Combined Cyclosporin A and Hypothermia Treatment Inhibits Activation of BV-2 Microglia but Induces an Inflammatory Response in an Ischemia/Reperfusion Hippocampal Slice Culture Model

Introduction: Hypothermia attenuates cerebral ischemia-induced neuronal cell death associated with neuroinflammation. The calcineurin inhibitor cyclosporin A (CsA) has been shown to be neuroprotective by minimizing activation of inflammatory pathways. Therefore, we investigated whether the combination of hypothermia and treatment with CsA has neuroprotective effects in an oxygen-glucose deprivation/reperfusion (OGD/R) injury model in neuronal and BV-2 microglia monocultures, as well as in an organotypic hippocampal slice culture (OHSC). Methods: Murine primary neurons, BV-2 microglia, and OHSC were pretreated with CsA and exposed to 1 h OGD (0.2% O2) followed by reperfusion at normothermia (37°C) or hypothermia (33.5°C). Cytotoxicity was measured by lactate dehydrogenase and glutamate releases. Damage-associated molecular patterns (DAMPs) high mobility group box 1 (HMGB1), heat shock protein 70 (Hsp70), and cold-inducible RNA-binding protein (CIRBP) were detected in cultured supernatant by western blot analysis. Interleukin-6 (IL-6), Interleukin-1α and -1β (IL-1α/IL1-β), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP1), inducible nitric oxide synthase (iNOS), glia activation factors ionized calcium-binding adapter molecule 1 (Iba1), and transforming growth factor β1 (TGF-β1) gene expressions were analyzed by RT-qPCR. Results: Exposure to OGD plus 10 μM CsA was sufficient to induce necrotic cell death and subsequent release of DAMPs in neurons but not BV-2 microglia. Moreover, OGD/R-induced secondary injury was also observed only in the neurons, which was not attenuated by cooling and no increased toxicity by CsA was observed. BV-2 microglia were not sensitive to OGD/R-induced injury but were susceptible to CsA-induced toxicity in a dose dependent manner, which was minimized by hypothermia. CsA attenuated IL-1β and Iba1 expressions in BV-2 microglia exposed to OGD/R. Hypothermia reduced IL-1β and iNOS expressions but induced TNF-α and Iba1 expressions in the microglia. However, these observations did not translate to the ex vivo OHCS model, as general high expressions of most cytokines investigated were observed. Conclusion: Treatment with CsA has neurotoxic effects on primary neurons exposed to OGD but could inhibit BV-2 microglia activation. However, CsA and hypothermia treatment after ischemia/reperfusion injury results in cytotoxic neuroinflammation in the complex ex vivo OHSC

Fe XIII coronal line emission in cool M dwarfs

We report on a search for the Fe xiii forbidden coronal line at 3388.1 \AA in a sample of 15 M-type dwarf stars covering the whole spectral class as well as different levels of activity. A clear detection was achieved for LHS 2076 during a major flare and for CN Leo, where the line had been discovered before. For some other stars the situation is not quite clear. For CN Leo we investigated the timing behaviour of the Fe xiii line and report a high level of variability on a timescale of hours which we ascribe to microflare heating.Comment: 13 pages, 10 figure

Post-TTM Rebound Pyrexia after Ischemia-Reperfusion Injury Results in Sterile Inflammation and Apoptosis in Cardiomyocytes

Introduction. Fever is frequently observed after acute ischemic events and is associated with poor outcome and higher mortality. Targeted temperature management (TTM) is recommended for neuroprotection in comatose cardiac arrest survivors, but pyrexia after rewarming is proven to be detrimental in clinical trials. However, the cellular mechanisms and kinetics of post- TTM rebound pyrexia remain to be elucidated. Therefore, we investigated the effects of cooling and post-TTM pyrexia on the inflammatory response and apoptosis in a cardiomyocyte ischemia-reperfusion (IR) injury model. Methods. HL-1 cardiomyocytes were divided into the following groups to investigate the effect of oxygen-glucose deprivation/reperfusion (OGD/R), hypothermia (33.5°C), and pyrexia (40°C): normoxia controls maintained at 37°C and warmed to 40°C, OGD/R groups maintained at 37°C and cooled to 33.5°C for 24 h with rewarming to 37°C, and OGD/R pyrexia groups further warmed from 37 to 40°C. Caspase-3 and RBM3 were assessed by Western blot and TNF-α, IL-6, IL-1β, SOCS3, iNOS, and RBM3 transcriptions by RT-qPCR. Results. OGD-induced oxidative stress (iNOS) in cardiomyocytes was attenuated post-TTM by cooling. Cytokine transcriptions were suppressed by OGD, while reperfusion induced significant TNF-α transcription that was exacerbated by cooling. Significant inductions of TNF-α, IL-6, IL-1β, and SOCS3 were observed in noncooled, but not in cooled and rewarmed, OGD/R-injured cardiomyocytes. Further warming to pyrexia induced a sterile inflammatory response in OGD/R-injured groups that was attenuated by previous cooling, but no inflammation was observed in pyrexic normoxia groups. Moreover, cytoprotective RBM3 expression was induced by cooling but suppressed by pyrexia, correlating with apoptotic caspase-3 activation. Conclusion. Our findings show that maintaining a period of post-TTM “therapeutic normothermia” is effective in preventing secondary apoptosis-driven myocardial cell death, thus minimizing the infarct area and further release of mediators of the innate sterile inflammatory response after acute IR injury

A new strongly X-ray flaring M9 dwarf in the solar neighborhood

We report on the discovery of a very low mass (VLM) star in the solar neighborhood, originally identified as an optical counterpart of a flaring X-ray source detected in the ROSAT All-Sky survey. Optical spectroscopy and infrared photometry consistently reveal a spectral type of M9 \pm 0.5 and a distance of ~11 pm 2pc. The optical counterpart of 1RXS J115928.5-524717 shows a large proper motion of 1.08\pm0.06 "/year. 1RXS~J115928.5-524717 is the fourth object among the VLM stars displaying a huge X-ray flare, reaching the unprecedent value of L_X/L_{bol}~0.1.Comment: 8 pages, 5 figures. A&A, accepte

X-ray emission from a brown dwarf in the Pleiades

We report the first detection of X-ray emission from a brown dwarf in the Pleiades, the M7-type Roque 14, obtained using the EPIC detectors on XMM-Newton. This is the first X-ray detection of a brown dwarf intermediate in age between ~12 and ~320 Myr. The emission appears persistent, although we cannot rule out flare-like behaviour with a decay time-scale > 4 ks. The time-averaged X-ray luminosity of Lx = (3.3 +/- 0.8) x 10^{27} erg/s, and its ratios with the bolometric (Lx/Lbol = 10^{-3.05}) and Halpha (Lx/LHa = 4.0) luminosities suggest magnetic activity similar to that of active main-sequence M dwarfs, such as the M7 old-disc star VB 8, though the suspected binary nature of Roque 14 merits further attention. No emission is detected from four proposed later-type Pleiades brown dwarfs, with upper limits to Lx in the range 2.1-3.8 x 10^{27} erg/s and to log(Lx/Lbol) in the range -3.10 to -2.91.Comment: 8 pages, 4 figures (6 eps files), accepted for publication in MNRAS, Na I "emission" corrected to "absorption" in description of target

Simultaneous X-ray, radio, near-infrared, and optical monitoring of Young Stellar Objects in the Coronet cluster

Multi-wavelength (X-ray to radio) monitoring of Young Stellar Objects (YSOs) can provide important information about physical processes at the stellar surface, in the stellar corona, and/or in the inner circumstellar disk regions. While coronal processes should mainly cause variations in the X-ray and radio bands, accretion processes may be traced by time-correlated variability in the X-ray and optical/infrared bands. Several multi-wavelength studies have been successfully performed for field stars and approx. 1-10 Myr old T Tauri stars, but so far no such study succeeded in detecting simultaneous X-ray to radio variability in extremely young objects like class I and class 0 protostars. Here we present the first simultaneous X-ray, radio, near-infrared, and optical monitoring of YSOs, targeting the Coronet cluster in the Corona Australis star-forming region, which harbors at least one class 0 protostar, several class I objects, numerous T Tauri stars, and a few Herbig AeBe stars. [...] Seven objects are detected simultaneously in the X-ray, radio, and optical/infrared bands; they constitute our core sample. While most of these sources exhibit clear variability in the X-ray regime and several also display optical/infrared variability, none of them shows significant radio variability on the timescales probed. We also do not find any case of clearly time-correlated optical/infrared and X-ray variability. [...] The absence of time-correlated multi-wavelength variability suggests that there is no direct link between the X-ray and optical/infrared emission and supports the notion that accretion is not an important source for the X-ray emission of these YSOs. No significant radio variability was found on timescales of days.Comment: 11 pages, 11 figures, accepted for publication in A&A (06 Dec 2006

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure

MAGIC upper limits on the very high energy emission from GRBs

The fast repositioning system of the MAGIC Telescope has allowed during its first data cycle, between 2005 and the beginning of year 2006, observing nine different GRBs as possible sources of very high energy gammas. These observations were triggered by alerts from Swift, HETE-II, and Integral; they started as fast as possible after the alerts and lasted for several minutes, with an energy threshold varying between 80 and 200 GeV, depending upon the zenith angle of the burst. No evidence for gamma signals was found, and upper limits for the flux were derived for all events, using the standard analysis chain of MAGIC. For the bursts with measured redshift, the upper limits are compatible with a power law extrapolation, when the intrinsic fluxes are evaluated taking into account the attenuation due to the scattering in the Metagalactic Radiation Field (MRF).Comment: 25 pages, 9 figures, final version accepted by ApJ. Changet title to "MAGIC upped limits on the VERY high energy emission from GRBs", re-organized chapter with description of observation, removed non necessaries figures, added plot of effective area depending on zenith angle, added an appendix explaining the upper limit calculation, added some reference