114 research outputs found
Dominant Role of CD80âCD86 Over CD40 and ICOSL in the Massive Polyclonal B Cell Activation Mediated by LATY136F CD4+ T Cells
Coordinated interactions between T and B cells are crucial for inducing physiological B cell responses. Mutant mice in which tyrosine 136 of linker for activation of T cell (LAT) is replaced by a phenylalanine (LatY136F) exhibit a strong CD4+ T cell proliferation in the absence of intended immunization. The resulting effector T cells produce high amounts of TH2 cytokines and are extremely efficient at inducing polyclonal B cell activation. As a consequence, these LatY136F mutant mice showed massive germinal center formations and hypergammaglobulinemia. Here, we analyzed the involvement of different costimulators and their ligands in such TâB interactions both in vitro and in vivo, using blocking antibodies, knockout mice, and adoptive transfer experiments. Surprisingly, we showed in vitro that although B cell activation required contact with T cells, CD40, and inducible T cell costimulator molecule-ligand (ICOSL) signaling were not necessary for this process. These observations were further confirmed in vivo, where none of these molecules were required for the unfolding of the LAT CD4+ T cell expansion and the subsequent polyclonal B cell activation, although, the absence of CD40 led to a reduction of the follicular B cell response. These results indicate that the crucial functions played by CD40 and ICOSL in germinal center formation and isotype switching in physiological humoral responses are partly overcome in LatY136F mice. By comparison, the absence of CD80âCD86 was found to almost completely block the in vitro B cell activation mediated by LatY136F CD4+ T cells. The role of CD80âCD86 in TâB cooperation in vivo remained elusive due to the upstream implication of these costimulatory molecules in the expansion of LatY136F CD4+ T cells. Together, our data suggest that CD80 and CD86 costimulators play a key role in the polyclonal B cell activation mediated by LatY136F CD4+ T cells even though additional costimulatory molecules or cytokines are likely to be required in this process
Parallélisation d'un simulateur d'agents situés
Colloque avec actes et comitĂ© de lecture. nationale.National audienceNous avons rĂ©alisĂ© un simulateur d'un ensemble de robots, oĂč chaque robot est reprĂ©sentĂ© par un agent, se dĂ©plaçant dans un environnement rĂ©el, constituĂ© des couloirs du Loria. Ce simulateur repose sur un modĂšle stochastique d'interaction entre l'agent et son environnement que nous avons proposĂ©. La modĂ©lisation de ces phĂ©nomĂšnes peut entraĂźner une complexitĂ© importante du modĂšle et un grand besoin en capacitĂ© de calcul pour la simulation. Ceci nous a amenĂ© Ă une implantation parallĂšle du simulateur, aprĂšs une Ă©tude des problĂšmes posĂ©s, tout en profitant du parallĂ©lisme intrinsĂšque des SMA
An R-based reproducible and user-friendly preprocessing pipeline for CyTOF data
Mass cytometry (CyTOF) has become a method of choice for in-depth characterization of tissue heterogeneity in health and disease, and is currently implemented in multiple clinical trials, where higher quality standards must be met. Currently, preprocessing of raw files is commonly performed in independent standalone tools, which makes it difficult to reproduce. Here, we present an R pipeline based on an updated version of CATALYST that covers all preprocessing steps required for downstream mass cytometry analysis in a fully reproducible way. This new version of CATALYST is based on Bioconductorâs SingleCellExperiment class and fully unit tested. The R-based pipeline includes file concatenation, bead-based normalization, single-cell deconvolution, spillover compensation and live cell gating after debris and doublet removal. Importantly, this pipeline also includes different quality checks to assess machine sensitivity and staining performance while allowing also for batch correction. This pipeline is based on open source R packages and can be easily be adapted to different study designs. It therefore has the potential to significantly facilitate the work of CyTOF users while increasing the quality and reproducibility of data generated with this technology
Monoslope and Multislope MUSCL Methods for unstructured meshes
International audienceWe present new MUSCL techniques associated with cell-centered Finite Volume method on triangular meshes. The first reconstruction consists in calculating a one vectorial slope per control volume by a minimization procedure with respect to a prescribed stability condition. The second technique we propose is based on the computation of three scalar slopes per triangle (one per edges) still respecting some stability condition. The resulting algorithm provides a very simple scheme which is extensible to higher dimensional problems. Numerical approximations have been performed to obtain the convergence order for the advection scalar problem whereas we treat a nonlinear vectorial example, namely the Euler system, to show the capacity of the new MUSCL technique to deal with more complexe situations
TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts.
The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R-dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons
Single-cell proteomics defines the cellular heterogeneity of localized prostate cancer
Localized prostate cancer exhibits multiple genomic alterations and heterogeneity at the proteomic level. Single-cell technologies capture important cell-to-cell variability responsible for heterogeneity in biomarker expression that may be overlooked when molecular alterations are based on bulk tissue samples. This study aims to identify prognostic biomarkers and describe the heterogeneity of prostate cancer and the associated microenvironment by simultaneously quantifying 36 proteins using single-cell mass cytometry analysis of over 1.6 million cells from 58 men with localized prostate cancer. We perform this task, using a high-dimensional clustering pipeline named Franken to describe subpopulations of immune, stromal, and prostate cells, including changes occurring in tumor tissues and high-grade disease that provide insights into the coordinated progression of prostate cancer. Our results further indicate that men with localized disease already harbor rare subpopulations that typically occur in castration-resistant and metastatic disease
An Immune Atlas of Clear Cell Renal Cell Carcinoma
Immune cells in the tumor microenvironment modulate cancer progression and are attractive therapeutic targets. Macrophages and T cells are key components of the microenvironment, yet their phenotypes and relationships in this ecosystem and to clinical outcomes are ill defined. We used mass cytometry with extensive antibody panels to perform in-depth immune profiling of samples from 73 clear cell renal cell carcinoma (ccRCC) patients and five healthy controls. In 3.5 million measured cells, we identified 17 tumor-associated macrophage phenotypes, 22 T cell phenotypes, and a distinct immune composition correlated with progression-free survival, thereby presenting an in-depth human atlas of the immune tumor microenvironment in this disease. This study revealed potential biomarkers and targets for immunotherapy development and validated tools that can be used for immune profiling of other tumor types.ISSN:0092-8674ISSN:1097-417
Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat
Les jeunes et le cyclomoteur
Die jugendlichen und das moped steuerungspraxis
Das Moped nimmt einen grossen Platz im «Herzen» und im Leben der jungen Fahrer ein. Die Praxis und die Benutzung dieses technischen Gegenstandes haben jedoch die Aufmerksamkeit der Forscher im Bereich der Human-und Sozialwissenschaften kaum auf sich V. O. gelenkt. Dieser Artikel versucht diese LĂŒcke auszufĂŒllen und richtet dabei seine Aufmerksamkeit auf die Steuerung eines Mopeds. Welche Beziehung unterhĂ€lt der junge Fahrer mit seinem eigenen Körper, seiner Maschine, der Strasse und seinem Umfeld, wenn er Moped fĂ€hrt ? Durch die Analyse dieser angewandten Praxis, davon gehen wir aus, kann man die risikoreichen «Verhaltensweisen» besser verstehen und die normative Sprache abbrechen.Young people and the moped : pragmatics of driving
The moped occupies an important place in the heart and existence of young users. However, the practice and use of this technical object have not caught much attention from the social and human sciences researchers. This paper aims to fill the gap and focuses on the action of driving or «piloting» a moped. Which kind of relationship does the young user have with his body, the vehicle, the road and his environment when he is riding his moped ? The analysis of this located and equipped practice allows us, according to our hypothesis, to have a better understanding of the at risk «driving» and to break with a normative discourseQuelle relation le jeune utilisateur entretient-il avec son propre corps, sa machine, la route et son environnement lorsquâil conduit son cyclomoteur ? Lâanalyse de cette pratique situĂ©e et appareillĂ©e nous permet, de mieux comprendre les «conduites» Ă risque et de rompre avec un discours normatif.Los jĂłvenes y el ciclomotor, pragmĂĄtica del pilotaje
El ciclomotor ocupa un lugar importante en el âącorazĂłnâ y la existencia de los jĂłvenes utilizadores. Sin embargo la prĂĄctica y el uso de este objeto tĂ©cnico apenas han llamado la atenciĂłn de los investigadores en Ciencias Humanas y Sociales. Este documento intenta colmar esta laguna enfocando su atenciĂłn en el acto de conducir o âąpilotarâ un ciclomotor. Âż QuĂ© relaciĂłn mantiene el joven utilizador con su propio cuerpo, su mĂĄquina y su entorno, cuando conduce su ciclomotor ? El anĂĄlisis de esta prĂĄctica enmarcada y contrastada nos permite, o asĂ lo suponemos, comprender mejor las âąconductasâ de riesgo y romper con un discurso normativo.Chevrier StĂ©phane. Les jeunes et le cyclomoteur. In: Agora dĂ©bats/jeunesses, 27, 2002. Les jeunes et le risque. pp. 86-97
ĂvĂ©nements et sĂ©curitĂ©
La ville se reconfigure lors des grands Ă©vĂ©nements (festival, manifestation, match de foot, etc.), les foules sont contenues par le cadre bĂąti urbain et sâen emparent, les publics vibrent au rythme des attracteurs proposĂ©s par les organisateurs ou crĂ©Ă©s par eux-mĂȘmes. Un climat sâinstalle, qui doit toujours ĂȘtre unique pour faire Ă©vĂ©nement, qui attire ou qui repousse, qui se prĂ©pare, qui va crescendo mais qui doit aussi savoir progressivement descendre pour revenir au calme puis laisser des traces dans les mĂ©moires et dans les mĂ©dias. Les spĂ©cialistes de la sĂ©curitĂ© urbaine et du maintien de lâordre, quâils soient publics ou privĂ©s, ont appris Ă anticiper sur ces Ă©tats toujours instables, Ă prĂ©-positionner des forces et des moyens opĂ©rationnels, mais aussi Ă rĂ©viser leurs plans car des incidents viennent toujours ponctuer ces grands Ă©vĂ©nements urbains. Trois Ă©vĂ©nements (un match de foot, un festival de musique, une manifestation syndicale) ont Ă©tĂ© suivis grĂące Ă des mĂ©thodes dâobservation originales et minutieuses permettant de restituer tous les points de vue, sans jamais les totaliser mais en montrant leurs articulations. Lâouvrage permet ainsi de restituer « lâart du bon moment » (le kairos) qui fait lâexpertise de ces professionnels du climat urbain et de leurs Ă©quipements
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