Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: implications for dermatitis.

Fas ligand (FasL) causes apoptosis of epidermal keratinocytes and triggers the appearance of spongiosis in eczematous dermatitis. We demonstrate here that FasL also aggravates inflammation by triggering the expression of proinflammatory cytokines, chemokines, and adhesion molecules in keratinocytes. In HaCaT cells and in reconstructed human epidermis (RHE), FasL triggered a NF-kappaB-dependent mRNA accumulation of inflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1beta), chemokines (CCL2/MCP-1, CXCL1/GROalpha, CXCL3/GROgamma, and CXCL8/IL-8), and the adhesion molecule ICAM-1. Oligomerization of Fas was required both for apoptosis and for gene expression. Inhibition of caspase activity abolished FasL-dependent apoptosis; however, it failed to suppress the expression of FasL-induced genes. Additionally, in the presence of caspase inhibitors, but not in their absence, FasL triggered the accumulation of CCL5/RANTES (regulated on activation normal T cell expressed and secreted) mRNA. Our findings identify a novel proinflammatory role of FasL in keratinocytes that is independent of caspase activity and is separable from apoptosis. Thus, in addition to causing spongiosis, FasL may play a direct role in triggering and/or sustaining inflammation in eczemas

1989 as a mimetic revolution: Russia and the challenge of post-communism

Various terms have been used to describe the momentous events of 1989, including Jürgen Habermas’s ‘rectifying revolution,’ and my own notion of 1989 as a type of ‘anti-revolution’: repudiating not only what had come before, but also denying the political logic of communist power, as well as the emancipatory potential of revolutionary socialism in its entirety. In the event, while the negative agenda of 1989 has been fulfilled, it failed in the end to transcend the political logic of the systems that collapsed at that time. This paper explores the unfulfilled potential of 1989. Finally, 1989 became more of a counter- rather than an anti-revolution, replicating in an inverted form the practices of the mature state socialist regimes. The paucity of institutional and intellectual innovation arising from 1989 is striking. The dominant motif was ‘returnism,’ the attempt to join an established enterprise rather than transforming it. Thus, 1989 can be seen as mimetic revolution, in the sense that it emulated systems that were not organically developed in the societies in which they were implanted. For Eastern Europe ‘returning’ to Europe appeared natural, but for Russia the civilizational challenge of post-communism was of an entirely different order. There could be no return, and instead of a linear transition outlined by the classic transitological literature, Russia’s post-communism demonstrated that the history of others could not be mechanically transplanted from one society to another

Suppression of Ribosomal Function Triggers Innate Immune Signaling through Activation of the NLRP3 Inflammasome

Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by inducing efflux of cellular potassium. Loss of cellular potassium is known to potently suppress protein synthesis, leading us to test whether the inhibition of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of IL-1ß from cells in response to these agents was detected by immunoblotting and ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition of translation by each of the tested translation inhibitors led to processing of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are known to activate the NLRP3 inflammasome, also substantially inhibited protein translation, supporting a close association between inhibition of translation and inflammasome activation. These data demonstrate that translational inhibition itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent inflammatory signaling and that other physical, chemical, or pathogen-associated agents that impair translation may lead to IL-1ß-dependent inflammation through activation of the NLRP3 inflammasome. For agents that inhibit translation through decreased cellular potassium, the application of high extracellular potassium restores protein translation and suppresses activation of the NLRP inflammasome. For agents that inhibit translation through mechanisms that do not involve loss of potassium, high extracellular potassium suppresses IL-1ß processing through a mechanism that remains undefined

Multi-resolution wavelet analysis of high time resolution millimeter wavelength observations of solar bursts

By means of the wavelet representation of multi-resolution analysis, we study millimeter wavelength (mm-w) radio solar bursts obtained at 48 GHz with high time resolution (less than or equal to8 ms), observed at Itapetinga (Brazil). The multi-resolution analysis decomposes the signal locally both in time and in frequency. allowing us to identify the different temporal structures which underlie the flux density time series and the transient phenomena characteristic of solar bursts. The analysis was applied to the flux time profile of four solar bursts observed at a mm-w, studying separately the pre-flare, impulsive and post-flare phases when possible. We find that a wide range of time scales contributes to the radio flux. The minimum time scale found for the impulsive phase is 32 ms, after which the noise dominates the emission the maximum is 8 s. Pre- and post-flare phases have a minimum time scale of 256 ms and a maximum between 1 to 8 s. Multi-resolution 'spectral indexes', which are a measure of the self-similar behavior of the signal. are in some cases bigger for the impulsive phase than for the pre- and post-flare phases. We find that as the Aux becomes higher the contribution from shorter time scales is enhanced.366131732

Multi-resolution wavelet analysis of high time resolution millimeter wavelength observations of solar bursts

By means of the wavelet representation of multi-resolution analysis, we study millimeter wavelength (mm-w) radio solar bursts obtained at 48 GHz with high time resolution (≤ 8 ms); observed at Itapetinga (Brazil). The multi-resolution analysis decomposes the signal locally both in time and in frequency, allowing us to identify the different temporal structures which underlie the flux density time series and the transient phenomena characteristic of solar bursts. The analysis was applied to the flux time profile of four solar bursts observed at a mm-w, studying separately the pre-flare, impulsive and post-flare phases when possible. We find that a wide range of time scales contributes to the radio flux. The minimum time scale found for the impulsive phase is 32 ms, after which the noise dominates the emission; the maximum is 8 s. Pre- and post-flare phases have a minimum time scale of 256 ms and a maximum between 1 to 8 s. Multi-resolution "spectral indexes", which are a measure of the self-similar behavior of the signal, are in some cases bigger for the impulsive phase than for the pre- and post-flare phases. We find that as the flux becomes higher the contribution from shorter time scales is enhanced