372 research outputs found
Human memory CD8+ T-cells exhibit an intrinsic metabolic advantage as reflected by increased mitochondrial functionality and high glycolytic potential
No full textIntrinsic differences between na•ve and memory CD8+ T-cells affect both quality and quantity of cognate antigen response. Cellular immune function and metabolic pathways are closely linked. The metabolic repertoire of na•ve and memory T-cells remains largely unknown. Here we assessed key metabolic features of human na•ve and effector-memory CD8+ T-cells under basal, metabolic stress, and activating conditions. Basal mitochondrial respiration was similar in both subsets. Memory cells, however, possessed more complex, tubular mitochondria, and displayed greater respiratory capacity and enhanced fatty acid oxidation. Basal glycolysis was also comparable in both subsets. Memory cells, however, showed an exclusive capacity to rapidly upregulate glycolysis after mitochondrial respiration blockage. In line with this finding, effector memory CD8+ T-cells expressed more cytoplasmic GAPDH levels with enhanced activity compared to na•ve CD8+ T-cells.
Protective immunologic memory depends on antigen-experienced T-cells that are able to: (a) rapidly acquire effector function and (b) expand as secondary effector cells (Masopust and Picker, 2012). The clonal re-expansion of memory cells requires aerobic glycolysis (Warburg effect) in order to meet added biosynthetic and energetic demands (Vander Heiden et al., 2009). The metabolic requirements of rapidly responding effector memory CD8+ T-cells are unknown. Here we show that human effector memory CD8+ T-cells possess the intrinsic ability to upregulate aerobic glycolysis with unexpected rapid dynamics. In contrast to prototypical aerobic switch in activated T-cells, this early phase is insensitive to blockage of mTORC1, a known regulator of glucose metabolism in proliferating T-cells (Finlay et al., 2012; Fox et al., 2005). CD28 signaling via mTORC2 and AKT is required to sustain this early increased glycolyis. Importantly, preventing this early glycolytic phase by either blocking AKT activity or glucose deprivation, led to an impairment of IFN-gamma secretion.
Therefore, increased metabolic capacities in effector memory CD8+ T-cells promote a primed state to immediately support high glycolytic activity upon activation. This early glycolytic phase is prerequisite for immediate effector function and therefore linking metabolic features with CD8+ T-cells recall functionality.
Our findings established differential metabolic repertoires between na•ve and effector-memory CD8+ T-cells, with implications for strategies aiming to therapeutically manipulate CD8+ T-cell memory
The discovery of SycO reveals a new function for type three secretion effector chaperones
No full textThe Type Three Secretion (T3S) system is a device used by many Gram-negative pathogens that allows bacteria to deliver effector proteins straight into the eukaryotic cell cytosol. These effectors interfere with various signaling pathways to subvert the host cell functions. The secretion machinery of the T3S system consist of a basal body spanning the bacterial inner and outer membrane followed by a stiff hollow needle outside the bacterium. The fully assembled secretion apparatus constitute a continuous hollow conduit that connects the bacteria to the eukaryotic target cell. After cell contact, virulence proteins -called effectors- are injected directly into the cytosol of the host cell via the T3S apparatus. Several effectors of the T3S system require the assistance of specific cytosolic chaperones to be efficiently exported. There are three classes of T3S chaperones. Effector proteins are assisted by Class I chaperones. Although Class I chaperones are well characterized, their main function is still a matter of controversy. In this thesis, we demonstrate that orf155 encodes a specific chaperone for the effector YopO that we called SycO. We showed that SycO enhances YopO secretion in vitro and is required for translocation of YopO into infected cells. By pulldown assay we demonstrated that residues 20 to 77 of YopO are required and sufficient for SycO binding. Using crosslinking experiments and size exclusion chromatography analysis, we determined the stoichiometry of purified SycO and YopO-SycO complexes. SycO alone forms dimers in solution and the YopO-SycO complex has a 1:2 stoichiometry. These results suggested that SycO is a typical chaperone of the Class I. YopO is a serine/theronine kinase that interacts with Rho and Rac and disrupts the cytoskeleton of the target cells. YopO has been shown to localize at the cell plasma-membrane. By transfection of YopO-EGFP hybrid proteins into HEK293T cells, we demonstrated that the chaperone-binding domain (CBD) coincides with the membrane localization domain of YopO. Nevertheless, the CBD was not needed for the kinase activity of YopO. By ultracentrifugation, we also showed that the CBD causes YopO aggregation in the bacteria, when SycO does not cover it. Further, we show that the CBD of YopE and YopT also caused aggregation in the bacteria in the absence of SycE and SycT respectively. YopE, YopT and T3S effectors in other systems also act at the membrane of the eukaryotic host cell. We propose a new hypothesis concerning the role of T3S chaperones. The sub-cellular localization domain of effectors is aggregation-prone and creates the need for a chaperone inside bacteria. We propose that masking such aggregation-prone localization domains may be a general function for type III effector chaperones
Du non-lieu au lieu : pratique spatiale et construction identitaire dans Texaco, de Patrick Chamoiseau
No full text[À l'origine dans / Was originally part of : Thèses et mémoires - FAS - Département de littérature comparée]Le présent ouvrage propose une lecture spatiale du roman Texaco, de l’auteur martiniquais Patrick Chamoiseau. Texaco retrace l’histoire de la Martinique, principalement celle de sa population noire créolophone, depuis le XIXe siècle – époque de la traite et de l’esclavage – jusqu’à la fin du XXe siècle. Considérant que l’identité d’un individu (ou d’une communauté) est étroitement corrélée au rapport qu’entretient celui-ci avec son espace de vie, notre travail vise à mettre au jour les particularités identitaires des personnages du roman au travers d’une analyse des espaces qu’ils occupent et façonnent dans le récit. En nous appuyant sur des concepts spatiaux empruntés à Henri Lefebvre (l’espace tripartite), à Michel de Certeau (le lieu, l’espace et la pratique spatiale) et à Marc Augé (le lieu et le non-lieu), nous souhaitons montrer de quelle manière et dans quelle mesure ces différentes entités spatiales expriment, consolident ou oblitèrent l’identité singulière des personnages chamoisiens, c’est-à-dire leur « créolité ».This work presents a spatial analysis of the novel Texaco, written by the Martinican author Patrick Chamoiseau. Texaco follows the story of Martinique, mainly its black Creole population, from the 19th century – the time of slave trade and slavery – until the end of the 20th century. Considering that the identity of an individual (or a community) is closely related to the link it maintains with its living space, our work aims to unveil the particularities of identity of the characters through the analysis of the spaces they occupy and create. Basing ourselves on spatial concepts borrowed from Henri Lefebvre (the tripartite space), Michel de Certeau (the space, the place and the spatial practices) and Marc Augé (the place and the non-place), we wish to show how and to what extent those different spaces express, consolidate or obliterate the distinct identity of Chamoisian characters, in other words their “creoleness”
Du non-lieu au lieu : pratique spatiale et construction identitaire dans Texaco, de Patrick Chamoiseau
No full text[À l'origine dans / Was originally part of : Thèses et mémoires - FAS - Département de littérature comparée]Le présent ouvrage propose une lecture spatiale du roman Texaco, de l’auteur martiniquais Patrick Chamoiseau. Texaco retrace l’histoire de la Martinique, principalement celle de sa population noire créolophone, depuis le XIXe siècle – époque de la traite et de l’esclavage – jusqu’à la fin du XXe siècle. Considérant que l’identité d’un individu (ou d’une communauté) est étroitement corrélée au rapport qu’entretient celui-ci avec son espace de vie, notre travail vise à mettre au jour les particularités identitaires des personnages du roman au travers d’une analyse des espaces qu’ils occupent et façonnent dans le récit. En nous appuyant sur des concepts spatiaux empruntés à Henri Lefebvre (l’espace tripartite), à Michel de Certeau (le lieu, l’espace et la pratique spatiale) et à Marc Augé (le lieu et le non-lieu), nous souhaitons montrer de quelle manière et dans quelle mesure ces différentes entités spatiales expriment, consolident ou oblitèrent l’identité singulière des personnages chamoisiens, c’est-à-dire leur « créolité ».This work presents a spatial analysis of the novel Texaco, written by the Martinican author Patrick Chamoiseau. Texaco follows the story of Martinique, mainly its black Creole population, from the 19th century – the time of slave trade and slavery – until the end of the 20th century. Considering that the identity of an individual (or a community) is closely related to the link it maintains with its living space, our work aims to unveil the particularities of identity of the characters through the analysis of the spaces they occupy and create. Basing ourselves on spatial concepts borrowed from Henri Lefebvre (the tripartite space), Michel de Certeau (the space, the place and the spatial practices) and Marc Augé (the place and the non-place), we wish to show how and to what extent those different spaces express, consolidate or obliterate the distinct identity of Chamoisian characters, in other words their “creoleness”
Art and the artist in the literary works of Elsa Triolet
No full textThis thesis takes a representative selection of Triolet's works to study the themes of writing and creativity as they are presented in the novels. These are all portraits of artists and the accounts of the search for a synthesis of aesthetic freedom and ethical responsibility. It considers Triolet's importance as a foreign writer, adopting a new creative language to be adopted by a different cultural
environment, to be essential in understanding her importance to the French literary tradition. By emphasising her formative years in the avant-garde circles of prerevolutionary Russia, my study demonstrates her considerable contribution to the meeting of Russian and French aesthetic theories. I extend this with close textual
readings of certain works to demonstrate her techniques in novelistic construction which reveal many Formalist practices before Formalist works in translation made
their official influence on creative methods.
The introduction considers the reasons for Triolet's neglect as a writer. It then considers various contemporary and recent critical appraisals which indicate
the interest she has received until present and which allow me to define my own critical approach. Part One traces Triolet's literary evolution from her formative
years in Russia, through exile to her first publications in Russian. It then considers her insertion into French literary activity, and her association with the schools of
socialist realism and the "nouveau roman".
Part Two examines two traditional novels which portray the creative and metaphorical roles of the artist and his work, showing the constant conflict between private and public lives. In Part Three, I show how aspects of novelistic
traditionalism are gradually foregrounded so that the work develops a dual-sided character where it both narrates and examines the processes of its own narration. In Part Four, this move to highly self-conscious aesthetics demonstrates an idiosyncratic exploration of new paths for the novel that bring visual, auditive and cinematographic media into the traditional domain of written art. Accompanying
the very post-modernist experimentation, I show how this research within the novel into the novel's own future has an ethical and redemptive purpose whose final conclusion is that creativity and human freedom are inexorably interwoven
Communication, Communion and Conflict in the Theologies of Gregory Baum and Patrick Granfield
No full textDegree Awarded: Ph.D. Systematic Theology. The Catholic University of AmericaCommunion, communication, and conflict are interrelated realities of great importance for the life and mission of the church. These realities themselves and the relationships between them are in need of theological refinement and assessment, because conflict necessarily affects the church's ability to communicate the message of salvation, and to experience communion.Within a North American and Roman Catholic context, Canadian theologian Gregory Baum (b.1923) and U.S. theologian Patrick Granfield (1930-2014) present ways of perceiving the relationships between these three realities. Through an analysis of the salient dimensions of their respective theologies, this dissertation explores their respective understandings of the church, and identifies ways in which their approaches complement each other, with particular attention paid to the themes of communion, communication and conflict.Baum reflected on these three realities with respect to the church's life and mission to the world, articulating an ecclesial spirituality. Granfield did so primarily with respect to the church's institutional life. Considering their works together offers a means to deepen the church's experience of the mystery of communion via a renewed approach to its communication of the divine promise, while acknowledging conflict as a force which need not be destructive, but which can be harnessed for creative growth.The works of both men show that the implementation of an ecclesiology of communion in the church today requires an awareness that communion is more than simply a theological notion of union with God, that communication in the church is more than speech alone, and that conflict in the church need not be divisive or destructive. Rather, communion in the church must always be concretely expressed in order to be experienced, communication is the sharing of the whole person, and conflict can be attended to in a way which strengthens communion and does not undermine it. By their attention to these three realities in the church, both Baum and Granfield have provided important reflections, not only on how the church lives and functions, but on how it can remain faithful to its divine calling and mission in a continually challenging and complex era
The German Occupation in recent French fiction : an analysis of the literary “mode retro”
No full textThis thesis attempts to analyse and characterise the mode rétro, the remarkable renewal of interest in the German Occupation of France, which is coloured by an extensive re-evaluation of the period's significance. An introduction places this fashion in its literary, social and historical context, revealing how, from 1940 to 1969, a collective and predominantly Gaullist 'myth' of the Resistance became established, with the result that the national response to invasion was accepted to be one of wide-spread heroism and revolt. Part I studies the reaction to such résistancialisme, showing how this orthodox interpretation of events was undermined and, for many, discredited, and offering explanations of the timing and direction of the new view. Part II focuses on the fiction, memoirs, autobiographies and biographies of the younger authors, those who have no direct adult experience of the années noires. It is suggested that their obvious obsession with absent parent-figures reflects their awareness that the past has been misrepresented and their heritage rendered problematic. Their sole means of escape from this predicament, their only source of emotional relief is seen to lie in the creation of a personal account of the early 1940s running contrary to the prevalent orthodoxy, the fabrication of a 'counter-myth'. It is thus the notion of myth which links the various sections of the survey, and so gives the thesis its overall unity
Progressive methods in multiple criteria decision analysis
No full textInternational audienceThis is a summary of the authors Ph.D. thesis, defended on 8 October 2007 at the University of Luxembourg and the Faculté Polytechnique de Mons, under the joint supervision of Raymond Bisdorff and Marc Pirlot. The thesis is written in English and is available from the author upon request. The work is situated in the field of multiple criteria decision analysis. It mostly deals with what we call progressive methods, i.e., iterative procedures presenting partial conclusions to the decision maker that can be refined at further steps of the analysis. Such progressive methods have been studied in the context of multiattribute value theory and outranking methods
Modeling composite materials with respect to reinforcement textile construction
No full textTo address the ongoing efforts to virtually design complex composite materials and theirhigh-performance structures and to contribute to the increasing developments towards Industry 4.0,research and development of fiber-reinforced composites is shifting from an experimental domain to avirtually controlled environment. Material models to account for the specific failure mechanisms oflayered fiber-reinforced materials have been developed and can be used for largescale numericalstructural simulations. However, these models do not account for the individual properties of thereinforcing materials and therefore lack information on microstructural effects and behavior. A near-microscale approach for modeling textile and fiber-based reinforcement structures is presented thatallows studies based on the individual textile structure. The digital beam approach is well established inliterature for modeling textile processes and textile unit-cells. It allows simulations where the parametersof the manufacturing process are considered, and the resulting reinforcement structure is obtainedbecause of these simulations. This paper addresses such microscale geometric models of reinforcementtextiles for use in a virtual composite development chain. The resulting mechanical properties can bepredicted for the dry reinforcement textiles by virtual testing and are available as material inputparameters for further investigations, such as textile drape simulations. In addition, an approach ispresented in which the textile models are used directly for composite modeling. Superimposed modelsare presented that take advantage of LS-DYNA's ability to Lagrangian-couple solids and provideinformation about the mechanical behavior of textile-reinforced composites. In addition to thehomogenized mechanical properties, additional information such as load distribution within the fibers andother properties based on the specific design of the reinforcement textile can be derived and analyzed
Wide single lap shear samples for examination of environmental effects of bonded repairs
No full textIn the frame of the EU FP7 BOPACS (Boltless Assembling of Primary Aerospace Structures) project, the new Wide Single Lap Shear (WSLS) specimen was developed to test a more realistic application scenario for bonded joints. It represents a typical high load transfer configuration as e.g. a fuselage longitudinal joint or a repair joint. The implementation of artificial disbonds and different crack stoppers were part of the validation concept. The concept of this test sample was presented during ECCM17. Derived from the Single Lap Shear and the Cracked Lap Shear Coupon, the Wide Single Lap Shear (WSLS) specimen was developed. It marked the next level test setup beyond the basic coupon level for demonstration and investigation of crack growth behavior in bonded joints. In the BOPACS project two different sizes of WSLS specimens were used. While the test samples for validation tests were made with a width of 500mm, a smaller sample with only 180mm width was developed at ZHAW in order to allow parameter studies at lower cost. The small WSLS is used only for crack growth investigations on a comparative basis. However further work has been performed at ZHAW to develop this set up into a useful examination tool
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