Role of Interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression

Background: The use of TNF inhibitors has been a major progress in the treatment of chronic inflammation. However, not all patients respond. In addition, response will be often lost when treatment is stopped. These clinical aspects indicate that other cytokines might be involved and we focus here on the role of IL-17. In addition, the chronic nature of joint inflammation may contribute to reduced response and enhanced chronicity. Therefore we studied the capacity of IL-17 to regulate synoviolin, an E3 ubiquitin ligase implicated in synovial hyperplasia in human rheumatoid arthritis (RA) FLS and in chronic reactivated streptococcal cell wall (SCW)-induced arthritis.<p></p> Methodology/Principal Findings: Chronic reactivated SCW-induced arthritis was examined in IL-17R deficient and wild-type mice. Synoviolin expression was analysed by real-time RT-PCR, Western Blot or immunostaining in RA FLS and tissue, and p53 assessed by Western Blot. Apoptosis was detected by annexin V/propidium iodide staining, SS DNA apoptosis ELISA kit or TUNEL staining and proliferation by PCNA staining. IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17-RC) or synoviolin inhibition were achieved by small interfering RNA (siRNA) or neutralizing antibodies. IL-17 induced sustained synoviolin expression in RA FLS. Sodium nitroprusside (SNP)-induced RA FLS apoptosis was associated with reduced synoviolin expression and was rescued by IL-17 treatment with a corresponding increase in synoviolin expression. IL-17RC or IL-17RA RNA interference increased SNP-induced apoptosis, and decreased IL-17-induced synoviolin. IL-17 rescued RA FLS from apoptosis induced by synoviolin knockdown. IL-17 and TNF had additive effects on synoviolin expression and protection against apoptosis induced by synoviolin knowndown. In IL-17R deficient mice, a decrease in arthritis severity was characterized by increased synovial apoptosis, reduced proliferation and a marked reduction in synoviolin expression. A distinct absence of synoviolin expressing germinal centres in IL-17R deficient mice contrasted with synoviolin positive B cells and Th17 cells in synovial germinal centre-like structures.<p></p> Conclusion/Significance: IL-17 induction of synoviolin may contribute at least in part to RA chronicity by prolonging the survival of RA FLS and immune cells in germinal centre reactions. These results extend the role of IL-17 to synovial hyperplasia.<p></p&gt

Spatial distribution of low-energy plasma around 2 comet 67P/CG from Rosetta measurements

International audienceWe use measurements from the Rosetta plasma consortium (RPC) Langmuir probe (LAP) and mutual impedance probe (MIP) to study the spatial distribution of low-energy plasma in the near-nucleus coma of comet 67P/Churyumov-Gerasimenko. The spatial distribution is highly structured with the highest density in the summer hemisphere and above the region connecting the two main lobes of the comet, i.e. the neck region. There is a clear correlation with the neutral density and the plasma to neutral density ratio is found to be ∼1-2·10 −6 , at a cometocentric distance of 10 km and at 3.1 AU from the sun. A clear 6.2 h modulation of the plasma is seen as the neck is exposed twice per rotation. The electron density of the collisonless plasma within 260 km from the nucleus falls of with radial distance as ∼1/r. The spatial structure indicates that local ionization of neutral gas is the dominant source of low-energy plasma around the comet

Frequency analysis of vocalisations in relation to the growth in broiler chicken

Poultry is one of the lowest cost sources of animal protein in the world and, more than 40 billion chickens are produced every year globally. For reasons of public concern and due to the large number of animals involved, it is considered by many people to be important to take care of the welfare and health status of the chickens reared under intensive farm conditions. Precision Livestock Farming (PLF) can support the farmer in his day to day routine management through the use of sensors, cameras and microphones, and these have the potential to improve production and to enable monitoring of welfare status. In this context, the 7FP EU-PLF project aims to test the efficiency of the use of those sensors at farm level. In particular, the aim of this study was to record and analyse broiler vocalisations under normal farm conditions and to identify the relation between animal sounds, and growth trends. Recordings were made at regular intervals, for the entire short production life of the birds, in order to evaluate the variation of frequency and bandwidth of the sounds emitted by the animals during the cycle of production. The recordings were made in an automated, non-invasive and non-intrusive way and the sound data was compared with the weight of the birds automatically measured by a 'step on scale' placed on the floor of the broiler house. Sound analysis was performed based on the amplitude and frequency of the sound signal in audio files recorded at farm level. Through analysis of the sounds recorded, a significant correlation (P<0.001) between the frequencies of the vocalisations recorded and the weight of the broilers was found across all production cycles and farms assessed. The ongoing goal will be the development of a tool able to automatically detect the growth of the animals based on the frequency of the vocalisation emitted by the birds at different ages, and as a possible tool for determining deviations from their expected growth trend

Risk factor for footpad dermatitis and hock burns in broiler chickens

Footpad dermatitis (FPD) and hock burn (HB) are a major welfare concern in broiler chicken farming. In general, foot lesions are linked to poor environmental conditions. Ulcers caused by advanced lesions can negatively affect the gait of the birds, with effects on the welfare of animals, including, in the worst cases, inability to reach the feed or water. FPD and HB score data were collected manually at two broiler farms across Europe, during welfare assessments performed within the EU-PLF (Precision Livestock Farming) project, which is supported by the European Commission. This ongoing project aims to create "added value" for the farmer through the application of sensors and information technology at farm level. On those broiler farms, a number of variables such as temperature, relative humidity, ventilation rate, bird weight, light schedule, and feed and water consumption rates are measured automatically. The welfare of the chickens was assessed three times per cycle (at week 3, 4 and 5), scoring FPD, HB, gait score, cleanliness of the birds and litter quality. Data analysis was performed by combining data from the welfare assessments with environmental data collected by the automatic monitoring systems. The analysis showed that FPD and HB were more frequent when the flock was exposed to poor environmental conditions for prolonged periods of time. As environmental conditions can be measured continuously, and the risk factor for FPD and HB increases with poor environmental conditions, there is potential to develop a detection and control system for foot and hock lesions.</p

First detection of a diamagnetic cavity at comet 67P/Churyumov-Gerasimenko

International audienceContext: The Rosetta magnetometer RPC-MAG has been exploring the plasma environment of comet 67P/Churyumov-Gerasimenko since August 2014. The first months were dominated by low-frequency waves which evolved into more complex features. However, at the end of July 2015, close to perihelion, the magnetometer detected a region that did not contain any magnetic field at all.Aims: These signatures match the appearance of a diamagnetic cavity as was observed at comet 1P/Halley in 1986. The cavity here is more extended than previously predicted by models and features unusual magnetic field configurations, which need to be explainedMethods: The onboard magnetometer data were analyzed in detail and used to estimate the outgassing rate. A minimum variance analysis was used to determine boundary normals.Results. Our analysis of the data acquired by the Rosetta Plasma Consortium instrumentation confirms the existence of a diamagnetic cavity. The size is larger than predicted by simulations, however. One possible explanation are instabilities that are propagating along the cavity boundary and possibly a low magnetic pressure in the solar wind. This conclusion is supported by a change in sign of the Sun-pointing component of the magnetic field. Evidence also indicates that the cavity boundary is moving with variable velocities ranging from 230−500 m/s

Observation of a New Type of Low Frequency Waves at Comet 67P/Churyumov-Gerasimenko

We report on magnetic field measurements made in the innermost coma of 67P/Churyumov-Gerasimenko in its low activity state. Quasi-coherent, large-amplitude ($\delta B/B \sim 1$), compressional magnetic field oscillations at $\sim$ 40 mHz dominate the immediate plasma environment of the nucleus. This differs from previously studied comet-interaction regions where waves at the cometary ion gyro-frequencies are the main feature. Thus classical pick-up ion driven instabilities are unable to explain the observations. We propose a cross-field current instability associated with newborn cometary ion currents as a possible source mechanism.Comment: 6 pages, 3 Figure

Birth of a comet magnetosphere: A spring of water ions

The Rosetta mission shall accompany comet 67P/Churyumov-Gerasimenko from a heliocentric distance of >3.6 astronomical units through perihelion passage at 1.25 astronomical units, spanning low and maximum activity levels. Initially, the solar wind permeates the thin comet atmosphere formed from sublimation, until the size and plasma pressure of the ionized atmosphere define its boundaries: A magnetosphere is born. Using the Rosetta Plasma Consortium ion composition analyzer, we trace the evolution from the first detection of water ions to when the atmosphere begins repelling the solar wind (~3.3 astronomical units), and we report the spatial structure of this early interaction. The near-comet water population comprises accelerated ions (<800 electron volts), produced upstream of Rosetta, and lower energy locally produced ions; we estimate the fluxes of both ion species and energetic neutral atoms