Acute neuroinflammation induces AIS structural plasticity in a NOX2-dependent manner

Background Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression. While it is clear that chronic microglial inflammation and enhanced ROS production impact neuronal integrity, little is known about how acute microglial inflammation influences AIS stability. Here, we demonstrate that acute neuroinflammation induces AIS structural plasticity in a ROS-mediated and calpain-dependent manner. Methods C57BL/6J and NOX2−/− mice were given a single injection of lipopolysaccharide (LPS; 5 mg/kg) or vehicle (0.9% saline, 10 mL/kg) and analyzed at 6 h–2 weeks post-injection. Anti-inflammatory Didox (250 mg/kg) or vehicle (0.9% saline, 10 mL/kg) was administered beginning 24 h post-LPS injection and continued for 5 days; animals were analyzed 1 week post-injection. Microglial inflammation was assessed using immunohistochemistry (IHC) and RT-qPCR, and AIS integrity was quantitatively analyzed using ankyrinG immunolabeling. Data were statistically compared by one-way or two-way ANOVA where mean differences were significant as assessed using Tukey’s post hoc analysis. Results LPS-induced neuroinflammation, characterized by enhanced microglial inflammation and increased expression of ROS-producing enzymes, altered AIS protein clustering. Importantly, inflammation-induced AIS changes were reversed following resolution of microglial inflammation. Modulation of the inflammatory response using anti-inflammatory Didox, even after significant AIS disruption occurred, increased the rate of AIS recovery. qPCR and IHC analysis revealed that expression of microglial NOX2, a ROS-producing enzyme, was significantly increased correlating with AIS disruption. Furthermore, ablation of NOX2 prevented inflammation-induced AIS plasticity, suggesting that ROS drive AIS structural plasticity. Conclusions In the presence of acute microglial inflammation, the AIS undergoes an adaptive change that is capable of spontaneous recovery. Moreover, recovery can be therapeutically accelerated. Together, these findings underscore the dynamic capabilities of this domain in the presence of a pathological insult and provide evidence that the AIS is a viable therapeutic target

Different stellar rotation in the two main sequences of the young globular cluster NGC1818: first direct spectroscopic evidence

We present a spectroscopic analysis of main sequence (MS) stars in the young globular cluster NGC1818 (age~40 Myrs) in the Large Magellanic Cloud. Our photometric survey on Magellanic Clouds clusters has revealed that NGC1818, similarly to the other young objects with age 600 Myrs, displays not only an extended MS Turn-Off (eMSTO), as observed in intermediate-age clusters (age~1-2 Gyrs), but also a split MS. The most straightforward interpretation of the double MS is the presence of two stellar populations: a sequence of slowly-rotating stars lying on the blue-MS and a sequence of fast rotators, with rotation close to the breaking speed, defining a red-MS. We report the first direct spectroscopic measurements of projected rotational velocities vsini for the double MS, eMSTO and Be stars of a young cluster. The analysis of line profiles includes non-LTE effects, required for correctly deriving v sini values. Our results suggest that: (i) the mean rotation for blue- and red-MS stars is vsini=71\pm10 km/s (sigma=37 km/s) and vsini=202\pm23 km/s (sigma=91 km/s), respectively; (ii) eMSTO stars have different vsini, which are generally lower than those inferred for red-MS stars, and (iii) as expected, Be stars display the highest vsini values. This analyis supports the idea that distinct rotational velocities play an important role in the appearence of multiple stellar populations in the color-magnitude diagrams of young clusters, and poses new constraints to the current scenarios.Comment: 16 pages, 1 table, 9 figures. Accepted for publication in AJ (11/07/2018

X-Ray Determination of the Variable Rate of Mass Accretion onto TW Hydrae

Diagnostics of electron temperature (T_e), electron density (n_e), and hydrogen column density (N_H) from the Chandra High Energy Transmission Grating spectrum of He-like Ne IX in TW Hydrae (TW Hya), in conjunction with a classical accretion model, allow us to infer the accretion rate onto the star directly from measurements of the accreting material. The new method introduces the use of the absorption of Ne IX lines as a measure of the column density of the intervening, accreting material. On average, the derived mass accretion rate for TW Hya is 1.5 x 10^{-9} M_{\odot} yr^{-1}, for a stellar magnetic field strength of 600 Gauss and a filling factor of 3.5%. Three individual Chandra exposures show statistically significant differences in the Ne IX line ratios, indicating changes in N_H, T_e, and n_e by factors of 0.28, 1.6, and 1.3, respectively. In exposures separated by 2.7 days, the observations reported here suggest a five-fold reduction in the accretion rate. This powerful new technique promises to substantially improve our understanding of the accretion process in young stars

High temperature structure in cool binary stars

Strong high temperature emission lines in the EUVE spectra of binary stars containing cool components (Alpha Aur (Capella), 44 iota Boo, Lambda And, and VY Ari) provide the basis to define reliably the differential emission measure of hot plasma. The emission measure distributions for the short-period (P less than or equal to 13 d) binary systems show a high temperature enhancement over a relatively narrow temperature region similar to that originally found in Capella (Dupree et al. 1993). The emission measure distributions of rapidly rotating single stars 31 Com and AB Dor also contain a local enhancement of the emission measure although at different temperatures and width from Capella, suggesting that the enhancement in these objects may be characteristic of rapid rotation of a stellar corona. This feature might be identified with a (polar) active region, although its density and absolute size are unknown; in the binaries Capella and VY Ari, the feature is narrow and it may arise from an interaction region between the components

X-ray Doppler Imaging of 44i Boo with Chandra

Chandra High-Energy Transmission Grating observations of the bright eclipsing contact binary 44i Boo show X-ray line profiles which are Doppler-shifted by orbital motions. The X-ray emission spectrum contains a multitude of lines superimposed on a weak continuum, with strong lines of O VIII, Ne X, Fe XVII, and Mg XII. The profiles of these lines from the total observed spectrum show Doppler-broadened widths of ~ 550 km s^{-1}. Line centroids vary with orbital phase, indicating velocity changes of > 180 km s^{-1}. The first-order light curve shows significant variability, but no clear evidence for either primary or secondary eclipses. Flares are observed for all spectral ranges; additionally, the light curve constructed near the peak of the emission measure distribution (T_e = 5 to 8 X 10^6 K) shows quiescent variability as well as flares. The phase-dependences of line profiles and light curves together imply that at least half of the emission is localized at high latitude. A simple model with two regions on the primary star at relatively high latitude reproduces the observed line profile shifts and quiescent light curve. These first clear X-ray Doppler shifts of stellar coronal material illustrate the power of Chandra.Comment: 15 pages, 6 figures to be published in Astrophysical Journal Letter