Silver nanoparticles impair retinoic acid-inducible gene I mediated mitochondrial anti-viral immunity by blocking the autophagic flux in lung epithelial cells

Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as alternative to antivirals to treat human infectious diseases, especially Influenza virus infection where antivirals have generally proven unsuccessful. However, concerns about the use of AgNPs on humans arise from their potential toxicity, although mechanisms are not well-understood. We show here, in the context of Influenza virus infection of lung epithelial cells, that AgNPs down-regulated Influenza induced-CCL-5 and -IFN-β release (two cytokines important in anti-viral immunity) through RIG-I inhibition, while enhancing IL-8 production, a cytokine important for mobilizing host antibacterial responses. AgNPs activity was independent of coating and was not observed with gold nanoparticles. Down-stream analysis indicated that AgNPs disorganized the mitochondrial network and prevented the anti-viral IRF-7 transcription factor influx into the nucleus. Importantly, we showed that the modulation of RIG-I-IRF-7 pathway was concomitant with inhibition of either classical or alternative autophagy (ATG-5- and Rab-9 dependent, respectively), depending on the epithelial cell type used. Altogether, this demonstration of a AgNPs-mediated functional dichotomy (down-regulation of IFN-dependent anti-viral responses and up-regulation of IL-8 -dependent antibacterial responses) may have practical implications for their use in the clinic

From lows to highs: using low-resolution models to phase X-ray data

The study of virus structures has contributed to methodo­logical advances in structural biology that are generally applicable (molecular replacement and noncrystallographic symmetry are just two of the best known examples). Moreover, structural virology has been instrumental in forging the more general concept of exploiting phase information derived from multiple structural techniques. This hybridization of structural methods, primarily electron microscopy (EM) and X-ray crystallography, but also small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) spectroscopy, is central to integrative structural biology. Here, the interplay of X-ray crystallography and EM is illustrated through the example of the structural determination of the marine lipid-containing bacteriophage PM2. Molecular replacement starting from an ∼13 Å cryo-EM reconstruction, followed by cycling density averaging, phase extension and solvent flattening, gave the X-ray structure of the intact virus at 7 Å resolution This in turn served as a bridge to phase, to 2.5 Å resolution, data from twinned crystals of the major coat protein (P2), ultimately yielding a quasi-atomic model of the particle, which provided significant insights into virus evolution and viral membrane biogenesis

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Arrêt cardiaque peropératoire et œdème pulmonaire retardé consécutif à l’injection intramuqueuse accidentelle de naphazoline chez un adulte

International audienceDuring neurosurgery for hypophysary adenoma under general anaesthesia in a prone position, a 34 year-old-women received accidental 6 ml intramucosal injection of lidocaine with naphazoline. The patient presented a severe bradycardia associated with a major increase in arterial blood pression followed by a brief cardiac arrest. She also presented a prolonged awakening and a pulmonary oedema, which lead to mechanical ventilation. The patient rapidly recovered a normal clinical state.Au cours d’une chirurgie d’exérèse d’un adénome hypophysaire à prolactine par voie transrhinoseptale sous anesthésie générale en position assise, une patiente de 34 ans a reçu accidentellement l’injection intramuqueuse sous-rhino-labiale de 6 ml de lidocaïne naphazolinée. Au décours de celle-ci, elle a présenté une bradycardie majeure et une hypertension artérielle majeure suivies d’un arrêt cardiaque. Elle a secondairement présenté un retard de réveil et un œdème pulmonaire qui a nécessité une réintubation. Sous ventilation assistée, l’état de la patiente s’est amélioré rapidement et les suites ont été simples

Effect of isotopic composition on the lattice parameter of germanium measured by x-ray backscattering

We have measured, by x-ray backscattering, the lattice constant of four highly enriched Ge isotopes: A=70, 73, 74, and 76 at temperatures ranging from 8 to 300 K. Comparing with Ge-70, values of Deltaa/a ranged from -10 to -46 p.p.m. A good quantitative agreement over the whole temperature range (8-300 K) was found with values calculated from a theory that takes into account the zero point motion and the anharmonicity of the lattice

The NLRP3 inflammasome is activated by nanoparticles through ATP, ADP and adenosine.

International audienceThe NLR pyrin domain containing 3 (NLRP3) inflammasome is a major component of the innate immune system, but its mechanism of activation by a wide range of molecules remains largely unknown. Widely used nano-sized inorganic metal oxides such as silica dioxide (nano-SiO2) and titanium dioxide (nano-TiO2) activate the NLRP3 inflammasome in macrophages similarly to silica or asbestos micro-sized particles. By investigating towards the molecular mechanisms of inflammasome activation in response to nanoparticles, we show here that active adenosine triphosphate (ATP) release and subsequent ATP, adenosine diphosphate (ADP) and adenosine receptor signalling are required for inflammasome activation. Nano-SiO2 or nano-TiO2 caused a significant increase in P2Y1, P2Y2, A2A and/or A2B receptor expression, whereas the P2X7 receptor was downregulated. Interestingly, IL-1β secretion in response to nanoparticles is increased by enhanced ATP and ADP hydrolysis, whereas it is decreased by adenosine degradation or selective A2A or A2B receptor inhibition. Downstream of these receptors, our results show that nanoparticles activate the NLRP3 inflammasome via activation of PLC-InsP3 and/or inhibition of adenylate cyclase (ADCY)-cAMP pathways. Finally, a high dose of adenosine triggers inflammasome activation and IL-1β secretion through adenosine cellular uptake by nucleotide transporters and by its subsequent transformation in ATP by adenosine kinase. In summary, we show for the first time that extracellular adenosine activates the NLRP3 inflammasome by two ways: by interacting with adenosine receptors at nanomolar/micromolar concentrations and through cellular uptake by equilibrative nucleoside transporters at millimolar concentrations. These findings provide new molecular insights on the mechanisms of NLRP3 inflammasome activation and new therapeutic strategies to control inflammation