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Régulation de la dynamique des microtubules par la kinase de stress JNK dans les cellules épithéliales : caractérisation de CLIP-170 comme un nouveau substrat. / Microtubule dynamics regulation by the stress kinase JNK in epithelial cells : characterization of CLIP-170 as a new substrate.Henrie, Hélène 15 December 2017 (has links)
Les microtubules sont des éléments dynamiques du cytosquelette qui contrôlent à la fois l’organisation du cytoplasme, la polarité, la migration et la division cellulaire. Notre laboratoire a précédemment montré que la kinase de stress JNK (c-Jun NH2-terminal Kinase) régule la dynamique des microtubules dans les cellules épithéliales de mammifères, en augmentant les vitesses de polymérisation, ainsi que les fréquences de sauvetage (transition vers une phase de repolymérisation). Alors que certaines protéines neuronales capables de réguler la dynamique des microtubules ont été identifiées comme des substrats de JNK, leurs équivalents dans les cellules épithéliales sont largement méconnus. Dans le but de comprendre comment JNK module la dynamique des microtubules dans les cellules épithéliales de mammifère, nous avons étudié deux substrats potentiels de JNK : la -tubuline et le facteur de sauvetage CLIP-170. Nous avons bien mis en évidence in vitro, une phosphorylation de la -tubuline par JNK sur une thréonine non-consensus, mais cette phosphorylation n’a pas été retrouvée dans les cellules HeLa, suggérant que la -tubuline n’est pas un substrat naturel de JNK in vivo. Nous avons mis en évidence par ailleurs que CLIP-170 est un nouveau substrat de JNK. Dans les cellules épithéliales, JNK activée phosphoryle trois résidus (Thr25, Thr45 et Ser147) situés dans la partie N-terminale de CLIP-170 de part et d’autre du premier domaine CAP-Gly qui est nécessaire pour l’interaction avec les microtubules. Ces acides aminés présentent des différences aussi bien dans leur phosphorylation basale que dans leurs cinétiques de phosphorylation par JNK sous divers stress. De plus, nous avons trouvé que dans différentes cellules épithéliales, la phosphorylation de ces sites est conservée. In vitro, ces résidus sont directement phosphorylés par JNK, préférentiellement quand le domaine N-terminal de CLIP-170 lie la tubuline. De plus, l’expression de mutants de CLIP-170 phospho-mimétiques et non-phosphorylables a montré que la phosphorylation de chaque site augmente la fréquence des sauvetages microtubulaires. Cette modulation n’est pas corrélée à une augmentation de la capacité de CLIP-170 à former des comètes aux extrémités plus en croissance ou à être retenue aux croissements microtubulaires, qui sont des sites de sauvetage potentiels.Ce travail a permis de décrire les premières phosphorylations de CLIP-170 qui stimulent sa fonction de sauvetage in vivo. Il souligne par ailleurs la complexité des mécanismes de sauvetage, qui demeurent un aspect encore énigmatique de l’instabilité dynamique des microtubules. L’activité de JNK sur CLIP-170 ne permet d’expliquer qu’une partie des effets de la kinase sur la dynamique des microtubules, aussi la recherche d’autres protéines cibles de JNK pouvant réguler notamment leur vitesse de polymérisation, reste à entreprendre. / Microtubules are dynamic cytoskeleton elements, which control cytoplasm organization, cell polarity, migration and division. Our laboratory has previously shown that the stress kinase JNK (c-Jun NH2-terminal Kinase) regulates microtubule dynamics in mammalian epithelial cells, by increasing their growth rates, and their rescue frequencies (transition towards phases of repolymerization). While several neuronal proteins regulating microtubule dynamics have been identified as JNK substrates, their counterparts in epithelial cells are largely unknown. With the aim to understand how JNK modulates microtubule dynamics in mammalian epithelial cells, we studied two putative substrates of JNK: -tubulin and the rescue factor CLIP-170. Regarding -tubulin, using an in vitro kinase assay, we found that a non-consensus threonine is actually phosphorylated by JNK, but we were not able to find this phosphorylation in HeLa cells, suggesting that -tubulin is not a natural JNK substrate. In parallel, we found that CLIP-170 is a new substrate of JNK in epithelial cells. Activated JNK phosphorylates three residues (Thr25, Thr45 and Ser147) located in the N-terminal part of CLIP-170, on each side of the first CAP-Gly domain, which is required for CLIP-170 interaction with microtubules. These residues exhibit differences in their level of basal phosphorylation and their kinetics of phosphorylation by JNK under various stresses. Moreover, we found that in different epithelial cells, the phosphorylation of these sites is conserved. Using an in vitro kinase assay, we found that all these residues are directly phosphorylated by JNK, preferentially when the N-terminal domain of CLIP-170 binds tubulin. Furthermore, using phospho-mimetic and non-phosphorylatable CLIP-170 mutants in epithelial cells, we revealed that the phosphorylation of each site increases microtubule rescues. Such modulation operates without increasing CLIP-170 capability to form comets at the microtubule growing plus ends or to accumulate at microtubule crossings, which are potential rescue sites.This work described the first phosphorylations that enhance CLIP-170 rescue factor function in vivo. It also points out to which extent rescue mechanisms are complex and remain an elusive aspect of dynamic instability. JNK-mediated phosphorylation of CLIP-170 only partly explains the kinase effects on microtubule dynamics. Therefore, identifying other JNK targets that may regulate microtubule polymerization rate, remains to be addressed.
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Magnetization Study of the Heavy-Fermion System Yb(Rh1-xCox)2Si2 and of the Quantum Magnet NiCl2-4SC(NH2)2Pedrero Ojeda, Luis 25 June 2013 (has links) (PDF)
This thesis presents a comprehensive study of the magnetic properties and of quantum phase transitions (QPTs) of two different systems which have been investigated by means of low-temperature magnetization measurements. The systems are the heavy-fermion Yb(Rh1-xCox)2Si2 (metallic) and the quantum magnet NiCl2-4SC(NH2)2 (insulator). Although they are very different materials, they share two common properties: magnetism and QPTs. Magnetism originates in Yb(Rh1-xCox)2Si2 from the trivalent state of the Yb3+ ions with effective spin S = 1=2. In NiCl2-4SC(NH2)2, the magnetic Ni2+ ions have spin S = 1. These magnetic ions are located on a body-centered tetragonal lattice in both systems and, in this study, the QPTs are induced by an external magnetic field.
In Yb(Rh1-xCox)2Si2 the evolution of magnetism from itinerant in slightly Co-doped YbRh2Si2 to local in YbCo2Si2 is examined analyzing the magnetic moment versus chemical pressure x phase diagram in high-quality single crystals, which indicates a continuous change of dominating energy scale from the Kondo to the RKKY one. The physics of the antiferromagnet YbCo2Si2 can be completely understood. On the other hand, the physics of pure and slightly Co-containing YbRh2Si2 is much more complex, due to the itinerant character of magnetism and the vicinity of the system to an unconventional quantum critical point (QCP). The field-induced AFM QCP in Yb(Rh0.93Co0.07)2Si2 and in pure YbRh2Si2 under a pressure of 1.5GPa is characterized by means of the magnetic Grüneisen ratio. The final part of this thesis describes quantum criticality near the field-induced QCP in NiCl2-4SC(NH2)2 .
These results will be compared to the theory of QPTs in Ising and XY antiferromagnets. Since the XY -AFM ordering can be described as BEC of magnons by mapping the spin-1 system into a gas of hardcore bosons, the temperature dependence of the magnetization for a BEC is analytically derived and compared to the results just below the critical field. The remarkable agreement between the BEC theory and experiments in this quantum magnet is one of the most prominent examples of the concept of universality.
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Magnetization Study of the Heavy-Fermion System Yb(Rh1-xCox)2Si2 and of the Quantum Magnet NiCl2-4SC(NH2)2Pedrero Ojeda, Luis 28 May 2013 (has links)
This thesis presents a comprehensive study of the magnetic properties and of quantum phase transitions (QPTs) of two different systems which have been investigated by means of low-temperature magnetization measurements. The systems are the heavy-fermion Yb(Rh1-xCox)2Si2 (metallic) and the quantum magnet NiCl2-4SC(NH2)2 (insulator). Although they are very different materials, they share two common properties: magnetism and QPTs. Magnetism originates in Yb(Rh1-xCox)2Si2 from the trivalent state of the Yb3+ ions with effective spin S = 1=2. In NiCl2-4SC(NH2)2, the magnetic Ni2+ ions have spin S = 1. These magnetic ions are located on a body-centered tetragonal lattice in both systems and, in this study, the QPTs are induced by an external magnetic field.
In Yb(Rh1-xCox)2Si2 the evolution of magnetism from itinerant in slightly Co-doped YbRh2Si2 to local in YbCo2Si2 is examined analyzing the magnetic moment versus chemical pressure x phase diagram in high-quality single crystals, which indicates a continuous change of dominating energy scale from the Kondo to the RKKY one. The physics of the antiferromagnet YbCo2Si2 can be completely understood. On the other hand, the physics of pure and slightly Co-containing YbRh2Si2 is much more complex, due to the itinerant character of magnetism and the vicinity of the system to an unconventional quantum critical point (QCP). The field-induced AFM QCP in Yb(Rh0.93Co0.07)2Si2 and in pure YbRh2Si2 under a pressure of 1.5GPa is characterized by means of the magnetic Grüneisen ratio. The final part of this thesis describes quantum criticality near the field-induced QCP in NiCl2-4SC(NH2)2 .
These results will be compared to the theory of QPTs in Ising and XY antiferromagnets. Since the XY -AFM ordering can be described as BEC of magnons by mapping the spin-1 system into a gas of hardcore bosons, the temperature dependence of the magnetization for a BEC is analytically derived and compared to the results just below the critical field. The remarkable agreement between the BEC theory and experiments in this quantum magnet is one of the most prominent examples of the concept of universality.:1 Introduction 1
2 Theoretical concepts 5
2.1 Ce- and Yb-based 4f-electron systems . . . . . . . . . . . . . . . . 5
2.1.1 Crystalline electric field . . . . . . . . . . . . . . . . . . . . 6
2.2 Heavy-fermion systems . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.2.1 Fermi liquid theory . . . . . . . . . . . . . . . . . . . . . . . 8
2.2.2 Kondo eff ect . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2.3 RKKY interaction . . . . . . . . . . . . . . . . . . . . . . . 11
2.2.4 Doniach phase diagram . . . . . . . . . . . . . . . . . . . . . 12
2.3 Quantum phase transitions . . . . . . . . . . . . . . . . . . . . . . . 14
2.3.1 Spin density wave scenario . . . . . . . . . . . . . . . . . . . 16
2.3.2 Local quantum critical point scenario . . . . . . . . . . . . . 17
2.3.3 Global phase diagram . . . . . . . . . . . . . . . . . . . . . 18
2.3.4 The Grüneisen ratio . . . . . . . . . . . . . . . . . . . . . . 21
2.4 Spins are almost bosons . . . . . . . . . . . . . . . . . . . . . . . . 22
3 Experimental methods 31
3.1 Magnetization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.1.1 Magnetization measurements . . . . . . . . . . . . . . . . . 32
3.2 Experimental techniques . . . . . . . . . . . . . . . . . . . . . . . . 34
3.2.1 Faraday magnetometer . . . . . . . . . . . . . . . . . . . . . 35
3.2.1.1 Measurement of the force . . . . . . . . . . . . . . 35
3.2.1.2 Capacitive cell . . . . . . . . . . . . . . . . . . . . 35
3.2.1.3 Design and performance of the cell . . . . . . . . . 37
3.2.1.4 Sensitivity . . . . . . . . . . . . . . . . . . . . . . . 42
3.2.1.5 Background contributions . . . . . . . . . . . . . . 42
3.2.1.6 Calibration . . . . . . . . . . . . . . . . . . . . . . 42
3.2.1.7 Magnets characteristics . . . . . . . . . . . . . . . 44
3.2.1.8 Installation in a dilution refrigerator . . . . . . . . 45
3.2.2 SQUID magnetometer . . . . . . . . . . . . . . . . . . . . . 47
3.3 Magnetization measurements at high pressure . . . . . . . . . . . . 48
3.3.1 Experimental setup for M(H - T) under pressure . . . . . . . 50
4 Yb(Rh1-xCox)2Si2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .51
4.1 Introduction and motivation . . . . . . . . . . . . . . . . . . . . . . 51
4.1.1 The heavy-fermion compound YbRh2Si2 . . . . . . . . . . . 53
4.1.2 The antiferromagnet YbCo2Si2 . . . . . . . . . . . . . . . . 58
4.1.3 Isoelectronic substitution of Co for Rh: Yb(Rh1-xCox)2Si2 . . . .62
4.2 Itinerant vs. local magnetism in Yb(Rh1-xCox)2Si2 . . . . . . . . . 67
4.2.1 Magnetization of Yb(Rh1-xCox)2Si2 with 0 x 0.27 . . . 67
4.2.1.1 YbRh2Si2 and Yb(Rh0.93Co0.07)2Si2 . . . . . . . . . 67
4.2.1.2 Yb(Rh0.88Co0.12)2Si2 . . . . . . . . . . . . . . . . . 71
4.2.1.3 Yb(Rh0.82Co0.18)2Si2 . . . . . . . . . . . . . . . . . 73
4.2.1.4 Yb(Rh0.73Co0.27)2Si2 . . . . . . . . . . . . . . . . . 74
4.2.1.5 Summary . . . . . . . . . . . . . . . . . . . . . . . 78
4.2.2 Magnetization of Yb(Rh1-xCox)2Si2 with x = 0.58 and x = 1 . . . . . 79
4.2.3 Evolution from itinerant to local magnetism . . . . . . . . . 83
4.3 Field-induced QCP in Yb(Rh0.93Co0.07)2Si2 . . . . . . . . . . . . . . 88
4.4 YbRh2Si2 under hydrostatic pressure . . . . . . . . . . . . . . . . . 96
4.4.1 Magnetization vs. field . . . . . . . . . . . . . . . . . . . . . 97
4.4.2 Comparison with 1.28 GPa . . . . . . . . . . . . . . . . . . . 99
4.4.3 Magnetization vs. temperature . . . . . . . . . . . . . . . . 101
4.4.4 Field-induced QCP at 1.5 GPa . . . . . . . . . . . . . . . . 103
4.4.5 The magnetic Grüneisen ratio . . . . . . . . . . . . . . . . . 105
4.5 The magnetic phase diagrams of YbCo2Si2 . . . . . . . . . . . . . . 107
4.5.1 Magnetization vs. temperature . . . . . . . . . . . . . . . . 107
4.5.2 Magnetization vs. fi eld . . . . . . . . . . . . . . . . . . . . . 109
4.5.3 H - T phase diagrams . . . . . . . . . . . . . . . . . . . . 114
4.5.4 Ac-susceptibility . . . . . . . . . . . . . . . . . . . . . . . . 117
4.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
5 NiCl2-4SC(NH2)2 . . . . . . . . . . . . . . . . . . . . . . . .121
5.1 Introduction and motivation . . . . . . . . . . . . . . . . . . . . . . 121
5.2 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
5.2.1 Magnetization . . . . . . . . . . . . . . . . . . . . . . . . . . 124
5.2.2 Comparison between theory and experiment . . . . . . . . . 126
5.2.3 Magnetic phase diagram . . . . . . . . . . . . . . . . . . . . 129
5.2.4 Speci c heat . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
5.2.5 The magnetic Grüneisen ratio . . . . . . . . . . . . . . . . . 131
5.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
6 General conclusions . . . . . . . . . . . . . . . . . . . . . . . .135
Appendix 1 . . . . . . . . . . . . . . . . . . . . . . . .139
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Synthèse et applications des sulfamidates cycliquesGalaud, Fabrice January 2005 (has links)
Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.
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Ein Baukastensystem zum universellen Aufbau kleiner rigidifizierter Peptidomimetika und spirocyclopropanierter Wirkstoffanaloga / A toolbox-system for the formation of small rigid peptidomimetics and spirocyclopropanated drug-analoguesLimbach, Michael 02 November 2004 (has links)
No description available.
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Growth and Studies of Phase Transitions in Multifunctional Perovskite MaterialsYadav, Ruchika January 2015 (has links) (PDF)
Crystal growth and characterization of few multifunctional materials with perovskite (ABX3) structure are discussed in this thesis. Efforts were made to modify the magnetic and electric behaviour of these materials by selective tuning of A, B and X components. Structural, magnetic and dielectric characterization are detailed in various chapters for doped (A and B site) rare-earth manganites and organometallic compounds with different (Chloride or formate) anions.
The relevant aspects of crystal structure and its relationship with ordered ground states are discussed in the introductory chapter. A detailed review of prominent theories pertaining to magnetic and ferroelectric ordering in the literature is provided. Growth of various inorganic compounds by solid-state reaction and floating zone method as well as use of solvothermal techniques for growing organometallic compounds are discussed. Material preparation, optimization of crystal growth processes and results of characterization are addressed in various chapters.
The effect of Yttrium doping on structural, magnetic and dielectric properties of rare-earth manganites (RMnO3 where R = Nd, Pr) has been investigated. Neutron diffraction studies (Pr compounds) confirm A-type antiferromagnetic structure and fall in transition temperature as the Yttrium doping level increases. Diffraction experiments in conjunction with dc magnetization and ac susceptibility studies reveal magnetic frustration in excess Yttrium dopedcompounds. When mutliglass properties of 50% B-site doped Nd2NiMnO6 were investigated, evidence of re-entrant cluster glass phase was seen probably due to presence of anti-site disorder. The relaxor-like dielectric behaviour arises from crossover of relaxation time in grain and grain boundary regions. Multiferroic behaviour of the organometallic compound (C2H5NH3)2CuCl4 as well as the ferroelectric transition were investigated in detail. The role of Hydrogen bond ordering in driving structural transitions is elucidated by low temperature dielectric and Raman studies in (C2H5NH3)2CdCl4. It was found possible to tune the magnetic and ferroelectric properties in metal formate compounds (general formula AB(HCOO)3) by selectively choosing organic cations [(CH3)2NH2+; C(NH3)3+] and transition metal ion [B = Mn, Co and Cu]. The nature of magnetic ordering and transition temperature could be altered by the transition metal ion. The effect of reorientation of organic cations which leads to ferroelectric nature is discussed using dielectric and pyroelectric data. Significant results are summarized in the chapter outlining general conclusions. Future prospects of work based on these observations are also provided. The conclusions are corroborated by detailed analysis of experimental data.
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β-Aminosubstituted α,β-Unsaturated Fischer Carbene Complexes as Precursors for Complex Oligocyclic Molecules - Basics and Applications / β-Amino-substituierte α,β-Ungesättigte Fischer Carben-Komplexeals Vorläufer für Kompexe Oligocyclische Moleküle - Grundforschung und AnwendungenWu, Yao-Ting 03 July 2003 (has links)
No description available.
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Untersuchungen zur Synthese von Yohimban- und Campthoteca-Alkaloiden durch Domino-Knoevenagel-Hetero-Diels-Alder-Reaktion / Efforts toward the total synthesis of yohimban and campthoteca alkaloids via domino Knoevenagel-hetero-Diels-Alder reactionKlapa, Katharina Anna 17 January 2007 (has links)
No description available.
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