Search

En disposant inauguralement l'opposition du sensible et de l'intelligible, de l'apparaître et de l'être, la métaphysique idéaliste a imposé un coup de force ontologique qui est au fondement de la détermination de la philosophie comme nihilisme, prométhéisme de la volonté et narcissime de l'intériorité. Il faut substituer à l'être le disparaître pour faire entrer le questionnement dans des contenus positifs et existentiels, entre naître et mourir, vivre et éprouver, venir au monde et exister. La philosophie est un nihilisme mais, dans sa dynamique de pharmakon, elle peut aussi offrir le remède à ses propres démons. La "relâche" cartésienne, le "willing suspension of disbelief" (Coleridge), le conatus interruptus , le "dépouillement" de "l'intelligence", la probité ou encore les poétiques de l'involontaire sont autant de brèches dans son édifice imprenable., Ao inaugurar a oposição entre o sensível e o inteligível, entre o ser e o aparecer, a metafísica idealista impôs um golpe de força ontológico que está na origem da determinação da filosofa como niilismo, como um prometeísmo da vontade e narcisismo da interioridade. É necessário substituir o ser pelo desaparecer a fim de imprimir um questionamento no interior dos conteúdos positivos e existenciais, o nascer e o morrer, o viver e o experimentar, o vir ao mundo e o existir. A filosofia é um niilismo, mas, na sua condição de Pharmakon, ela também pode oferecer um remédio para os seus próprios demônios. O “desprendimento” cartesiano, a “suspensão voluntária da descrença” (Coleridge), o conatus interruptus, o despojamento da inteligência, a probidade ou, ainda, as poéticas do involuntário são todos brechas no interior do seu edifício inexpugnável, En disposant inauguralement l’opposition du sensible et de l’intelligible, de l’apparaître et de l’être, la métaphysique idéaliste a imposé un coup de force ontologique qui est au fondement de la détermination de la philosophie comme nihilisme, prométhéisme de la volonté et narcissime de l’intériorité. Il faut substituer à l’être le disparaître pour faire entrer le questionnement dans des contenus positifs et existentiels, entre naître et mourir, vivre et éprouver, venir au monde et exister. La philosophie est un nihilisme mais, dans sa dynamique de pharmakon, elle peut aussi offrir le remède à ses propres démons. La “relâche” cartésienne, le “willing suspension of disbelief” (Coleridge), le conatus interruptus, le “dépouillement” de “l’intelligence”, la probité ou encore les poétiques de l’involontaire sont autant de brèches dans son édifice imprenable.

En disposant inauguralement l'opposition du sensible et de l'intelligible, de l'apparaître et de l'être, la métaphysique idéaliste a imposé un coup de force ontologique qui est au fondement de la détermination de la philosophie comme nihilisme, prométhéisme de la volonté et narcissime de l'intériorité. Il faut substituer à l'être le disparaître pour faire entrer le questionnement dans des contenus positifs et existentiels, entre naître et mourir, vivre et éprouver, venir au monde et exister. La philosophie est un nihilisme mais, dans sa dynamique de pharmakon, elle peut aussi offrir le remède à ses propres démons. La "relâche" cartésienne, le "willing suspension of disbelief" (Coleridge), le conatus interruptus , le "dépouillement" de "l'intelligence", la probité ou encore les poétiques de l'involontaire sont autant de brèches dans son édifice imprenable., Ao inaugurar a oposição entre o sensível e o inteligível, entre o ser e o aparecer, a metafísica idealista impôs um golpe de força ontológico que está na origem da determinação da filosofa como niilismo, como um prometeísmo da vontade e narcisismo da interioridade. É necessário substituir o ser pelo desaparecer a fim de imprimir um questionamento no interior dos conteúdos positivos e existenciais, o nascer e o morrer, o viver e o experimentar, o vir ao mundo e o existir. A filosofia é um niilismo, mas, na sua condição de Pharmakon, ela também pode oferecer um remédio para os seus próprios demônios. O “desprendimento” cartesiano, a “suspensão voluntária da descrença” (Coleridge), o conatus interruptus, o despojamento da inteligência, a probidade ou, ainda, as poéticas do involuntário são todos brechas no interior do seu edifício inexpugnável, En disposant inauguralement l’opposition du sensible et de l’intelligible, de l’apparaître et de l’être, la métaphysique idéaliste a imposé un coup de force ontologique qui est au fondement de la détermination de la philosophie comme nihilisme, prométhéisme de la volonté et narcissime de l’intériorité. Il faut substituer à l’être le disparaître pour faire entrer le questionnement dans des contenus positifs et existentiels, entre naître et mourir, vivre et éprouver, venir au monde et exister. La philosophie est un nihilisme mais, dans sa dynamique de pharmakon, elle peut aussi offrir le remède à ses propres démons. La “relâche” cartésienne, le “willing suspension of disbelief” (Coleridge), le conatus interruptus, le “dépouillement” de “l’intelligence”, la probité ou encore les poétiques de l’involontaire sont autant de brèches dans son édifice imprenable.

OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment). METHODS: Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19). RESULTS: A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19-0.6%), P < 0.0001; active SLE: median = 0.61 (0.55-0.77), P < 0.0001 vs healthy controls: 2.32% (1.18-4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood. CONCLUSION: In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Natural regulatory T cells (nTregs) ensure the control of self-tolerance and are currently used in clinical trials to alleviate autoimmune diseases and graft-versus-host disease after hematopoietic stem cell transfer. Based on CD39/CD26 markers, blood nTreg analysis revealed the presence of five different cell subsets, each representing a distinct stage of maturation. Ex vivo added microenvironmental factors, including IL-2, TGFβ, and PGE2, direct the conversion from naive precursor to immature memory and finally from immature to mature memory cells, the latest being a no-return stage. Phenotypic and genetic characteristics of the subsets illustrate the structural parental maturation between subsets, which further correlates with the expression of regulatory factors. Regarding nTreg functional plasticity, both maturation stage and microenvironmental cytokines condition nTreg activities, which include blockade of autoreactive immune cells by cell-cell contact, Th17 and IL-10 Tr1-like activities, or activation of TCR-stimulating dendritic cell tolerization. Importantly, blood nTreg CD39/CD26 profile remained constant over a 2-y period in healthy persons but varied from person to person. Preliminary data on patients with autoimmune diseases or acute myelogenous leukemia illustrate the potential use of the nTreg CD39/ CD26 profile as a blood biomarker to monitor chronic inflammatory diseases. Finally, we confirmed that naive conventional CD4 T cells, TCR-stimulated under a tolerogenic conditioned medium, could be ex vivo reprogrammed to FOXP3 lineage Tregs, and further found that these cells were exclusively committed to suppressive function under all microenvironmental contexts., SCOPUS: ar.j, info:eu-repo/semantics/published

Item does not contain fulltext, BACKGROUND: Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII. PATIENTS AND METHODS: We performed the first genome-wide association study to identify the causal genes for RCDII and the molecular pathways perturbed in RCDII. The genome-wide association study was performed in 38 Dutch patients with RCDII, and the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5x10) were replicated in 56 independent French and Dutch patients with RCDII. RESULTS: After replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37x10, odds ratio=2.36) but not with CeD susceptibility. SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratification of RCDII biopsies based on rs2041570 genotype showed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells. CONCLUSION: We have identified a novel SNP associated with the severe progression of CeD to RCDII. Our data suggest that genetic susceptibility to CeD might be distinct from the progression to RCDII and suggest a role for Paneth cells in RCDII progression.

Item does not contain fulltext, BACKGROUND: Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII. PATIENTS AND METHODS: We performed the first genome-wide association study to identify the causal genes for RCDII and the molecular pathways perturbed in RCDII. The genome-wide association study was performed in 38 Dutch patients with RCDII, and the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5x10) were replicated in 56 independent French and Dutch patients with RCDII. RESULTS: After replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37x10, odds ratio=2.36) but not with CeD susceptibility. SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratification of RCDII biopsies based on rs2041570 genotype showed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells. CONCLUSION: We have identified a novel SNP associated with the severe progression of CeD to RCDII. Our data suggest that genetic susceptibility to CeD might be distinct from the progression to RCDII and suggest a role for Paneth cells in RCDII progression.

Item does not contain fulltext, BACKGROUND: Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII. PATIENTS AND METHODS: We performed the first genome-wide association study to identify the causal genes for RCDII and the molecular pathways perturbed in RCDII. The genome-wide association study was performed in 38 Dutch patients with RCDII, and the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5x10) were replicated in 56 independent French and Dutch patients with RCDII. RESULTS: After replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37x10, odds ratio=2.36) but not with CeD susceptibility. SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratification of RCDII biopsies based on rs2041570 genotype showed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells. CONCLUSION: We have identified a novel SNP associated with the severe progression of CeD to RCDII. Our data suggest that genetic susceptibility to CeD might be distinct from the progression to RCDII and suggest a role for Paneth cells in RCDII progression.

Par la guerre, la philosophie en son entier, “l’idéalisme”, s’avère selon Rosenzweig dans son mensonge, c’est-à-dire dans sa fausseté à la fois épistémologique et existentielle. Cette double leçon le portera à esquisser les contours d’un “nouveau penser” issu du bris de la totalisation universelle de toutes les particularités. Ce bris passera par la voix revivifiée de la résistance du singulier. Il faut alors s’interroger sur ce que Rosenzweig nomme lui-même dans La pensée nouvelle le “système” de l’Etoile. En lisant ce maître-ouvrage, et en particulier sa deuxième partie, on remarque la double fonctionnalité de la Révélation. D’une part, elle irradie l’ensemble du livre, le “système” en son entier en quelque sorte, c’est-à-dire les parties I et III, la Création aussi bien que la Rédemption. D’autre part, la Révélation revêt un sens étroit: elle révèle la Création, elle révèle la Rédemption et elle s’autorévèle comme “âme aimée” dans l’ipséité tragique du soi. Au sens fort, ou large, seule existe la Révélation d’un passé créationnel et d’un avenir rédimant. L’Etoile dessine donc une économie générale des flux, des multiplicités ouvertes les unes sur les autres. Le “système” est un système des temps (Schelling). Le Système, c’est la Révélation. Le “philosopher dans la forme du monde “ que promeut Rosenzweig s’éclaire de ce constat qui emporte à son tour une repensée du rapport de la philosophie à la religion.

Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules. We used the MasSpec Pen for ex vivo molecular analysis of 20 human cancer thin tissue sections and 253 human patient tissue samples including normal and cancerous tissues from breast, lung, thyroid, and ovary. The mass spectra obtained presented rich molecular profiles characterized by a variety of potential cancer biomarkers identified as metabolites, lipids, and proteins. Statistical classifiers built from the histologically validated molecular database allowed cancer prediction with high sensitivity (96.4%), specificity (96.2%), and overall accuracy (96.3%), as well as prediction of benign and malignant thyroid tumors and different histologic subtypes of lung cancer. Notably, our classifier allowed accurate diagnosis of cancer in marginal tumor regions presenting mixed histologic composition. Last, we demonstrate that the MasSpec Pen is suited for in vivo cancer diagnosis during surgery performed in tumor-bearing mouse models, without causing any observable tissue harm or stress to the animal. Our results provide evidence that the MasSpec Pen could potentially be used as a clinical and intraoperative technology for ex vivo and in vivo cancer diagnosis.

Ce livre voudrait éclairer l’actualité de la pensée de Rosenzweig, aujourd’hui toujours aussi « nouvelle » qu’en son temps, sous bien des aspects. Il la confronte aux questions emportées par la philosophie contemporaine, d’Arendt à Derrida, en passant par Benjamin, Strauss ou Levinas. Il l’interroge aussi sur sa capacité à nous aider à mieux penser, « dans la forme du monde », la politique, l’histoire, la religion, l’Islam par exemple, l’enseignement, l’éthique, l’Europe. L’auteur fait ainsi travailler la cohérence des grandes thèses rosenzweigiennes, articulées autour de l’hypothèse d’une non-immanence de l’histoire à elle-même, dans la réflexion qu’il engage sur ces thèmes et sur ces penseurs. Gérard Bensussan est professeur de philosophie à l’Université de Strasbourg et chercheur aux Archives Husserl de Paris. Spécialiste de l’idéalisme allemand et de la philosophie juive de langue allemande, il est l’auteur de nombreux ouvrages, traduits en plusieurs langues, où se croisent l’éthique et la politique, le temps et la justice, l’existence et l’histoire.

Ce livre voudrait éclairer l’actualité de la pensée de Rosenzweig, aujourd’hui toujours aussi « nouvelle » qu’en son temps, sous bien des aspects. Il la confronte aux questions emportées par la philosophie contemporaine, d’Arendt à Derrida, en passant par Benjamin, Strauss ou Levinas. Il l’interroge aussi sur sa capacité à nous aider à mieux penser, « dans la forme du monde », la politique, l’histoire, la religion, l’Islam par exemple, l’enseignement, l’éthique, l’Europe. L’auteur fait ainsi travailler la cohérence des grandes thèses rosenzweigiennes, articulées autour de l’hypothèse d’une non-immanence de l’histoire à elle-même, dans la réflexion qu’il engage sur ces thèmes et sur ces penseurs. Gérard Bensussan est professeur de philosophie à l’Université de Strasbourg et chercheur aux Archives Husserl de Paris. Spécialiste de l’idéalisme allemand et de la philosophie juive de langue allemande, il est l’auteur de nombreux ouvrages, traduits en plusieurs langues, où se croisent l’éthique et la politique, le temps et la justice, l’existence et l’histoire.

Ce livre voudrait éclairer l’actualité de la pensée de Rosenzweig, aujourd’hui toujours aussi « nouvelle » qu’en son temps, sous bien des aspects. Il la confronte aux questions emportées par la philosophie contemporaine, d’Arendt à Derrida, en passant par Benjamin, Strauss ou Levinas. Il l’interroge aussi sur sa capacité à nous aider à mieux penser, « dans la forme du monde », la politique, l’histoire, la religion, l’Islam par exemple, l’enseignement, l’éthique, l’Europe. L’auteur fait ainsi travailler la cohérence des grandes thèses rosenzweigiennes, articulées autour de l’hypothèse d’une non-immanence de l’histoire à elle-même, dans la réflexion qu’il engage sur ces thèmes et sur ces penseurs. Gérard Bensussan est professeur de philosophie à l’Université de Strasbourg et chercheur aux Archives Husserl de Paris. Spécialiste de l’idéalisme allemand et de la philosophie juive de langue allemande, il est l’auteur de nombreux ouvrages, traduits en plusieurs langues, où se croisent l’éthique et la politique, le temps et la justice, l’existence et l’histoire.

Ce livre voudrait éclairer l’actualité de la pensée de Rosenzweig, aujourd’hui toujours aussi « nouvelle » qu’en son temps, sous bien des aspects. Il la confronte aux questions emportées par la philosophie contemporaine, d’Arendt à Derrida, en passant par Benjamin, Strauss ou Levinas. Il l’interroge aussi sur sa capacité à nous aider à mieux penser, « dans la forme du monde », la politique, l’histoire, la religion, l’Islam par exemple, l’enseignement, l’éthique, l’Europe. L’auteur fait ainsi travailler la cohérence des grandes thèses rosenzweigiennes, articulées autour de l’hypothèse d’une non-immanence de l’histoire à elle-même, dans la réflexion qu’il engage sur ces thèmes et sur ces penseurs. Gérard Bensussan est professeur de philosophie à l’Université de Strasbourg et chercheur aux Archives Husserl de Paris. Spécialiste de l’idéalisme allemand et de la philosophie juive de langue allemande, il est l’auteur de nombreux ouvrages, traduits en plusieurs langues, où se croisent l’éthique et la politique, le temps et la justice, l’existence et l’histoire.

Ce livre voudrait éclairer l’actualité de la pensée de Rosenzweig, aujourd’hui toujours aussi « nouvelle » qu’en son temps, sous bien des aspects. Il la confronte aux questions emportées par la philosophie contemporaine, d’Arendt à Derrida, en passant par Benjamin, Strauss ou Levinas. Il l’interroge aussi sur sa capacité à nous aider à mieux penser, « dans la forme du monde », la politique, l’histoire, la religion, l’Islam par exemple, l’enseignement, l’éthique, l’Europe. L’auteur fait ainsi travailler la cohérence des grandes thèses rosenzweigiennes, articulées autour de l’hypothèse d’une non-immanence de l’histoire à elle-même, dans la réflexion qu’il engage sur ces thèmes et sur ces penseurs. Gérard Bensussan est professeur de philosophie à l’Université de Strasbourg et chercheur aux Archives Husserl de Paris. Spécialiste de l’idéalisme allemand et de la philosophie juive de langue allemande, il est l’auteur de nombreux ouvrages, traduits en plusieurs langues, où se croisent l’éthique et la politique, le temps et la justice, l’existence et l’histoire.

Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C-sequences flanking it differ entirely from those of MUC1-TM. In vitro protein synthesis assays and extensive immunohistochemical as well as western blot analyses with MUC1-ARF specific monoclonal antibodies confirmed MUC1-ARF expression. Rather than being expressed at the cell membrane like MUC1-TM, immunostaining showed that MUC1-ARF protein localizes mainly in the nucleus: Immunohistochemical analyses of MUC1-expressing tissues demonstrated MUC1-ARF expression in the nuclei of secretory luminal epithelial cells. MUC1-ARF expression varies in different malignancies. While the malignant epithelial cells of pancreatic cancer show limited expression, in breast cancer tissue MUC1-ARF demonstrates strong nuclear expression. Proinflammatory cytokines upregulate expression of MUC1-ARF protein and co-immunoprecipitation analyses demonstrate association of MUC1-ARF with SH3 domain-containing proteins. Mass spectrometry performed on proteins coprecipitating with MUC1-ARF demonstrated Glucose-6-phosphate 1-dehydrogenase (G6PD) and Dynamin 2 (DNM2). These studies not only reveal that the MUC1 gene generates a previously unidentified MUC1-ARF protein, they also show that just like its 'parent' MUC1-TM protein, MUC1-ARF is apparently linked to signaling and malignancy, yet a definitive link to these processes and the roles it plays awaits a precise identification of its molecular functions. Compris

Le rapport Rosenzweig / Schelling est le plus souvent, et à bon droit, étudié à partir de l’influence des Âges du monde sur l’écriture de l’Etoile de la rédemption. Le présent texte suggère une autre voie, non exclusive de la première, constituée autour de la dette rosenzweigienne contractée à l’endroit de la pensée schellingienne de l’historicité. Cette étude retrace les contenus et les attendus de cette dette sous quatre registres : 1. L’histoire, chez Schelling, est soumise à sa disposition comme articulation de temporalités sédimentées et coexistantes ; 2. Une véritable pensée de l’histoire peut être ainsi déterminée, très différente d’une « philosophie de l’histoire » : elle accueille l’histoire comme ce par quoi se fait connaître à l’expérience un imprépensable ; 3. Cette histoire « expériencielle » se surprend sans cesse en effectuant l’événement de ce qui ne cesse d’advenir dans sa Wirklichkeit ; 4. L’acte fondatif et inaugural de l’histoire est un mouvement que les hommes ne peuvent reconnaître comme quelque chose qu’ils auraient accompli. L’histoire avance, mais sans voir. Elle s’avance sans se voir selon un « progrès anti-historique ». Le parcours de Rosenzweig refait à sa façon ce chemin. Il va d’une conception néo-hégélienne de l’histoire universelle à l’idée d’une histoire discontinue, et même d’une méta- ou d’une extrahistoricité, c’est-à-dire d’une d’extériorité à l’histoire sans laquelle celle-ci s’aplatirait dans sa pure immanence et ne se laisserait pas penser dans sa concrétude opaque et chaotique.

Le rapport Rosenzweig / Schelling est le plus souvent, et à bon droit, étudié à partir de l’influence des Âges du monde sur l’écriture de l’Etoile de la rédemption. Le présent texte suggère une autre voie, non exclusive de la première, constituée autour de la dette rosenzweigienne contractée à l’endroit de la pensée schellingienne de l’historicité. Cette étude retrace les contenus et les attendus de cette dette sous quatre registres : 1. L’histoire, chez Schelling, est soumise à sa disposition comme articulation de temporalités sédimentées et coexistantes ; 2. Une véritable pensée de l’histoire peut être ainsi déterminée, très différente d’une « philosophie de l’histoire » : elle accueille l’histoire comme ce par quoi se fait connaître à l’expérience un imprépensable ; 3. Cette histoire « expériencielle » se surprend sans cesse en effectuant l’événement de ce qui ne cesse d’advenir dans sa Wirklichkeit ; 4. L’acte fondatif et inaugural de l’histoire est un mouvement que les hommes ne peuvent reconnaître comme quelque chose qu’ils auraient accompli. L’histoire avance, mais sans voir. Elle s’avance sans se voir selon un « progrès anti-historique ». Le parcours de Rosenzweig refait à sa façon ce chemin. Il va d’une conception néo-hégélienne de l’histoire universelle à l’idée d’une histoire discontinue, et même d’une méta- ou d’une extrahistoricité, c’est-à-dire d’une d’extériorité à l’histoire sans laquelle celle-ci s’aplatirait dans sa pure immanence et ne se laisserait pas penser dans sa concrétude opaque et chaotique.

Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C-sequences flanking it differ entirely from those of MUC1-TM. In vitro protein synthesis assays and extensive immunohistochemical as well as western blot analyses with MUC1-ARF specific monoclonal antibodies confirmed MUC1-ARF expression. Rather than being expressed at the cell membrane like MUC1-TM, immunostaining showed that MUC1-ARF protein localizes mainly in the nucleus: Immunohistochemical analyses of MUC1-expressing tissues demonstrated MUC1-ARF expression in the nuclei of secretory luminal epithelial cells. MUC1-ARF expression varies in different malignancies. While the malignant epithelial cells of pancreatic cancer show limited expression, in breast cancer tissue MUC1-ARF demonstrates strong nuclear expression. Proinflammatory cytokines upregulate expression of MUC1-ARF protein and co-immunoprecipitation analyses demonstrate association of MUC1-ARF with SH3 domain-containing proteins. Mass spectrometry performed on proteins coprecipitating with MUC1-ARF demonstrated Glucose-6-phosphate 1-dehydrogenase (G6PD) and Dynamin 2 (DNM2). These studies not only reveal that the MUC1 gene generates a previously unidentified MUC1-ARF protein, they also show that just like its 'parent' MUC1-TM protein, MUC1-ARF is apparently linked to signaling and malignancy, yet a definitive link to these processes and the roles it plays awaits a precise identification of its molecular functions. Compris

Contains fulltext : 154818.pdf (publisher's version ) (Closed access), Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self-constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell-specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut-associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life.

Contains fulltext : 154818.pdf (publisher's version ) (Closed access), Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self-constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell-specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut-associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life.

BACKGROUND: Recently, a new enteropathy has been described: olmesartan-associated enteropathy. However, the association has been questioned: a phase 3 trial and a cohort study found no association between gastrointestinal events and olmesartan. AIM: To collect French cases of sartan-associated enteropathy to describe further this entity, confirm or refute causality, and determine if the association exists with other sartans. METHODS: French gastroenterologists were invited to report cases of sartan-associated enteropathy and collect clinical, biological and histological data. Patients with diarrhoea and histological duodenal abnormalities were included. RESULTS: Thirty-six patients with olmesartan-associated enteropathy were reported, including 32 with villous atrophy and four without. There was only one patient with irbesartan-associated enteropathy. None of the patients died. Patients with villous atrophy had diarrhoea, vomiting, renal failure, hypokalaemia, body weight loss and hypoalbuminaemia. Thirty-one patients were hospitalised; four required intensive care. Anti-transglutaminase and anti-enterocyte antibodies were negative; anti-nuclear antibodies were positive (9/11). Endoscopic duodenal biopsies showed villous atrophy (32/32) and polyclonal intra-epithelial CD3+CD8+ lymphocytosis (11/11). Exactly, 14/15 patients responded to steroids and/or immunosuppressants, prescribed because of suspected autoimmune enteropathy. Ten olmesartan interruptions were followed by reintroductions before steroids or immunosuppressants. Interruptions were followed by remissions (9/10), but reintroductions were followed by relapses (9/9). Twenty-nine patients were in remission since olmesartan interruption, including 26 without immunosuppressants. Patients with normal villi had similar clinical characteristics, but mild histological abnormalities (intra-epithelial lymphocytosis and lamina propria lymphocytic infiltration). CONCLUSIONS: Olmesartan causes a severe and immune-media

Par la guerre, la philosophie en son entier, “l’idéalisme”, s’avère selon Rosenzweig dans son mensonge, c’est-à-dire dans sa fausseté à la fois épistémologique et existentielle. Cette double leçon le portera à esquisser les contours d’un “nouveau penser” issu du bris de la totalisation universelle de toutes les particularités. Ce bris passera par la voix revivifiée de la résistance du singulier. Il faut alors s’interroger sur ce que Rosenzweig nomme lui-même dans La pensée nouvelle le “système” de l’Etoile. En lisant ce maître-ouvrage, et en particulier sa deuxième partie, on remarque la double fonctionnalité de la Révélation. D’une part, elle irradie l’ensemble du livre, le “système” en son entier en quelque sorte, c’est-à-dire les parties I et III, la Création aussi bien que la Rédemption. D’autre part, la Révélation revêt un sens étroit: elle révèle la Création, elle révèle la Rédemption et elle s’autorévèle comme “âme aimée” dans l’ipséité tragique du soi. Au sens fort, ou large, seule existe la Révélation d’un passé créationnel et d’un avenir rédimant. L’Etoile dessine donc une économie générale des flux, des multiplicités ouvertes les unes sur les autres. Le “système” est un système des temps (Schelling). Le Système, c’est la Révélation. Le “philosopher dans la forme du monde “ que promeut Rosenzweig s’éclaire de ce constat qui emporte à son tour une repensée du rapport de la philosophie à la religion.

Par la guerre, la philosophie en son entier, “l’idéalisme”, s’avère selon Rosenzweig dans son mensonge, c’est-à-dire dans sa fausseté à la fois épistémologique et existentielle. Cette double leçon le portera à esquisser les contours d’un “nouveau penser” issu du bris de la totalisation universelle de toutes les particularités. Ce bris passera par la voix revivifiée de la résistance du singulier. Il faut alors s’interroger sur ce que Rosenzweig nomme lui-même dans La pensée nouvelle le “système” de l’Etoile. En lisant ce maître-ouvrage, et en particulier sa deuxième partie, on remarque la double fonctionnalité de la Révélation. D’une part, elle irradie l’ensemble du livre, le “système” en son entier en quelque sorte, c’est-à-dire les parties I et III, la Création aussi bien que la Rédemption. D’autre part, la Révélation revêt un sens étroit: elle révèle la Création, elle révèle la Rédemption et elle s’autorévèle comme “âme aimée” dans l’ipséité tragique du soi. Au sens fort, ou large, seule existe la Révélation d’un passé créationnel et d’un avenir rédimant. L’Etoile dessine donc une économie générale des flux, des multiplicités ouvertes les unes sur les autres. Le “système” est un système des temps (Schelling). Le Système, c’est la Révélation. Le “philosopher dans la forme du monde “ que promeut Rosenzweig s’éclaire de ce constat qui emporte à son tour une repensée du rapport de la philosophie à la religion.

Background: To assess the increased cellular immunity of Peripheral Blood Mononuclear Cells (PBMC) derived LAK cells from endometriosis patients towards endometriosis cell cultures after stimulation with IL-2. Methods: This study is a quasi-experimental study of pre and post treatment using controls. Phenotype evaluation of CD3+CD4+, CD3+CD8+ and CD56+ effector cells of PBMC from endometriosis patients and controls was performed. Cytotoxicity test of PBMC from endometriosis patients and control towards Daudi, K562 cell line and endometriosis cell cultures using 51Chromium release assay was also carried out. Results: Phenotype evaluation of PBMC from endometriosis patients (n = 10) and controls (n = 6) were done prior to and after IL-2 stimulation. Before IL-2 stimulation, CD3+CD4+, CD56+ from endometriosis group (n = 10) tend to be lower than control (n=6) whereas CD3+CD8+ were higher in endometriosis group than controls. After IL-2 stimulation, CD3+ CD8+, CD56+ of PBMC from endometriosis group were significantly increased (p < 0.05). Cytotoxicity test revealed a significant increase (p < 0.05) in both PBMC's effector cells from endometriosis and control group towards target cells, Daudi, and K562 cell lines after IL-2 stimulation. PBMC's effector cells cytotoxicity from both endometriosis and control towards target endometriosis cell cultures were also elevated after IL-2 stimulation. Conclusion: LAK cells derived IL-2 stimulated PBMC from endometriosis patients increased cellular immunity towards endometriosis cell cultures. (Med J Indones 2011; 20:87-93)

Background: To assess the increased cellular immunity of Peripheral Blood Mononuclear Cells (PBMC) derived LAK cells from endometriosis patients towards endometriosis cell cultures after stimulation with IL-2. Methods: This study is a quasi-experimental study of pre and post treatment using controls. Phenotype evaluation of CD3+CD4+, CD3+CD8+ and CD56+ effector cells of PBMC from endometriosis patients and controls was performed. Cytotoxicity test of PBMC from endometriosis patients and control towards Daudi, K562 cell line and endometriosis cell cultures using 51Chromium release assay was also carried out. Results: Phenotype evaluation of PBMC from endometriosis patients (n = 10) and controls (n = 6) were done prior to and after IL-2 stimulation. Before IL-2 stimulation, CD3+CD4+, CD56+ from endometriosis group (n = 10) tend to be lower than control (n=6) whereas CD3+CD8+ were higher in endometriosis group than controls. After IL-2 stimulation, CD3+ CD8+, CD56+ of PBMC from endometriosis group were significantly increased (p < 0.05). Cytotoxicity test revealed a significant increase (p < 0.05) in both PBMC's effector cells from endometriosis and control group towards target cells, Daudi, and K562 cell lines after IL-2 stimulation. PBMC's effector cells cytotoxicity from both endometriosis and control towards target endometriosis cell cultures were also elevated after IL-2 stimulation. Conclusion: LAK cells derived IL-2 stimulated PBMC from endometriosis patients increased cellular immunity towards endometriosis cell cultures. (Med J Indones 2011; 20:87-93)

Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptiveimmune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10-secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact- mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL-10, an effect potentiated by IFN-α. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-αand that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti-IFN-α Ab immunotherapy in lupus patients., SCOPUS: ar.j, info:eu-repo/semantics/published

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.

Pathogenesis of allergic inflammatory disorders is characterized by allergen-induced IgE stimulated by Th2 cytokines including mainly IL-4 overproduction. To counteract IL-4 effects in sensitized-BALB/c mice, we prepared an IL-4 derivative immunogen, made of KLH and murine IL-4 heterocomplex, termed mIL-4 kinoid. Murine IL-4 kinoid immunized mice produced high titer of anti-IL-4 neutralizing Abs. In contrast to KLH control immunization kinoid immunization reversed the allergic IgE:IgG ratio hallmark in rBet v 1a sensitized mice and reduced pulmonary eosinophil recruitment and bronchial hyperreactivity in Ova-sensitized mice. These data pave the way to alternative therapies to combat allergic conditions. © 2007 Elsevier Ltd. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

Pathogenesis of allergic inflammatory disorders is characterized by allergen-induced IgE stimulated by Th2 cytokines including mainly IL-4 overproduction. To counteract IL-4 effects in sensitized-BALB/c mice, we prepared an IL-4 derivative immunogen, made of KLH and murine IL-4 heterocomplex, termed mIL-4 kinoid. Murine IL-4 kinoid immunized mice produced high titer of anti-IL-4 neutralizing Abs. In contrast to KLH control immunization kinoid immunization reversed the allergic IgE:IgG ratio hallmark in rBet v 1a sensitized mice and reduced pulmonary eosinophil recruitment and bronchial hyperreactivity in Ova-sensitized mice. These data pave the way to alternative therapies to combat allergic conditions. © 2007 Elsevier Ltd. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

The immune system works through leukocytes interacting with each other, with other cells, with tissue matrices, with infectious agents, and with other antigens. These interactions are mediated by cell-surface glycoproteins and glycolipids. Antibodies against these leukocyte molecules have provided powerful tools for analysis of their structure, function, and distribution. Antibodies have been used widely in hematology, immunology, and pathology, and in research, diagnosis, and therapy. The associated CD nomenclature is commonly used when referring to leukocyte surface molecules and antibodies against them. It provides an essential classification for diagnostic and therapeutic purposes. The most recent (8th) Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Adelaide, Australia, in December 2004, allocated 95 new CD designations and made radical changes to its aims and future operational strategy in order to maintain its relevance to modern human biology and clinical practice.

CD100 represents the first semaphorin described in the immune system. It is expressed as a 300-kDa homodimer at the surface of most hematopoietic cells, but is also found in a soluble form following a proteolytic cleavage upon cell activation. We herein established that soluble CD100 (sCD100) impaired the migration of human monocytes and immature dendritic cells (DCs), but not of mature DCs. Performing competition assays, we identified plexin C1 (VESPR/CD232) as being involved in sCD100-mediated effects on human monocytes. Interestingly, we observed a complete down-regulation of plexin C1 expression during the in vitro differentiation process of monocytes to immature DCs, while concomitantly the surface expression of plexin B1 was induced. The latter receptor then binds sCD100 on immature DCs, mediating its inhibitory effect on cell migration. Finally, we showed that sCD100 modulated the cytokine production from monocytes and immature DCs. Together these results suggest that sCD100 plays a critical role in the regulation of antigen-presenting cell migration and functions via a tightly regulated process of receptor expression.

The capacity of non-pathogenic enteric bacteria to induce a pro-inflammatory response is under debate in terms of its effect on the symbiosis between the mammalian host and its commensal gut microflora. Activation of NF-kappaB and induction of interleukin-8 (IL-8) and CCL-20 by the commensal Escherichia coli strain MG1655 were first studied in vitro in the human intestinal epithelial cell (IECs) lines HT29-19A and Caco-2, transfected or not with plasmids encoding dominant negative Toll-like receptor (TLR) 5 and myeloid differentiation factor-88 (MyD88) adaptor protein. The response of enterocytes in situ was then assessed using murine ileal biopsies mounted in Ussing chambers. Commensal E. coli induced NF-kappaB DNA binding, NF-kappaB transcriptional activity, CCL-20 expression, and IL-8 secretion in the human IEC lines. E. coli MG1655 flagellin was necessary and sufficient to trigger this pro-inflammatory pathway via its interaction with TLR5 and the subsequent recruitment of the adaptor protein MyD88. Following epithelial cell polarization, signaling could be induced by live E. coli and flagellin on the apical side of HT29-19A. The in vivo relevance of our findings was confirmed, because immunohistochemical staining of murine ileum demonstrated expression of TLR5 in the apical part of enterocytes in situ. Furthermore, flagellin added on the mucosal side of murine ileal biopsies mounted in Ussing chambers induced a basolateral production of KC, a functional murine homolog of human IL-8. These findings provide strong evidence that flagellin released by flagellated commensal bacteria in the intestinal lumen can induce a pro-inflammatory response in enterocytes in vivo.

L'ouvrage examine la pensée de Léo Strauss (1899-1973) et étudie à partir d'elle les stratégies d'exposition et de dissimulation de la philosophie. Les études qu'il réunit mesurent la portée de l'hypothèse d'un "art d'écrire oublié" et examinent la fécondité et les limites de la conception straussienne de l'écriture philosophique., info:eu-repo/semantics/published

L'ouvrage examine la pensée de Léo Strauss (1899-1973) et étudie à partir d'elle les stratégies d'exposition et de dissimulation de la philosophie. Les études qu'il réunit mesurent la portée de l'hypothèse d'un "art d'écrire oublié" et examinent la fécondité et les limites de la conception straussienne de l'écriture philosophique., info:eu-repo/semantics/published

A two part research program was conducted to study the mechanics of creep crack growth in (1) nickel base superalloys as a function of alloy chemistry and test environment at 704 degrees C; (2) a high strength aluminum alloy 2219-T851 at 175 degrees C. The creep crack growth rate data is reported and analyzed in terms of fracture mechanics parameters. The automated test procedures used for the aluminum alloys is discussed in detail in view of the need for standardized testing procedures to measure creep crack growth rates.

A two part research program was conducted to study the mechanics of creep crack growth in (1) nickel base superalloys as a function of alloy chemistry and test environment at 704 deg C; (2) a high strength aluminum alloy 2219-T851 at 175 deg C. The creep crack growth rate data is reported and analyzed in terms of fracture mechanics parameters. The automated test procedures used for the aluminum alloys are discussed in detail. An iterative model based on creep damage accumulation was derived to predict the creep crack growth rates.

Collection : Philosophie d'aujourd'hui ; 36, Collection : Philosophie d'aujourd'hui ; 36, Comprend : Socialisme et communisme ; Philosophie de l'action ; Le dernier des philosophes, Contient une table des matières, Avec mode texte

Collection : Philosophie d'aujourd'hui ; 36, Collection : Philosophie d'aujourd'hui ; 36, Comprend : Socialisme et communisme ; Philosophie de l'action ; Le dernier des philosophes, Contient une table des matières, Avec mode texte

Contient une table des matières, Avec mode texte