking could be established: G:C:G:T ≥ G:C:G:C >> G:T:G:T, exhibiting monomeric structures enhanced stability. Interestingly, a consensus sequence was outlined based on the results obtained for the set of mini i-motif-forming sequences. The mapping of this sequence throughout the human genome by bioinformatics analysis revealed a statistical prevalence. The distribution found for these sequences is not random, being much more frequent in regulatory regions
Finally, a fluorescent cytidine analogue (1,3-diaza-2-oxophenoxazine, tCo), capable to hybridize as a cytosine and maintaining the ability to form Watson-Crick as well as hemiprotonated base pairs, was tested as an internal probe for the characterization of local environments within i-motif structures. NMR spectroscopy indicated both types of hybridization (tCo:C+ and G:tCo) are compatible with the mini i-motif structure at neutral pH. Interestingly, the fluorescence signal of tCo suffers a sever quenching when forming an hemiprotonated base pair, compared to the very little quenching that shows upon WC hybridization. Hence, tCo was successfully used as fluorescent probe for monitoring conformational transitions between different species of tCo-containing sequences. Moreover, when replacing a cytosine residue involved in a C:C+ pair, the favorable stacking between tCo and G:C base pairs from the capping minor groove assemblies provokes enhanced stability of the structure against both pH and temperature. Very remarkably, the visualization of mini i-motif structures in cellular media was accomplished by confocal fluorescence microscopy after the successful transfection of HeLa cells with tCo-containing oligonucleotides.En el marc de les estructures no canòniques dels àcids nucleics i les seves possibles implicacions biològiques, aquesta tesi te com a objectiu principal l’obtenció i caracterització estructural d’estructures i- motif que siguin estables a pH neutre. El punt de partida és l’estructura mini i-motif, un tipus de motiu que presenta una inusual elevada estabilitat front pH i temperatura. Es tracta d’una estructura dimèrica estabilitzada per la formació de dos parells hemiprotonats C:C+ que interaccionen per apilament amb dues tètrades G:T:G:T de solc menor que actuen de tapa de l’estructura. Per a aprofundir en l’estudi d’aquest tipus de motius i augmentar-ne la seva estabilitat a pH fisiològic, diferents aproximacions s’han dut a terme. En la primera aproximació, s’ha explorat la incorporació d’un anàleg neutre de citidina protonada (pseudoisocitidina, psC), capaç de formar parells neutres isomòrfics als parells hemiprotonats C:C+. Els estudis realitzats demostren que l’efecte de la psC en depèn fortament de la posició dins l’estructura. La formació de parells hemiprotonats al centre de l’estructura és fonamental i la formació de parells neutres només és tolerada pels parells terminals, produint-se en aquest cas una certa estabilització. Una segona línia de treball s’ha centrat en explorar la compatibilitat d’estructures i-motif amb altres tètrades de solc menor. S’han estudiat diferents seqüències, lineals i cícliques, que donarien lloc a estructures mini i-motif amb diferents associacions de nucleobases a les tètrades. Els estudis demostren que el mini i-motif és compatible amb diferents tètrades de solc menor i s’ha pogut establir el següent rànquing d’estabilitat G:C:G:T ≥ G:C:G:C >> G:T:G:T. Cal destacar que, la seqüència consens per aquest tipus d’estructures s’ha determinat que és prevalent al genoma humà. Finalment, s’ha incorporat un anàleg de citidina fluorescent (1,3-diaza-2-oxofenoxazina, tCo), substituint citosines en posicions especifiques de l’estructura. Els resultats demostren que tCo actua de forma eficient com a sonda local per a monitoritzar transicions conformacionals i que, en posicions específiques te un efecte força positiu en l’estabilitat tèrmica del motiu. Aquest fet ha permès utilitzat un d’aquests derivats per a visualitzar el plegament de l’estructura en medi cel·lular.
3
Boissieras, Joseph. "Étude des interactions de ligands et d'anticorps avec les i-motifs de l'ADN". Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASF080.
Testo completoAbstract (sommario):
Les i-motifs sont des structures tétramériques d'ADN constituées de paires de bases CH+:C intercalées et qui peuvent se former dans des séquences d'ADN riches en cytosine, notamment dans les conditions légèrement acides (pH≈6,0) où certaines cytosines seront protonées. Bien qu'elles soient connues depuis plus de 30 ans, du fait de leur forte dépendance au pH ces structures ont longuement été considérées comme uniquement présentes in vitro. Plus récemment, en 2018, un anticorps iMab a été développé pour cibler les i-motifs et les études ont suggéré leur présence au niveau cellulaire. De nombreuses séquences pouvant former des i-motifs ont été identifiées dans des zones actives du génome, au niveau de télomères ou de promoteurs d'oncogènes, suggérant alors de potentiels rôles biologiques de cette structure. Afin de déterminer ces effets, des outils complémentaires à l'anticorps doivent être développés afin de pouvoir contrôler la formation et la stabilité du i-motif. Ces composés chimiques, capables de stabiliser la structure et ainsi de contrôler sa formation, sont appelés ligands. De nombreux composés ont été décrits au fil des années mais aucun composé n'a aujourd'hui été unanimement admis comme ligand de i-motif de l'ADN. Cette absence de ligand de référence s'explique notamment par les méthodes utilisées jusqu'à présent pour observer les interactions des molécules avec la structure du i-motif. En effet, les techniques employées ont été héritées des études d'autres structures d'ADN et de nombreux biais introduits par celles-ci ont été identifiés, remettant en question les effets précédemment observés. Afin d'éclaircir le sujet et de conclure sur les différents effets de composés, nous avons alors proposé une méthode d'étude spécifique aux i-motifs permettant d'évaluer les effets de ligands sur la structure. Pour cela, une méthode dite de titration potentiométrique, basée sur des études de dichroïsme circulaire à différents pH à température constante, a été développée et validée sur le i-motif. Cette technique permet d'observer sans marquage de l'ADN l'état de ce dernier à différents pH, et ainsi de détecter une stabilisation causée par un ligand. Cette méthode a ensuite été couplée à des études thermiques et les deux ont alors été utilisées pour tester différents composés issus de la littérature et observer leurs effets sur la stabilité du i-motif vis-à-vis du pH. Nos résultats montrent que parmi tous les composés testés, aucune des petites molécules testées n'est capable de stabiliser un i-motif natif. Si trois composés (TMPyP4, BRACO-19 et Mitoxantrone) ont montré un effet déstabilisant sur la structure, seul le complexe [Ru(phen)2dppz]2+ a montré une certaine capacité de stabilisation. Néanmoins, cette stabilisation n'a été observée que sur une séquence spécifique à longues boucles, suggérant que cette interaction ne se fait que par des interactions avec des boucles d'ADN. Les effets des autres composés ont également été étudiées sur ces boucles, suggérant que les effets précédemment observés dans la littérature ne résultent que d'interactions à longues boucles, non spécifiques au i-motif. Dans la seconde partie, la spécificité de l'anticorps iMab a également été testée et les résultats démontrent que cet anticorps cible des séquences d'ADN riches en cytosines et non spécifiquement le i-motif. D'autres résultats indiquent même que cet anticorps est capable de déplier le i-motif suggérant là encore que cet anticorps se lie aux séquences C-riches dépliées. Dans l'ensemble, les résultats présentés dans cette thèse ne montrent qu'aucun des composés testés n'est capable de stabiliser le i-motif en interagissant directement avec le i-motif, mettant en lumière les difficultés de cibler la structure. De plus, les résultats concernant l'anticorps remettent en question l'interprétation des foyers nucléaires observés dans d'autres études et qui représentent aujourd'hui les seules observations de i-motifs natifs au niveau cellulaireI-Motifs are tetrameric DNA structures constituted by mutually intercalated CH+:C base pairs that can form in cytosine-rich DNA sequences under slightly acidic conditions (pH ≈ 6.0) where some of cytosines are protonated. They have been known for over thirty years, but due to their strong pH dependence, these structures were long considered to exist only in vitro. Quite recently, in 2018, studies renewed interest in the i-motif suggesting its presence at the cellular level, especially due to the development of the iMab antibody, raised against i-motifs. Numerous sequences capable of forming i-motifs have been identified in active regions of the genome, such as at telomeres or oncogene promoters, suggesting potentially important biological roles for this structure. To determine these effects, tools complementary to antibodies need to be developed to control i-motif formation and stability. These chemical compounds capable of stabilizing the structure and thus controlling its formation are called ligands. Many compounds have been described over the years, but none has yet been unanimously accepted as a ligand for DNA motifs. This absence of a reference ligand is partly explained by the methods used so far to observe small-molecule interactions with the i-motif structure. Indeed, the techniques employed were inherited from studies of other DNA structures, and many biases introduced by them have been identified, calling previous observations into question. To clarify the subject and conclude on the various effects of compounds, we proposed a specific method for studying i-motifs that allows the evaluation of ligands' effects on these structures. Toward this end, a potentiometric titration method, based on circular dichroism studies at different pH, was developed and validated for the i-motif. This technique allows the observation of DNA conformation without labelling at different pH, thereby detecting stabilization caused by a ligand by measuring the transition pH between folded and unfolded DNA, in isothermal conditions. This method was then coupled with thermal studies, and both were used to test different compounds previously described in the literature and observe their effects on the i-motif's stability in relation to pH. The results show that among all the tested compounds, none were capable of stabilizing native i-motifs. While three compounds (TMPyP4, BRACO-19, and Mitoxantrone) did indeed show a destabilizing effect on the structure, only the complex [Ru(phen)2dppz]2+ demonstrated some stabilizing capacity. However, this stabilization was only observed with a specific sequence with long loops, suggesting that this interaction occurs through interactions with DNA loops. The effects of other compounds on these loops were also studied, suggesting that the effects previously observed in the literature resulted from secondary, non-specific interactions with the i-motif loops. In the second part of this thesis, the selectivity of the iMab antibody was also assessed, and the results show that this antibody targets cytosine-rich DNA sequences rather than the i-motif specifically. Other results even indicate that this antibody can unfold the i-motif, further suggesting that it binds to unfolded C-rich sequences rather than to i-motifs. Overall, the results presented in this study show that none of the tested compounds could stabilize the i-motif by directly interacting with it, highlighting the difficulties of targeting this DNA structure. Additionally, the results concerning the iMab antibody call into question the interpretation of nuclear foci observed in other studies, which currently represent the only evidence of native i-motifs at the cellular level
4
Sharma, Amit. "The In Vitro Interactions Between Tubulin and HIV-1 Rev Require Rev’s Multimerization and Arginine-Rich Motifs". Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1261408567.
Testo completo
5
Collin, Delphine. "Etudes par methodes spectroscopiques de complexes d'oligonucleotides (motifs-i et interaction boucle-boucle) (doctorat : pharmacochimie)". Paris 11, 1999. http://www.theses.fr/1999PA114835.
Testo completo
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Salisbury, Richard L. Jr. "TCDD represses 3'IghRR activation through an AhR-dependent shift in the NF-κB/Rel protein complexes binding to κB motifs within the hs1,2 and hs4 enhancers". Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1401136335.
Testo completo
7
Rais, Nabila. "Représentation de la pensée politique italienne à la croisée du dix-neuvième et vingtième siècle : Lire "I Viceré" de De Roberto et "I vecchi e i giovani" de Pirandello à la lumière du "Prince" de Machiavel". Grenoble 3, 2007. http://www.theses.fr/2007GRE39012.
Testo completoAbstract (sommario):
Cette thèse a pour thème la représentation de la pensée politique italienne à travers la lecture de deux romans situés à la croisée du 19e et 20e siècle. L'objectif de notre recherche est de lire ces deux romans historiques à la lumière d'une pensée politique révolutionnaire celle de Nicolas Machiavel. Après avoir tenté de cerner les particularités du secrétaire florentin, exposé ses idées révolutionnaires et la spécificité de sa pensée, cette étude se poursuit avec un double objectif. Le premier est l'élaboration d'une approche analytique des deux romans : "I Viceré" de Federico De Roberto et "I vecchi e i giovani" de Luigi Pirandello, de même qu'un essai critique, basé sur la consultation de la spécificité et de la tendance narrative de chaque auteur, pour enfin venir à l'étude approfondie des différentes galeries des personnages. En effet, cette thèse propose une étude des personnages qui nous renvoie sans cesse aux sentences de Machiavel et souligne la présence irrévocable de l'esprit de ce dernier dans les deux romans respectifs. L'étude se précise par son aspect comparatif, l'objectif principal étant d'établir une correspondance entre d'une part, ces deux romans du 19e et 20e siècle et d'autre part, les préceptes politiques de Machiavel, principalement contenu dans son opuscule "Le Prince". Cette seconde démarche précise l'authenticité et la véracité de la théorie de Machiavel en corrélation avec une certaine réalité politique italienne qui malgré une constante évolution, reste soumise aux mêmes et éternelles lois du champ politique tel que l'aperçoit MachiavelThis thesis has for subject the representation of the Italian political through the reading of two novels situated between the 19th and 20th century. The Objective of our research is to read these historical novels in the light of a revolutionary political thought that of Nicola Machiavelli. Having tried to encircle the characteristics of the Florentine secretary, and so explain its revolutionary ideas and the specificity of its thought, this study continues with a double objective. The first one is the elaboration of an analytical approach of both novels : "I Viceré" Federico of De Roberto and "I vecchi e I giovani" o Luigi Pirandello, as well as a critical essay based on the consultation of the specificity and the narrative tendency of every author, to come finally to the detailed study of the various galleries of characters of both respective novels. Indeed, this thesis proposes a study of the characters which always sends us back to Macchiavelli's judgments and underlines the irrevocable presence of the spirit of this last one. The study becomes clearer by its comparative aspect, the main objective being to establish a correspondence between on one hand these two novels of the 19th and 20th century and on the other hand Machiavelli's political rules, mainly contained in his opuscule "The Prince". This second step clarifies the authenticity and the truthfulness of Machiavelli's theory in correlation with a certain Italian political reality which in spite of a constant evolution, remains subjected to the same and the eternal laws of the political arena such as Machiavelli perceives it
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Sanchez, David Raul Yusef. "Identification of the viral RNA ligands and host protein partners of the Rig-I Like Receptors in an active infection by viruses of positive and negative polarity". Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC262.
Testo completoAbstract (sommario):
Les infections virales peuvent avoir des conséquences dévastatrices pour l'hôte et doivent donc être contrôlés rapidement et efficacement par l'immunité innée antivirale. Les récepteurs de type Rig-I-like (RLR: Rig-I, MDA5 et LGP2) sont en première ligne de la course de l'évolution entre les virus et le système immunitaire de l'hôte. Ils jouent un rôle majeur dans la détection des infections par les virus à ARN pour initier et moduler l'immunité antivirale. Lors de la liaison de l'ARN, les RLR déclenchent une cascade de signalisation en aval résultant dans l'expression des interférons de type I, de cytokines pro-inflammatoires et d'un ensemble diversifié de gènes antiviraux. Une décennie après leur découverte, la cascade de signalisation impliquée dans la réponse RLR est bien connue, cependant, les mécanismes moléculaires qui conduisent à leur activation ont encore besoin d'être éclaircis. En effet, à l'intérieur d'une cellule infectée, les RLR interagissent avec des ARNs viraux, mais aussi avec des partenaires protéiques cellulaires. La plupart d'entre eux sont encore méconnus. Ainsi des stratégies novatrices sont nécessaires pour identifier les réseaux spatio-temporels d'interactions moléculaires des RLR à l'intérieur des cellules infectées. Afin d'éclaircir la nature des agonistes et des partenaires protéiques des RLR lors d'une infection virale, nous avons généré un ensemble de lignées cellulaires stables exprimant Rig-I, MDA5 et LGP2 marqués. Des approches biochimiques modernes basées sur la purification par chromatographie d'affinité des RLR suivie du séquençage à haut débit des ARNs co-purifiés, et l'analyse par spectrométrie de masse des complexes protéiques co-précipités, ont été utilisées. Comme une preuve de concept, un virus à ARN de polarité négative (virus de la rougeole, MV) et un virus de polarité positive (virus du chikungunya, CHIKV) ont été choisis. Nous avons obtenu une liste exhaustive d'interactions spécifiques virus-hôte des RLRs. Les analyses de séquençage ont révélé que des régions distinctes des génomes de MV et CHIKV sont spécifiquement reconnues. Nos résultats suggèrent que lors de l'infection MV, Rig-I reconnaît les génomes défectifs lorsque la souche virale utilisée en produit. Par contre, MDA5 et LGP2 s'associent spécifiquement avec des ARN provenant de la région codant le gène de la nucléoprotéine. Lors de l'infection CHIKV, seulement Rig-I s'associe spécifiquement à la région 3 'du génome viral. Par notre approche protéomique, nous avons établi trois listes abondantes de protéines cellulaires interagissant directement ou indirectement avec chacun des trois RLRs. Ces interactions protéine-protéine sont hautement spécifiques à la fois des RLR et des conditions. En outre plusieurs partenaires des RLR décrits précédemment ont été retrouvés dans nos listes de protéines. À notre connaissance, cette étude fournit la première visualisation simultanée des agonistes ARN et des partenaires protéiques des trois RLRs dans des cellules vivantes et en présence d'infection par différents virus à ARNVirus infections can have deVastating consequences for the host and must therefore be controlled rapidly and effectively by antiviral innate immunity. The Rig-I-like receptors (RLRs: Rig-I, MDA5 and LGP2) are at the frontline of the evolutionary race between viruses and the host immune system. They play a major role in sensing RNA virus infection to initiate and modulate antiviral immunity. Upon RNA binding, RLRs trigger a downstream signalling cascade resulting in the expression of type-I interferons, proinflammatory cytokines and a diverse set of antiviral genes. One decade after RLRs discovery, much is known on the signalling cascade involved in their response, however molecular mechanisms that lead to RLRs activation still need further elucidation. Indeed, inside an infected tell RLRs interact with particular signatures of viral RNA but also with cellular protein partners, most of them being still unknown. Thus, innovative strategies are needed to obtain spatiotemporal networks of macromolecular interactions involving RLRs inside infected tells. In order to shed light on RNA and protein partners of RLRs in physiological conditions during an active viral infection, we generated a set of stable tell fines expressing tagged Rig-I, MDA5 and LGP2 proteins. Modern biochemical approaches based on affinity purification of tagged proteins, next-generation sequencing (NGS) of RNA molecules and mass spectrometry analysis (LC-MS/MS) of protein complexes were applied. As a proof of principle one negative-sense (measles virus, MV) and one positive-sense (chikungunya virus, CHIKV) viruses were chosen. We obtained an extensive list of specific virus-host interactions between RLRs and both protein and RNA molecules. NGS analysis fi revealed that distinct regions of the MV and CHIKV genomes were specifically recognized in an RLR-dependent manner. Our findings suggests that during MV infection, Rig-I recognizes defective interfering genomes only if the viral strain produces them, whereas MDA5 and LGP2 specifically associate with RNA species originating from the MV nucleoprotein coding region. During CHIKV infection, only Rig-I was found to bind specifically the 3' untranslated region of the viral genome. Using our proteomic approach we established three prosperous lists of cellular proteins interacting either directly or indirectly with each of the three RLRs. These protein-protein interactions were highly specific because they were RLR-specific and conditions-dependent. Additionally, several previously described specific RLR partners were present in our protein lists. To our knowledge this study provides the first simultaneous visualisation of specific RNA and protein partners for Rig-I, MDA5 and LGP2 in living tells in the presence of different RNA viruses
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D'Amours, Benoît. "Retourner la bêche : les fonctions de l'autobiographie dans l'œuvre de Stanley Cavell". Doctoral thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/69493.
Testo completoAbstract (sommario):
Mon objectif ici sera de montrer que Cavell fait de l’autobiographie un exercice d’investigation philosophique. Afin d’atteindre ce but, j’emprunte une approche chronologique. Analysant une par une ses publications les plus importantes, je démontre que l’autobiographie remplit cinq fonctions distinctes dans son œuvre à savoir, une fonction descriptive, une fonction anthropologique, une fonction révisionniste, une fonction morale et une fonction perfectionniste. Ensuite, j’analyse le rapport entre le perfectionnisme moral et le récit autobiographie de Cavell intitulé Si j’avais su. Ma thèse trouve son originalité dans le fait que les commentateurs accordent généralement une faible attention au rôle de l’autobiographie dans l’œuvre de ce penseur. D’ailleurs, ce n’est que tardivement que celui-ci indique que l’autobiographie a toujours joué un rôle important dans ses écrits. Mon intention était donc de relire l’œuvre de Cavell afin de mettre en évidence l’importance de l’autobiographie dans sa pensée.
10
Bergmann, Tobias [Verfasser]. "Determination of quantitative peptide-binding motifs of four common equine MHC class I alleles, and identification of an equine herpesvirus type 1-derived cytotoxic T lymphocyte epitope / Tobias Bergmann". Berlin : Freie Universität Berlin, 2017. http://d-nb.info/1126505285/34.
Testo completo
11
Guibbert, Sylvie. "Les representations d'isabelle la catholique dans l'espagne du xxeme siecle". Montpellier 3, 1991. http://www.theses.fr/1991MON30029.
Testo completoAbstract (sommario):
Isabelle la catholique est l'un des personnages les plus celebres de l'histoire d7espagne. Ses representations sont nombreuses au xxe siecle dans les media qui touchent le public le plus large l'ecole et le cinema. L'etude des manuels scolaires montre une grande stabilite dans les representations bien que les auteurs utilisent des formes variees pour decrire la vie de la reine. Cependant, ce portrait lisse et parfois naif n'est pas denue de preoccupations morales et politiques. Le cinema presente une image aussi parfaite de la reine, mais les variations remporelles sont beaucoup plus senseibles. Ces representations s'affrontent et se completent. C'est de cette combinaison harmonieuse ou conflictuelle-catalysee par d7autres images vehiculees par des chansons ou des recits populaires. Que naissent les personnages de la mythologie nationale dans l'imaginaire d'un peuple. L'etude du cas d'isabelle la catholique est revelatrice : son personnage est d'une plasticite et d'une richesse extraordinaire. Sa foi, son nationalisme, son intransigeance mais aussi son caractere, sa liberte et son emancipation ont ete maintes fois mis en avant si bien qu'elle a ete un symbole pour des feministes du debut du siecle comme le regime franquisteIsabel the catholic is one of the most famous characters of the spanish history. In the xxth century, her representations are numerous in the mass media which have an effect on the largest audience : school and cinema. When studying school books a great steadiness can be noticed in her representations although writers use various formes to depict the queen's life. However, this smooth and sometimes unaffected portrait is not deprived of moral and political inducement. The cinema shows such a perfect picture of the queen, but the temporal variations are much more perceptible. These representations face each other or complete each other. From this harmonious or incompatible union - some pictures conveyed by songs or popular tales act a catalyst - the characters of the national mythology are born in the popular imagination. The investigation in the particular case of isabel the catholic is very revealing. Her character is of an extraordinary plasticy and richness. Her faith, her nationalism, her intransigence, her freedom and her emancipation have been many a time put forward, so that she has been a symbol for the feminists in the beginning of the century as well as during the government of general franco
12
Adams, Jeramie J. "New classes of bridging and chelating ligand motifs emphasizing: ruthenium(II) molecular squares, ruthenium(II) diphosphino carborane complexes, and acceptor PCP complexes of platinum(II), iridium(I/III), and ruthenium(II)". Laramie, Wyo. : University of Wyoming, 2008. http://proquest.umi.com/pqdweb?did=1663059861&sid=2&Fmt=2&clientId=18949&RQT=309&VName=PQD.
Testo completo
13
Jolad, Vandana V. "Structure and dynamics of a DNA i-motif". Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414277.
Testo completo
14
Fink, Wolfgang, Alexander J. W. Brooks, Mark A. Tarbell e James M. Dohm. "Tier-scalable reconnaissance: the future in autonomous C4ISR systems has arrived: progress towards an outdoor testbed". SPIE-INT SOC OPTICAL ENGINEERING, 2017. http://hdl.handle.net/10150/626010.
Testo completoAbstract (sommario):
Autonomous reconnaissance missions are called for in extreme environments, as well as in potentially hazardous (e.g., the theatre, disaster-stricken areas, etc.) or inaccessible operational areas (e.g., planetary surfaces, space). Such future missions will require increasing degrees of operational autonomy, especially when following up on transient events. Operational autonomy encompasses: (1) Automatic characterization of operational areas from different vantages (i.e., spaceborne, airborne, surface, subsurface); (2) automatic sensor deployment and data gathering; (3) automatic feature extraction including anomaly detection and region-of-interest identification; (4) automatic target prediction and prioritization; (5) and subsequent automatic (re-) deployment and navigation of robotic agents. This paper reports on progress towards several aspects of autonomous (CISR)-I-4 systems, including: Caltech-patented and NASA award-winning multi-tiered mission paradigm, robotic platform development (air, ground, water-based), robotic behavior motifs as the building blocks for autonomous telecommanding, and autonomous decision making based on a Caltech-patented framework comprising sensor-data-fusion (feature-vectors), anomaly detection (clustering and principal component analysis), and target prioritization (hypothetical probing).
15
Kool, Carine. "La broderie dans l’oeuvre de Tracey Emin : piquer, percer, fixer, Jouissance filaire et art de l’intime". Thesis, Rennes 2, 2018. http://www.theses.fr/2018REN20071.
Testo completoAbstract (sommario):
Cette recherche propose de rendre compte de l'usage de la broderie en art contemporain dans les oeuvres deTracey Emin, première artiste à avoir exposé le récit des trente-deux premières années de sa vie dans une tentebrodée intitulée Everyone I Have Ever Slept With 1963-1995. Une analyse de réception de type sémio-anthropologiquede cette oeuvre monumentale met en évidence, dřune part, que la broderie est une écriture contemporaine incluant un geste manuel, une loi textile et une jouissance filaire et, d'autre part, que son effet de présence et son pouvoir narratif en font un art de l'intime.En tant qu'écriture filaire, la broderie est singulière. Ecriture universelle, elle est première chez les peuples sans écriture, elle est sésame social en tant que sampler, elle est historiographique par son potentiel narratif, son statut d'objet de prestige ou de mémorandum. Elle est encore écriture monumentale dans la Tapisserie de Bayeux, autre broderie phénoménale, simultanément manuscrit, témoignage documentaire et oeuvre d'art plastique reconnue.La broderie se fait art de l'intime dans d'autres oeuvres de Tracey Emin, telles ses couvertures, dont la première, Hotel International, incarne le curriculum vitae de l'artiste. Mais l'intime peut s'envisager de plusieurs manières. Or, comme en Angleterre la broderie a été considérée comme un art national dès le VIIe siècle, elle se conçoit aussi comme art de l'intime dans le rapport que les oeuvres brodées d'Emin entretiennent avec celles du passé. Si l'intime est un lien puissant entre le public et l'artiste, en brodant sa vie et son intimité, Tracey Emin a transformé le « personnel est politique » des années 1970 en universelThis research proposes to account for the use of contemporary art embroidery in the works of Tracey Emin, the first artist to have exhibited the story of the first thirty-two years of her life in an embroidered tent entitled Everyone I Have Ever Slept With 1963-1995. A semio-anthropological reception analysis of this monumental work highlights, on the one hand, that embroidery is a contemporary writing that includes a manual gesture, a textile law and a thread jouissance and, on the other hand, that its effect of presence and its narrative power make it an art of intimacy.As thread writing, embroidery is a singular one. As universal writing, it is first among people without written language, it is a social open sesame as sampler, it is historiographical thanks to its narrative power, its status as an object of prestige or as a memorandum. It is also a monumental writing in the Bayeux Tapestry, another phenomenal embroidery, simultaneously manuscript, documentary testimony and recognized visual work of art. Embroidery is also an art of intimacy in other works of Tracey Emin, such as her blankets, whose first, Hotel International, embodies the curriculum vitae of the artist. However, intimacy can be considered in many ways.And, as in England embroidery was regarded as a national art from the seventh century onwards, it can thus be conceived as an art of intimacy in the relationship that the embroidered works of Emin maintain with those of the past. If intimacy is a powerful bond between the public and the artist, by embroidering her life and her intimacy, Tracey Emin has transformed the "personal is political" of the 1970s into a universal one
16
Poch, i. Rodrigo Chantal. "Cineastes d’un món caigut: una interpretació de l’obra d’Andrei Tarkovski, Werner Herzog i Terrence Malick". Doctoral thesis, Universitat Pompeu Fabra, 2020. http://hdl.handle.net/10803/670314.
Testo completoAbstract (sommario):
Aquesta tesi és una interpretació de l’obra dels cineastes Andrei Tarkovski, Terrence Malick i Werner Herzog des de la idea de la pèrdua d’un vincle entre home i món i la possibilitat de restaurar-lo a través del cinema.This thesis is an interpretation of the work by filmmakers Andrei Tarkovski, Terrence Malick and Werner Herzog from the idea of the loss of a link between man and world and the possibility of restoring it through cinema.
17
Vegué, Marina. "A study of cortical network models with realistic connectivity". Doctoral thesis, Universitat Politècnica de Catalunya, 2018. http://hdl.handle.net/10803/481984.
Testo completoAbstract (sommario):
Structure is fundamental in shaping the types of computations that neuronal circuits can perform. Explaining the laws that determine the connectivity properties of brain networks and their implications in neuronal dynamics is therefore an important step in the understanding of how brains operate. The local circuits of cortex, which are considered to carry out the basic and essential computations for brain functioning, exhibit a highly stereotyped and organized architecture, which is, in very general terms, conserved across different species, brain areas and individuals. An appropriate way to mathematically represent this family of networks is by means of models defined by a set of connectivity laws that include a certain degree of randomness. These laws reflect the common structural scaffold, whereas the randomness should be interpreted as the variability across the different networks in the ensemble. There is growing experimental evidence that the local circuits of cerebral cortex are far from the simplest random model, according to which connections appear independently with a fixed probability. This evidence is based on a set of observed features that have been collectively called the "nonrandomness" of the cortical circuitry. In this thesis we have explored to what extent several alternative architectures (clustered networks, networks with distance-dependent connectivity and networks that exhibit a given in/out-degree distribution) could be compatible with the reported nonrandom features. We showed that all these structural models can explain the experimental observations, which implies that these nonrandom properties do not provide much information about the underlying organization. This is mainly due to the fact that real data are collected from sparse neuronal samples due to experimental limitations. We sought a local measure that can nevertheless help to distinguish between different alternatives, and we found it in the "sample degree correlation" (SDC), or the correlation coefficient between in- and out-degrees in small groups of neurons. The analysis of the SDC in real data suggests that cortical microcircuits are heterogeneous in structure and possibly shaped through a mixture of distance-dependent and non-symmetrical organizational principles. We finally explored some of the dynamical consequences of imposing a heterogeneous structure in models of neuronal activity. This heterogeneity appears through an arbitrary joint in/out-degree distribution in the entire network. By means of both mean-field approximations and spectral analysis, we demonstrate that broad and positively correlated degree distributions can have an important effect on neuronal dynamics, which suggests that this particular type of structural heterogeneity might allow for richer network computations as compared to standard random models.L'estructura té un paper fonamental a l'hora de determinar els tipus d'operacions que els circuits neuronals poden dur a terme. Entendre les lleis que defineixen la connectivitat de les xarxes del cervell i les seves implicacions en la dinàmica neuronal és, per tant, un pas important en la comprensió del funcionament d'aquestes xarxes. Els circuits locals del còrtex, que es creu suporten les computacions essencials i bàsiques de la funció cerebral, estan organitzats de manera altament ordenada i estereotipada, i aquesta arquitectura, en termes molt generals, s'ha conservat al llarg de les diferents espècies, de les diverses àrees cerebrals i dels individus. Una bona manera de representar matemàticament aquesta família de xarxes és mitjançant models definits per una sèrie de lleis de connectivitat que inclouen un cert grau d'aleatorietat. Les lleis reflecteixen el patró estructural comú, mentre que l'aleatorietat ha de ser interpretada com la variabilitat quan es comparen diferents xarxes del conjunt. Cada vegada hi ha més evidència experimental que els circuits locals del còrtex estan lluny del model aleatori més simple, segons el qual les connexions apareixen de manera independent amb una probabilitat fixada. Aquesta troballa es fonamenta en un conjunt d'observacions a les quals ens referim col·lectivament com la ?no aleatorietat? dels circuits corticals. En aquesta tesi hem explorat fins a quin punt diverses arquitectures alternatives (xarxes amb agrupació, xarxes amb connectivitat dependent de la distància i xarxes definides a través d'una certa distribució de graus d'entrada i de sortida) podrien ser compatibles amb les propietats de no aleatorietat. Hem mostrat que tots els models estructurals alternatius que havíem proposat poden explicar les observacions esmentades, per tant aquestes propietats no aporten gaire informació sobre el tipus d'organització subjacent. Això es deu principalment al fet que les dades reals provenen d'anàlisis molt restringides, en les quals l'estructura s'estudia a partir de mostres locals formades per poques neurones. Vam buscar un estadístic local que permetés, malgrat aquestes dificultats, distingir entre les diverses estructures alternatives, i l'hem trobat en el coeficient de correlació entre els graus d'entrada i de sortida en mostres petites, que hem anomenat "sample degree correlation" (SDC) en anglès. L'anàlisi d'aquesta mesura en dades reals suggereix que els microcircuits corticals tenen una configuració heterogènia -en el sentit que semblen diferir dels models simples proposats- i estan modelats possiblement per factors dependents de la distància física entre neurones però també per principis addicionals que actuen de manera no simètrica. Finalment, hem estudiat algunes de les conseqüències dinàmiques d'imposar una estructura heterogènia en models d'activitat neuronal. Aquesta heterogeneïtat apareix en els nostres models a través de la distribució conjunta de graus d'entrada i de sortida a la xarxa completa. Fent ús d'aproximacions de camp mitjà i de l'anàlisi espectral, hem mostrat que les distribucions de grau amb elevada variància i correlació positiva poden tenir un efecte rellevant en la dinàmica neuronal, fet que suggereix que aquest tipus d'heterogeneïtat estructural podria facilitar uns modes de computació més rics en comparació dels models aleatoris estàndard.
18
Merlo, Alessandra. "À côté des objets. Leur présence et visibilité a l’écran". Thesis, Paris 3, 2010. http://www.theses.fr/2010PA030154.
Testo completoAbstract (sommario):
Le thème de cette thèse est le questionnement autour des objets cinématographiques. Par le terme « objet » on entend ici toute chose manipulable, tout outil ou objet décoratif qui se situe dans la scène filmique et à l’intérieur du cadre. On a choisi le terme « objet » - au lieu de « chose » - pour son caractère d’opposition étymologique et conceptuelle au « sujet ». L’objet en question – au-delà de las séparations entre l’accessoire et le décoratif, entre fonctionnel et contextuel – est donc présent, mais sa visibilité varie selon le cadrage, la mise au point, les relations de compositions, la vraisemblance. Mais elle dépend aussi des prédispositions du spectateur. Par conséquent, à partir d’une définition et d’une première étude des ses caractéristiques physiques [de position, de gosseur, de mouvement et de relation], le travail aborde la question de comment, quand et pourquoi l’objet se montre [et le spectateur le perçoit]. D’un point de vue méthodologique, le travail enrichit chaque cas par un exemple analysé et illustré à partir d’un répertoire iconographique. Cependant, au moment d’exposer et développer un système d’objets cinématographiques, l’analyse a été conduite sur un seul film, I pugni in tasca, de Marco Bellocchio [1965] : ce qui nous intéressait ici c’était la possibilité d’arriver à établir – dans le cas particulier – le fonctionnement systématique des objetsThe present thesis examines cinematographic objects. It is here understood by the term “object” anything that is able of being manipulated, each utensil or decorative apparel that is placed in the filmic scene and inside its frame. The decision of using the term “object” - instead of “thing”- was taken because of its conceptual and etymological opposition to the term “subject”. Hence, the object under inquiry –trying to go further than the mere distinctions between accessories and decoration, functional and contextual- is present; its visibility varies depending on the chosen scene, its composition, focalization and veracity. Moreover, its visibility also depends on the spectator’s dispositions. Therefore, departing from a definition and an initial study of its physical characteristics [position, size, movements and relations], this thesis addresses the questions about how, when and why the object is shown [and the spectator perceives and sees it]. From a methodological standpoint, the present thesis enriches each one of its study cases with the analysis of an example, which is illustrated from an iconographic repertoire. Nonetheless, at the moment of presenting and developing a system of cinematographic objects, the analysis focuses itself on a single film: I pugni in tasca, by Marco Bellocchio [1965]. This is done with the aim of establishing –for a particular case- the systemic workings of objects
19
Maza, Quiroga Ricardo José. "Nucleophilic boryl motifs and alpha-borylcarbanions: reactivity and trends". Doctoral thesis, Universitat Rovira i Virgili, 2021. http://hdl.handle.net/10803/673184.
Testo completoAbstract (sommario):
En el Capítol 2, coure(I) catalitza la ciclació borilativa de gamma-alquenil aldehids mitjançant una adició quimio- i regioselectiva de Cu-B sobre C=C, seguida d'una reacció intramolecular d'adició de Cu-C sobre C=O. Els productes s'han format amb diastereoselectivitat i un anàlisi computacional ha identificat els punts claus que determinen la quimio- i diastereoselectivitat observada.
En el capítol 3, s'estudia la reactivitat dels compostos diborats amb diens 1,3 en un context lliure de metalls de transició. Unicament, l'addició de Na2CO3 sobre bis(pinacolat)diboro, en MeOH, permet la 1,4-hidroboració de 1,3-diens no cíclics i cíclics. La influencia electrònica del sustrat garanteix la hidroboración conjugada 1,4 versus la 1,2. Càlculs DFT mostran que la distribució de la càrrega en l'anió alílic intermedi governa la selectivitat en la 1,4-hidroboració, mentres que la configuració trans del diè determina la preferència pel producte alil-borilat E.
En el capítol 4, s'estudia la química dels carbanions alpha-borilats, ja que mostren una gran diversitat i permeten la formació d'enllaços C-C eficients. La deficiència electrònica del centre borilat trisubstituit és responsable de l'estabilizació del carbanió, facilitant la seva formació i modelant la reactivitat. Es descriuen aspectes electrònics de la estructura i tendèncias reactives d'un conjunt ampli d'alpha-boril carbanions. Mitjançant estudis de DFT s'ha determinat un mapa de tendencies sobre la reactivitar nucleòfila dels carbanions alpha-borilats, variant la naturalesa del grup borilo, el número de grups borilo en el carbanió i la naturalesa del catió estabilizant. Aquest mapa de tendencies permet la selecció del sintó apropiat, en funció de la reactivitat objecte d'estudi.egioselectiva de Cu-B sobre C=C, seguida de una reacción intramolecular de adición de Cu-C sobre C=O. Los productos se han formado con diastereoselectividad y un análisis computacional ha identificado los puntos clave que determinan la quimio- y diastereoselectividad observada. En el Capítulo 3, es estudia la reactividad de los compuestos diborados con 1,3-dienos en un contexto libre de metales de transición. La única adición de Na2CO3 sobre bis(pinacolato)diboro, en MeOH, permite la 1,4-hidroboración de 1,3-dienos no cíclicos y cíclicos. La influencia electrónica del sustrato garantiza la hidroboración conjugada 1,4 versus la 1,2. Cálculos DFT muestran que la distribución de la carga en el anión alílico intermedio gobierna la selectividad en la reacción de 1,4-hidroboración, mientras que la configuración trans del dieno determina la preferencia por el producto alil-borilado E. En el capítulo 4, se estudia la química de los carbaniones alpha-borilados, ya que muestran una gran diversidad y permiten la formación de enlaces C-C eficientes. La deficiencia electrónica del centro borilado trisustituido es responsable de la estabilización del carbanión, facilitando su formación y modelando su reactividad. Se describen aspectos electrónicos de la estructura y tendencias reactivas de un conjunto amplio de alpha-boryl carbanions. Mediante estudios de DFT se ha determinado un mapa de tendencias sobre la reactividad nucleófila de los carbaniones alpha-borilados, variando la naturaleza del grupo borilo, el número de grupos borilo en el carbanión y la naturaleza del catión estabilizante. Este mapa de tendencias permite la selección del sintón apropiado, en función de la reactividad objeto de estudio.
In Chapter 2, copper (I) catalyzes the borylative cyclization of gamma-alkenyl aldehydes through chemo- and regioselective addition of Cu-B to C=C and concomitant intramolecular 1,2-addition of Cu-C on the C=O. The products are formed in an exclusive diastereoselective manner and computational analysis identify the key points for the chemo- and diastereoselectivity observed. In Chapter 3, we study the reactivity of diboron reagents with 1,3-dienes in a transition-metal-free context. The sole addition of Na2CO3 to bis(pinacolato)diboron, in MeOH, allows the 1,4-hydroboration of cyclic and noncyclic 1,3- dienes. The electronic influence on the substrate guarantees the conjugated 1,4-hydroboration versus 1,2-diboration. DFTcalculations show that the distribution of charge in the allylic anion intermediate governs the selectivity toward 1,4- hydroboration, while the favored trans configuration in diene reagents determines the preference for the E allyl boronate products. In Chapter 4, we studied the chemistry of alpha-boryl carbanions since they show a remarkable diversity, and enable efficient C-C bond formation. The electron-deficient, trivalent boron center stabilizes the carbanion facilitating its generation and tunning its reactivity. We describe the electronic structure and the reactivity trends of a large dataset of apha-boryl carbanions. We use DFT-parameters for capturing their electronic and steric properties, computational reactivity towards model substrates, and crystallographic analysis within the Cambridge Structural Dataset. This study maps the reactivity space by systematically varying the nature of the boryl moiety, the substituents of the carbanionic carbon, the number of alpha-boryl motifs, and the metal countercation. Furthermore, we can classify the alpha-boryl alkylidene metal precursors into three classes directly related to their reactivity. This trend map aids the selection of the appropriate reactive synthon depending on the sought reactivity.
20
Fenech, Kroke Antonella. "Culture et fonction de l'allégorie dans l'oeuvre de Giorgio Vasari". Paris 1, 2008. http://www.theses.fr/2008PA010557.
Testo completoAbstract (sommario):
Giorgio Vasari est l'un des plus prolifiques créateurs et metteurs en scène de personnifications du XVIe siècle. Toute son oeuvre est marquée par la présence de ces figures: elles sont présentes au premier plan ou dissimulées à la périphérie de la représentation, elles se mêlent aux protagonistes et aux comparses de la storia ou aux éléments des architectures peintes. Ce qui caractérise la production allégorique de Vasari n'est pas tant l'originalité, dont l'artiste a pourtant fait preuve, que l'abondance et la pertinence de sa 'fabrique' de l'allégorie. Cette dernière condense, à elle seule, les composantes les plus significatives de la culture de cette période, l’''ecriture'' de Vasari étant à plusieurs égards un phénomène socioculturel des plus représentatifs. Le monde de ses figures allégoriques parle en fait le même langage que l'univers rhétorique, philosophique, érudit et courtisan à l'intérieur duquel évoluait l'artiste arétin. Par une étude spécifique des personnifications vasariennes, cette recherche se propose d'entreprendre une archéologie cinquecentesca de la figure allégorique avant la normalisation mise en œuvre à la fin du siècle par Cesare Ripa.
21
Mujkanovic, Elma. "Gorgon motifs on Archaic Greek coins". Thesis, Uppsala universitet, Institutionen för arkeologi och antik historia, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-418134.
Testo completoAbstract (sommario):
The Gorgon is a creature described as terrible in ancient literature. It was depicted with glaring eyes, tusks and a hanging tongue and was a part of Greek antiquity from Archaic to Roman Period. The Gorgon motif has frequently been adorned on different materials. The reason as to why such a creature was depicted has been a subject of interest in earlier studies. The Gorgon motif has been elaborately studied in combination with buildings, armours and vases. A gap of knowledge that is still to be filled is a deeper examination of the Gorgon motifs on coins, which is the inspiration for this study in which the main aim is to approach an understanding of what function the Gorgon motif could have had on Archaic Greek coins. The study is based on a collection of 42 Archaic coins from Athens and Neapolis in Macedon. Through Panofsky's theory of iconography the material is analyzed and discussed via a series of sub-questions; ‘Did the Gorgon motifs differ depending on the location?’, ‘What combination of features appear on the coins?’, ‘To what extent was the Gorgon myth linked to the locations that used the motif and what other myths were used on coins during the same period? ’, ‘Is there a link between the use of Gorgon motifs on coins and on other material objects?’ The paper measures the possible explanations of the Gorgon motif with archaeological finds and ancient texts dealing with the Gorgon, many of which point to the fact that the Gorgon’s function generally served a purpose as an apotropaic symbol. Its function as a possible amulet is investigated using previous research that studies the symbolic significance of the Gorgon, as well as tracing its background and examination of the Gorgon myth to find possible connections with other mythical creatures.Gorgonen är en varelse som beskrivs som fruktansvärd i den grekiska antikens litteratur. Den avbildas med stirrande ögon, betar och en hängande tunga. Gorgonen har varit en del av den grekiska antiken sedan dess början och har varit ett populärt motiv på olika material. Det har funnits stort intresse i tidigare studier kring anledningarna till att en sådan varelse valts att avbildas. Motivet har studerats omsorgsfullt när det har smyckat byggnader, rustningar och vaser. En lucka som inte har fyllts än inom ämnet är en djupare undersökning av gorgonmotiven på mynt, vilket även är ämnet för denna studie med syftet att närma sig en förståelse för de funktioner som Gorgonmotiven fyllde på mynt under arkaisk grekisk tid. Studien baseras på ett urval av 42 arkaiska mynt från Aten och Neapolis i Makedonien. Genom Panofskys trestegsmodell analyseras gorgonmotiv som framkommer på mynten och svarar på en rad viktiga underfrågor: Skiljer sig gorgonmotiv åt mellan platser Vilka kombinationer av gorgoner förekommer på mynten? I vilken utsträckning var gorgonmyten kopplad till de platser som använde motivet, vilka andra myter användes på mynten under samma period? Finns det ett samband mellan användningen av gorgonmotiv på mynt och på andra objekt? I uppsatsen bedöms möjliga förklaringar till gorgonmotivet med arkeologiska fynd och antika texter som behandlar gorgonen, varav många pekar mot att gorgonens funktion i allmänhet fyllde ett apotropeiskt syfte. Detta undersöks med hjälp av tidigare forskning av gorgonens symboliska betydelse samt kopplingen med andra mytiska varelser genom att spåra dess bakgrund och granskning av gorgonmyten.
22
Vasudevan, Aditya Vangal. "Deciphering triangular fracture patterns in PMMA : how crack fragments in mixed mode loading". Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS067/document.
Testo completoAbstract (sommario):
Dans cette thèse, j’ai conçu un nouveau test de rupture adapté à l’étude des matériaux fragiles sur une grande gamme de vitesse de fissure. Il a été mis en œuvre sur le PMMA, permettant de caractériser la transition entre un régime de rupture à grande vitesse v>vc=15 mms-1 avec des faciès optiquement plats et un autre régime pour vDuring this PhD thesis, a new fracture test geometry is designed for the accurate measurement of the fracture properties of brittle solids, subsequently applied to study failure in PMMA. At high crack speeds, their fracture surfaces are optically smooth. But below vc = 15 mms-1, a transition to rough surfaces occurs through the formation of puzzling triangular patterns. These patterns lead to significant toughening of the material that reflects through the pinned shape of the crack front as it crosses triangles. In addition, these triangles are found to be decorated by faceted features reminiscent of the crack front fragmentation instability in mode I+III. Assuming a shear-dependent fracture energy Gc(KIII/KI) = GcI[1+ (KIII/KI)2] we theoretically predict a fragmentation threshold (KIII/KI)thc that can be as low as a few percent while earlier models (that assumes = 0) predict a much larger value, inconsistent with various experimental observations. Applied to our experiments, this model allows us to measure exp from the deformation amplitude of the pinned front and the amount of applied shear (KIII/KI)exp from the facet inclination which is found to be compatible with the theoretically predicted threshold (KIII/KI)thc . Using the values (KIII/KI)exp and exp thus determined, one finally predict a drift of the facets from the propagation direction accounting for the triangle angle observed experimentally. To conclude, our study shows that the roughening transition in PMMA is a signature of front fragmentation under mode I+III. As a result, deciphering the triangular patterns at the transition led to significant improvements in the understanding of this instability
23
Campos, Lucie. "Fictions contemporaines et conscience historique : J. M. Coetzee, I. Kertész, W. G. Sebald". Poitiers, 2010. https://acces.bibliotheque-diderot.fr/login?url=https://doi.org/10.15122/isbn.978-2-8124-4250-6.
Testo completoAbstract (sommario):
Les oeuvres de J. M Coetzee, I. Kertész, W. G. Sebald témoignent d'un effort spécifique du littéraire pour répliquer à la violence des évènements qui ont forgé la conscience historique du 20e siècle. A la pression d'un réel historique des évènements inassimilable et destructeur, ces écrivains répondent par un travail d'écriture et de clarification soucieux à la fois de son inscription dans un champ politique et de ses limites philosophiques. .The literary works of J. M Coetzee, I. Kertész and W. G. Sebald confront the violent events that have shaped the historical consciousness of the twentieth century with the specific tools of literature and fiction. In an effort to respond to the pressure of a destructive historical reality that is difficult to assimilate, these writers have sought to clarify their position within a political and philosophical field. .
24
Song, Minho. "Suffering and glory the double motif of the christology of I Peter /". Theological Research Exchange Network (TREN), 1989. http://www.tren.com.
Testo completo
25
Neeb, Megan Ann. "MYC Inhibition Through Small Compound Targeting of the NHE III₁ i-Motif". Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/579322.
Testo completoAbstract (sommario):
Current cancer therapies often fail to eradicate a patient's tumors completely due to complications arising from protein mutations, tumor cell migration, and interference with DNA replication. These issues can be circumvented by inhibiting the oncogenes responsible for tumor growth through targeting of secondary non-helical structures present in the oncogenes' promoters. Through screening of NCI compound libraries we have found two compounds, IMC 30 and IMC 31, that are capable of reducing the expression of the oncogene MYC through interaction with the i-motif structure in its promoter region. These compounds are also capable of inducing cell death in cells that are reliant on MYC overexpression for growth. A third compound, IMC 16, was capable of inducing an increase in MYC expression in addition to inducing apoptosis in MYC dependent cells. This result indicates a possibility that increasing the expression of MYC in MYC dependent tumors may cause a shift in its primary function from cell growth to induction of apoptosis. The compounds IMC 30, IMC 31, and IMC 16 will be subjected to further experimentation with more complicated biological systems in an effort to develop them as cancer therapeutics.
26
Dhakal, Soma. "Mechanical stability evaluation of i-motif and G-quadruplex structures under diverse circumstances". Thesis, Kent State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3618902.
Testo completoAbstract (sommario):
G-quadruplex is the most widely known four-stranded nucleic acid structure which has shown to alter gene regulation both in vitro and in vivo. Under certain conditions, another four-stranded structure, i-motif, is also formed in the strand complementary to the G-quadruplex forming sequence. Recent studies suggest gene regulatory roles for the i-motif structure as well. Although there is substantial understanding on the folding topology of G-quadruplex and i-motif structures, their mechanical stability which determines the interaction with motor proteins, such as DNA/RNA polymerases, are poorly studied. Since DNA exists as a double stranded form in vivo, the investigation of i-motif becomes highly important to fully understand the biological functions of G-quadruplexes. Using laser tweezers based single-molecule study, we investigated the mechanical stability of an i-motif structure in the predominant variant of human ILPR fragment (5'-TGTC4ACAC4TGTC4ACAC4TGT). In addition, we have shown that a partially folded structure composed of only three tandem C-rich repeats coexists with the i-motif. Both structures share similar unfolding forces of 22-26 pN. Discovery of stable structures in less than four C-rich repeats suggested that the structure can serve as an intermediate during the i-motif folding/unfolding pathway. Using chemical footprinting and single-molecule approaches, we show that a dsDNA fragment in ILPR, 5'-(ACAG4TGTG4ACAG4TGTG4ACA), can fold into G-quadruplex or i-motif structure under specific conditions. Surprisingly, under a condition that favors the formation of both G-quadruplex and i-motif, changes in free energy of unfolding provided compelling evidence that only one species is present in each dsDNA. Based on this observation, we propose that G-quadruplex and i-motif are mutually exclusive in human ILPR. Furthermore, we show that these two species have an unfolding force >17 pN. From mechanical perspective, this could justify the regulatory role a DNA tetraplex may play in the expression of human insulin inside cells in which dsDNA is the predominate form.
27
Dhakal, Soma Nath. "Mechanical stability evaluation of i-motif and G-quadruplex structures under diverse circumstances". Kent State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1365083492.
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28
Cui, Yunxi. "Regulation Analysis of DNA G-quadruplex and i-Motif bySingle-Molecule Laser Tweezers". Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1480231076937581.
Testo completo
29
Day, Henry. "Investigating the effect of small molecule ligands and cations on i-motif DNA". Thesis, University of East Anglia, 2015. https://ueaeprints.uea.ac.uk/53444/.
Testo completoAbstract (sommario):
The i-motif is an alternative DNA secondary structure motif formed in sequences rich in cytosine, consisting of four strands, stabilised by hemi-protonated cytosine-cytosine+ base pairs. The motif forms in sequences complimentary to the G-quadruplex however, far less is known about the i-motif and most research to date has focused on its application in nanotechnology. Despite this, recent progress in the field has indicated that the i-motif may be a possible therapeutic target in certain cases. In order to study this structure in more detail a chemical tool box of ligands and conditions is needed, which can be used to probe its potential biological function. Herein the effect of small molecule ligands and cations has been investigated. A previously identified i-motif binding compound BisA has been characterised in detail with a range of biophysical experiments, showing that it does bind to the i-motif but causes the DNA to condense. A high throughput screen has been carried out finding a number of potential new i-motif binding ligands and, through a range of experiments, two lead compounds mitoxantrone and tilorone have been identified with micromolar affinities from which novel i-motif binding analogues and structure activity relationships can be developed. Finally, the effect of cations on the i-motif has been studied, including a wider selection from across the periodic table than has previously been investigated. This has shown that at neutral pH, silver (I) ions have the ability to induce i-motif formation and that this is reversible in the presence of cysteine. While at acidic pH, copper (II) ions have the ability to induce hairpin formation reversibly in the presence of EDTA. This could enable the formation of multiple structures from the same oligonucleotide sequence in response to different conditions. The combination of these results should provide useful tools to further study the i-motif structure.
30
Butcher, David S. "Thermodynamics and Kinetics of Ligand Photodissociation in Heme Proteins and Formation of DNA i-Motif". FIU Digital Commons, 2017. http://digitalcommons.fiu.edu/etd/3259.
Testo completoAbstract (sommario):
Heme proteins carry out a diverse array of functions in vivo while maintaining a well-conserved 3-over-3 α-helical structure. Human hemoglobin (Hb) is well-known for its oxygen transport function. Type 1 non-symbiotic hemoglobins (nsHb1) in plants and bacterial flavohemoglobins (fHb) from a variety of bacterial species have been predicted to carry out a nitric oxide dioxygenase function. In nsHb1 and fHb this function has been linked to protection from nitrosative stress. Herein, I combine photoacoustic calorimetry (PAC), transient absorption spectroscopy (TA), and classical molecular dynamics (cMD) simulations to characterize molecular mechanism of diatomic ligand interactions with a hexa-coordinate globin from plant (rice hemoglobin), bacterial flavohemoglobins and human hemoglobin.
In rice type 1 non-symbiotic hemoglobin (rHb1), the dynamics and energetics of structural changes associated with ligand photodissociation is strongly impacted by solvent and temperature, namely CO escape from the protein matrix is slower at pH = 6.0 compare to neutral pH (ns) due to the CD loop reorganization which forms a pathway for ligand escape. In human hemoglobin, exogenous allosteric effectors modulate energetics of conformational changes associated with the CO and O2 escape although the effectors impact on rate constants for ligand association is small. The conformational dynamics associated with ligand photorelease from fHbs from Cupriavidus necator (FHP) and Staphylococcus aureus (HMPSa) are strongly modulated by the presence of azole drugs indicating that drug association modulates structural properties of the heme binding pocket.
In addition, we carried out a study of the formation of the DNA intercalated motif (i-motif). The formation of the structure is strongly favored at acidic pH; therefore, PAC was combined with a 2-nitrobenzaldehyde pH-jump to probe formation of the i-motif on fast timescales. i-Motif folding is two-step process with the initial protonation of cytosine residues being endothermic with ΔHfast=8.5 ± 7.0 kcal mol-1 and ΔVfast=10.4 ± 1.6 mL mol-1 and subsequent nucleation/i-motif folding (τ = 140 ns) with ΔHslow=-51.5 ± 4.8 kcal mol-1 and ΔVslow=-6.6 ± 0.9 mL mol-1. The above results indicate that PAC can be employed to study diverse biochemical reactions such as DNA folding, drug binding and ligand photorelease from proteins.
31
Jacobs, Mitchell. "Studies and synthesis of nucleic acid mimics towards template directed synthesis and i-motif formation". Thesis, University of Manchester, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.549091.
Testo completo
32
Zeitoun, Franck. "Rêves et liberté chez les écrivains de langue anglaise des XIVe et XVe siècles : étude de "Troilus and Criseyde", du "Nun's Priest's Tale" et du "Kingis Quair"". Paris 4, 2001. http://www.theses.fr/2001PA040165.
Testo completoAbstract (sommario):
Cette thèse étudie les liens entre le thème de la liberté et le motif onirique dans trois œuvres de la littérature de langue anglaise du moyen-âge tardif : Troilus and Criseyde et The nun's priest's tale de Geoffrey Chaucer (XIVe siècle) et The Kingis quair de Jacques Ier d’Écosse (XVe siècle). Après avoir employé les rêves de ses personnages comme des prolepses et comme des symboles de leur emprisonnement et de leur parcours prédestiné, Chaucer remet en question cette tradition littéraire en montrant que rêves et prédestination ne sont pas synonymes tandis que Jacques Ier d’Écosse, en transformant le rêve de son héros emprisonné en illumination, en fait le remède de fortune qui annonce sa libération finaleThis thesis examines the links between the theme of freedom and the dream motif in three poems of the late medieval literature in English: Chaucer’s Troilus and Criseyde and Nun's priest's tale (14th century) and James I of Scotland’s Kingis quair (15th century). After using his characters' dreams as prolepses and as symbols of their imprisonment and predestined lives, Chaucer questions this literary tradition by showing that dreams and predestination are not synonymous while James I of Scotland transforms his imprisoned hero's dream into an illumination so that the dream motif heralds his final
33
Kendrick, Samantha Lynn. "Characterization and Molecular Targeting of the Bcl-2 i-Motif for Modulation of Gene Expression and Induction of Chemosensitivity in Lymphoma". Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/193638.
Testo completoAbstract (sommario):
The nature of DNA has captivated scientists for more than fifty years. The discovery of the double-helix model of DNA by Watson and Crick in 1953 not only established the primary structure of DNA, but also provided the mechanism behind DNA function. Since then, the demonstration of DNA secondary structure formation has allowed for the proposal that the dynamics of DNA itself can function to modulate transcription. We demonstrate for the first time the i-motif DNA secondary structure formed from an element within the Bcl-2 promoter region has potential to serve as a cellular molecular target for modulation of gene expression. Unlike typical oncogenes, Bcl-2 acts by promoting cellular survival rather than increasing cellular proliferation. The over-expression of Bcl-2, most notably in lymphomas, has been associated with the development of chemoresistance.Transcriptional regulation of Bcl-2 is highly complex and a guanine- and cytosine-rich (GC-rich) region directly upstream of the P1 site has been shown to be integral to Bcl-2 promoter activity. We have demonstrated that the C-rich strand is capable of forming an intramolecular i-motif DNA secondary structure with a transition pH of 6.6 and a predominant 8:5:7 loop using mutational studies coupled with circular dichroic spectra and thermal stability analyses. In addition, a novel assay involving the sequential incorporation of a fluorescent thymine analog at each thymine position provided evidence of a capping structure within the top loop region of the i-motif. Two different classes of steroids either stabilize or destabilize the i-motif structure and this differential interaction results in the activation or repression of Bcl-2 expression. The i-motif stabilizing steroid significantly up-regulated Bcl-2 gene and protein expression in BJAB Burkitt's lymphoma cells while the destabilizing steroid down-regulated Bcl-2 expression in B95.8 Burkitt's and Granta-519 mantle cell lymphoma cells, as well as in a SCID mouse lymphoma model. More importantly, the down-regulation of Bcl-2 led to chemosensitization of etoposide-resistant lymphoma cells demonstrating that Bcl-2 i-motif interactive small molecules can act as chemosensitizing agents. Conversely, compounds that up-regulate Bcl-2 by stabilization of the i-motif have potential for use as neuroprotective agents.
34
Benabou, Zdaou Sanae. "Application of analytical and chemometric methodologies to study complex bioanalytical processes involving DNA i-motif structures". Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663796.
Testo completoAbstract (sommario):
The i-motif is a DNA structure formed by cytosine-rich sequences that consists of parallel- stranded duplexes held together by intercalated base pairs. The in vitro formation of this structure in DNA sequences corresponding to the promoter regions of several oncogenes, such as c-kit, c-myc or bcl-2, has been demonstrated. Recently, the first direct evidence for its in vivo presence in human cells and control regulatory functions has been proven. This structure is not only interesting from a biophysical and biomedical point of view, but also for their potential application in Analytical Chemistry or Nanotechnology.
The present Doctoral Thesis deals with the application of analytical and chemometric methodologies to study complex bioanalytical processes involving DNA i-motif structures. The sequences studied correspond to those found at cytosine-rich regions found near the promoter regions of the nmyc and SMARCA4 genes. On the one hand, the stability of the i- motif structures formed by these sequences according to variations of pH, temperature, ionic strength, or presence of ligands in steady-state conditions has been studied. On the other hand, the potential of ultrafast spectroscopies for the study of fast kinetic processes triggered by light has been evaluated. Through the Thesis, curve resolution methods, either based on soft-, hard- or hybrid-modelling have been used extensively to model the biochemical processes of interest.
The steady-state studies have demonstrated that the stability against pH or temperature variations of the three different kinds of cytosine-rich sequences mentioned above is strongly dependent on the number of the C·C+ base pairs, but also on the contribution of other factors, such as the base composition and length of the loops and the presence of additional stabilising structures (hairpins) in the DNA sequence. The studies performed at ultrafast time scales have revealed that the photochemical process induced by UV-lamp irradiation and monitored by rapid-scan FTIR involves the formation of dimeric photoproducts in folded and unfolded sequences. The study of processes monitored by time-resolved fluorescence in the scale of picoseconds has shown that i-motif relaxation is detected by the presence of fast lifetimes in the pH range between 4 and 6, associated with intrinsic conformational changes at the fluorescent site. In this last study, one or two
different i-motif structures have been detected in the nmyc and in the shortest DNA sequences studied, respectively.
Finally, the application of multivariate resolution methods, based either on hard- or soft- modelling, has allowed the recovery of valuable chemical information from evolutionary processes of DNA. Besides, the adaptation and application of hybrid hard- and soft- modelling has been shown to be a useful approach to detect intermediate temperature- dependent conformational transitions and to avoid the effect of baseline drifts in the estimation of the melting temperature, as well to retrieve rate constants from the kinetic information present in rapid-scan FTIR difference spectra.La estructura de l’ADN coneguda com “i-motif” es forma en seqüències riques en bases citosina (C). L’esquelet de l’i-motif està format per parells de bases C·C+ intercalats i estabilitzats per ponts d’hidrogen. S'ha demostrat la formació in vitro d'aquesta estructura en seqüències d'ADN corresponents a les regions promotores de diversos oncògens, com el c-kit, el c-myc o el bcl-2. Recentment, s'ha demostrat la primera evidència de la seva presència in vivo. La present Tesi Doctoral tracta de l'aplicació de metodologies analítiques i quimiomètriques per estudiar processos bioanalítics complexos que en els que intervenen aquestes estructures. Les seqüències estudiades corresponen a les regions promotores dels gens nmyc i SMARCA4. D'una banda, s'ha estudiat l'estabilitat de les estructures formades per aquestes seqüències segons variacions de pH, temperatura, força iònica o presència de lligands en condicions d'estat estacionari. D'altra banda, s'ha avaluat el potencial d'espectroscòpia ultraràpida per a l'estudi de processos cinètics ràpids provocats per la llum. Al llarg de la Tesi, els mètodes de resolució multivariant, ja sigui basats en models flexibles, rígids o híbrids, s'han utilitzat àmpliament per modelitzar els processos d'interès. Els estudis d'estat estacionari han demostrat que l'estabilitat davant el pH o les variacions de temperatura de les tres diferents seqüències riques en citosina esmentades anteriorment depèn molt del nombre de parells de bases de C·C+, però també de la contribució d'altres factors, com ara la composició de la base i la longitud dels bucles. A partir d'estudis ultraràpids, el procés fotoquímic induït per la irradiació de llum UV i l'IR d'escaneig ràpid s'ha relacionat amb la formació de fotoproductes dimèrics en seqüències plegades i desplegades. L'estudi dels processos seguits mitjançant fluorescència resolta en el temps ha demostrat l’existència de més d’una espècie associada amb l’estructura i-motif en el cas de les seqüencies curtes. Finalment, l'aplicació de mètodes de resolució multivariant, basats tant en models rígids o flexibles, han permès extreure informació química valuosa dels processos evolutius de l'ADN. A més, s'ha demostrat que l'adaptació i l'aplicació del modelatge híbrid ha permet calcular les constants cinètiques i detectar transicions dependents de la temperatura.
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Robidoux, Sébastien. "Association of branched oligonucleotides into the i-motif and synthesis of dendrimers based on nucleic acids". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0022/NQ50245.pdf.
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36
Boillet, Elise. "Les premières oeuvres religieuses de l'Arétin (1492-1556) : l'Ecriture réécrite". Paris 3, 2001. http://www.theses.fr/2001PA030113.
Testo completoAbstract (sommario):
En moins d'un an, de juin 1534 à mai 1535, l'Arétin publie à Venise La passion de Jésus-Christ, Les sept psaumes de la pénitence de David et L'humanité du Christ. Ces oeuvres en langue vulgaire et en prose reposent sur une même problématique, la réécriture de textes bibliques. Le chapitre premier éclaire cette problématique en fonction du contexte des années 1530, qui se situe entre Réforme et Contre-réforme, et dans lequel Venise joue le rôle de plaque tournante dans la circulation des nouvelles idées religieuses. C'est aux idées érasmiennes de libre accès à la Bible et de fidélité à la pureté et à la simplicité évangéliques, fortement affirmées dans la Passion de Jésus-Christ, que se rattache l'entreprise de l'Arétin. Les trois chapitres suivants sont consacrés à chacune des oeuvres. .In less than a year, between 1534 and May 1535, Pietro Aretino publishes in Venice The Passion of Jesus-Christ, The seven psalms of David's penitence and The humanité of Christ. Each work proposes a different way of rewriting the Scriptures. The first chapter replaces this production in the context of the years between Protestant Reformation and Counter Reformation, when Venice was a center in the diffusion of new religious ideas. The erasmian ideas of free access to the Scriptures and of evangelical pureness and simplicity, asserted in the passion of Jesus-Christ, are important to understand Aretino's enterprise. The three following chapters are dedicaded to each work. .
37
Meineke, Eva-Tabea. "I Misteri della città nella narrativa europea". Paris 8, 2004. http://www.theses.fr/2004PA082323.
Testo completoAbstract (sommario):
Within the English, German and French prose of the first half of the nineteenth century, mystery turns out to be a fundamental element in the imagery of the city. It does not only reflect the anxiety of the individual who has to confront himself with the new context, but it represents a new method for attracting the reader's attention. The images of urban mystery are here analysed within a series of works (Balzac, Sue, Dickens, Tieck and Grillparzer) and distinguished in three categories: the city as a labyrinth, as a woman and as a monster. Within these categories, some traditional images are adapted to the new context of the metropolis. The authors' intention is, on the one hand, to take advantage of the sense of mystery in order to awake the reader's curiosity. On the other hand, he reassures the reader by providing points of reference in the form of recurrent images and possible interpretationsDans la prose anglaise, française et allemande de la première moitié du XIXe siècle le mystère apparaît comme élément fondamental de l'imaginaire urbain. Non seulement il reflète l'angoisse de l'individu confronté au contexte nouveau, mais il correspond aussi aux nouveaux moyens employés pour attirer l'attention du lecteur. Les images de mystère urbain sont analysées à l'intérieur d'un corpus d'ouvrages (Balzac, Sue, Dickens, Tieck et Grillparzer) et distinguées en trois catégories: la ville comme labyrinthe, comme femme et comme monstre. A l'intérieur de ces catégories, des images traditionnelles sont adaptées au contexte nouveau de la métropole. L'intention des auteurs est, d'un côté, de profiter du sens du mystère afin de réveiller la curiosité du lecteur et, de l'autre, de rassurer le lecteur en lui proposant des points de repère sous la forme des images récurrentes et des interprétations possibles
38
Devaux, Alexandre. "Conception et application d'ADN tétraplexe à topologie contrôlée". Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALV020.
Testo completoAbstract (sommario):
Les acides nucléiques riches en cytosines ou en guanines peuvent se replier pour former des structures i-motifs ou G-quadruplexes (G4). G4 et i-motifs sont localisés au niveau des télomères et dans les régions promotrices de nombreux gènes, y compris des oncogènes. Il a été démontré que ces derniers contribuent à la régulation des cellules normales et pathologiques et sont désormais considérés comme des cibles thérapeutiques potentielles pour le traitement de nombreuses maladies et anomalies. Une caractéristique majeure des G4 est leur susceptibilité à adopter, en particulier in vitro, différentes topologies. D’autre part, les i-motifs nécessitent des conditions acides pour se former invitro. Dans ce contexte, notre laboratoire a développé le concept de TASQ (pour « Template Assembled Synthetic G-Quadruplex ») pour assembler des mimes stables de G4 et d’i-motif.La première partie de notre étude a consisté à synthétiser une structure stable i-motif provenant de la séquence télomérique en utilisant une plateforme cyclopeptidique fonctionnelle et des ligations chimiosélectives distinctes. Puis dans un second temps, une nouvelle ligation a été introduite aux trois autres chimies déjà en place dans notre laboratoire afin de synthétiser de nouvelles structures tétraplexes. Enfin, un panel de topologies G4 a été synthétisé afin de réaliser des études d’interactions visant à identifier des protéines qui interagissent avec des G4 adoptant des topologies bien définiesCytosines or guanines rich nucleic acids can fold into i-motifs or G-quadruplex (G4) structures. G4s and i-motifs are found at telomeres and in promoter regions of numerous genes including oncogenes. Both have been shown to contribute to the regulation of normal and pathological cells and are now viewed as potential therapeutic targets for the treatment of numerous diseases and defects. One major feature of G4s is their susceptibility to adopt, especially in vitro, different topologies. On the other hand i-motifs require acidic conditions to fold in vitro. In this context, our laboratory has developed the concept of TASQ (for « Template Assembled Synthetic G-Quadruplex ») to assemble stable mimics of G4 and i-motif structures.The first part of our study consisted in synthesizing a stable i-motif structure from the telomeric sequence using an addressable cyclopeptide platform and distinct chemoselective ligations. Then in a second part of the study, a novel ligation was introduced along with three other chemistries already optimized in our laboratory in order to synthetize novel tetraplex structures. Finally, a panel of G4 mimics adopting various topologies were synthesized and used in pull-down assays to identify the proteins that interact with G4 of specific topologies
39
Sutherland, Caleb, Yunxi Cui, Hanbin Mao e Laurence H. Hurley. "A Mechanosensor Mechanism Controls the G-Quadruplex/i-Motif Molecular Switch in the MYC Promoter NHE III 1". AMER CHEMICAL SOC, 2016. http://hdl.handle.net/10150/621939.
Testo completoAbstract (sommario):
MYC is overexpressed in many different cancer types and is an intensively studied oncogene because of its contributions to tumorigenesis. The regulation of MYC is complex, and the NHE III1 and FUSE elements rely upon noncanonical DNA structures and transcriptionally induced negative superhelicity. In the NHE III1 only the G-quadruplex has been extensively studied, whereas the role of the i-motif, formed on the opposite C-rich strand, is much less understood. We demonstrate here that the i-motif is formed within the 4CT element and is recognized by hnRNP K, which leads to a low level of transcription activation. For maximal hnRNP K transcription activation, two additional cytosine runs, located seven bases downstream of the i-motif-forming region, are also required. To access these additional runs of cytosine, increased negative superhelicity is necessary, which leads to a thermodynamically stable complex between hnRNP K and the unfolded i-motif. We also demonstrate mutual exclusivity between the MYC G-quadruplex and i-motif, providing a rationale for a molecular switch mechanism driven by SP1-induced negative superhelicity, where relative hnRNP K and nucleolin expression shifts the equilibrium to the on or off state.
40
Mattei, Silvia. "Voltaire e i viaggi della ragione". Paris 10, 2007. http://www.theses.fr/2007PA100040.
Testo completoAbstract (sommario):
La thèse porte sur la figure du voyage dans l’œuvre de Voltaire. Plus précisément, elle compte de déterminer la portée de la notion de voyage chez Voltaire, en repérant les différentes manières par lesquelles elle se constitue en discours philosophique, ou en est simplement l’expression. La démarche proposée est thématique et chronologique à la fois : en partant des Lettres philosophiques (1733) jusqu’au Philosophe ignorant (1767), en passant par les Romans et contes philosophiques (1739 – 1774), lesquels constituent le matériel le plus copieux de la recherche, elle analyse cinq variantes des voyages voltairiens : 1) Le Voyage en Angleterre ; 2) Les Voyages cosmiques ; 3) Les Voyages philosophiques ; 4) Les Voyages culturels ; 5) Le Voyage dans l’histoire de la pensée philosophiqueThe thesis focuses on the figure of travel in Voltaire’s works and means determine notion and dimension of travel, finding the different ways it translate and express philosophical discourse of the author. Processes are thematic and chronologic at the same time: from Lettres philosophiques (1733) to Le Philosophe ignorant (1767), across the Romans et contes philosophiques (1739 – 1774), the research analyses five variants of Voltaire’s travels : 1) Travel to England; 2) Cosmic travels; 3) Philosophical travels; 4) Cultural travels; 5) Travel trough the history of philosophical thought
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Uribe, Diana Judith. "Defining the Role of Secondary DNA Structures and Transcription Factors on the Transcriptional Control of the HIF-1alpha and VEGF Promoters". Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/145466.
Testo completoAbstract (sommario):
Angiogenesis is known to be induced and maintained in tumors by the constant expression of the hypoxia inducible factor 1 alpha (HIF-1α) and human vascular endothelial growth factor (VEGF). In fact, tumor recurrence, aggressive metastatic legions and patient mortality rates are known to be positively correlated with overexpression of these two proteins. The HIF-1α and VEGF promoters contain a polypurine/polypyrimidine (pPu/pPy) tract, which are known to play critical roles in their transcriptional regulation, and are structurally dynamic where they can undergo a conformational transition between B-DNA, single stranded DNA and atypical secondary DNA structures such as G-quadruplexes and i-motifs. We hypothesize that the i-motif and G-quadruplex structures can form within the pPu/pPy tracts of the HIF-1α and VEGF proximal promoters, which play important roles in the transcriptional regulation of these genes by acting as scaffolds for alternative transcription factor binding sites. The purpose of this dissertation was to elucidate the transcriptional regulation of the HIF-1α and VEGF genes through the atypical DNA structures that form within the pPu/pPy tracts of their proximal promoters. We investigated the interaction of the C-rich and guanine-rich (G-rich) strands of both of these tracts with transcription factors heterogeneous nuclear ribonucleoprotein (hnRNP) K and nucleolin, respectively, both in vitro and in vivo and their potential role in the transcriptional control of HIF-1α and VEGF. In this dissertation, we demonstrate that both nucleolin and hnRNP K bind selectively to the G- and C-rich sequences, respectively, in the pPu/pPy tract of the HIF-1α and VEGF promoters. Specifically, the small interfering RNA-mediated silencing of either nucleolin or hnRNP K resulted in the down-regulation of basal VEGF gene, and the opposite effect was seen when the transcription factors were overexpressed, suggesting that they act as activators of VEGF transcription. Taken together, the identification of transcription factors that can recognize and bind to atypical DNA structures within pPu/pPy tracts will provide new insight into mechanisms of transcriptional regulation of the HIF-1α and VEGF gene.
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Bonnet, Romaric. "Synthèse et utilisation de mimes de quadruplexes pour l'évaluation de ligands". Phd thesis, Université de Grenoble, 2012. http://tel.archives-ouvertes.fr/tel-00824972.
Testo completoAbstract (sommario):
Synthèse et utilisation de mimes de quadruplexes contraints pour l'évaluation de ligands II est maintenant bien connu que l'ADN simple brin peut s'associer sous différentes conformations telles que la double hélice, les triplexes, les i-motifs ou bien encore les G-quadruplexes. Ces dernières années les structures de type quadruplexes (G-quadruplexes et i-motif) ont suscité un certain intérêt notamment pour leur implications au niveau cellulaire (maintenance des télomères, activation de gènes...). C'est pourquoi de nombreuses équipes travaillent sur le développement de ligands affins pour ces structures qui pourraient agir en tant qu'anticancéreux. Cependant, le fait que les quadruplexes présentent un polymorphisme important(variabilité du nombre de brins dans la structure, des différents types de boucles et de l'orientation des brins) rend la compréhension des interactions entre un ligand et le quadruplexe plus difficile. Dans ce contexte, l'équipe développe un nouveau concept, " Template Assisted Synthesis of Quadruplexes " (TASQ) dont le but est d'obtenir un quadruplexe ne présentant qu'une topologie de façon contrôlée afin de permettre des études plus précises sur la façon dont un ligand pourrait interagir avec les quadruplexes. La première partie de ce manuscrit reporte l'évaluation par résonnance plasmonique de surface de complexes métalliques en tant que ligands de G-quadruplexe. Ces études reposent sur l'utilisation d'un premier mime de G-quadruplexe parallèle sur lequel deux séries de complexes sont testées : des métalloporphyrines et des ligands de type salphen. La seconde partie du manuscrit décrit la synthèse de mimes de G-quadruplexes antiparallèle. Elle repose sur l'utilisation du gabarit peptidique qui relié aux séquences spécifiques d'oligonucléotides de façon adéquat contraint la structure. Pour se faire, deux réactions chimiosélectives ont été utilisées : la cycloaddition 1,3 dipolaire de Huisgen et la ligation oxime. Les travaux reportés concernent trois types de structure mimant un i-motifs, des G-quadruplexes tétramoléculaires ou bimoléculaires.
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Sutherland, Caleb Daniel. "Characterization and Molecular Targeting of a Mechanosensor Mechanism Controlled By the G-Quadruplex/I-Motif Molecular Switch in the MYC Promoter NHE III₁". Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/566983.
Testo completoAbstract (sommario):
MYC is overexpressed in most types of tumors, but a means to selectively decrease its expression is yet to be found. Our recent findings on modulation of BCL2 gene expression through protein interactions with the BCL2 i-motif have provided a basis for further investigation of MYC gene control. It is proposed that the MYC i-motif could function by a similar molecular switch mechanism as in BCL2.Binding sites for heterogeneous nuclear ribonucleoprotein K (hnRNP K) within the MYC promoter also exist in the i-motif-forming sequence. Circular dichroism and bromine footprinting confirmed that this DNA sequence is able to form an i-motif, and systematic mutation of the cytosine residues in this sequence has revealed a 5:5:5 loop configuration. Indeed, all loops of the i-motif, when folded into a 5:5:5 loop configuration, contain the hnRNP K consensus sequence (CCCT). Previous studies show that hnRNP K binds to this i-motif-forming sequence, but it was assumed to be single-stranded. Binding studies revealed that hnRNP K has more binding affinity to its consensus sequence in the i-motif compared to a mutant sequence where the i-motif cannot form. Further investigation of the MYC promoter revealed an additional two runs of cytosine seven bases downstream of the MYC i-motif. Biophysical studies showed that the additional two runs were not involved in i-motif formation, however recent studies describe their importance for transcriptional activation. We found that hnRNP K preferred the longer 5CT sequence compared to the i-motif forming 4CT sequence when using a competitive binding assay. Utilizing luciferase reporters containing either the 4CT or 5CT sequence validated that hnRNP K required both the i-motif and 5th CT element for maximum transcriptional activation. Competition binding studies and bromine footprinting showed that hnRNP K bound to the downstream 5th CT element and the central and lateral loops of the i-motif.Additionally, we found that co-overexpression of Sp1 and hnRNP K induced a 10-fold increase in luciferase activity in the 5CT reporter only. We hypothesize that Sp1 continuously primes the promoter to initiate transcription inducing more negative superhelicity and increasing the melting of duplex DNA. This increased melting grants hnRNP K’s three KH domains access to the i-motif loops and the 5Th CT element. Confirmation by ChIP analysis validated that Sp1 overexpression causes an increase in hnRNP K occupancy at the MYC promoter. These findings provide new insight into the mechanisms of MYC transcriptional control by the i-motif and G-quadruplex.Recently, our group has demonstrated that two small molecules IMC-48 and IMC-76 can interact with the i-motif and can be an effective means to modulate BCL2 expression. Based on these results with the BCL2 i-motif, we employed a similar strategy and screened and identified small drug-like molecules that interact with MYC i-motif, using a FRET high-throughput assay. We then further validated that IMC-16 stabilizes the MYC i-motif through the interactions with the loops of the i-motif. No stabilization by IMC-16 treatment was observed with the MYC G-quadruplex and the BCL2 and PDGFRβi-motifs demonstrating selectivity for the MYC i-motif.Finally, we investigated the effects of IMC-16 on MYC expression in three lymphoma cell lines all expressing different levels of MYC. In the case of both Daudi and RAJI Burkitt’s lymphoma cell lines we demonstrated that selectively stabilizing the i-motif by IMC-16 could increase MYC expression. Furthermore, we demonstrated that the MYC G-quadruplex stabilizing compound GQC-05 and IMC-16, which stabilizes the MYC i-motif, have antagonistic effects on MYC expression, providing further evidence of a molecular switch mechanism in the NHEIII1. Directly targeting MYC expression through the i-motif offers advantages over targeting the G-quadruplex, because of the reduced stability and dynamic nature of the i-motif, additionally the i-motif is only found in DNA. The use of such i-motif interactive compounds is the first step into the development of new innovative approaches to treat cancers.
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HAN, XIAOGANG. "Etude rmn du motif i intramoleculaire forme par des oligodesoxynucleotides derives des brins riches en cytidine des telomeres et centromeres". Palaiseau, Ecole polytechnique, 1997. http://www.theses.fr/1997EPXX0040.
Testo completoAbstract (sommario):
Des etudes rmn multidimensionnelles ont montre que des sequences riches en cytidines adoptaient une structure constituee de deux duplexes intercales tete-beche l'un dans l'autre : le motif i. Nous etudions dans cette these la structure en motif i intramoleculaire adoptee par des oligodesoxynucleotides derivees des sequences telomeriques et centromeriques. Nous avons montre que la structure formee par la sequence d(5mcct#3c#2t#3ac#2t#3c#2) adopte le motif-i par un repliement intramoleculaire. Cette structure est stable a ph neutre, oc. Le cur de cette structure est forme par l'intercalation de quatre paires c. C#+, trois boucles liant les suites de cytidines. Dans la boucle centrale ttta, qui traverse le grand sillon, une liaison hydrogene entre les bases t8 et a11 a ete observee. Les deux boucles ttt, qui pontent les petits sillons, sont connectees par une paire symetrique t. T. Le travail concernant les sequences d(5mcct#3cct#2acct#3cc), d(5mcct#2ac#2t#3ac#2-t#2ac#2), d(5mccat#2c#2t#2ac#2at#2c#2) et d(5mccta#2c#2t#2ac#2ta#2c#2), montre une structure en motif i intramoleculaire, et la topologie de repliement est identique a celle decrite dans le cas precedent. Leur stabilite depend largement des longueurs et des compositions des boucles. La formation des appariements dans la boucle centrale et entre les deux petites boucles stabilise le motif i. Les valeurs de la temperature de denaturation thermique des sequences du telomere de bombyx d(5mcc(taacc)#3) et du centromere humain d(5mcc(attcc)#3) indiquent que les structures formees par ces deux sequences sont moins stables que les autres. Nous avons aussi etudie la possibilite de prolonger le repliement intramoleculaire en motif i, en ajoutant des sequences susceptibles de former un duplex d'adn b. L'existence de cette jonction entre le motif i et le duplex a ete observee.
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Khalsi, Khalil. "Par-delà le rêve et la veille ˸ la fin du monde. Une approche cosmologique de l'entre-deux. S. Hedayat, I. al-Koni et A. Volodine". Electronic Thesis or Diss., Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCA036.
Testo completoAbstract (sommario):
Cette thèse propose d’étudier l’entre-deux du rêve et de la veille sous un angle cosmologique. Notre hypothèse est que chacun des textes du corpus véhicule une vision particulière du monde médiée par un plan interstitiel à travers lequel les protagonistes négocient leur identité ainsi que leur rapport au monde, notamment en contexte d’apocalypse culturelle. Dans le chapitre zéro, nous inscrivons notre propos dans le champ discursif contemporain s’attelant à réévaluer le concept de « grand partage » sur lequel se base l’ontologie moderne (Descola, Latour, Morin). Cette déconstruction nous amène à considérer le rapport de médiation que rêve et réel peuvent entretenir dans un contexte de crise de l’imagination (Augé), de sorte à interroger le type de réel porteur d’avenir que cette logique dialectique (Benjamin) permet d’envisager. À l’aune de ce dispositif épistémologique, le premier chapitre s'intéresse au roman La Chouette aveugle (Bouf-e-kour) de l’Iranien Sadegh Hedayat (1936). À travers l’entre-deux du rêve et de la veille, transparaît l’effondrement de la cosmologie perse antique, qu’un ange-femme signifie au narrateur en venant mourir dans son lit ; l’analyse herméneutique et sémantique du texte révèle le basculement d’une vision du monde prémoderne, basée sur le déchiffrement du Réel imaginal par l’« angélophanie » (Corbin), à une perspective spectrale soumettant le présent à l’intempestivité d’une origine irrévocablement morte (Derrida). Dans le second chapitre, l’analyse de Poussière d’or (al-Tibr) du Touareg Ibrahim al-Koni (1990) fait apparaître l’entre-deux comme le socle d’une structure cosmique où les êtres s’opposent et se complètent entre visible et invisible (Claudot-Hawad) ; à travers la descente aux enfers que vit le protagoniste entre rêve et veille, l’étude cosmologique dévoile toute une écologie qui étend le territoire de l’humain à travers celui de l’esprit et de l’animal, de sorte à le faire accéder à « l’unité de l’existence » dont le désert est l’équation. Le troisième et dernier chapitre se consacre à l’analyse du Port intérieur d’Antoine Volodine (1995), et du post-exotisme en général, qui imagine l’entre-deux du rêve et de la veille comme un médium de transmigration ; nous proposons de voir comment l’apocalypse, sans cesse réactivée, lève le voile sur l’horreur du réel que les personnages réélaborent dans une éternelle transition. Enfin, la mise en écho de ces trois œuvres permet de considérer la capacité du rêve à générer du réel au seuil de l’inconnu de l’avenir, que la littérature invite à reconcevoir par le biais d’une refondation cosmologiqueThis dissertation aims to study the in-between of dreams and wake from a cosmological angle. We will argue that every text of our corpus conveys a particular vision of the world mediated by an interstitial level, through which the characters negotiate their identity and relationship with the world, notably in a context of cultural apocalypse. In chapter zero, we situate our statement vis a vis the contemporary field of discourse aiming to re-evaluate the concept of ‘‘Great Divide”, on which modern ontology is based (Descola, Latour, Morin). This deconstruction leads us to con-sider the mediation link interrelating dreams with reality in a context of imagination crisis (Augé), so as to interrogate the type of forward-looking reality that the dialectical logic (Benja-min) makes us consider. In light of this epistemological device, the first chapter focuses on the novel The Blind Owl (Bouf-e-kour) by Iranian writer Sadegh Hedayat (1936). Between the states of dream and wake is revealed the collapse of ancient Persian cosmology, signified to the narra-tor by a female angel coming to die in his bed. The hermeneutic and semantic analysis of the text reveals the shift from a premodern vision of the world, based on the deciphering of the Imaginal Real through « angélophanie » (Corbin), to a spectral perspective subjecting the present to an irrevocably dead origin (Derrida). In the second chapter, the Tuareg Ibrahim al-Koni’s (al-Tibr, 1990) Gold Dust shows the in-between as the pedestal of a cosmic structure where beings op-pose and complement each other between the visible and the invisible (Claudot-Hawad). Through the protagonist’s descent into hell between dream and wake, a cosmological study re-veals an ecology extending human territory through the spirit and animal domains, so as to make it reach the ‘‘unity of existence’’ which desert is the equation. The third and final chapter is de-voted to the analysis of Antoine Volodine's Le Port intérieur (1995) and post-exoticism in gen-eral, which describes the in-between as a transmigration medium. We aim to investigate how the apocalypse, constantly reactivated, lifts the veil on the horrific reality that the characters reimag-ine in an eternal transition between life and death, dream and wake. Finally, the echoing of these three works leads us to question the dream's ability to generate reality on the threshold of the future’s unknown, which literature invites us to redesign through a cosmological refoundation
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Lemercier, de Richemont Marie-Alix. "La Rhétorique de la prudence dans les Maximes de La Rochefoucauld, ou le je des Maximes". Electronic Thesis or Diss., Paris 3, 2024. http://www.theses.fr/2024PA030023.
Testo completoAbstract (sommario):
Cette thèse scrute les Maximes de La Rochefoucauld à travers le prisme de la prudence, rationalité ancienne, art du jugement et de la prise de décision, principe de réflexion et d’action. Les Maximes se présentent comme l’expression d’un je qui se profile en tant que Prudens doté de la vertu de prudence. Cet ethos permet au locuteur d’articuler une parole de vérité et un rôle de parrhêsias mondanisé. À travers lui se joue à la fois l’infaillibilité du discours des Maximes, qui ne peuvent jamais être prises en défaut, et la fascination qu’elles exercent sur leurs lecteurs successifs, invités à déceler un sens malgré leur auteur. La prudence du locuteur agit comme une clé transcendant les variations des multiples énonciations spécifiques aux Maximes. Elle s’accomplit dans une opacification du langage qui constitue la substance de leur enseignementThis thesis examines La Rochefoucauld’s Maxims through the prism of prudence, ancient rationality, the art of judgement and decision-making, and the principle of reflection and action. The Maxims are presented as the expression of an “I” that emerges as a Prudens endowed with the virtue of prudence. This ethos allows the speaker to articulate a word of truth and a role as a wordly parrhesias. Through him, both the infallibility of the discourse of the Maxims, which can never be faulted, and the fascination they exert on their successive readers, invited to detect a meaning in spite of their author, is played out. The speaker’s caution acts as a key transcending the variations of the multiple utterances specific to the Maxims. It is accomplished in an opacification of language which constitutes the substance of their teaching
47
Canalia, Muriel. "Structure et mouvement internes d'oligonucléotides d'ADN et ARN". Paris 6, 2005. http://www.theses.fr/2005PA066388.
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Carvalho, Simoes Francisco Manuel de. "Fish and mammalian glut4 traffic characteristics: an evolutionary perspective on the importance of glut4 protein motifs for trafficking". Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/662890.
Testo completoAbstract (sommario):
Glucose transporters (GLUTs) are extremely important for glucose metabolism. Glucose transporters uptake glucose from blood stream into the cells where it can be metabolized. Among the glucose transporters family, GLUT4, which is solely expressed in muscle and adipose tissues, displays a unique feature as it can change its cellular distribution within minutes in response to insulin to regulate glucose uptake. Therefore, the study of GLUT4 cellular trafficking is fundamental to understand its functioning and to deepen our knowledge on glucose homeostasis.
In this work, we utilized a GLUT4 fish variant, brown trout GLUT4, to study GLUT4 trafficking and the role of GLUT4 protein motifs in this process, in 3T3-L1 adipocytes. We observed that, in comparison to mammalian GLUT4 (RatGLUT4), brown trout GLUT4 (BtGLUT4) had a much weaker translocation to the plasma membrane in response to insulin which was in part due to a slower cellular trafficking (exocytosis and endocytosis) and to a poor targeting to the GLUT4 storage vesicles responsible for “holding” GLUT4 inside the cell in the absence of insulin; these vesicles represent the main pool of insulin-responsive GLUT4. In this thesis we also studied the most common GLUT4 endocytic routes. We analyzed the contribution of the clathrin-mediated and the cholesterol-dependent endocytic pathways for RatGLUT4 and BtGLUT4 internalization. We observed that whilst RatGLUT4 internalizes through both the clathrin-mediated and the cholesterol-dependent pathways, BtGLUT4 only utilizes the former. It has been suggested that in adipocytes, the main cholesterol-dependent internalization pathway is the caveolar route. The internalization through this pathway is mediated by plasma membrane structures called caveolae. The formation of these structures is dependent on the caveolin-1 protein. To analyze the role of caveolae in GLUT4 internalization we blocked its formation by knocking down caveolin-1 and observed an increase of RatGLUT4 and BtGLUT4 internalization; however, both GLUT4 isoforms showed less internalization through the clathrin-mediated and cholesterol-dependent pathways in the absence of cavolin-1. Therefore, we suggest that in 3T3-L1 adipocytes caveolin-1 knockdown induces internalization of GLUT4 through alternative pathways.
GLUT4 trafficking is regulated by cellular machinery that interacts with GLUT4 protein motifs. To analyze the role of the mammalian N-terminal FQQI8 and C-terminal TELEY502 motifs in GLUT4 trafficking we mutated the corresponding motifs in BtGLUT4 (FQHL8 and TELDY495, respectively) and observed that mutations in the C-terminal had little effect on BtGLUT4 trafficking whereas mutations on the N-terminal (especially FQQL8 mutant) improved BtGLUT4 intracellular retention in the absence of insulin. Furthermore, we verified that FQQL8 mutation increased BtGLUT4 retention in a syntaxin-6-rich compartment, possibly the trans-Golgi network. In addition to studying BtGLUT4 mutants we also analyzed the trafficking of a chimera consisting of a RatGLUT4 backbone with the large cytoplasmic loop of BtGLUT4 (L-GLUT4). We observed that L-GLUT4 possessed higher plasma membrane levels in the absence of insulin and as a result a weaker translocation. Moreover, we observed that this was caused, at least in part, by a reduction in the endocytosis of L-GLUT4 in the absence of insulin. We also analyzed the contribution of the clathrin-mediated and cholesterol-dependent pathways for L-GLUT4 internalization and observed that the loop substitution (L-GLUT4) reduced RatGLUT4 internalization through the cholesterol-dependent route. Moreover, in the absence of insulin and in caveolin-1, L-GLUT4 internalization did not increase as much as that of RatGLUT4. The internalization of L-GLUT4 in the absence of caveolin-1 and insulin occurred through a clathrin-mediated pathway, similarly to BtGLUT4, but it also internalized through a cholesterol-dependent pathway, unlike RatGLUT4 and BtGLUT4.
In summary, in this thesis we have contributed to increase the knowledge on GLUT4 trafficking and on the roles of the FQQI8 motif and large cytoplasmic loop in this process, in 3T3-L1 adipocytes.El transportador de glucosa GLUT4 tiene la capacidad de, en respuesta a insulina, cambiar su localización celular y de esta forma regular el transporte de glucosa. En este trabajo, hemos utilizado una variante de GLUT4 de trucha (BtGLUT4) para estudiar el trafico de GLUT4, así como sus dominios proteicos involucrados en este proceso, en adipocitos 3T3-L1. Hemos observado que en comparación con el GLUT4 de mamíferos (RatGLUT4), el BtGLUT4 tenia una menor capacidad de translocación a la membrana plasmática en respuesta a insulina y que esto se debía a una trafico celular mas lento (exocitosis y endocitosis) y a una peor retención en las vesículas responsables por retener el transportador dentro de la célula en ausencia de insulina. En este trabajo hemos observado que RatGLUT4 ha internalizado por la vía de endocitosis mediada por clatrina y por la vía dependiente de colesterol, mientras que BtGLUT4 solo ha utilizado la primera. Además, hemos inhibido la internalización caveolar, mediante bajada de la expresión de caveolina-1, y hemos observado un aumento de la internalización de RatGLUT4 y BtGLUT4. Con el objetivo de estudiar el papel del dominio FQQI8 (extremo -N) de mamífero en el trafico de GLUT4, hemos mutado la secuencia correspondiente en BtGLUT4 (FQHL8) y hemos observado que mutaciones en este dominio han mejorado la retención intracelular de BtGLUT4 en ausencia de insulina. También hemos estudiado el trafico de una quimera que consiste en la secuencia de RatGLUT4 con el lazo citoplasmático largo de BtGLUT4 (L-GLUT4). Hemos observado que la sustitución del lazo ha aumentado los niveles de RatGLUT4 en superficie en ausencia de insulina y que esto era debido, por lo menos en parte, a una menor endocitosis en ausencia de la hormona. También hemos observado que la sustitución del lazo de RatGLUT4 ha reducido su internalización a través de la vía dependiente de colesterol en ausencia de insulina. Además, en ausencia de caveolina-1 y insulina, la internalización de L-GLUT4 ha aumentado menos que la de RatGLUT4 y ha ocurrido a través de las vías mediada por clatrina y dependiente de colesterol.
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Jonchhe, Sagun. "SINGLE-MOLECULE MECHANOCHEMICAL STUDY OF DNA STRUCTURES INSIDE NANOCONFINEMENT". Kent State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=kent1626344589505522.
Testo completo
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Brown, Robert Vincent. "The Regulatory Significance and Molecular Targeting of Novel Non-B-DNA Secondary Structures Formed from the PDGFR-Beta Core Promoter Nuclease Hypersensitivity Element". Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/337361.
Testo completo