IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

Whilst BCG inhibits allergic airway responses in murine models, IL-18 has adversary effects depending on its environment. We therefore constructed a BCG strain producing murine IL-18 (BCG-IL-18) and evaluated its efficiency to prevent an asthma-like reaction in mice. BALB/cByJ mice were sensitized (day (D) 1 and D10) by intraperitoneal injection of ovalbumin (OVA)-alum and primary (D20–22) and secondary (D62, 63) challenged with OVA aerosols. BCG or BCG-IL-18 were intraperitonealy administered 1 hour before each immunization (D1 and D10). BCG-IL-18 and BCG were shown to similarly inhibit the development of AHR, mucus production, eosinophil influx, and local Th2 cytokine production in BAL, both after the primary and secondary challenge. These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation

Caractérisation du système de sécrétion Ess/Type VII (SST7) chez Staphylococcus lugdunensis

International audienc

fbl-typing of Staphylococcus lugdunensis: a frontline tool for epidemiological studies

International audienc

Caractérisation du Système de Sécrétion Ess/Type VII de Staphylococcus lugdunensis

International audienc

Apport de la MLVA dans l'épidémiologie moléculaire des infections à Staphylococcus lugdunensis

International audienc

Biallelic variants in FLII cause pediatric cardiomyopathy by disrupting cardiomyocyte cell adhesion and myofibril organization

Pediatric cardiomyopathy (CM) represents a group of rare, severe disorders that affect the myocardium. To date, the etiology and mechanisms underlying pediatric CM are incompletely understood, hampering accurate diagnosis and individualized therapy development. Here, we identified biallelic variants in the highly conserved flightless-I (FLII) gene in 3 families with idiopathic, early-onset dilated CM. We demonstrated that patient-specific FLII variants, when brought into the zebrafish genome using CRISPR/Cas9 genome editing, resulted in the manifestation of key aspects of morphological and functional abnormalities of the heart, as observed in our patients. Importantly, using these genetic animal models, complemented with in-depth loss-of-function studies, we provided insights into the function of Flii during ventricular chamber morphogenesis in vivo, including myofibril organization and cardiomyocyte cell adhesion, as well as trabeculation. In addition, we identified Flii function to be important for the regulation of Notch and Hippo signaling, crucial pathways associated with cardiac morphogenesis and function. Taken together, our data provide experimental evidence for a role for FLII in the pathogenesis of pediatric CM and report biallelic variants as a genetic cause of pediatric CM.</p

New method to characterize a machining system: application in turning

Many studies simulates the machining process by using a single degree of freedom spring-mass sytem to model the tool stiffness, or the workpiece stiffness, or the unit tool-workpiece stiffness in modelings 2D. Others impose the tool action, or use more or less complex modelings of the efforts applied by the tool taking account the tool geometry. Thus, all these models remain two-dimensional or sometimes partially three-dimensional. This paper aims at developing an experimental method allowing to determine accurately the real three-dimensional behaviour of a machining system (machine tool, cutting tool, tool-holder and associated system of force metrology six-component dynamometer). In the work-space model of machining, a new experimental procedure is implemented to determine the machining system elastic behaviour. An experimental study of machining system is presented. We propose a machining system static characterization. A decomposition in two distinct blocks of the system "Workpiece-Tool-Machine" is realized. The block Tool and the block Workpiece are studied and characterized separately by matrix stiffness and displacement (three translations and three rotations). The Castigliano's theory allows us to calculate the total stiffness matrix and the total displacement matrix. A stiffness center point and a plan of tool tip static displacement are presented in agreement with the turning machining dynamic model and especially during the self induced vibration. These results are necessary to have a good three-dimensional machining system dynamic characterization

Commissioning and operation of the readout system for the solid neutrino detector

The SoLid experiment aims to measure neutrino oscillation at a baseline of 6.4 m from the BR2 nuclear reactor in Belgium. Anti-neutrinos interact via inverse beta decay (IBD), resulting in a positron and neutron signal that are correlated in time and space. The detector operates in a surface building, with modest shielding, and relies on extremely efficient online rejection of backgrounds in order to identify these interactions. A novel detector design has been developed using 12800 5 cm cubes for high segmentation. Each cube is formed of a sandwich of two scintillators, PVT and 6LiF:ZnS(Ag), allowing the detection and identification of positrons and neutrons respectively. The active volume of the detector is an array of cubes measuring 80x80x250 cm (corresponding to a fiducial mass of 1.6 T), which is read out in layers using two dimensional arrays of wavelength shifting fibres and silicon photomultipliers, for a total of 3200 readout channels. Signals are recorded with 14 bit resolution, and at 40 MHz sampling frequency, for a total raw data rate of over 2 Tbit/s. In this paper, we describe a novel readout and trigger system built for the experiment, that satisfies requirements on: compactness, low power, high performance, and very low cost per channel. The system uses a combination of high price-performance FPGAs with a gigabit Ethernet based readout system, and its total power consumption is under 1 kW. The use of zero suppression techniques, combined with pulse shape discrimination trigger algorithms to detect neutrons, results in an online data reduction factor of around 10000. The neutron trigger is combined with a large per-channel history time buffer, allowing for unbiased positron detection. The system was commissioned in late 2017, with successful physics data taking established in early 2018