600 research outputs found
Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation
Inflammasomes are high-molecular-weight protein complexes that are formed in the cytosolic compartment in response to danger- or pathogen-associated molecular patterns. These complexes enable activation of an inflammatory protease caspase-1, leading to a cell death process called pyroptosis and to proteolytic cleavage and release of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Along with caspase-1, inflammasome components include an adaptor protein, ASC, and a sensor protein, which triggers the inflammasome assembly in response to a danger signal. The inflammasome sensor proteins are pattern recognition receptors belonging either to the NOD-like receptor (NLR) or to the AIM2-like receptor family. While the molecular agonists that induce inflammasome formation by AIM2 and by several other NLRs have been identified, it is not well understood how the NLR family member NLRP3 is activated. Given that NLRP3 activation is relevant to a range of human pathological conditions, significant attempts are being made to elucidate the molecular mechanism of this process. In this review, we summarize the current knowledge on the molecular events that lead to activation of the NLRP3 inflammasome in response to a range of K (+) efflux-inducing danger signals. We also comment on the reported involvement of cytosolic Ca (2+) fluxes on NLRP3 activation. We outline the recent advances in research on the physiological and pharmacological mechanisms of regulation of NLRP3 responses, and we point to several open questions regarding the current model of NLRP3 activation
Fluorescent markers of the microtubule cytoskeleton in Zymoseptoria tritici
AbstractThe microtubule cytoskeleton supports vital processes in fungal cells, including hyphal growth and mitosis. Consequently, it is a target for fungicides, such as benomyl. The use of fluorescent fusion proteins to illuminate microtubules and microtubule-associated proteins has led to a break-through in our understanding of their dynamics and function in fungal cells. Here, we introduce fluorescent markers to visualize microtubules and accessory proteins in the wheat pathogen Zymoseptoria tritici. We fused enhanced green-fluorescent protein to α-tubulin (ZtTub2), to ZtPeb1, a homologue of the mammalian plus-end binding protein EB1, and to ZtGrc1, a component of the minus-end located γ-tubulin ring complex, involved in the nucleation of microtubules. In vivo observation confirms the localization and dynamic behaviour of all three markers. These marker proteins are useful tools for understanding the organization and importance of the microtubule cytoskeleton in Z. tritici
Model Reduction for Multiscale Lithium-Ion Battery Simulation
In this contribution we are concerned with efficient model reduction for
multiscale problems arising in lithium-ion battery modeling with spatially
resolved porous electrodes. We present new results on the application of the
reduced basis method to the resulting instationary 3D battery model that
involves strong non-linearities due to Buttler-Volmer kinetics. Empirical
operator interpolation is used to efficiently deal with this issue.
Furthermore, we present the localized reduced basis multiscale method for
parabolic problems applied to a thermal model of batteries with resolved porous
electrodes. Numerical experiments are given that demonstrate the reduction
capabilities of the presented approaches for these real world applications
Largest Lyapunov Exponent for Many Particle Systems at Low Densities
The largest Lyapunov exponent for a dilute gas with short range
interactions in equilibrium is studied by a mapping to a clock model, in which
every particle carries a watch, with a discrete time that is advanced at
collisions. This model has a propagating front solution with a speed that
determines , for which we find a density dependence as predicted by
Krylov, but with a larger prefactor. Simulations for the clock model and for
hard sphere and hard disk systems confirm these results and are in excellent
mutual agreement. They show a slow convergence of with increasing
particle number, in good agreement with a prediction by Brunet and Derrida.Comment: 4 pages, RevTeX, 2 Figures (encapsulated postscript). Submitted to
Phys. Rev. Let
Chaotic Properties of Dilute Two and Three Dimensional Random Lorentz Gases II: Open Systems
We calculate the spectrum of Lyapunov exponents for a point particle moving
in a random array of fixed hard disk or hard sphere scatterers, i.e. the
disordered Lorentz gas, in a generic nonequilibrium situation. In a large
system which is finite in at least some directions, and with absorbing boundary
conditions, the moving particle escapes the system with probability one.
However, there is a set of zero Lebesgue measure of initial phase points for
the moving particle, such that escape never occurs. Typically, this set of
points forms a fractal repeller, and the Lyapunov spectrum is calculated here
for trajectories on this repeller. For this calculation, we need the solution
of the recently introduced extended Boltzmann equation for the nonequilibrium
distribution of the radius of curvature matrix and the solution of the standard
Boltzmann equation. The escape-rate formalism then gives an explicit result for
the Kolmogorov Sinai entropy on the repeller.Comment: submitted to Phys Rev
Foresight Review on Design for Safety
This review explores how a culture of design for safety can enhance the safety of the world around us. Design for safety goes beyond legislation, regulations and standards. These all play an important role for established products and services but their limited scope often leads to missed opportunities to enhance safety by taking a broader perspective.
Design is applied to both mature industries (which have many years of experience and
a good understanding of risks and how to reduce them) and emerging industries (that use new technologies requiring new ways of controlling risk which may not yet be known or understood). An example of an emerging risk is the internet that is enabling rapid innovation of new products which generate data. This data is widely shared across the internet and the risks associated with this are as yet not fully understood by the public.
A design for safety culture takes a holistic approach to understanding the influences that affect safety. Such influences are varied and take into account the broader environment within which design operates, including complex interactions, behaviour and culture.
It goes beyond traditional design methods and focuses on the goal of a safer design.
Implementing design for safety requires an understanding of the challenges and the methods to address them. It needs multidisciplinary teams that bring together people with the relevant skills to understand the challenges and a collaborative approach of âdesigning withâ rather than the more traditional approach of âdesigning forâ. This can be achieved through an international diverse community that works together to identify and share best practices
Electrochemical polarization-based fast charging of lithium-ion batteries in embedded systems
Charcot-Leyden Crystals activate the NLRP3 inflammasome and cause IL-1ÎČ inflammation [preprint]
Charcot-Leyden crystals (CLCs) are Galectin-10 protein crystals that can form after eosinophils degranule. CLCs can appear and persist in tissues from patients with eosinophilic disorders, such as asthma, allergic reactions, fungal, and helminthic infections. Despite abundant reports of their occurrence in human disease, the inflammatory potential of CLCs has remained unknown. Here we show that CLCs induce IL-1ÎČ release upon their uptake by primary human macrophages in vitro, and that they induce inflammation in vivo in mouse models of acute peritonitis and bronchitis. CLC-induced IL-1ÎČ was dependent on NLRP3 and caspase-1, and their instillation in inflammasome reporter mice promoted the assembly of ASC complexes and IL-1ÎČ secretion in the lungs. Our findings reveal that CLCs are recognized by the NLRP3 inflammasome, which may sustain inflammation that follows eosinophilic inflammatory processes
Dynamical field theory for glass-forming liquids, self-consistent resummations and time-reversal symmetry
We analyse the symmetries and the self-consistent perturbative approaches of
dynamical field theories for glassforming liquids. In particular, we focus on
the time-reversal symmetry (TRS), which is crucial to obtain
fluctuation-dissipation relations (FDRs). Previous field theoretical treatment
violated this symmetry, whereas others pointed out that constructing symmetry
preserving perturbation theories is a crucial and open issue. In this work we
solve this problem and then apply our results to the mode-coupling theory of
the glass transition (MCT). We show that in the context of dynamical field
theories for glass-forming liquids TRS is expressed as a nonlinear field
transformation that leaves the action invariant. Because of this nonlinearity,
standard perturbation theories generically do not preserve TRS and in
particular FDRs. We show how one can cure this problem and set up
symmetry-preserving perturbation theories by introducing some auxiliary fields.
As an outcome we obtain Schwinger-Dyson dynamical equations that automatically
preserve FDRs and that serve as a basis for carrying out symmetry-preserving
approximations. We apply our results to MCT, revisiting previous field theory
derivations of MCT equations and showing that they generically violate FDR. We
obtain symmetry-preserving mode-coupling equations and discuss their advantages
and drawbacks. Furthermore, we show, contrary to previous works, that the
structure of the dynamic equations is such that the ideal glass transition is
not cut off at any finite order of perturbation theory, even in the presence of
coupling between current and density. The opposite results found in previous
field theoretical works, such as the ones based on nonlinear fluctuating
hydrodynamics, were only due to an incorrect treatment of TRS.Comment: 54 pages, 21 figure
Light scattering spectra of supercooled molecular liquids
The light scattering spectra of molecular liquids are derived within a
generalized hydrodynamics. The wave vector and scattering angle dependences are
given in the most general case and the change of the spectral features from
liquid to solidlike is discussed without phenomenological model assumptions for
(general) dielectric systems without long-ranged order. Exact microscopic
expressions are derived for the frequency-dependent transport kernels,
generalized thermodynamic derivatives and the background spectra.Comment: 12 page
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