ATP Induced Brain-Derived Neurotrophic Factor Expression and Release from Osteoarthritis Synovial Fibroblasts Is Mediated by Purinergic Receptor P2X4

Brain-derived neurotrophic factor (BDNF), a neuromodulator involved in nociceptive hypersensitivity in the central nervous system, is also expressed in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We investigated the role of P2 purinoreceptors in the induction of BDNF expression in synovial fibroblasts (SF) of OA and RA patients. Cultured SF from patients with symptomatic knee OA and RA were stimulated with purinoreceptor agonists ATP, ADP, or UTP. The expression of BDNF mRNA was measured by quantitative TaqMan PCR. BDNF release into cell culture supernatants was monitored by ELISA. P2X4 expression in synovial tissue was detected by immunohistochemistry. Endogenous P2X4 expression was decreased by siRNA transfection before ATP stimulation. Kinase pathways were blocked before ATP stimulation. BDNF mRNA expression levels in OASF were increased 2 h and 5 h after ATP stimulation. Mean BDNF levels in cell culture supernatants of unstimulated OASF and RASF were 19 (±9) and 67 (±49) pg/ml, respectively. BDNF levels in SF supernatants were only elevated 5 h after ATP stimulation. BDNF mRNA expression in OASF was induced both by P2X receptor agonists ATP and ADP, but not by UTP, an agonist of P2Y purinergic receptors. The ATP-induced BDNF mRNA expression in OASF was decreased by siRNA-mediated reduction of endogenous P2X4 levels compared to scrambled controls. Inhibition of p38, but not p44/42 signalling reduced the ATP-mediated BDNF mRNA induction. Here we show a functional role of the purinergic receptor P2X4 and p38 kinase in the ATP-induced expression and release of the neurotrophin BDNF in SF

DREAM is reduced in synovial fibroblasts of patients with chronic arthritic pain: is it a suitable target for peripheral pain management?

INTRODUCTION: The endogenous pain-relieving system depends in part on the regulation of nociceptive signals through binding of opioids to the corresponding opioid receptor. Interfering with the trans-repression effect of downstream regulatory element antagonist modulator (DREAM) on the transcription of the opioid dynorphin-encoding prodynorphin (pdyn) gene might enhance pain relief in the periphery. METHODS: Expression levels were measured in osteoarthritis (OA) synovial fibroblast-like cells (SFLCs) (n = 8) and in peripheral blood mononuclear cells (PBMCs) from OA patients (n = 53) and healthy controls (n = 26) by real-time polymerase chain reaction. Lysed OA SFLCs were analyzed by immunoprecipitation. Translation of DREAM mRNA was inhibited by small interfering RNAs (siRNAs). Expressions of DREAM, pdyn, and c-fos mRNAs were measured at 24, 48, and 72 hours after transfection. RESULTS: The expression of DREAM mRNA was shown in both healthy and OA SFLCs as well as PBMCs. Inhibiting transcription using siRNAs led to a marked reduction in DREAM expression after 24, 48, and 72 hours. However, no significant changes in c-fos and pdyn expression occurred. In addition, DREAM mRNA expression was significantly reduced in OA patients with chronic pain (pain intensity as measured by a visual analog scale scale of greater than 40), but no pdyn expression was detectable. CONCLUSION: To our knowledge, this is the first report showing the expression of DREAM in SFLCs and PBMCs on the mRNA level. However, DREAM protein was not detectable. Since repression of pdyn transcription persists after inhibiting DREAM translation, DREAM appears to play no functional role in the kappa opioid receptor system in OA SFLCs. Therefore, our data suggest that DREAM appears not to qualify as a target in peripheral pain management

Lower function, quality of life, and survival rate after total knee arthroplasty for posttraumatic arthritis than for primary arthritis

International audienceBackground and purpose - Total knee arthroplasty (TKA) for treatment of end-stage posttraumatic arthritis (PTA) has specific technical difficulties and complications. We compared clinical outcome, postoperative quality of life (QOL), and survivorship after TKA done for PTA with those after TKA performed for primary arthritis (PA). Patients and methods - We retrospectively reviewed patients who were operated on at our institution for PTA between 1998 and 2005 (33 knees), and compared them to a matched group of patients who were operated on for PA during the same period (407 knees). Clinical outcomes and postoperative QOL were compared in the 2 groups using Knee Society score (KSS), range of motion (ROM) of the knee, and the knee osteoarthritis outcomes score (KOOS). Implant survival rate was calculated using Kaplan-Meier analysis. Results - At a mean follow-up of 11 (5-15) years, KSS knee increased from mean 39 (SD 18) to 87 (SD 16) in the PA group (p = 0.003), and from 31 (SD 11) to 77 (SD 15) in the PTA group (p = 0.003). KSS function increased from 55 (12) to 89 (25) in the PA group (p = 0.008) and from 44 (SD 14) to 81 (SD 10) in the PTA group (p = 0.008). Postoperative ROM also improved in both groups, from 83 degrees to 108 degrees in the PTA group (p < 0.001) as opposed to 116 degrees to 127 degrees in the PA group (p = 0.001), with lower results in the PTA group (p < 0.001). KOOS was lower in the PTA group (p < 0.001). The survival rate of TKA at 10 years with an endpoint defined as "any surgery on the operated knee" showed better results in the PA group (99%, CI: 98-100 vs. 79%, CI: 69-89; p < 0.001). Interpretation - Patients and surgeons should be aware that clinical outcome and implant survival after TKA for PTA are lower than after TKA done for P

Hadron Production in the Nucleus Fragmentation Region

The RHIC hadron production data in hadronic collisions at the forward rapidities may hint the evidence of the Color Glass Condensate (CGC). However, in the opposite region, backward rapidities, new effects should be important in order to describe the observables. In this work, the charged hadron and π 0 productions are investigated in the fragmentation region of the nucleus (backward rapidities) considering dAu and pp collisions in the context of the Color Glass Condensate. In the backward rapidity region, only the proton can be treated as a CGC, and the large x nuclear effects need to be considered in order to describe the cross section. The results are shown by means of the nuclear modification ratio comparing the proton-nucleus and proton-proton cross sections and such ratio presents some dependences on the large x nuclear effects

Emotions in context: examining pervasive affective sensing systems, applications, and analyses

Pervasive sensing has opened up new opportunities for measuring our feelings and understanding our behavior by monitoring our affective states while mobile. This review paper surveys pervasive affect sensing by examining and considering three major elements of affective pervasive systems, namely; “sensing”, “analysis”, and “application”. Sensing investigates the different sensing modalities that are used in existing real-time affective applications, Analysis explores different approaches to emotion recognition and visualization based on different types of collected data, and Application investigates different leading areas of affective applications. For each of the three aspects, the paper includes an extensive survey of the literature and finally outlines some of challenges and future research opportunities of affective sensing in the context of pervasive computing

L'imaginaire urbain dans les régions ouvrières en reconversion: Le bassin stéphanois et le bassin minier du Nord Pas de Calais

Cette recherche est une recherche sociologique et anthropologique coordonnée par Michel Rautenberg rassemblant le Centre Max Weber de Saint-Étienne, le Centre Lillois d'études et de recherches sociologiques et économiques (sous la responsabilité du professeur Licia Valladarès) et l' Université de Sofia (sous la responsabilité du professeur Ivaylo Ditchev). Démarrée en décembre 2007 elle s'est terminée en avril 2011 et a bénéficié d'une aide de l'ANR de 180 k€ pour un montant global de 250 k€ de subventions publiques (non comprise une allocation de recherche).The general hypothesis at the origin of this research is that urban transformations do not go without social representations and the field of the imagination. It is essential for each image, word or story to be related to concrete situations that the researcher can describe. The choice of cities is thus not negligible. In this research programme, it has focussed on cities which have a had a difficult economic history characterised by brutal de-industrialization - more in people's minds than by its suddenness. This has left a traumatic effect on individual and collective memories, an urban landscape of industrial wasteland and 3 decades later it continues to strongly influence urban renovation policies. The first issue of this research, which in its second phase was extended to include Bulgarian cities thanks to the support of the Ministry for Foreign Affairs, was to establish a method making it possible to describe this imagination. So researchers agreed to work on imagination "operators", that is to say means (administrative, artistic or social) used by socially identified actors : artists, associations, inhabitants, former miners, municipal authorities. The second issue was to favour the imagination of cites which cannot be measured against communication strategies but which considers the "popular" social imagination which is sufficiently autonomous to exist outside municipal institutions - without asserting that it is completely independent. The third issue was to find common features in the comparison between situations close enough in their history to justify a pertinent comparison.L'hypothèse générale à l'origine de cette recherche est que les transformations urbaines ne font pas l'économie des représentations et des imaginaires sociaux. Il est donc nécessaire que chaque image, parole ou récit recueilli soit rapporté à des situations concrètes que le chercheur peut décrire. Le choix des villes n'est alors pas anodin. Dans ce programme de recherche, il s'est porté sur des villes qui ont eu une histoire économique difficile caractérisée par une désindustrialisation brutale -dans les esprits peut-être plus que par sa soudaineté. Celle ci a laissé des traumatismes dans les mémoires individuelles et collectives, un paysage urbain de friches industrielles, et continue après 3 décennies d'influencer fortement sur les politiques de rénovation urbaine

The lectin-specific activity of Toxoplasma gondii microneme proteins 1 and 4 binds Toll-like receptor 2 and 4 N-glycans to regulate innate immune priming.

Infection of host cells by Toxoplasma gondii is an active process, which is regulated by secretion of microneme (MICs) and rhoptry proteins (ROPs and RONs) from specialized organelles in the apical pole of the parasite. MIC1, MIC4 and MIC6 assemble into an adhesin complex secreted on the parasite surface that functions to promote infection competency. MIC1 and MIC4 are known to bind terminal sialic acid residues and galactose residues, respectively and to induce IL-12 production from splenocytes. Here we show that rMIC1- and rMIC4-stimulated dendritic cells and macrophages produce proinflammatory cytokines, and they do so by engaging TLR2 and TLR4. This process depends on sugar recognition, since point mutations in the carbohydrate-recognition domains (CRD) of rMIC1 and rMIC4 inhibit innate immune cells activation. HEK cells transfected with TLR2 glycomutants were selectively unresponsive to MICs. Following in vitro infection, parasites lacking MIC1 or MIC4, as well as expressing MIC proteins with point mutations in their CRD, failed to induce wild-type (WT) levels of IL-12 secretion by innate immune cells. However, only MIC1 was shown to impact systemic levels of IL-12 and IFN-γ in vivo. Together, our data show that MIC1 and MIC4 interact physically with TLR2 and TLR4 N-glycans to trigger IL-12 responses, and MIC1 is playing a significant role in vivo by altering T. gondii infection competency and murine pathogenesis

All-sky Search for High-Energy Neutrinos from Gravitational Wave Event GW170104 with the ANTARES Neutrino Telescope

Advanced LIGO detected a significant gravitational wave signal (GW170104) originating from the coalescence of two black holes during the second observation run on January 4$^{\textrm{th}}$, 2017. An all-sky high-energy neutrino follow-up search has been made using data from the ANTARES neutrino telescope, including both upgoing and downgoing events in two separate analyses. No neutrino candidates were found within $\pm500$ s around the GW event time nor any time clustering of events over an extended time window of $\pm3$ months. The non-detection is used to constrain isotropic-equivalent high-energy neutrino emission from GW170104 to less than $\sim4\times 10^{54}$ erg for a $E^{-2}$ spectrum

Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope

The ANTARES telescope is well-suited for detecting astrophysical transient neutrino sources as it can observe a full hemisphere of the sky at all times with a high duty cycle. The background due to atmospheric particles can be drastically reduced, and the point-source sensitivity improved, by selecting a narrow time window around possible neutrino production periods. Blazars, being radio-loud active galactic nuclei with their jets pointing almost directly towards the observer, are particularly attractive potential neutrino point sources, since they are among the most likely sources of the very high-energy cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions with the surrounding medium. Moreover, blazars generally show high time variability in their light curves at different wavelengths and on various time scales. This paper presents a time-dependent analysis applied to a selection of flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012. The results are compatible with fluctuations of the background. Upper limits on the neutrino fluence have been produced and compared to the measured gamma-ray spectral energy distribution.Comment: 27 pages, 16 figure

The Antares Collaboration : Contributions to the 34th International Cosmic Ray Conference (ICRC 2015, The Hague)

The ANTARES detector, completed in 2008, is the largest neutrino telescope in the Northern hemisphere. Located at a depth of 2.5 km in the Mediterranean Sea, 40 km off the Toulon shore, its main goal is the search for astrophysical high energy neutrinos. In this paper we collect the 21 contributions of the ANTARES collaboration to the 34th International Cosmic Ray Conference (ICRC 2015). The scientific output is very rich and the contributions included in these proceedings cover the main physics results, ranging from steady point sources, diffuse searches, multi-messenger analyses to exotic physics