STAT3 regulated ARF expression suppresses prostate cancer metastasis.

Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19(ARF) as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF-Mdm2-p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14(ARF) expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.Lukas Kenner and Jan Pencik are supported by FWF, P26011 and the Genome Research-Austria project “Inflammobiota” grants. Helmut Dolznig is supported by the Herzfelder Family Foundation and the Niederösterr. Forschungs-und Bildungsges.m.b.H (nfb). Richard Moriggl is supported by grant SFB-F2807 and SFB-F4707 from the Austrian Science Fund (FWF), Ali Moazzami is supported by Infrastructure for biosciences-Strategic fund, SciLifeLab and Formas, Zoran Culig is supported by FWF, P24428, Athena Chalaris and Stefan Rose-John are supported by the Deutsche Forschungsgemeinschaft (Grant SFB 877, Project A1and the Cluster of Excellence --“Inflammation at Interfaces”). Work of the Aberger lab was supported by the Austrian Science Fund FWF (Projects P25629 and W1213), the European FP7 Marie-Curie Initial Training Network HEALING and the priority program Biosciences and Health of the Paris-Lodron University of Salzburg. Valeria Poli is supported by the Italian Association for Cancer Research (AIRC, No IG13009). Richard Kennedy and Steven Walker are supported by the McClay Foundation and the Movember Centre of Excellence (PC-UK and Movember). Gerda Egger is supported by FWF, P27616. Tim Malcolm and Suzanne Turner are supported by Leukaemia and Lymphoma Research.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms873

De la musicothérapie à la "musico-phonologie" à distance: émergence de nouvelles pratiques en période de confinement par des ateliers vocaux en visioconférence

National audienceThe constraints of the generalized containment of spring 2020 have prompted our association Musicothérapie Expressions 45 (MUS’E) to invent new practices accompanying by sound mediations at a distance, to ensure the continuity of individual and collective follow-ups and to remedy social isolation. Among these devices, the collective voice workshops in videoconferencing have proved very beneficials by creating playful and caring communication spaces, where each participant becomes, by his quality of listening and by his voice, co-creator of a relationship of care. Analyzing the implementation of adapted protocols, illustrated by a few clinical cases, especially in the tinnitus ology, let us testify here the rather gratifying implications of this new paradigm on our interdisciplinary approach to "musico-phonology". An art of the in-between, between phoniatry and music therapy, speech and singing, corps and psyche, favoring listening in relational harmony between physical and remote presences.Les contraintes du confinement généralisé du printemps 2020 ont incité notre association Musicothérapie Expressions 45 (MUS’E) à inventer de nouvelles pratiques d’accompagnement par les médiations sonores à distance, afin d’assurer la continuité des suivis individuels et collectifs et remédier à l’isolement social. Parmi ces dispositifs, les ateliers vocaux collectifs en visioconférence se sont révélés très bénéfiques en créant des espaces de communication ludiques et bienveillants, où chaque participant devient, par sa qualité d’écoute et par sa voix, cocréateur d’une relation de soin. Analysant la mise en place de protocoles adaptés, illustrés par quelques cas cliniques, notamment en acouphénologie, nous témoignons ici des incidences, plutôt réjouissantes, de ce nouveau paradigme sur notre démarche interdisciplinaire en "musico-phonologie". Un art de l’entre-deux, entre phoniatrie et musicothérapie, parole et chant, corps et psychisme, privilégiant l'écoute en accordage relationnel, entre présences physiques et à distance

Jean-Claude Daumas, géographe

Marié Michel, Dreyfus Jacques, Billiard Isabelle. Jean-Claude Daumas, géographe. In: Les Annales de la recherche urbaine, N°25, 1985. Villes des tiers et quart mondes. pp. 3-7

Small intestinal bacterial overgrowth in systemic sclerosis

International audienc

PKR Transduces MDA5-Dependent Signals for Type I IFN Induction.

Sensing invading pathogens early in infection is critical for establishing host defense. Two cytosolic RIG-like RNA helicases, RIG-I and MDA5, are key to type I interferon (IFN) induction in response to viral infection. Mounting evidence suggests that another viral RNA sensor, protein kinase R (PKR), may also be critical for IFN induction during infection, although its exact contribution and mechanism of action are not completely understood. Using PKR-deficient cells, we found that PKR was required for type I IFN induction in response to infection by vaccinia virus lacking the PKR antagonist E3L (VVΔE3L), but not by Sendai virus or influenza A virus lacking the IFN-antagonist NS1 (FluΔNS1). IFN induction required the catalytic activity of PKR, but not the phosphorylation of its principal substrate, eIF2α, or the resulting inhibition of host translation. In the absence of PKR, IRF3 nuclear translocation was impaired in response to MDA5 activators, VVΔE3L and encephalomyocarditis virus, but not during infection with a RIG-I-activating virus. Interestingly, PKR interacted with both RIG-I and MDA5; however, PKR was only required for MDA5-mediated, but not RIG-I-mediated, IFN production. Using an artificially activated form of PKR, we showed that PKR activity alone was sufficient for IFN induction. This effect required MAVS and correlated with IRF3 activation, but no longer required MDA5. Nonetheless, PKR activation during viral infection was enhanced by MDA5, as virus-stimulated catalytic activity was impaired in MDA5-null cells. Taken together, our data describe a critical and non-redundant role for PKR following MDA5, but not RIG-I, activation to mediate MAVS-dependent induction of type I IFN through a kinase-dependent mechanism

Colistin Resistance Mechanism in Enterobacter hormaechei subsp. steigerwaltii Isolated from Wild Boar (Sus scrofa) in France

International audienceWild animals may act as efficient antimicrobial-resistance reservoirs and epidemiological links between humans, livestock, and natural environments. By using phenotypic and genotypic characterization, the present study highlighted the occurrence of an antimicrobial-resistant (i.e., amoxicillin, amoxicillin–clavulanic acid, cephalothin, and colistin) Enterobacter hormaechei subsp. steigerwaltii strain in wild boar (Sus scrofa) from France. The molecular analysis conducted showed non-synonymous mutations in the pmrA/pmrB and phoQ/phoP operons and the phoP/Q regulator mgrB gene, leading to colistin resistance. The present data highlight the need for continuous monitoring of multidrug-resistant bacteria in wild animals to limit the spread of these threatening pathogens

Colistin Resistance Mechanism in Enterobacter hormaechei subsp. steigerwaltii Isolated from Wild Boar (Sus scrofa) in France

International audienceWild animals may act as efficient antimicrobial-resistance reservoirs and epidemiological links between humans, livestock, and natural environments. By using phenotypic and genotypic characterization, the present study highlighted the occurrence of an antimicrobial-resistant (i.e., amoxicillin, amoxicillin–clavulanic acid, cephalothin, and colistin) Enterobacter hormaechei subsp. steigerwaltii strain in wild boar (Sus scrofa) from France. The molecular analysis conducted showed non-synonymous mutations in the pmrA/pmrB and phoQ/phoP operons and the phoP/Q regulator mgrB gene, leading to colistin resistance. The present data highlight the need for continuous monitoring of multidrug-resistant bacteria in wild animals to limit the spread of these threatening pathogens