Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation

Because of their outstanding physical properties, carbon nanotubes (CNTs) are promising new materials in the field of nanotechnology. It is therefore imperative to assess their adverse effects on human health. Monocytes/macrophages that recognize and eliminate the inert particles constitute the main target of CNTs. In this article, we report our finding that double-walled CNTs (DWCNTs) synergize with Tolllike receptor agonists to enhance IL-1β release in human monocytes. We show that DWCNTs–induced IL-1β secretion is exclusively linked to caspase-1 and to Nlrp3 inflammasome activation in human monocytes. We also establish that this activation requires DWCNTs phagocytosis and potassium efflux, but not reactive oxygen specied (ROS) generation. Moreover, inhibition of lysosomal acidification or cathepsin-B activation reduces DWCNT-induced IL-1β secretion, suggesting that Nlrp3 inflammasome activation occurs via lysosomal destabilization. Thus, DWCNTs present a health hazard due to their capacity to activate Nlrp3 inflammasome, recalling the inflammation caused by asbestos and hence demonstrating that they should be used with caution. From the Clinical Editor: This is a very important biosafety/toxicity study regarding double walled carbon nanotubes. The investigators demonstrate that such nanotubes do represent a health hazard due to their capacity to activate Nlrp3 inflammasome, resembling the inflammation caused by asbestos. While further study of this phenomenon is definitely needed, the above findings clearly suggest that special precautions need to be taken when applying these nanoparticles in human disease research

Synthesis of optimal electrical stimulation patterns for functional motion restoration: applied to spinal cord-injured patients

We investigated the synthesis of electrical stimulation patterns for functional movement restoration in human paralyzed limbs. We considered the knee joint system, co-activated by the stimulated quadriceps and hamstring muscles. This synthesis is based on optimized functional electrical stimulation (FES) patterns to minimize muscular energy consumption and movement efficiency criteria. This two-part work includes a multi-scale physiological muscle model, based on Huxley’s formulation. In the simulation, three synthesis strategies were investigated and compared in terms of muscular energy consumption and co-contraction levels. In the experimental validation, the synthesized FES patterns were carried out on the quadriceps-knee joint system of four complete spinal cord injured subjects. Surface stimulation was applied to all subjects, except for one FES-implanted subject who received neural stimulation. In each experimental validation, the model was adapted to the subject through a parameter identification procedure. Simulation results were successful and showed high co-contraction levels when reference trajectories were tracked. Experimental validation results were encouraging, as the desired and measured trajectories showed good agreement, with an 8.4 % rms error in a subject without substantial time-varying behavior. We updated the maximal isometric force in the model to account for time-varying behavior, which improved the average rms errors from 31.4 to 13.9 % for all subjects

PPARγ ligands switched high fat diet-induced macrophage M2b polarization toward M2a thereby improving intestinal Candida elimination.

International audienceObesity is associated with a chronic low-grade inflammation that predisposes to insulin resistance and the development of type 2 diabetes. In this metabolic context, gastrointestinal (GI) candidiasis is common. We recently demonstrated that the PPARγ ligand rosiglitazone promotes the clearance of Candida albicans through the activation of alternative M2 macrophage polarization. Here, we evaluated the impact of high fat diet (HFD)-induced obesity and the effect of rosiglitazone (PPARγ ligand) or WY14643 (PPARα ligand) both on the phenotypic M1/M2 polarization of peritoneal and cecal tissue macrophages and on the outcome of GI candidiasis. We demonstrated that the peritoneal macrophages and the cell types present in the cecal tissue from HF fed mice present a M2b polarization (TNF-α(high), IL-10(high), MR, Dectin-1). Interestingly, rosiglitazone induces a phenotypic M2b-to-M2a (TNF-α(low), IL-10(low), MR(high), Dectin-1(high)) switch of peritoneal macrophages and of the cells present in the cecal tissue. The incapacity of WY14643 to switch this polarization toward M2a state, strongly suggests the specific involvement of PPARγ in this mechanism. We showed that in insulin resistant mice, M2b polarization of macrophages present on the site of infection is associated with an increased susceptibility to GI candidiasis, whereas M2a polarization after rosiglitazone treatment favours the GI fungal elimination independently of reduced blood glucose. In conclusion, our data demonstrate a dual benefit of PPARγ ligands because they promote mucosal defence mechanisms against GI candidiasis through M2a macrophage polarization while regulating blood glucose level

The Asymptotic Number of Attractors in the Random Map Model

The random map model is a deterministic dynamical system in a finite phase space with n points. The map that establishes the dynamics of the system is constructed by randomly choosing, for every point, another one as being its image. We derive here explicit formulas for the statistical distribution of the number of attractors in the system. As in related results, the number of operations involved by our formulas increases exponentially with n; therefore, they are not directly applicable to study the behavior of systems where n is large. However, our formulas lend themselves to derive useful asymptotic expressions, as we show.Comment: 16 pages, 1 figure. Minor changes. To be published in Journal of Physics A: Mathematical and Genera

Non-quantum liquefaction of coherent gases

We show that a gas-to-liquid phase transition at zero temperature may occur in a coherent gas of bosons in the presence of competing nonlinear effects. This situation can take place both in atomic systems like Bose-Einstein Condensates in alkalii gases with two and three-body interactions of opposite signs, as well as in laser beams which propagate through optical media with Kerr (focusing) and higher order (defocusing) nonlinear responses. The liquefaction process takes place in absence of any quantum effect and can be formulated in the frame of a mean field theory, in terms of the minimization of a thermodynamic potential. We also show numerically that the effect of linear gain and three-body recombination also provides a rich dynamics with the emergence of self-organization behaviour.Comment: 6 pages, 5 figures. Submitted to Physica D: Nonlinear Phenomen

Global obstructions to gauge-invariance in chiral gauge theory on the lattice

It is shown that certain global obstructions to gauge-invariance in chiral gauge theory, described in the continuum by Alvarez-Gaume and Ginsparg, are exactly reproduced on the lattice in the Overlap formulation at small non-zero lattice spacing (i.e. close to the classical continuum limit). As a consequence, the continuum anomaly cancellation condition $d_R^{abc}=0$ is seen to be a necessary (although not necessarily sufficient) condition for anomaly cancellation on the lattice in the Overlap formulation.Comment: 31 pages, latex. v4: A few minor corrections, to appear in Nucl. Phys.

Discrete Nonholonomic Lagrangian Systems on Lie Groupoids

This paper studies the construction of geometric integrators for nonholonomic systems. We derive the nonholonomic discrete Euler-Lagrange equations in a setting which permits to deduce geometric integrators for continuous nonholonomic systems (reduced or not). The formalism is given in terms of Lie groupoids, specifying a discrete Lagrangian and a constraint submanifold on it. Additionally, it is necessary to fix a vector subbundle of the Lie algebroid associated to the Lie groupoid. We also discuss the existence of nonholonomic evolution operators in terms of the discrete nonholonomic Legendre transformations and in terms of adequate decompositions of the prolongation of the Lie groupoid. The characterization of the reversibility of the evolution operator and the discrete nonholonomic momentum equation are also considered. Finally, we illustrate with several classical examples the wide range of application of the theory (the discrete nonholonomic constrained particle, the Suslov system, the Chaplygin sleigh, the Veselova system, the rolling ball on a rotating table and the two wheeled planar mobile robot).Comment: 45 page

Hamiltonian dynamics and constrained variational calculus: continuous and discrete settings

The aim of this paper is to study the relationship between Hamiltonian dynamics and constrained variational calculus. We describe both using the notion of Lagrangian submanifolds of convenient symplectic manifolds and using the so-called Tulczyjew's triples. The results are also extended to the case of discrete dynamics and nonholonomic mechanics. Interesting applications to geometrical integration of Hamiltonian systems are obtained.Comment: 33 page

Farnesoid X Receptor and its ligands inhibit the function of platelets

Objective - While initially seemingly paradoxical due to the lack of nucleus, platelets possess a number of transcription factors that regulate their function through DNA-independent mechanisms. These include the Farnesoid X Receptor (FXR), a member of the superfamily of ligand-activated transcription factors that has been identified as a bile acid receptor. In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6-ECDCA, modulate platelet activation nongenomically. Approach and Results - FXR ligands inhibited the activation of platelets in response to stimulation of collagen or thrombin receptors, resulting in diminished intracellular calcium mobilization and secretion, fibrinogen binding and aggregation. Exposure to FXR ligands also reduced integrin alphaIIbbeta3 outside-in signaling and thereby reduced the ability of platelets to spread and to stimulate clot retraction. FXR function in platelets was found to be associated with the modulation of cGMP levels in platelets and associated downstream inhibitory signaling. Platelets from FXR-deficient mice were refractory to the actions of FXR agonists on platelet function and cyclic nucleotide signaling, firmly linking the non-genomic actions of these ligands to the FXR receptor. Conclusion – This study provides support for the ability of FXR ligands to modulate platelet activation. The athero-protective effects of GW4064, with its novel antiplatelet effects, indicate FXR as a potential target for prevention of athero-thrombotic disease

Traveling waves for nonlinear Schr\"odinger equations with nonzero conditions at infinity, II

We prove the existence of nontrivial finite energy traveling waves for a large class of nonlinear Schr\"odinger equations with nonzero conditions at infinity (includindg the Gross-Pitaevskii and the so-called "cubic-quintic" equations) in space dimension $N \geq 2$. We show that minimization of the energy at fixed momentum can be used whenever the associated nonlinear potential is nonnegative and it gives a set of orbitally stable traveling waves, while minimization of the action at constant kinetic energy can be used in all cases. We also explore the relationship between the families of traveling waves obtained by different methods and we prove a sharp nonexistence result for traveling waves with small energy.Comment: Final version, accepted for publication in the {\it Archive for Rational Mechanics and Analysis.} The final publication is available at Springer via http://dx.doi.org/10.1007/s00205-017-1131-