Genetic Dissection of the Cellular Pathways and Signaling Mechanisms in Modeled Tumor Necrosis Factor–induced Crohn's-like Inflammatory Bowel Disease

Recent clinical evidence demonstrated the importance of tumor necrosis factor (TNF) in the development of Crohn's disease. A mouse model for this pathology has previously been established by engineering defects in the translational control of TNF mRNA (TnfΔAREmouse). Here, we show that development of intestinal pathology in this model depends on Th1-like cytokines such as interleukin 12 and interferon γ and requires the function of CD8+ T lymphocytes. Tissue-specific activation of the mutant TNF allele by Cre/loxP-mediated recombination indicated that either myeloid- or T cell–derived TNF can exhibit full pathogenic capacity. Moreover, reciprocal bone marrow transplantation experiments using TNF receptor–deficient mice revealed that TNF signals are equally pathogenic when directed independently to either bone marrow–derived or tissue stroma cell targets. Interestingly, TNF-mediated intestinal pathology was exacerbated in the absence of MAPKAP kinase 2, yet strongly attenuated in a Cot/Tpl2 or JNK2 kinase–deficient genetic background. Our data establish the existence of redundant cellular pathways operating downstream of TNF in inflammatory bowel disease, and demonstrate the therapeutic potential of selective kinase blockade in TNF-mediated intestinal pathology

CD4+ T cell immunity to Salmonella is transient in the circulation

While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently. Circulating Salmonella-reactive CD4+ T cells expressed the liver-homing chemokine receptor CXCR6, accumulated over time in the liver and assumed phenotypic characteristics associated with tissue-associated T cells. Liver memory CD4+ T cells showed TCR selection bias and their accumulation in the liver could be inhibited by blocking CXCL16. These data showed that the circulation of CD4+ T cells mediating immunity to Salmonella is limited to a brief window after which Salmonella-specific CD4+ T cells migrate to peripheral tissues. Our observations highlight the importance of triggering tissue-specific immunity against systemic infections

Beyond tears

CatalogingThomas S. Hansen2010102

MotiQ: an open-source toolbox to quantify the cell motility and morphology of microglia

Microglia are the primary resident innate immune cells of the central nervous system (CNS). They possess branched, motile cell processes that are important for their cellular functions. To study the pathways that control microglial morphology and motility under physiological and disease conditions, it is necessary to quantify microglial morphology and motility precisely and reliably. Several image analysis approaches are available for the quantification of microglial morphology and motility. However, they are either not automated, not freely accessible, and/or limited in the number of morphology and motility parameters that can be assessed. Thus, we have developed MotiQ, an open-source, freely accessible software for automated quantification of microglial motility and morphology. MotiQ allows quantification of a diverse set of cellular motility and morphology parameters, including the parameters that have become gold standard in the microglia field. We demonstrate that MotiQ can be applied to in vivo, ex vivo, and in vitro data from confocal, epifluorescence, or two-photon microscopy and we compare its results to other analysis approaches. We suggest MotiQ as a versatile and customizable tool to study microglia

IX Sinfonie in D-Moll op. 125 ; Egmont. Ouverture ; Leonore III. Ouverture / Beethoven, comp. ; Irmgard Seefried, S ; Maureen Forrester, A ; Ernst Haefliger, T... [et al.] ; Berliner Philharmoniker, orch. ; Chor der St. Hedwigs-Kathedrale ; Karl Forster, chef de choeur ; Ferenc Fricsay, dir.

Titre uniforme : Beethoven, Ludwig van (1770-1827). Compositeur. [Symphonies. No 9. Op. 125. Ré mineur]Titre uniforme : Beethoven, Ludwig van (1770-1827). Compositeur. [Leonore. No 3. Ouverture]Titre uniforme : Beethoven, Ludwig van (1770-1827). Compositeur. [Egmont. Op. 84. Ouverture]BnF-Partenariats, Collection sonore - BelieveContient une table des matière

CANTATE BWV 73 : N °3 : "Recitativo : "Ach, unser Wille bleibt verkehrt" - N °4 : Aria : "Herr, so du willt" ; CANTATE BWV 8 - N °4 : Aria : "Doch weichet, ihr tollen" ; CANTATE BWV 158 (Intégrale) - N °1 : Recitativo : "Der Friede sei mit dir" - N °2 : Aria : "Welt, ade !" - N °3 : Recitativo e Arioso : "Nun Herr, regiere meinen Sinn" - N °4 : "Choral : "Hier ist das rechte Osterlamm" ; CANTATE BWV 13 - N °5 : "Aria" : "Aechzen und erbärmlich Weinen" N °6 "Choral : "So sei nun, Seele, seine" ; CANTATE BWV 157 - N °4 : Aria : "Ja, ja, ich halte Jesum feste" N °5 : Choral : "Meinen Jesum lass' ich nicht" ; CANTATE BWV 159 - N °4 : Aria : "Ja, ja, ich halte Jesum feste" N °5 : Choral : "Jesu, deine Passion ist mir lauter Freude" / Jean-Sébastien BACH ; Dietrich FISCHER-DIESKAU, baryton - les Choeurs de la Cathedrale Sainte-Edwige de Berlin et l'Orchestre Philharmonique de Berlin dir. Karl FORSTER - Solistes : M. SCHWALBE, violon - A. NICOLET, flûte - L. KOCH, hautbois - I. POPPEN, basse - E. PICHT-AXENFELD, clavecin

Titre uniforme : [Der Friede sei mit dir. BWV 158]BnF-Partenariats, Collection sonore - BelieveContient une table des matière

AIRS DE CANTATES / BACH ; DIETRICH FISCHER-DIESKAU

Titre uniforme : [Der Friede sei mit dir. BWV 158]BnF-Partenariats, Collection sonore - BelieveContient une table des matière