Les monnaies de nécessité à Lyon (1914-1922)

La Première Guerre mondiale est l’événement catalyseur pour la création de monnaie de nécessité : d’août 1914, première émission de coupures, à novembre 1922, dernière émission de jetons. Les institutions consulaires sont, durant cette période, les principales émettrices : les chambres de commerce sont des établissements d’utilité publique, dont les attributions et les actions sont fixées par la loi et contrôlées par l’Etat. La zone de diffusion des monnaies de nécessité peut varier : à Lyon,..

Retinoic acid receptor α as a novel contributor to adrenal cortex structure and function through interactions with Wnt and Vegfa signalling

International audiencePrimary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. Mutations in different genes increase aldosterone production in PA, but additional mechanisms may contribute to increased cell proliferation and aldosterone producing adenoma (APA) development. We performed transcriptome analysis in APA and identified retinoic acid receptor alpha (RARα) signaling as a central molecular network involved in nodule formation. To understand how RARα modulates adrenal structure and function, we explored the adrenal phenotype of male and female Rarα knockout mice. inactivation of Rarα in mice led to significant structural disorganization of the adrenal cortex in both sexes, with increased adrenal cortex size in female mice and increased cell proliferation in males. Abnormalities of vessel architecture and extracellular matrix were due to decreased Vegfa expression and modifications in extracellular matrix components. On the molecular level, Rarα inactivation leads to inhibition of non-canonical Wnt signaling, without affecting the canonical Wnt pathway nor PKA signaling. Our study suggests that Rarα contributes to the maintenance of normal adrenal cortex structure and cell proliferation, by modulating Wnt signaling. Dysregulation of this interaction may contribute to abnormal cell proliferation, creating a propitious environment for the emergence of specific driver mutations in PA. Primary aldosteronism (PA) is the most common and curable form of secondary arterial hypertension, with prevalence estimations of up to 10% of cases in referred hypertensive patients, 4% of patients in primary care 1,2 and 20% of patients with resistant hypertension 3,4. Rapid diagnosis and treatment are important to prevent severe cardiovas-cular consequences of long term aldosterone exposure, which are independent of blood pressure levels and are du

Ventral Tegmental Area Cannabinoid Type-1 Receptors Control Voluntary Exercise Performance

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Effet de l’abrocitinib et du dupilumab sur les taux d’éosinophiles dans l’essai de phase III JADE COMPARE

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Effect of abrocitinib and dupilumab on eosinophil levels in patients with moderate‐to‐severe atopic dermatitis

Abstract Background Eosinophilia is common in patients with atopic dermatitis (AD). Abrocitinib, an oral Janus kinase‐1 inhibitor and dupilumab, an anti–interleukin‐4 receptor‐α antibody, are approved for moderate‐to‐severe AD. Dupilumab has been associated with transient eosinophilia. Objectives To assess the effect of abrocitinib and dupilumab on eosinophils in patients from the phase 3 JADE COMPARE (NCT03720470) and JADE EXTEND (NCT03422822) trials. Methods In JADE COMPARE, patients received once‐daily oral abrocitinib (200/100 mg), placebo or subcutaneous dupilumab (300 mg, biweekly) with background topical therapy. In the ongoing long‐term JADE EXTEND study (Data cutoff: April 22, 2020), dupilumab‐treated patients from JADE COMPARE received once‐daily abrocitinib (200/100 mg) with background topical therapy. The proportion of patients with eosinophilia and hypereosinophilia, and association of eosinophilia with clinical efficacy was assessed. Adverse events (AEs) were also assessed. Results Of the 837 patients in JADE COMPARE, 58 (25.7%), 47 (19.7%) and 51 (21.1%) had eosinophilia at baseline in the abrocitinib 200 mg, abrocitinib 100 mg and dupilumab groups, respectively. At Week 16, eosinophilia decreased with abrocitinib 200 mg (9.3%) and abrocitinib 100 mg (19.0%) but not dupilumab (21.5%); no cases of hypereosinophilia were observed with abrocitinib 200 mg compared with abrocitinib 100 mg (1.9%) and dupilumab (2.3%). Decreases in median eosinophil counts were greater with abrocitinib 200 mg (difference, −100/mm 3 ) and abrocitinib 100 mg (−70/mm 3 ) than dupilumab (+25/mm 3 ) or placebo (+30/mm 3 ) at Week 16. Similar trends were observed in patients with comorbid asthma and allergic rhinitis. Eosinophilia decreased from baseline to Week 12 in dupilumab‐treated patients who switched to abrocitinib in JADE EXTEND. Decreased eosinophil counts with abrocitinib correlated positively with improvements in AD severity, itch and sleep loss. No eosinophilia‐associated AEs occurred. Conclusions Abrocitinib decreased eosinophilia in patients with moderate‐to‐severe AD who had baseline eosinophilia. Resolution of eosinophilia was associated with abrocitinib clinical efficacy

Étude observationnelle multicentrique française prospective de survenue d’effets indésirables ophtalmologiques chez les patients traités par dupilumab pour une dermatite atopique. Étude DUPI ŒIL

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Effectiveness and tolerance of Janus kinase inhibitors for the treatment of recalcitrant atopic dermatitis in a real-life French multicenter adult cohort

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CX3CL1 homo-oligomerization drives cell-to-cell adherence

International audienceDuring inflammatory response, blood leukocytes adhere to the endothelium. This process involves numerous adhesion molecules, including a transmembrane chemokine, CX3CL1, which behaves as a molecular cluster. How this cluster assembles and whether this association has a functional role remain unknown. The analysis of CX3CL1 clusters using native electrophoresis and single molecule fluorescence kinetics shows that CX3CL1 is a homo-oligomer of 3 to 7 monomers. Fluorescence recovery after photobleaching assays reveal that the CX3CL1-transmembrane domain peptide self-associates in both cellular and acellular lipid environments, while its random counterpart (i.e. peptide with the same residues in a different order) does not. This strongly indicates that CX3CL1 oligomerization is driven by its intrinsic properties. According to the molecular modeling, CX3CL1 does not associate in compact bundles but rather with monomers linearly assembled side by side. Finally, the CX3CL1 transmembrane peptide inhibits both the CX3CL1 oligomerization and the adhesive function, while its random counterpart does not. This demonstrates that CX3CL1 oligomerization is mandatory for its adhesive potency. Our results provide a new direction to control CX3CL1-dependent cellular adherence in key immune processes. The migration of blood leukocytes to damaged tissues is the first step of the inflammation process and involves a sequence of coordinated interactions between leukocytes and endothelial cells 1-3. The chemotactic cytokines called chemokines that primarily attract leukocytes, are central to the physiological and pathological inflamma-tory processes 4-6. Chemokines trigger leukocyte activation and their firm adhesion to the inflamed endothelium, mainly through integrins 7-9. Two members of the chemokine family are exceptions: CXCL16 and CX3CL1. In addition to their chemokine domain (CD), these two chemokines possess three domains: a mucin-like stalk, a transmembrane (TM) domain, and a cytosolic tail 10,11. When interacting with their cognate receptors (CXCR6 and CX3CR1, respectively), these chemokines induce cell-cell adhesion 12. CXCL16 and CX3CL1 can also be cleaved by metalloproteinases, such as ADAM10 and ADAM17 13-15 , to produce a soluble form with chemotactic functions. The CX3CL1 chemokine, with its unique CX3CR1 receptor 16 , is involved in adherence to the endothelium of the inflammatory monocyte population (CD14 hi CD16-CX3CR1 + CCR2 + in humans, Ly6C hi CX3CR1 + CCR2 + in mice) 12,17-20 likely through interaction with platelets 21,22. This chemokine is also involved in the recruitment of NK lymphocytes 23,24 and in lymphocyte survival as in allergic diseases 25 , as well as in monocytic 26,27 and neuronal survival 28-31. An additional function of the CX3CR1-CX3CL1 pair is the regulation of the patrolling behavior and the margination of monocytes in blood vessels 32,33 or their adherence to the bone marrow 34. The CX3CL1 chemokine is also involved in cytoadhesion of red blood cells infected with the malaria parasite Plasmodiu

Intravenous and subcutaneous immunoglobulins-associated eczematous reactions occur with a broad range of immunoglobulin types: A French national multicenter study

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