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1
Lodhia, Puja. "Investigating the intracellular interactions of CLEC14A and the characterisation of monoclonal antibodies targeting CLEC14A." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/7014/.
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CLEC14A is a tumour endothelial marker known to regulate sprouting angiogenesis. While the extracellular interactions of CLEC14A have previously been studied, the intracellular interactions of CLEC14A are unknown. Fascin was identified as a binding partner for the cytoplasmic tail of CLEC14A using a yeast two hybrid screen. Interaction of CLEC14A with fascin was confirmed by proximity ligation and co-localisation was observed in HUVEC filopodia. This data indicated that interaction of CLEC14A and fascin may be important for filopodia formation during sprouting angiogenesis. Binding studies with domain deletion mutants of fascin revealed the CLEC14A binding site to be located within a highly conserved region of the β-trefoil 3 domain between amino acids 323 and 384. In addition, phosphorylation of S274 was found to regulate this interaction. Five monoclonal antibodies against CLEC14A had the potential to be developed into anti-angiogenic cancer therapeutics. The functional properties of these antibodies were explored in in vitro assays. Clones 1 and 3 were found to inhibit cell migration while clone 4 disrupted tubule formation. Clones 3 and 4 were developed into antibody drug conjugates (ADCs). These ADCs demonstrated potent cytotoxicity localised to the tumour endothelium in vivo. These results indicate that targeting CLEC14A could be an effective strategy to disrupt the tumour vasculature.
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Haddad, Yacine. "Rôle de Clec9a dans l'athérosclérose." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB099/document.
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L’athérosclérose est une maladie inflammatoire chronique. L’une des caractéristiques des lésions d’athérosclérose est l’accumulation anormale de corps apoptotiques et nécrotiques, due à un défaut d’efferocytose, ceci entraînant la formation du cœur nécrotique. L’évolution de ce cœur nécrotique est également associée à une augmentation de l’inflammation et de la taille des plaques d’athérosclérose, mais aussi dans la survenue de complications telle que la rupture de plaque. Clec9a est un récepteur transmembranaire de type lectine C, majoritairement exprimé par une sous population de cellules dendritiques les DC-CD8α+. Il est capable de reconnaître un ligand spécifiquement exprimé par les corps nécrotiques, l’actine F. L’objectif de notre travail a été de savoir si Clec9a, qui est capable de reconnaître les corps nécrotiques, pouvait être impliqué dans la modulation de l’inflammation observée au cours du développement de l’athérosclérose. Au cours de cette étude, nous avons montré, in vivo partir de deux modèles murins (ApoE-/- et LDLr-/-), que la délétion de Clec9a entraîne une diminution significative de la taille des lésions dans un contexte d’hypercholestérolémie modérée. Cette athéro-protection observée en l’absence de Clec9a, est associée à une augmentation de l’expression de l’IL-10, qui est une interleukine anti-athérogène et anti-inflammatoire. Cet effet athéroprotecteur de l’absence de Clec9a n’est plus observé lorsque l’IL-10 est totalement invalidée. De plus, nous avons montré que l’invalidation de Clec9a spécifiquement dans les DC-CD8α+ entraîne, in vivo, une diminution de l’infiltration des macrophages et des lymphocytes T dans les lésions, ainsi qu’une augmentation de l’expression de l’IL-10, favorisant une diminution de la taille des lésions. La compréhension des mécanismes inflammatoires dans l’athérosclérose constitue un enjeu majeur pour prévenir les risques de complications comme la rupture de plaque ou la thrombose. Ainsi, ce travail met en évidence un nouveau rôle de Clec9a dans la régulation de l’inflammation dans l’athérosclérose et pourrait donc représenter une cible thérapeutique potentielleAtherosclerosis is a chronic inflammatory disease. One of the characteristics of atherosclerotic lesions is the abnormal accumulation of apoptotic and necrotic cells, due to a deficiency of efferocytosis, which leads to the formation of the necrotic heart. The evolution of this necrotic core is also associated with an increase in inflammation and lesions of atherosclerosis, but also in the occurrence of complications such as plaque rupture. Clec9a is a C type lectin receptor, mainly expressed by a subpopulation of dendritic cells, which are the CD8α+ dendritic cells. This receptor is able to recognize a ligand expressed by necrotic cells, the actin F. The aim of our work was to find out if Clec9a, which can sense necrotic cells, could be involved in modulating the inflammation observed during the development of atherosclerosis. In this study, we have shown, in vivo with two mouse models (ApoE - / - and LDLr - / -), that the deletion of Clec9a leads to a significant decrease in the incidence of moderate hypercholesterolemia. This athero-protection observed in the absence of Clec9a, is associated with an increase in the expression of IL-10, which is an anti-atherogenic and anti-inflammatory cytokine. This athero-protective effect of the absence of Clec9a is abolished after total invalidation of IL-10. Furthermore, we report that specific knockdown of Clec9a in CD8α+-DC, in vivo, leads to a decrease in macrophage and lymphocyte infiltration in lesions, as well as an increase in IL-1 expression. 10, which promotes a decrease in lesions size. Understanding of inflammatory mechanisms in atherosclerosis is a major challenge to prevent the risk of complications such as plaque rupture or thrombosis. Thus, this work highlights a new role of Clec9a in the regulation of inflammation in atherosclerosis and could be therefore a potential therapeutic target
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Khan, Kabir Ali. "Investigating the extracellular interactions of the tumour endothelial marker CLEC14A." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6909/.
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CLEC14A is an endothelial specific type I transmembrane glycoprotein, which is highly expressed on the vasculature of a wide range of different solid tumours. Identifying extracellular interactions of CLEC14A holds promise for new targets in anti-angiogenic strategies for cancer treatment. CLEC14A directly binds to the extracellular matrix protein multimerin-2 (MMRN2). Both proteins are upregulated with tumour progression and are implicated in endothelial cell function. The CLEC14A-MMRN2 interaction occurs when both proteins are expressed at endogenous levels in endothelial cells, and is dependent upon the C-type lectin domain of CLEC14A. Blocking the CLEC14A-MMRN2 interaction had anti-angiogenic effects and could inhibit the growth of mouse tumour models. Finally, the localisation and targeting of CLEC14A was investigated in vivo by use of humanised antibodies and antibody drug conjugates. Data presented in this thesis reinforce the pro-angiogenic functions of CLEC14A and the likelihood of it being a good target for cancer therapy.
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Smith, Peter. "The status of a presbyter who is no longer a cleric." Theological Research Exchange Network (TREN), 1987. http://www.tren.com.
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Painting-Stubbs, Clare. "Abraham Fleming : writer, cleric and preacher in Elizabethan and Jacobean London." Thesis, Royal Holloway, University of London, 2011. http://repository.royalholloway.ac.uk/items/89fa6719-8bde-2470-3a26-e850544e284e/9/.
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Since his death in 1607, Abraham Fleming has never been completely forgotten about. This thesis covers all aspects of Fleming's life. It begins with his time at Cambridge and the relationships he forged there. It studies his varied and sometimes groundbreaking contributions to the books associated with him (with a focus on his English texts and translations). It also covers his ordination into the Church of England and subsequent career as a chaplain to Charles Howard, earl of Nottingham. It also elucidates his previously unknown life as a curate in the parish of St Nicholas, Deptford and as a deacon and priest St Pancras, Soper Lane, and finally his sermons at Paul's Cross in the grounds of St Paul's Cathedral. Fleming's legacy of at least 52 printed books, which includes original godly protestant treatises, English translations of Latin and Greek classical works, and books commemorating unusual occasions, have ensured that his name lived on in bibliographic catalogues. Since the 1950s a few scholars have considered Fleming's work on Holinshed's Chronicles as significant contributions to the text. However, the subsequent articles that have been written about him have been narrow in scope and at times unreliable. Recent studies of Fleming have considered him only as a minor writer, yet this thesis demonstrates that he was a literary figure of considerable significance. Fleming made an important contribution to the emerging public sphere, as foregrounded by Jurgen Habermas, that was lauded by his contemporaries but he has largely slipped from view. Before this doctoral research little was known about Fleming's career as a preacher in the Church of England, a career in which he proved just as diligent as when he was a “learned corrector” of books. The aim of this thesis has been to throw fresh light on the multi-faceted career of Abraham Fleming and establish him as a leading figure in late-Sixteenth century political and print culture.
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Huysamen, Cristal. "The characterization of a novel C-type lectin-like receptor, CLEC9A." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3060.
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Messerer, Denise [Verfasser], and Sven [Akademischer Betreuer] Reese. "Bedeutung Clec9a-abhängiger Immunzellen in kardialen Entzündungsprozessen / Denise Messerer ; Betreuer: Sven Reese." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1215499965/34.
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Cochin, Christophe. "Marcel Le Clerc (Klerg) et la revue Barr-Heol." Rennes 2, 2005. http://www.theses.fr/2005REN20051.
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Originaire de Plémet, en Haute-Bretagne, l'Abbé Marcel Le Clerc passa sa vie de prêtre dans le Trégor. Militant nationaliste convaincu, il prit fait et cause pour le Mouvement breton. Pendant vingt-cinq ans, il lutta pour maintenir debout sa revue Barr-Heol, née de la rupture avec le Bleun-Brug, essentiellement pour des raisons d'orthographe. Il traduisit également de nombreux livres liturgiques à l'usage des églises catholiques. Il consacra toute sa vie à la défense de la langue bretonne. La période n'était pas propice : entre les années 50 et 80, le breton s'écroulait de toutes parts et il fallait le courage de l'abbé Le Clerc pour maintenir la langue au catéchisme de Buhulien ou dans son bulletin paroissial, " Koulmig ar Gindi ". Il était également passionné par le gallois et la toponymie. Sa mort laissa un vide dans le Mouvement Breton. Mais quelle a été l'influence de l'œuvre de Marcel Le Clerc sur la littérature bretonne aujourd'hui ? Lit-on encore les cent numéros de sa revue vingt-cinq ans après ? Par sa ténacité, sa volonté d'apprendre la langue, d'employer et de diffuser un breton simple et authentique, il restera une figure marquante du renouveau linguistiqueFather Marsel Klerg was born in Plemet, in Upper Brittany in 1912. He spent his working life as a priest in Tregor. He was an ardent nationalist and fought all his life for the Breton movement. In 1953, he cut off links with the “Bleun-brug” and managed for 25 years to keep alive his magazine “Barr-Heol” going. He translated many religious books for use in Church. Although he shared a great interest for the Welsh language with his friend Armans ar C'halvez, he spent all his life defending and promoting the Breton language which he began to learn while at school at Saint-Brieuc. This was not an easy task between the years 55 and 80. The use of the language was falling at a catastrophic rate, and Marsel Klerg had to fight to maintain the use of Breton in the catechism of Buhulien or in his parochial bulletin. When he died in 1984, his loss was deeply felt by the Emsav, the Breton movement. 25 years later, it is nearly impossible to find all 100 issues of his magazine. But who nowadays still remembers Father Klerg ? By his courage and his will to learn the language and to use a simple, true and authentic Breton, he will remain an example to all those who knex him, and indeed perhaps for others also
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BIANCHI, ANDREA. "HETERODOXY AND RATIONAL THEOLOGY: JEAN LE CLERC AND ORIGEN." Doctoral thesis, Università Cattolica del Sacro Cuore, 2020. http://hdl.handle.net/10280/73305.
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L’elaborato analizza la ricezione del pensiero di Origene di Alessandria (c. 184-c.253) nell’opera del teologo arminiano Jean Le Clerc (1657-1736), soffermandosi in particolare sulla concezione origeniana della libertà e sulle questioni che vi sono annesse. Tale analisi consente anche di chiarire alcune pratiche argomentative e dinamiche intellettuali, soprattutto riguardanti i dibattiti religiosi ed interconfessionali, nella seconda metà del XVII secolo. L’elaborato è diviso in tre sezioni. La prima, di carattere introduttivo, mira ad indagare le premesse epistemologiche di Le Clerc, nonché la sua relazione con le auctoritates religiose ed intellettuali del passato. La seconda sezione prende in esame le citazioni dirette di Origene presenti nella vasta produzione di Le Clerc, come pure i suoi rimandi all’opera dell’Alessandrino e al suo pensiero, consentendo in questo modo di delineare un quadro preciso dell’Origene letto e reinterpretato da Le Clerc. La terza sezione restringe infine il campo d’indagine allo sguardo che Le Clerc porta sulla dimensione più propriamente teologica di Origene ed in particolar modo su quel nodo di concetti che ruota attorno al tema della libertà umana (peccato originale, grazia e predestinazione, il problema del male). Questo studio mostra come, malgrado l’indubbia, e talvolta malcelata, simpatia per Origene, Le Clerc non possa essere definito tout court un ‘origenista’, dal momento che la sua visione epistemologica, scritturale e teologica lo distanzia da una acritica e piena adesione al pensiero dell’Alessandrino.The present thesis analyses the reception of the thought of Origen of Alexandria (c. 184-c. 253) in Jean Le Clerc (1657-1736). Its particular focus is on Origen's conception of freedom and the theological doctrines related to it. The goal of this thesis is to uncover, through Le Clerc's use of Origen, some of the argumentative practices and the intellectual dynamics of the time, in particular in religious, especially inter-confessional, debates. This thesis is divided into three main parts. The first part has mainly an introductory character and looks at the epistemological assumptions of Le Clerc and his relationship with intellectual and religious authorities of the past. The second part reviews the various ways in which Le Clerc quoted, referred to or otherwise made use of the thought or the name of Origen in his vast production. This part provides a first result in that it frames, in general, Le Clerc's reception of Origen. This step is, at the same time, also preparatory for the material contained in part three. In the third part, only the material is considered which is strictly related to Origen's idea of freedom and the related theological doctrines of original sin, grace/predestination, and the problem of evil. The result of this analysis, as it appears form the examination of argumentative practices in the previous sections, is that Le Clerc was no simple "Origenist" but neither was he was fully uncommitted to the Origenian cause. A full commitment to Origen, despite this strong sympathy, was still hindered by Le Clerc's epistemological, scriptural and theological outlook.
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BIANCHI, ANDREA. "HETERODOXY AND RATIONAL THEOLOGY: JEAN LE CLERC AND ORIGEN." Doctoral thesis, Università Cattolica del Sacro Cuore, 2020. http://hdl.handle.net/10280/73305.
Full textAbstract:
L’elaborato analizza la ricezione del pensiero di Origene di Alessandria (c. 184-c.253) nell’opera del teologo arminiano Jean Le Clerc (1657-1736), soffermandosi in particolare sulla concezione origeniana della libertà e sulle questioni che vi sono annesse. Tale analisi consente anche di chiarire alcune pratiche argomentative e dinamiche intellettuali, soprattutto riguardanti i dibattiti religiosi ed interconfessionali, nella seconda metà del XVII secolo. L’elaborato è diviso in tre sezioni. La prima, di carattere introduttivo, mira ad indagare le premesse epistemologiche di Le Clerc, nonché la sua relazione con le auctoritates religiose ed intellettuali del passato. La seconda sezione prende in esame le citazioni dirette di Origene presenti nella vasta produzione di Le Clerc, come pure i suoi rimandi all’opera dell’Alessandrino e al suo pensiero, consentendo in questo modo di delineare un quadro preciso dell’Origene letto e reinterpretato da Le Clerc. La terza sezione restringe infine il campo d’indagine allo sguardo che Le Clerc porta sulla dimensione più propriamente teologica di Origene ed in particolar modo su quel nodo di concetti che ruota attorno al tema della libertà umana (peccato originale, grazia e predestinazione, il problema del male). Questo studio mostra come, malgrado l’indubbia, e talvolta malcelata, simpatia per Origene, Le Clerc non possa essere definito tout court un ‘origenista’, dal momento che la sua visione epistemologica, scritturale e teologica lo distanzia da una acritica e piena adesione al pensiero dell’Alessandrino.The present thesis analyses the reception of the thought of Origen of Alexandria (c. 184-c. 253) in Jean Le Clerc (1657-1736). Its particular focus is on Origen's conception of freedom and the theological doctrines related to it. The goal of this thesis is to uncover, through Le Clerc's use of Origen, some of the argumentative practices and the intellectual dynamics of the time, in particular in religious, especially inter-confessional, debates. This thesis is divided into three main parts. The first part has mainly an introductory character and looks at the epistemological assumptions of Le Clerc and his relationship with intellectual and religious authorities of the past. The second part reviews the various ways in which Le Clerc quoted, referred to or otherwise made use of the thought or the name of Origen in his vast production. This part provides a first result in that it frames, in general, Le Clerc's reception of Origen. This step is, at the same time, also preparatory for the material contained in part three. In the third part, only the material is considered which is strictly related to Origen's idea of freedom and the related theological doctrines of original sin, grace/predestination, and the problem of evil. The result of this analysis, as it appears form the examination of argumentative practices in the previous sections, is that Le Clerc was no simple "Origenist" but neither was he was fully uncommitted to the Origenian cause. A full commitment to Origen, despite this strong sympathy, was still hindered by Le Clerc's epistemological, scriptural and theological outlook.
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Teng, Ooiean, and 丁瑋嫣. "Identification of CLEC5A in modulating host immune response after influenza A virus infection." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208615.
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Human infections with influenza A virus (IAV) exhibit mild to severe clinical outcomes as a result of differential virus-host interactions. C-type lectin receptors (CLRs) are pattern recognition receptors that may sense carbohydrates, proteins, or lipids derived from infected hosts or the invading microbes including bacteria, viruses, fungi, or parasites. CLR-viral interaction may lead to increased viral entry and spread; furthermore, their interactions have been reported to trigger downstream signaling that further modulates host’s innate immune responses through the induction of pro-inflammatory cytokines. To date, DC-SIGN and DC-SIGNR have been shown to mediate IAV entry; however, the potential interactions between other human transmembrane CLRs with IAV have not yet been systematically investigated. We utilized lentiviral-based pseudoparticles expressing influenza hemagglutinin (HA) to examine the binding potential between HA and a panel of human CLRs expressed in soluble form. CLEC5A was identified as a potential interacting target with the HA proteins derived from a highly pathogenic avian H5N1 virus A/VN/1203/04 (VN1203) or a human seasonal H1N1 virus A/HK/54/98 (HK5498), albeit at different binding intensity. Applying siRNA gene silencing, we confirmed that CLEC5A did not enhance influenza entry in human monocytic U937 cells that constitutively express CLEC5A or in the lentiviral-transduced stable CHO and CHO-Lec2 cells that overly expressed CLEC5A. To investigate downstream signaling upon engagement of CLEC5A to influenza virus, M-CSF or GM-CSF differentiated human macrophages with high expression levels of CLEC5A and DAP12, a known adaptor protein for CLEC5A upon phosphorylation to initiate signal transduction, was subjected to CLEC5A siRNA gene silencing followed by infection with recombinant A/PR/8/34 virus expressing HA and NA derived from either VN1203 (H5N1) or HK5498 (H1N1) viruses. RG-PR8xVN1203HA,NA (H5N1) exhibited a higher infectivity and induced higher levels of pro-inflammatory cytokines (TNF-( and IFN-α) and chemokines (IP-10, MCP-1, MIG and MIP-1α) secretion in M-CSF or GM-CSF differentiated macrophages while compared to that of the RG-PR8xHK5498HA,NA (H1N1) virus. Knocking-down CLEC5A in macrophages led to a universal reduction of cytokines and chemokines secretion after infection with either the RG-PR8xVN1203HA,NA, RG-PR8xHK5498HA,NA, RG-A/VN/1203/04 (H5N1) or A/Shanghai/2/2014 (H7N9) viruses, suggesting that CLEC5A plays a role as cytokine and chemokine amplifier after influenza infection. Since DAP12 phosphorylation is known to activate downstream signaling via Spleen tyrosine kinase (Syk), pre-incubation of M-CSF macrophages with a Syk inhibitor (Bay 61-3606) also lead to a significant reduction of TNF-α and IP-10 in infected macrophages. A higher mortality was observed in CLEC5A-/- mice while compared to the wild-type C57BL/6 mice after challenged with a lethal dose of RG-A/VN/1203/04 (H5N1) influenza virus suggesting that CLEC5A as a host innate response amplifier play a protective role upon influenza infection. In conclusion, we have identified CLEC5A as a novel host factor for influenza pathogenesis by modulating host innate inflammatory response.published_or_final_version
Public Health
Doctoral
Doctor of Philosophy
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Neulen, Marie-Luise. "Das Hühner CLEC-2 Homolog." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-151348.
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Clerc, Patrice Brunet Michel. "Mesure de champs de déplacements et de déformations par stéréovision et corrélation d'images numériques." Villeurbanne : Doc'INSA, 2004. http://docinsa.insa-lyon.fr/these/pont.php?id=clerc.
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Stouvenot, Clarisse. "L'Ovide moralise : les Metamorphoses d'Ovide revues et corrigees par un clerc." Thesis, University of Exeter, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251125.
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Van, Blijswijk J. M. "Mouse models to deplete or label dendritic cells via genetic manipulation of the Clec9a locus." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1472681/.
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Dendritic cells (DCs) play important roles at the interface between innate and adaptive immunity by priming and directing T cell responses. Much of our current knowledge of DC biology has come from mouse models in which DCs can be genetically manipulated, labelled or ablated. Here, novel models are presented using a strategy that targets DC precursors via genetic editing of the Clec9a locus. While validating a novel mouse model to inducibly deplete DCs using diphtheria toxin receptor (DTR) expression driven by Clec9a, it became clear that these Clec9a+/CreROSAiDTR mice suffer from unexpected lymph node (LN) hypocellularity and reduced frequencies of DCs in LNs, even in the absence of diphtheria toxin (DT) injection. This phenotype turned out to be a common feature of other mouse models in which DTR is expressed on DCs (e.g. CD11c-DTR and Langerin-DTR mice) and raises questions about the interpretation of results obtained with such animals. Therefore, in an alternative approach, mice were developed to constitutively lack DCs by expressing the diphtheria toxin alpha (DTA) subunit under control of the Clec9a locus. Unfortunately, these mice still harboured DCs and only showed partial reduction of one DC subset. Finally, seeding of tissues by DC precursors was examined. Clec9a+/CreROSA+/confetti mice were generated in which DC precursors stochastically express one of four fluorescent proteins, which is inherited by its daughter cells. 8- Colour microscopy of tissue sections and histo-cytometry analysis of the images was developed to analyse these mice. This approach will be used to determine how many daughter cells are produced when a single DC precursor seeds the small intestine (clonal burst size), whether these daughters are found among different DC subsets and whether seeding changes during inflammation. In summary, manipulation of the Clec9a locus proves to be an excellent way to study the DC lineage and DC precursor behaviour in the mouse.
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Fout, John. "The Explosive Cleric: Morgan Godwyn, Slavery, and Colonial Elites in Virginia and Barbados, 1665-1685." VCU Scholars Compass, 2005. http://scholarscompass.vcu.edu/etd/1517.
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Historians often describe how the ideas of national identity, race, religious affiliation, and political power greatly influenced the development of societies in colonial America. However, historians do not always make clear that these ideas did not exist independently of one another. Individuals in colonial Americans societies often conflated and incorporated one or more of these ideas with another. In other words, individuals did not always think of national identity and race and religious affiliation as independent entities. The specific case of the Reverend Morgan Godwyn illuminates just how connected these ideas were in the minds of some colonial Americans. As a minister in the Church of England, Godwyn spoke and wrote within an overtly religious context. His words, however, reveal that to him, religion and politics, national identity and race and ethnicity, could not be unpacked and viewed separately-each heavily influenced the others. Godwyn used his position as a cleric to challenge the authority of English colonial elites. He attempted to convince the English public of the necessity of reining in the growing powers of colonial elites in order to preserve the authority of the English monarch and the Church of England clergy. From studying Morgan Godwyn, one can see how complex and convoluted ideas-and simultaneously important-ideas of national identity, race, religion and political influence were in seventeenth-century colonial American societies.
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Manne, Bhanu Kanth. "CLEC-2 SIGNAL TRANSDUCTION IN PLATELET ACTIVATION." Diss., Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/340495.
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PhysiologyPh.D.
Platelets are involved in many processes ranging from fighting microbial infections and triggering inflammation to promoting tumor angiogenesis and metastasis. Nevertheless, the primary physiological function of platelets is to act as essential mediators in maintaining homeostasis of the circulatory system by forming hemostatic thrombi that prevent blood loss and maintain vascular integrity. CLEC-2 is a C-type lectin-like receptor that is highly expressed in platelets and lesser extent, in other cell types such as activated dendritic cells and B cells. Rhodocytin was the first ligand used to identify CLEC-2 receptor and it’s signaling on platelets. In the first chapter we identified a new agonist for CLEC-2 receptor. Fucoidan, a sulfated polysaccharide from fucus vesiculosus, decreases bleeding time and clotting time in hemophilia, possibly through inhibition of tissue factor pathway inhibitor. However, its effect on platelets and the receptor by which fucoidan induces cellular processes has not been elucidated. In this study, we demonstrate that fucoidan induces platelet activation in a concentration-dependent manner. Fucoidan-induced platelet activation was completely abolished by the pan-Src family kinase (SFK) inhibitor, PP2, or when Syk is inhibited. PP2 abolished phosphorylation of Syk and Phospholipase Cγ−2. Fucoidan-induced platelet activation had a lag phase, which is reminiscent of platelet activation by collagen and CLEC-2 receptor agonists. Platelet activation by fucoidan was only slightly inhibited in FcRγ chain null mice, indicating that fucoidan was not acting primarily through GPVI receptor. On the other hand, fucoidan-induced platelet activation was inhibited in platelet-specific CLEC-2 knock-out murine platelets revealing CLEC-2 as a physiological target of fucoidan. Thus, our data show fucoidan as a novel CLEC-2 receptor agonist that activates platelets through a SFK-dependent signaling pathway. Furthermore, the efficacy of fucoidan in hemophilia raises the possibility that decreased bleeding times could be achieved through activation of platelets. Lipid rafts are distinct areas of the plasma membrane implicated in the regulation of signaling in a variety of cells including platelets. A previous study C-type lectin like receptor 2 (CLEC-2) has been reported to activate platelets through a lipid raft-dependent manner. Secreted ADP potentiates CLEC-2-mediated platelet aggregation. We have investigated whether the decrease in CLEC-2-mediated platelet aggregation, previously reported in platelets with disrupted rafts, is a result of the loss of agonist potentiation by ADP. We disrupted platelet lipid rafts with methyl-β-cyclodextrin (MβCD) and measured signaling events downstream of CLEC-2 activation. Lipid raft disruption decreases platelet aggregation induced by CLEC-2 agonists. The inhibition of platelet aggregation by the disruption of lipid rafts was rescued by the exogenous addition of epinephrine but not 2-methylthioadenosine diphosphate (2MeSADP), which suggests that lipid raft disruption effects P2Y12-mediated Gi activation but not Gz. Phosphorylation of Syk (Y525/526) and PLCγ2 (Y759), were not affected by raft disruption in CLEC-2 agonist-stimulated platelets. Furthermore, tyrosine phosphorylation of the CLEC-2 hemi-ITAM was not effected when MβCD disrupts lipid rafts. Lipid rafts do not directly contribute to CLEC-2 receptor activation in platelets. The effects of disruption of lipid rafts in in vitro assays can be attributed to inhibition of ADP feedback that potentiates CLEC-2 signaling. Tyrosine kinase pathways are known to play an important role in the activation of platelets. In particular, the GPVI and CLEC-2 receptors are known to activate Syk upon tyrosine phosphorylation of an Immune Tyrosine Activation Motif (ITAM) and hemi-ITAM, respectively. However, unlike GPVI, the CLEC-2 receptor contains only one tyrosine motif in the intracellular domain. The mechanisms by which this receptor activates Syk are not completely understood. In chapter 3, we identified a novel signaling mechanism in CLEC-2-mediated Syk activation. CLEC-2-mediated, but not GPVI-mediated, platelet activation and Syk phosphorylation were abolished by inhibition of PI3-Kinase, which demonstrates that PI3-Kinase regulates Syk downstream of CLEC-2. Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets. Furthermore, embryos lacking both Btk and Tec exhibited cutaneous edema associated with blood-filled vessels in a typical lymphatic pattern similar to CLEC-2 or Syk-deficient embryos. Thus our data show, for the first time, that PI3-Kinase and Tec family kinases play a crucial role in the regulation of platelet activation and Syk phosphorylation downstream of CLEC-2 receptor.
Temple University--Theses
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Bougie, Karine. "Robert de Boron et l’invention du Saint Graal." Thesis, Bordeaux 3, 2014. http://www.theses.fr/2014BOR30043.
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L’étude des romans attribués à Robert de Boron s’inscrit dans le sillage des travaux sur l’autoréflexivité romanesque et auctoriale, ainsi que sur le développement et la diffusion du mythe du Saint-Graal. Robert de Boron apparaît comme le fondateur d’une importante tradition graalienne, explicitement associée à la figure du Christ et promise à un avenir littéraire considérable. Nous croyons que l’approche mythopoétique, qui permet à la littérature de créer des mythes, s’accorde avec les enjeux socio-historiques des laïcs, ce qui explique pourquoi le projet de Robert s’est étendu jusqu’au cycle du Lancelot -Graal où il a servi de fondation à la chevalerie célestiele. Dans la première partie de ce travail, nous examinons le Saint-Graal et la tradition incarnée par Robert (occurrences, scènes, senefiance et Hauts Livres). Dans la deuxième partie, nous étudions la figure de Robert (éléments de biographie, figure auctoriale, autorité). La dernière partie nous donne l’occasion de remettre les mythes littéraires dans leur contexte afin de montrer qu’ils sont transformés en mythes socio-historiques grâce au savant mélange du discours laïque et du discours cléricalThe study of the French romances attributed to Robert de Boron lies within the recent works on self reflexivity in medieval literature and on the rise and spreading of the Holy Grail myth. Robert de Boron has become known as the founder of a new Grail tradition, explicitly related to Jesus Christ and destined to a great popularity. We think that mythopoétique approach, which allows literature to create myths, is consistent with the socio-historical issues of the laity, which is why Robert’s undertaking has spread to the Lancelot-Grail cycle where it served as the foundation of celestial chivalry. This dissertation consists of three main parts. In the first one, we examine the occurrences of the « Holy Grail » expression in the selected books. Furthermore, we go deeper in our analysis of the Grail tradition embodied by Robert de Boron. In the second part of the thesis, we focus of the figure of Robert, by studying some biographical information, his status as a writer and the nature of medieval authority and authorship. The last section of our work gives us the opportunity to set the literary myths in context to show that they are transformed into socio-historical myths through both secular and clerical discourses in the Arthurian romances
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Meisen, Lydia. "Die Charakterisierung der Tiere in Buffons Histoire naturelle." Würzburg Königshausen & Neumann, 2007. http://d-nb.info/986961698/04.
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Köhler, Arnaud. "Rôle des cellules dendritiques pre-CD8α Clec9A+ dans la protection contre Listeria monocytogenes en début de vie." Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/235619.
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Selon un rapport de l’OMS, les maladies infectieuses figurent parmi les 3 causes les plus fréquentes de mortalité en début de vie. En effet, les nouveau-nés présentent une sensibilité particulièrement importante aux infections, de par leur système immunitaire toujours en développement et donc immature. Parmi les particularités de l’immunité néonatale, l’absence de cDCs CD11chigh CD8α+ durant la 1ère semaine de vie rend compte de l’incapacité du nouveau-né à développer des réponses de type Th1 et T CD8+ cytotoxiques, essentielles à la protection contre certains pathogènes comme Listeria monocytogenes (Lm). Mon travail de thèse a porté sur l’ontogénie des DCs conventionnelles CD11chigh CD8α+ et plus particulièrement sur la fonction de cette lignée de DCs en début de vie lors d’une infection par Lm. Au cours de cette étude, nous avons identifié, chez le nouveau-né, une population splénique de cDCs CD11chigh qui expriment les marqueurs CD24, CD205 et Clec9A mais pas le CD8α. Cette population, qui dépend du facteur de transcription Batf3, acquière le CD8α une fois transférée dans une souris adulte. Ces DCs néonatales, que nous nommerons DCs pre-CD8α Clec9A+, constituent donc les précurseurs des DCs CD8α+. L’étude fonctionnelle de ces DCs pre-CD8α Clec9A+ a montré qu’elles étaient capables de phagocyter Lm et de générer des réponses T CD8+ contre cette bactérie. De plus, ces cellules sécrètent de l’IL-12p40 et de manière unique de l’IL-10 en réponse à une stimulation par Lm. Par contre, contrairement aux cDCs CD8α+ adultes, nous n’avons observé aucune production d’IL-12p70 par les DCs pre-CD8α Clec9A+ en conditions physiologiques. Elles ne sécrètent pas non plus d’IL-23. Nous avons également montré que ces sécrétions d’IL-12p40 et d’IL-10 jouaient respectivement un rôle positif et négatif dans l’induction des réponses T CD8+ contre Lm. Ainsi, la génération des réponses T CD8+ contre Lm semble résulter, en début de vie, d’une balance entre la sécrétion de ces 2 cytokines aux propriétés antagonistes. Par ailleurs, nous avons démontré que ces cellules constituaient une cible privilégiée en vue d’améliorer les stratégies vaccinales en début de vie. En effet, l’administration à des nouveau-nés d’une construction anti-Clec9A/OVA, associée au poly(I:C), induit des réponses T CD8+ anti-Lm mémoires protectrices à l’âge adulte. Finalement, nous montrons que le TNF-α produit par les monocytes et les neutrophiles joue un rôle essentiel dans la génération des réponses T CD8+ en régulant notamment le statut et la fonction des DCs pre-CD8α Clec9A+ en début de vie. En effet, cette cytokine modifie, en faveur d’une production d’IL-12p40, la balance IL-12p40/IL-10 sécrétée par celles-ci. L’inhibition de la production d’IL-10 par le TNF-α pourrait s’expliquer au moins en partie par une inhibition de la β-caténine au sein des DCs pre-CD8α Clec9A+. En conclusion, nous avons caractérisé un précurseur des DCs CD8α+ biologiquement actif au sein de la rate du nouveau-né de 3 jours. Celui-ci représente une cible potentielle pour l’amélioration des stratégies vaccinales contre des bactéries intracellulaires ou des virus en début de vie, et ce pour autant que l’on puisse contrôler ses propriétés régulatrices.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished
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Gonçalves, Maia Maria João. "Le syndrome Xeroderma Pigmentosum : Un nouveau modèle pour l’étude du rôle des fibroblastes dans la modulation de la réponse immunitaire innée contre les cellules cutanées cancéreuses." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR4037.
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L’étiologie des cancers cutanées est liée à des mutations génétiques résultant de l’exposition aux rayonnements ultraviolets (UV) émis par le soleil. La propagation des cellules cancéreuses dépend aussi des interactions avec les cellules présentes dans le microenvironnement circulant, notamment des fibroblastes associés au cancer (FAC) et des cellules immunitaires. Xeroderma pigmentosum (XP) est une maladie génétique qui comprend 7 groupes de complémentation génétique (XP-A à XP-G). Les patients XP présentent une déficience du mécanisme de réparation des lésions de l’ADN provoquées par les UV. Ces patients sont susceptibles au développement précoce de très nombreux cancers cutanées. XP-C est le groupe de complémentation le plus représenté en Europe. Chez ces patients, les carcinomes spino-cellularies (CSC) sont plus fréquents que les carcinomes baso-cellulaires (CBC) (taux 5 : 1). Les CSC ont un potentiel métastatique plus élevé que les CBC. Des travaux précédents ont suggéré que la réponse immunitaire chez les patients XP pouvait être altérée, incluant un déficit de l’activité cytolytique des cellules Natural Killer (NK) et une diminution du nombre des lymphocytes T circulants.L’objectif central de cette thèse était, d’identifier des facteurs du microenvironnement impliqués dans la progression des cancer cutanées agressifs, en prenant comme modèle de susceptibilité au cancer, des cellules de patients XP-C. Une analyse transcriptomique comparant les fibroblastes WT et des patients XP-C a permis d’identifier que CLEC2A, un ligand activateur du récepteur NKp65 des cellules NK, est exprimé par les fibroblastes WT mais pas par les fibroblastes XP-C. Nos travaux ont pu montrer une diminution du niveau d’expression de CLEC2A au cours de la sénescence réplicative ; une absence dans les FAC et dans les CSC et que, des facteurs solubles secrétés para les CSC diminuent l’expression de CLEC2A. Ces résultats suggèrent que la perte de CLEC2A peut induire un déficit d’activation des cellules NK au sein du microenvironnement tumoral et dans les dermes des patients XP-C. Par la suite, nous avons élaboré un modèle de culture de peau 3D, dans lequel nous avons introduit des cellules NK, en présence ou absence d’anticorps bloquants CLEC2A. Ce modèle nous a permis de montrer que l’interaction CLEC2A/NKp65 régule l’invasion des CSC via un dialogue entre fibroblastes et cellules NK. Nos résultats suggèrent que l’expression de CLEC2A dans les fibroblastes WT contribue à la surveillance immunitaire dans la peau et que son absence, par des facteurs encore inconnus, favorise le développement des cancers agressifs chez les patients XP-C. CLEC2A peut être une cible dans le combat contre la progression des CSCSkin cancer etiology is related to genetic mutations arising after ultraviolet (UV) sun exposure. The propagation of cancer cells is also dependent of a crosstalk with cells present in the surrounding microenvironment, mainly cancer associated fibroblasts (CAF) and immune cells. Xeroderma pigmentosum (XP) is a genetic disease that comprises seven groups of genetic complementation (XP-A to XP-G). XP patients present a default in the mechanism responsible for the repair of UV-induced DNA lesions. They are prone to develop skin cancers with high frequencies early in their life. XP-C is the most represented complementation group in Europe and in XP-C patients squamous cell carcinoma (SCC) are more frequent than basal cell carcinoma (BCC) (ratio 5:1). SCC have high metastatic potential compared to BCC. Previous studies suggested that the immune responses in XP patients could be altered with defects in their NK lytic activity and a decrease in the levels of circulating T lymphocytes. The main objective of this thesis was to identify microenvironment factors that could contribute to the progression of aggressive skin cancers using XP-C disease cells as a model of skin cancer susceptibility. Comparative transcriptomic analysis of WT and XP-C dermal patient’s fibroblasts revealed that CLEC2A, a ligand of the activating NK receptor NKp65 implicated in the activation of the innate immune system, is expressed in WT fibroblasts and absent in XP-C fibroblasts. Additional work showed that CLEC2A level is decreased in WT fibroblasts during replicative senescence, is absent in CAF and SCC, and is down regulated by soluble factors secreted by SCC cells. These results suggest that the loss of CLEC2A may induce a deficit of NK cell activation in the tumor microenvironment of SCC and in the dermis of XP-C patients. Elaboration of 3D skin culture models including NK cells and, in the presence or absence of blocking anti-CLEC2A antibody, allowed us to show that CLEC2A/NKp65 interaction regulates SCC cells invasion through a crosstalk between fibroblasts and NK cells. Our results suggest that the expression of CLEC2A in fibroblasts contributes to skin immune surveillance while, conversely, its absence under yet unidentified factors, favors the development of aggressive cancers in XP-C patients. CLEC2A could be a potential target in the fight against SCC progression
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Miry, Jacques. "L' éducation des filles au XVIIème siècle selon Alix Le Clerc et Pierre Fourier : d'après les constitutions de la congrégation Notre-Dame, la relation d'Alix Le Clerc et la correspondance de Pierre Fourier: 1598-1640." Strasbourg, 2009. http://www.theses.fr/2009STRA5002.
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Yoshikawa, Fábio Seiti Yamada. "A participação dos receptores da imunidade inata na resposta contra Trichophyton rubrum." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-04052016-104324/.
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Dermatofitoses são infecções fúngicas de natureza crônica cujo principal agente etiológico é Trichophyton rubrum. Apesar de sua alta ocorrência mundial, pouco se sabe sobre os mecanismos imunológicos envolvidos nestas infecções. Neste trabalho investigamos a participação de duas classes de receptores de imunidade inata (NLRs e CLRs) na resposta a T.rubrum e avaliamos o perfil proteômico de macrófagos quando estimulados com o fungo. Observamos que T.rubrum foi capaz de induzir a produção de IL-1β dependente do inflamassomo NLRP3 e destacamos o papel da sinalização de IL-1 na modulação da resposta de IL-17. Determinamos os CLRs dectina-1 e dectina-2 como receptores essenciais na produção de citocinas inflamatórias e para o controle da infecção experimental. Curiosamente, a IL-17 e os linfócitos T e B foram dispensáveis para a eliminação do fungo. Também identificamos a proteína CLEC1A como uma novo receptor para fungos, envolvido no reconhecimento de glicolipídeos de T.rubrum. Por fim, a análise proteômica de macrofagos revelou a vimentina e a plastina-2 como duas proteínas potencialmente envolvidas na relação patógeno-hospedeiro.Dermatophytosis are chronic fungal infections whose main causative agent is Trichophyton rubrum. Despite its high incidence worldwide, the immunological mechanisms underlying these infections remain largely unknown. Here we investigated the involvement of two classes of innate immune receptors (NLRs and CLRs) in the reponse to T.rubrum and performed a proteomic profiling of macrophages upon T.rubrum stimulation. We observed that T.rubrum was able to drive NLRP3 inflammasome-derived IL-1β production and highlighted IL-1 signaling as an important component in the shaping of the IL-17 response. We defined the CLRs dectin-1 and dectin-2 as key receptors for the induction of inflammatory cytokines and for the infection control in the in vivo settings. Curiously, IL-17 cytokines and T and B lymphocytes were dispensable for fungal clearance. In addition, we uncovered CLEC1A as a new receptor in fungal sensing, involved in the recognition of T.rubrum glycolipids. Finally, the proteomic analysis revealed Vimentin and Plastin-2 as two proteins potentially involved in the host-pathogen interaction.
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Zanandrea, Fabiana. "Operários da fé: uma leitura da juventude operária católica a partir da Diocese de Caxias do Sul/RS." Universidade do Vale do Rio do Sinos, 2008. http://www.repositorio.jesuita.org.br/handle/UNISINOS/1856.
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Previous issue date: 28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Este projeto propõe-se a analisar como se deram as relações entre clérigos e leigos militantes da Juventude Operária Católica (JOC), em Caxias do Sul RS, e de que forma conviveram os preceitos ideológicos cristãos e marxistas presentes na literatura jocista, no período de 1955 e 1975. Além disso, o convívio de elementos mais progressistas da Igreja com o clero, em geral, conservador da região também é estudado pela pesquisa. Os aspectos mencionados são investigados à luz das transformações no contexto político e socioeconômico inerente ao período. A JOC, parte integrante da Ação Católica (Movimento Internacional de Formação e Evangelização de Leigos), configurou um dos mecanismos de mobilização do laicato utilizados pela Igreja no intuito de promover a transformação social, principalmente a partir da “opção pelos pobres” que caracterizou o Concílio Vaticano II. Tal postura, do segmento mais progressista do clero, encontrou obstáculos contundentes com o estabelecimento do regime autoritário no país, o que impl
This project intends to analyze how the relationship between cleric and lay militants of the JOC (Juventude Operária Católica – Catholic Youth Labor) were, in Caxias do Sul RS, and in which way Christian ideological precepts and Marxists present in the jocista literature lived together, in the period between 1955 and 1975. Besides, the conviviality of more progressive elements of the Church with the clergy, in general, conservative of the area is also studied in this research. The mentioned aspects are investigated under the light of transformations in political and socioeconomic context inherent to the period. JOC, integrant of the Catholic Action (Lay Formation and Evangelization International Movement), configured one of the laity mobilization mechanisms used by the Church in the intention of promoting social transformation, mainly starting from the "option for the poor" which characterized the Vatican Council II. Such posture, from the most progressive segment of the clergy, found contusing obstacles with
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Horan, Lucas H. "Testing the role of ribosomal intersubunit movement in translocation & discovery of the Clec2 hammerhead ribozyme /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2009. http://uclibs.org/PID/11984.
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Boers, Wil. "La Genèse d'Évrat. la spiritualité du clerc et du laïque [sic] au tournant du christianisme médiéval /." [Brive-la-Gaillarde] : [Éd. du Ver luisant], 2002. http://catalogue.bnf.fr/ark:/12148/cb39150714f.
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Cruz, Cesar A. "Letting Go of Clecha, While Holding Corazón; Developing a New Approach to Empowering Youth in Gangs the Homeboy Industries Way." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:27013337.
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This capstone seeks to assess and support Homeboy Industries (HBI), a leader in wrap-around services for formerly gang-involved and incarcerated men and women, in their co-creation of a youth services committee and a comprehensive system of care for young people. In doing so, my strategic project consists of conducting stakeholder interviews, focus groups, and synthesizing those findings to present to the organization. The second part of the strategic project involves building and working with a team of individuals from various departments, including case management, mental health, education, job services within two separate agencies, Homeboy Industries and Learning Works Charter School Network, to create a youth services committee that can carry the work forward. In service of evaluating the progress of the strategic project, I will utilize the 4I Framework of Organizational Learning, developed by management professor, Mary Crossan, and her associates from the Ivey School of Business. The 4I Framework contains “four related (sub)processes-intuiting, interpreting, integrating, and institutionalizing-that occur over three levels: individual, group, and organization” (Crossan et al., 1999, p. 524). Ultimately, the goal is to help an already successful leader in wrap-around support services for adults, Homeboy Industries, create an “organized system of care for young people” (Torres, 2015). This goal can be achieved by maximizing its strengths, coupling them with best practices in youth development, and in creating a team that can place the needs of young people in its core mission. Creating an organized system of care, Homeboy Industries-style, can have national implications as the new secretary of education, John King, has made it a point to visit with the leaders of Homeboy Industries (August 2015, Appendix A) in search of models for empowering the youth in a non-traditional way. If clecha, or knowledge that is passed down in prison is the old way of empowering young people, as it often goes in one ear and out the other, then this capstone seeks to capture the experience of Homeboy Industries and Learning Works, the profound work of founder Father Greg Boyle and many amazing practitioners on site at HBI, and combine it with the wisdom of young people, to offer a new approach to empower youth in gangs, the ever-evolving, Homeboy Industries Way. See, the idea of clecha or street wisdom has been passed down for generations as the way that older homies “lace” (give) younger homies advice. In the research on best practices to reach gang involved youth, this clecha notion dates back to the curbside counselor of the 1930s from the seminal work of psychologist Clifford Shaw, but often times, that form of advice has not worked. This has created what Reed Larson, a pioneer in positive youth development, calls the Intentionality Paradox. According to Larson, the paradox lies in that adults want to be intentional with their advice-giving to young people because “it is easier to think about molding clay than about helping the clay mold itself.” (Larson, 2006, p. 682) Larson along with many other experts in the field of youth development are telling us, what young people have been saying for a long time, “stop telling me what to do.” They don’t care to know how much we know (about life or the struggle), they need to know (and feel) how much we actually care. Many adults care so much that they struggle to balance letting youth learn on their own, and sharing their own experiences or clecha. While we are trying to figure it out in the field of youth development and education, too many young people are dying. Every 26 seconds a young person drops out of school in the U.S. (American Graduate, 2016). Over 1 million youth per year are system-involved in “courts with juvenile jurisdiction handling delinquency cases.” (Hockenberry, 2015, p. 6) Thousands of those youth are ending up caged in juvenile halls and prison, and many are dying in our cities nationwide. We must search for new ways to engage and walk with youth in gangs. This is part of that search.
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Lee, Timothy Shan Wei. "The effect of crystal form on the catalytic and mechanical stability of cross linked enzyme crystals (CLECs)." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312347.
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Clark, Alexandra Elsie. "Characterisation of the C-type lectin-like receptor 1 (CLEC-1)." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=210080.
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Hmedi, Khalil Al. "La question du réel dans la poésie de la seconde moitié du XXe siècle : survivance de la poésie réaliste du XIXe siècle dans les pratiques poétiques contemporaines (Philippe Jaccottet, James Sacré, Philippe Clerc)." Thesis, Toulouse 2, 2017. http://www.theses.fr/2017TOU20039.
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Les pratiques poétiques de Philippe Jaccottet (1925-), de Philippe Clerc (1935-) et de James Sacré (1939-) sont notablement traversées par l’impératif du réel qui marque la poésie contemporaine depuis 1950. Elles s’inscrivent, en partie, dans la continuité thématique du mouvement réaliste de la poésie du XIXe siècle (Max Buchon, François Coppée, Sully Prudhomme, Charles Baudelaire, Jean Richepin). Mais, le réel réapparait dans ces pratiques avec un nouveau regard, avec une nouvelle sollicitude, mais surtout avec un nouveau dire. Au contraire des poètes du XXe, encore imprégnés d’une volonté de plier le réel aux dires du poème, cette nouvelle génération est emblématique d’un retournement théorique et pratique : le réel est matière même de l’acte poétique. Mus par des pratiques souvent éloignées, façonnés par des cultures différentes, nos trois auteurs opèrent dans la langue des choix et montrent une volonté d’exigence et de simplicité pour rendre compte du réel. Notre travail vise, dans un premier temps, à mettre en lumière l’évolution du sens et de l’écriture du réel dans la poésie du XIXe siècle, avant d’analyser, dans un deuxième temps, les différents aspects des écritures du réel proposées par les trois auteurs choisis, d’en montrer les différences avec celles de leurs prédécesseurs, d’en déterminer les spécificités et la place au sein de la poésie contemporaineThe imperative of the real that characterizes contemporary poetry since 1950 is at the heart of the poetic practices of Philippe Jaccottet (1925-), Philippe Clerc (1935-) and James Sacré (1939-). Tthey are in part, keeping up with the themes of the realist movement of 19th century poetry, (Max Buchon, François Coppée, Sully Prudhomme, Charles Baudelaire, Jean Richepin). But the real reappears in these practices with a new gaze, a new concern, and above all a new claim. On the contrary to 20th century poets, still steeped in the desire to have the real comply with the poem’s claims, this new generation is representative of a theoretical and practical change: the real is in itself the material of the poetic act. Set in motion by practices far from each other, modeled by different cultures, they make choices in language and demand rigor and simplicity in order to account of the real. Our work aims first at showing the evolution of the meaning and the writing of the real in 19th century poetry. This study will bring us then to analyze the different aspects of the writing of the real in the works of the three poets we have chosen, and to underline how they differ from their predecessor, and determine their specificity and their position in contemporary poetry
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Lombard, Stephanie Eileen. "Role of platelet CLEC-2 and podoplanin in inflammation and vascular integrity." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7398/.
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Introduction: The platelet receptor CLEC‐2 is believed to play a key role in many of the newly emerging roles of platelets, such as development and inflammation. The aim of this thesis was to look further into the interaction of CLEC‐2 and podoplanin and to investigate the role these proteins play in inflammation. Methods: In‐vitro flow experiments using recombinant podoplanin and whole blood were used to investigate the interaction of CLEC‐2 and podoplanin under shear stress. The role of CLEC‐2 in inflammation was investigated using a range of mouse models such as LPS induced peritonitis model, DSS induced colitis and a mouse model of atherosclerosis. Results: Mouse podoplanin induces platelet aggregation under arterial rates of shear through the receptor CLEC‐2. The aggregation is likely due to the high affinity interaction between mouse CLEC‐2 and podoplanin. The results of role of CLEC‐2 in inflammation revealed a lack of CLEC‐2 from inception causes a more acute inflammatory reaction to LPS. CLEC‐2 (removed post development) also plays a protective role in an acute model of ulcerative colitis. Mice lacking CLEC‐2 do not upregulate podoplanin on lymphatic endothelial cells and epithelial cells in the colon to the same degree as their wildtype counterparts following induction of colitis. CLEC‐2 is also protective against atherosclerosis however there was a greater upregulation of podoplanin in the plaques of atheroprone platelet CLEC‐2 deficient mice. The results of this thesis highlight the complicated role of CLEC‐2 in inflammatory disorders. There is also a clear difference in the affinity of mouse and human forms of CLEC‐2 and podoplanin which has important consequences for the interpretation of mouse models examining the role of these proteins in human diseases.
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Fourcade, Sara. ""Clerc ne suis, (. . . ) livre ne ay point" : la noblesse française à la conquête du livre (vers 1300 - vers 1530)." Paris 4, 2008. http://www.theses.fr/2008PA040203.
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Nous cherchons à établir le cadre social, culturel, matériel et idéologique du développement des pratiques lettrées des nobles laïques en France à la fin du Moyen Âge. Un groupe formé de propriétaires de librairies, d'écrivains, de poètes et de rédacteurs d'écrits privés sert de base à ce travail. L'étude de ces individus met en évidence la transmission familiale d'un patrimoine matériel et culturel et l'élaboration de nouvelles normes lettrées dans les milieux fréquentant les cours. On caractérise ensuite la culture de la noblesse, partagée entre son caractère fonctionnel, l'assimilation d'éléments savants et la libre expression de goûts individuels ; son originalité s'affirme dans la littérature nobiliaire, empreinte d'un grand pragmatisme et conçue comme une réponse au contexte de crise. L'insertion des usages lettrés dans le mode de vie et l'idéologie nobiliaires apporte enfin une dénégation claire à l'idée d'une incompatibilité des armes et des lettresThis dissertation tries to state the social, cultural, material and ideological context of the development of the uses of book in the XIVth and XVth centuries french nobility. We establish a group of book owners, authors, poets and private diaries writers. Its analysis underlines the importance of familial assets, based on the handing down of a material and cultural heritage, and the working out of new literacy standards, especially among noble people linked with princely courts. Then, we identify the main features of noble culture, divided between its functional purposes, the assimilation of some parts of clerical knowledge and the expression of personal tastes and interests. The main originality of noble literature, conceived to answer the crisis of late Middle Ages, rests in its pragmatism. The deep integration of literacy in aristocratic way of life and ideology denies the supposedly incompatibility of sword and book
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Alshehri, Osama Mohammed D. "The role of GPVI and CLEC-2 in platelet activation by miscellaneous ligands." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6880/.
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Platelets are an essential factor in wound repair and blood clotting, where exposed sub-endothelial extracellular matrix (ECM) proteins induce activation during vascular injury. However, platelets can also be activated by a diverse range of stimuli that share little-to-no resemblance in structure to each other, or to recognized ligands of platelet receptors. These stimuli include diesel exhaust particles (DEP), various peptides including 4N1-1 and Champs, lipoproteins such as PAM3-CSK4, and large polysaccharides for example, fucoidan, and dextran. In this thesis, I demonstrate that this seemingly miscellaneous group of stimuli cause aggregation of human and mouse platelets through Src and Syk tyrosine kinases in association with stimulus-specific tyrosine phosphorylation of the GPVI/FcRγ-chain complex and/or CLEC-2. A critical role for GPVI and/or CLEC-2 in mediating aggregation is shown using platelets from receptor-deficient mouse platelets. Additionally, in double deficient mouse platelets these stimuli activate Src tyrosine kinases independent of GPVI and CLEC-2. DEP, fucoidan and dextran were shown to activate transfected GPVI or CLEC-2 in a cell line model. However, 4N1-1, Champs and PAM3-CSK4 did not activate transfected GPVI or CLEC-2 in a cell line model, nor could they bind to recombinant forms of either receptor. In addition, I demonstrate the unexpected observation that fibrin also activates GPVI revealing a new stage of haemostasis in which the generation of fibrin from fibrinogen reinforces platelet activation.
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Souto, Maior Mourão Sá D. "Characterisation of the C-type lectin receptor CLEC-2 : expression, ligands and functions." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1302407/.
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Myeloid cells express a plethora of C-type lectin receptors (CLR) that can regulate inflammatory responses. Dectin-1 belongs to a sub-family of CLRs that possesses an extracellular C-type lectin domain (CTLD) and a single YxxL intracellular motif (hemITAM) that allows signalling via Syk kinase and induction of downstream functions. Based on consensus sequences for the CTLD and hemITAM, we identified CLEC-2 as a dectin-1-like receptor. CLEC-2 was previously characterised as a Syk-coupled platelet receptor able to induce platelet aggregation when targeted by the snake venom rhodocytin and by cells expressing the endogenous protein podoplanin. I generated monoclonal antibodies against mouse CLEC-2 and found that CLEC-2 is also expressed on lymphoid and myeloid cells, including dendritic cells (DC). Notably, treatment with LPS increases CLEC-2 expression by myeloid cells and synergises with CLEC-2 signaling to induce increased secretion of IL-10 but not IL-12. This increased IL-10 production is also observed in the serum of mice administered with anti-CLEC-2 mAb and LPS, and is dependent on the presence of macrophages and DCs. Furthermore, I generated a CLEC-2 conditional KO mouse line that will provide a tool to study CLEC-2 function in myeloid cells in vivo. Collectively, these data indicate that CLEC-2 expression is not restricted to platelets and that it plays a role on the vascular development and modulation of TLR responses.
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Tomlinson, Neil David. "Regulation of C-type lectin-like receptors dectin-1 and CLEC-2 by tetraspanins." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/826/.
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Tetraspanins are a superfamily of glycoproteins that function as ‘organisers’ of membranes by clustering with each other to form tetraspanin-enriched microdomains, into which certain other receptors and signalling proteins are recruited and regulated. Tetraspanin microdomains have been implicated in a range of biological processes including cell signalling, adhesion, intracellular trafficking, cell-cell fusion and viral entry. The tetraspanin CD37 was recently shown to negatively regulate the C-type lectin-like receptor dectin-1, which is essential for innate immune responses to fungal pathogens. The aim of this thesis was to firstly develop a cell line model system to investigate the mechanism by which tetraspanins inhibit dectin-1, and to secondly extend this work to the dectin-1-related CLEC-2, which is essential for platelet thrombus formation and stability. Using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay in the Jurkat T-cell line, transient over-expression of CD37 was found to powerfully inhibit dectin-1 signalling following stimulation with its ligand, β-glucan. Over-expression of other tetraspanins also inhibited dectin-1 signalling, but did not globally inhibit receptor signalling because the platelet collagen receptor, GPVI, was unaffected. Similar to dectin-1, CLEC-2 signalling in response to its ligand, the snake venom toxin rhodocytin, was also abrogated following tetraspanin over-expression. However, stable tetraspanin over-expression only partially reduced signalling. Moreover, knockdown of the major Jurkat cell tetraspanin, CD81, and deletion of the major platelet tetraspanin, CD9, did not affect dectin-1 and CLEC-2 signalling, respectively. In summary, the importance of transient tetraspanin over-expression for dectin-1 and CLEC-2 inhibition, and the fact that any tetraspanin can inhibit, suggests that tetraspanin microdomains are disrupted by the presence of one over-expressed tetraspanin. This leads to a failure of dectin-1 and CLEC-2 signalling by a mechanism that is not clear, but suggests that tetraspanin microdomains are important for signalling by these C-type lectin-like receptors.
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Hughes, Craig Edward. "Comparison of CLEC-2 and GPVI signaling in platelets : the role of adaptor proteins." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/1204/.
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GPVI activates platelets through an ITAM pathway by activation of Src and Syk kinases leading to activation of PLC\(_y\)2. CLEC-2 has been shown to activate platelets using an ITAM-like sequence in its cytoplasmic tail that is also dependent on Src and Syk kinases, but shows a partial rather than an absolute dependence on adapter SLP-76 for activation of PLC\(_y\)2. The aim of this thesis is to understand some of the key differences in these signalling pathways. GPVI is in complex with FcRwhich contains the ITAM sequence (Yxx(L/I)x\(_{6-12}\)Yxx(L/I)). These two tyrosines provide a docking site for the tandem-SH2 domains of Syk. In this thesis I show that CLEC-2 signalling through Syk is mediated by phosphorylation of the CLEC-2 YxxL sequence, receptor dimerisation and cross-linking by the Syk SH2 domains. I also show that the differential requirement for SLP-76 is not mediated by Gads. Both signalling pathways also show partial dependency for LAT. I also show that a novel protein, G6f, is not able to substitute for LAT in this signalling pathway and also exclude the LAT-family proteins PAG, LIME, LAX and NTAL as potential LAT replacements in platelet activation by GPVI. These results extend our understanding of platelet activation by CLEC-2.
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Pavelková, Olga. "Význam a výsledky jednání ministerských konferencí WTO." Master's thesis, Vysoká škola ekonomická v Praze, 2007. http://www.nusl.cz/ntk/nusl-1111.
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Cílem práce je demonstrovat výsledky jednání vrcholného orgánu WTO, zhodnotit dopady na světovou ekonomiku a tím podpořit smysluplnost WTO. Nejdříve jsou popsány historické souvislosti vzniku WTO, tedy vývoj GATT. Dále se práce věnuje WTO, jejímu fungování, cílům, organizační struktuře, principům a struktuře dohod. Poslední část je zaměřena na vývoj jednání v rámci ministerských konferencí.
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Lopez, Sarah. "De nouveaux biocatalyseurs hétérogènes pour des réactions d'oxydation : des cristaux de métalloenzymes artificielles." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV022/document.
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Depuis la révolution industrielle, la chimie ne cesse de prospérer en développant des procédés de plus en plus performants souvent aux dépens de l’environnement. Dans le cadre du développement d’une chimie durable, des procédés catalytiques dans le domaine de la chimie d’oxydation sont mis en place en utilisant des métaux physiologiques et des oxydants doux. En combinant les avantages de la catalyse homogène et de la biocatalyse, de nouveaux catalyseurs bio-inspirés ont émergé, les métalloenzymes artificielles. Elles sont constituées d’un complexe inorganique, choisi en fonction de la réaction visée, qui est ancré au sein d’une protéine, qui apporte la sélectivité de la réaction. Au cours des travaux de cette thèse, de nouvelles métalloenzymes artificielles ont été créées par ancrage de divers complexes de Fe ou de Ru au sein de la protéine NikA. Dans un premier temps, l’hybride NikA/Ru-bpza a été synthétisé pour réaliser l’hydroxychloration d’alcènes en présence d’un iode hypervalent. Bien que d’excellentes propriétés catalytiques aient été obtenues, l’amélioration de la stabilité de ce type de catalyseurs, en particulier pour des réactions d’oxydation, reste un challenge important à relever pour leur utilisation au niveau industriel. Une des solutions originale est basée sur le développement de la catalyse hétérogène, en utilisant de cristaux de métalloenzymes artificielles grâce à la technologie CLEC (Cross-Linked Enzyme Crystals). Cette technologie permet, d’une part, d’améliorer la stabilité et la recyclabilité des catalyseurs, et d’autre part, d’élargir les conditions réactionnelles utilisées (solvants, pH, températures). Trois réactivités ont été développées à base de CLEC NikA/FeL : (i) la sulfoxydation de thioéthers, (ii) l’hydroxychloration d’alcènes en présence d’Oxone® et de chlore et (iii) la coupure oxydante d’alcènes par activation d’O2. Ces résultats ont permis d’explorer de nouvelles réactivités en chimie cascade soit en combinant les CLEC mis au point, soit en combinant différents catalyseurs homogènesSince the industrial revolution, chemistry has continually thriven by developing new efficient processes at the expense of the environment. As an example, oxidation reactions are performed under harsh conditions with the use of toxic oxidants. With the emergence of green chemistry, catalytic processes using physiological metals and soft oxidants are privileged. Combining the advantages of biocatalysis and homogeneous catalysis, the design of novel bioinspired catalysts, consisting on the synthesis of artificial enzymes has recently emerged. These hybrids are composed of an inorganic complex, driving the reactivity of the enzyme, inserted into a protein, which drives the reaction selectivity. The thesis described new developments in original artificial metalloenzymes, based on the use of the NikA protein and Fe or Ru catalysts. First, a new hybrid has been developed by anchoring the Ru-bpza complex to NikA to catalyze alkene hydroxychloration with hypervalent iodine. Although excellent catalytic efficiencies were obtained, the stability improvement remains a major challenge for the industrial use of these catalytic processes, especially when oxidation chemistry is concerned. One possible strategy is based on the development of heterogeneous catalysis, by using a crystal/solution version of the artificial metalloenzymes thank to the cross-linked enzyme crystals (CLEC) technology. On the one hand, this technology allows to increase the stability and the recyclability of the catalysts. On the other hand, catalysis can be performed under a various reactions conditions (organic solvent, temperature, pH). Three reactivities have been developed with NikA/FeL-CLEC catalysts: (i) thioether sulfoxidation with NaOCl, (ii) alkene hydroxychloration with Oxone® and chloride source and (iii) oxidative cleavage of alkenes by O2 activation. To go further, new reactivities in cascade reactions have been explored combining either NikA-based CLEC developed, or different homogenous catalysts
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Schmid, Julia Verfasser], Rüdiger [Gutachter] [Simon, and Michael [Gutachter] Feldbrügge. "On the Role of CLE40 - A Peptide with Antagonistic Functions in Arabidopsis thaliana Shoot Meristem Development / Julia Schmid ; Gutachter: Rüdiger Simon, Michael Feldbrügge." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1117134938/34.
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Neulen, Marie-Luise [Verfasser], and Thomas [Akademischer Betreuer] Göbel. "Das Hühner CLEC-2 Homolog : ein Trombozytenrezeptor mit aktivierender Funktion / Marie-Luise Neulen. Betreuer: Thomas Göbel." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2012. http://d-nb.info/1029662223/34.
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Lowe, Kate. "The roles of podoplanin and clec-2 in the development and maintenance of the cerebral vasculature." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5791/.
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The C-type lectin-like receptor, CLEC-2, is constitutively expressed on platelets, with reported expression on a number of leukocyte subsets in adult mice. Constitutive or platelet-specific deletion of CLEC-2 in mice induces cerebral haemorrhaging by midgestation. In this thesis, I investigated the basis of this defect, hypothesising that it is mediated by the loss of CLEC-2 activation by its endogenous ligand, podoplanin, expressed on the developing neural tube. Podoplaninfl/fl mice were crossed to mice expressing PGK-Cre to induce deletion of podoplanin at the two-cell stage. Developing blood vessels were visualized by 3-dimensional microscopy and found to be aberrantly patterned in CLEC-2- and podoplanin-deficient mice, culminating in widespread cerebral haemorrhaging by mid-gestation. Haemorrhages were also observed following Nestin-Cre driven deletion of podoplanin on neural progenitors and following deletion of the platelet integrin, αIIbβ3. Together these studies support that neuro-epithelial-derived podoplanin interacts with platelet-CLEC-2 to guide the maturation and integrity of the cerebral vasculature and to prevent haemorrhage by stimulating platelet aggregation. Using tamoxifen-inducible deletion of CLEC-2 in adult mice, the expression profile of CLEC-2 was investigated and shown to be restricted to platelets and circulating B-lymphocytes and CD11bhigh Gr1high myeloid cells. Furthermore, loss of CLEC-2 in adult mice was shown to be dispensable for maintaining blood-brain barrier permeability.
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Chauhan, Abhishek. "Contribution of the platelet receptor CLEC-2 and its ligand podoplanin to the pathogenesis of liver disease." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8234/.
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Increasing lines of evidence place platelets as having a central role in liver disease. Platelets are recruited to the liver and, depending upon stage and type of liver injury play varying roles ranging from driving liver fibrosis to aiding regeneration. However the molecular basis and consequences of platelet activation in the liver are less clear. The work presented in this thesis demonstrates for the first time that platelet activation via CLEC-2 is important in the pathogenesis of liver disease. In chronic human diseases (CLD) such as Primary Biliary Cirrhosis, and Alcoholic Liver disease I have demonstrated that the ligand for CLEC-2, podoplanin is upregulated on portal venules and increases proportionately to disease activity. I also note podoplanin staining on macrophage populations in CLD. Furthermore I show that this enhanced podoplanin expression may be a useful predictor of portal venous thrombosis, and correlates with MELD score for some categories of disease. In acute liver injury, CLEC-2-depended platelet activation has a profound effect on disease development. Here podoplanin expression occurs upon Kupffer cells in both humans and mice. Using carbon tetrachloride and paracetamol to induce acute liver injury in mice, I show that macrophage-expressed podoplanin activates platelets via CLEC-2. This interaction worsens liver injury, I next show that by blocking this interaction (using either CLEC-2 or podoplanin-deficient mice, or by using a function- blocking podoplanin antibody) liver recovery from toxic liver injury was remarkably enhanced. This was dependent upon enhanced hepatic neutrophil recruitment in a TNF dependent fashion.
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Kerrigan, Ann. "The functional characterisation of murine CLEC-2 and analysis of the expression of its ligand, podoplanin, on macrophages." Doctoral thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3169.
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Astarita, Jillian Leigh. "The role of the podoplanin-CLEC-2 pathway in stromal cell regulation of dendritic cell motility and lymph node architecture." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13065022.
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In addition to leukocytes, secondary lymphoid organs are populated by non-hematopoietic stromal cells. This diverse group of cells supports lymphocyte migration and homing, facilitates antigen delivery, and promotes T cell survival. However, there is relatively little known about the specific molecules governing the roles that these cells play in regulating dendritic cell (DC) motility and lymph node architecture. Here, we examine the interaction between two molecules, CLEC-2 and podoplanin (PDPN), that are critical for DC migration and maintaining structural integrity of lymph nodes. Together, these studies identify novel functions of lymph node stromal cells and a unique function for PDPN in the immune system.
In response detecting an potentially harmful antigen, DCs in peripheral tissues mature and travel to downstream lymph nodes by following chemokine gradients secreted by lymphatic endothelial cells (LECs) and fibroblastic reticular cells (FRCs) present in the lymph node paracortex. We discovered that, in addition to chemokines, DC migration requires CLEC-2 on DCs, as engagement of CLEC-2 with PDPN, which is expressed by LECs and FRCs, incites DC motility and is required for DC entry into the lymphatics, efficient arrival in the lymph node, and migration along the FRC network within the lymph node.
Next, we examined the effect of this interaction with respect to the stromal cell. Through a combination approaches, we discovered that PDPN is a master regulator of contractility in FRCs. The fact that FRCs are contractile cells was previously reported, but our study is the first to identify a function for this contractility: upon blockade of PDPN-mediated contractility, lymph nodes became enlarged, the FRC network became more sparse, and there were increased numbers of lymphocytes in the lymph node. Importantly, during an immune response, these changes resulted in more proliferation of antigen-specific T cells and impaired contraction of the lymph node upon resolution of inflammation. Finally, we found that CLEC-2 binding PDPN recapitulated the effect of PDPN deletion. Thus, during an immune response, CLEC-2+ DCs would use PDPN to efficiently migrate to the lymph node and simultaneously cause FRCs to relax and prepare the lymph node for expansion.
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Lopez, Robles Maria Dolores. "Étude de CLEC-1, un récepteur lectin-like de type C dans la fonction des cellules dendritiques et la tolérance immune." Thesis, Nantes, 2017. http://www.theses.fr/2017NANT1025.
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Les cellules dendritiques (DCs) sont essentielles pourconnecter l'immunité innée et adaptative et orienter lesréponses des lymphocytes T. Les récepteurs Lectin de type-Cprésents dans les DCs sont activés par des ligands exogènes etendogènes, ce qui dicte la réponse aux agents pathogènes parla modulation de la réponse T immunitaire. Nous avons déjàdécrit chez le rat, l'expression de CLEC-1 dans les DCs etnous avons démontré in vitro son rôle inhibiteur dansl'activation de la réponse T helper (Th17) ). Dans cette étude,nous avons examiné l'expression et la fonction de CLEC-1dans les DCs humaines et nous avons montré son expression àla surface cellulaire de la sous-population de DCs CD16- dansle sang et sur les DCs dérivées des monocytes (moDCs).L'expression de CLEC-1 sur les moDCs est diminuée par desstimuli inflammatoires et renforcée par le TGF-β. De plus,nous avons démontré que CLEC-1 est un récepteurfonctionnel sur les moDCs humains et que, bien qu'il nemodule pas la voie classique d’activation du facteur detranscription NFкB lié à la protéine kinase Syk, il réprime laréponse ultérieure Th17. De façon très importante, en utilisantdes rats déficients pour CLEC-1, nous avons montré que laperturbation de la signalisation de CLEC-1 conduit à unesurexpression de la sous-unité Il-12p40 dans les DCs, et à uneexacerbation des réponses CD4+ Th1 et Th17 in vitro et invivo. Collectivement, nos résultats établissent le rôleinhibiteur de CLEC-1 dans les DCs, capable d'amortir leuractivation et la réponse ultérieure Th17. CLEC-1 peutreprésenter une cible thérapeutique utile pour moduler lesréponses immunitaires T dans un contexte cliniqueDendritic cells (DCs) represent essential antigen-presentingcells that are critical for linking innate and adaptive immunity,and influencing T-cell responses. Among pattern recognitionreceptors, DCs express C-type lectin receptors triggered byboth exogenous and endogenous ligands, therefore dictatingpathogen response, and also shaping T-cell immunity. Wepreviously described in rat, the expression of the orphan Ctypelectin-like receptor-1 (CLEC-1) by DCs anddemonstrated in vitro its inhibitory role in downstream Thelper 17 (Th17) activation. In this study,we examined theexpression and functionality of CLEC-1 in human DCs, andshow a cell-surface expression on the CD16+ subpopulation ofblood DCs and on monocytederived DCs (moDCs). CLEC-1expression on moDCs is downregulated by inflammatorystimuli and enhanced by TGF- β. Moreover, we demonstratethat CLEC-1 is a functional receptor on human moDCs andthat although not modulating the spleen tyrosine kinase (Syk)dependent canonical nuclear factor-kB (NFкB) pathway,represses subsequent Th17 responses. Importantly, usingCLEC-1–deficient rats, we showed that disruption of CLEC-1signaling led to an enhanced Il-12p40 subunit expression inDCs, and to an exacerbation of downstream in vitro and invivo CD4+ Th1 and Th17 responses. Collectively, our resultsestablish a role for CLEC-1 as an inhibitory receptor in DCsable to dampen activation and downstream effector Thresponses. As a cell-surface receptor, CLEC-1 may representa useful therapeutic target for modulating T-cell immuneresponses in a clinical setting
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Loveland, Jeff. "Rhetoric and natural history : Buffon in polemical and literary context /." Oxford : Voltaire Foundation, 2001. http://www.gbv.de/dms/goettingen/32877135X.pdf.
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Clerc, Gaspard [Verfasser], de Kuilen Jan-Willem G. [Akademischer Betreuer] van, Peter [Gutachter] Niemz, de Kuilen Jan-Willem G. [Gutachter] van, and Christian U. [Gutachter] Große. "Analysis of the fatigue performance of adhesively bonded wood joints / Gaspard Clerc ; Gutachter: Peter Niemz, Jan-Willem G. van de Kuilen, Christian U. Große ; Betreuer: Jan-Willem G. van de Kuilen." München : Universitätsbibliothek der TU München, 2020. http://d-nb.info/122404701X/34.
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Dupuy, Marie. "La chair et l'esprit dans le Lancelot-Graal." Thesis, Paris 10, 2015. http://www.theses.fr/2015PA100131/document.
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Le Lancelot-Graal est un roman composite que traverserait un « double-esprit » articulé entre courtoisie et mystique. Le travail de recherche propose de mettre le cycle à l’épreuve d’une matrice dynamique mise en évidence par les historiens et montrant la structuration de la société médiévale en deux pôles, l’un charnel, l’autre spirituel, et dont le point central est la bonne circulation de l’amour, la caritas et d’examiner dans quelle mesure cette mise en tension des deux termes permet de résoudre l’aporie posée par ces deux versants, courtois et mystique. L’analyse du roman tend à montrer que le texte utilise lui-même un ensemble lexical qui permet d’organiser une structure dynamique, du bas vers le haut et de l’extérieur vers l’intérieur. Cette dynamique met en évidence une hiérarchie de valeurs qui structure aussi la narration, organisée en deux ensembles dont le trait commun est l’amour : ainsi, l’amour courtois pour la Dame serait du côté du charnel, l’amour mystique dont l’objet est le Graal serait du côté du spirituel. Néanmoins, l’objet d’étonnement que constituent la Dame et le Graal permet d’orienter la lecture vers une analyse de la merveille dans le texte, analyse qui montre non pas deux esprits mais bien une seule volonté de spiritualiser l’amour. L’amour organise aussi les réseaux de parenté qui permettent de mettre en évidence des stratégies de spiritualisation. En effet, en dernier ressort, l’analyse montre une prise de parole des grands aristocrates qui revendiquent un véritable modèle d’héroïcité laïque. Comme discours d’un groupe social, le roman se construit donc autour du nœud que constitue l’amour, qui circule, bien ou mal, dans le texteThe Lancelot Graal is a collection of tales, pervaded by two spirits, courtly love and the marvellous. The aim of this research paper is to use the Lancelot Graal to test an interpretation suggested by historians, showing the construction of society in the Middle-Ages as orientated around the two opposing notions of the physical and the spiritual, linked by love, by caritas, and to examine to what extent this resolves the aporia arising from the confrontation between the courtly and the marvellous. The analysis of the novel attempts to show that the text uses a lexicon which reveals a dynamic organization from the bottom to the top and from the outside to the inside. This dynamic organisation highlights a hierarchy of values which also structure the narration, organised into two elements linked by the common theme of love : thus courtly love for a Lady would be physical, love for the Grail would be spiritual. Nevertheless, the sense of astonishment inspired by the Lady and the Grail enables us to show that there aren’t two spirits but only the desire to spiritualise love. Love also organises the network of relationships, which create strategies of spirituality. / The kinship networks are also organised around love. These kinship networks create strategiesof spirituality. Finally, the analysis of the novel shows how aristocrats lay claim to a secular model of heroism. The novel is structured around love which runs its course well or badly in the text
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Bedoya, Ponte Victor. "Le dieu incompréhensible du dernier Bayle. Etude sur les notions communes dans les "Entretiens de Maxime et de Thémiste" (1707)." Thesis, Lyon, École normale supérieure, 2012. http://www.theses.fr/2012ENSL0710.
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Nous analysons le dernier ouvrage écrit par Pierre Bayle, les Entretiens de Maxime et de Themiste (1707), où il livre un combat de plume ultime avec deux théologiens réformés, Jean Le Clerc et Isaac Jaquelot. Il s’agit d’une querelle entamée après la publication du Dictionnaire historique et critique (1697) de Bayle, et dont tous les ouvrages directement concernés sont aussi examinés. À partir du problème du mal et du péché, Bayle formule une critique à la théologie chrétienne visant à mettre en évidence la faiblesse des arguments rationnels qui doivent l’affirmer. Les seules forces de la raison ne suffisent pas à éclairer les dogmes qui forment la religion, et il faut avoir recours à la lumière de la foi, à la Bible, pour les accepter. De l’étude de cette argumentation nous concluons que, pour Bayle, la religion est une question privée, qui ne se prête pas vraiment au dialogue philosophiqueWe analyze the last work written by Pierre Bayle, the Entretiens de Maxime et de Thémiste (1707), where he opposes for the last time two Arminian Theologians, Jean Le Clerc and Isaac Jaquelot. Their quarrel started with the publication of Bayle’s Dictionnaire historique et critique (1697) and continued until his death in 1706. By pointing to the insoluble problem of evil and sin, he proposes a refutation of rational arguments that attempt to prove Christian Theology. We examine all the writings involved in this controversy and review in great length its arguments. Bayle shows that Christianity is unable to demonstrate its dogmas by reason, and claims that only faith can legitimate them. Therefore it is concluded that religion for Bayle belongs to the private sphere, and cannot be rationalized through a philosophical dialogue
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Lorenz, Viola [Verfasser], and Bernhard [Gutachter] Nieswandt. "Cellular regulation of the hemITAM-coupled platelet receptor C-type lectin-like receptor 2 (CLEC-2): In vitro and in vivo studies in mice / Viola Lorenz ; Gutachter: Bernhard Nieswandt." Würzburg : Universität Würzburg, 2018. http://d-nb.info/1163536202/34.
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