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

Combined ultraviolet studies of astronomical sources

Topics addressed include: Cygnus Loop; P Cygni profiles in dwarf novae; YY Gem; nova shells; HZ Herculis; activity cycles in cluster giants; Alpha Ori; metal deficient giant stars; ultraviolet spectra of symbiotic stars detected by the Very Large Array; time variability in symbiotic stars; blue galaxies; and quasistellar objects with X-ray spectra

Combined ultraviolet studies of astronomical sources

Ultraviolet studies of astronomical sources are discussed. Some studies utilized IVE data. Non-radiative shock at the edge of the Cygnses Loop, stellar flares, local interestellar medium, hot galaxies, stellar mass ejection, contact binaries, double quasars, and stellar chromosphere and coronae are discussed

Discovery of long-period variable stars in the very-metal-poor globular cluster M15

We present a search for long-period variable (LPV) stars among giant branch stars in M15 which, at [Fe/H] ~ -2.3, is one of the most metal-poor Galactic globular clusters. We use multi-colour optical photometry from the 0.6-m Keele Thornton and 2-m Liverpool Telescopes. Variability of delta-V ~ 0.15 mag is detected in K757 and K825 over unusually-long timescales of nearly a year, making them the most metal-poor LPVs found in a Galactic globular cluster. K825 is placed on the long secondary period sequence, identified for metal-rich LPVs, though no primary period is detectable. We discuss this variability in the context of dust production and stellar evolution at low metallicity, using additional spectra from the 6.5-m Magellan (Las Campanas) telescope. A lack of dust production, despite the presence of gaseous mass loss raises questions about the production of dust and the intra-cluster medium of this cluster.Comment: 13 pages, 9 figures, accepted by MNRA

Morphogenic role for acetylcholinesterase in axonal outgrowth during neural development.

Acetylcholinesterase (AChE) is the enzyme that hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses and neuromuscular junctions. However, results from our laboratory and others indicate that AChE has an extrasynaptic, noncholinergic role during neural development. This article is a review of our findings demonstrating the morphogenic role of AChE, using a neuronal cell culture model. We also discuss how these data suggest that AChE has a cell adhesive function during neural development. These results could have additional significance as AChE is the target enzyme of agricultural organophosphate and carbamate pesticides as well as the commonly used household organophosphate chlorpyrifos (Dursban). Prenatal exposure to these agents could have adverse effects on neural development by interfering with the morphogenic function of AChE

The Emergence of the Modern Universe: Tracing the Cosmic Web

This is the report of the Ultraviolet-Optical Working Group (UVOWG) commissioned by NASA to study the scientific rationale for new missions in ultraviolet/optical space astronomy approximately ten years from now, when the Hubble Space Telescope (HST) is de-orbited. The UVOWG focused on a scientific theme, The Emergence of the Modern Universe, the period from redshifts z = 3 to 0, occupying over 80% of cosmic time and beginning after the first galaxies, quasars, and stars emerged into their present form. We considered high-throughput UV spectroscopy (10-50x throughput of HST/COS) and wide-field optical imaging (at least 10 arcmin square). The exciting science to be addressed in the post-HST era includes studies of dark matter and baryons, the origin and evolution of the elements, and the major construction phase of galaxies and quasars. Key unanswered questions include: Where is the rest of the unseen universe? What is the interplay of the dark and luminous universe? How did the IGM collapse to form the galaxies and clusters? When were galaxies, clusters, and stellar populations assembled into their current form? What is the history of star formation and chemical evolution? Are massive black holes a natural part of most galaxies? A large-aperture UV/O telescope in space (ST-2010) will provide a major facility in the 21st century for solving these scientific problems. The UVOWG recommends that the first mission be a 4m aperture, SIRTF-class mission that focuses on UV spectroscopy and wide-field imaging. In the coming decade, NASA should investigate the feasibility of an 8m telescope, by 2010, with deployable optics similar to NGST. No high-throughput UV/Optical mission will be possible without significant NASA investments in technology, including UV detectors, gratings, mirrors, and imagers.Comment: Report of UV/O Working Group to NASA, 72 pages, 13 figures, Full document with postscript figures available at http://casa.colorado.edu/~uvconf/UVOWG.htm

Long-lived space observatories for astronomy and astrophysics

NASA's plan to build and launch a fleet of long-lived space observatories that include the Hubble Space Telescope (HST), the Gamma Ray Observatory (GRO), the Advanced X Ray Astrophysics Observatory (AXAF), and the Space Infrared Telescope Facility (SIRTF) are discussed. These facilities are expected to have a profound impact on the sciences of astronomy and astrophysics. The long-lived observatories will provide new insights about astronomical and astrophysical problems that range from the presence of planets orbiting nearby stars to the large-scale distribution and evolution of matter in the universe. An important concern to NASA and the scientific community is the operation and maintenance cost of the four observatories described above. The HST cost about $1.3 billion (1984 dollars) to build and is estimated to require$160 million (1986 dollars) a year to operate and maintain. If HST is operated for 20 years, the accumulated costs will be considerably more than those required for its construction. Therefore, it is essential to plan carefully for observatory operations and maintenance before a long-lived facility is constructed. The primary goal of this report is to help NASA develop guidelines for the operations and management of these future observatories so as to achieve the best possible scientific results for the resources available. Eight recommendations are given

Photometric Variability in Kepler Target Stars: The Sun Among Stars -- A First Look

The Kepler mission provides an exciting opportunity to study the lightcurves of stars with unprecedented precision and continuity of coverage. This is the first look at a large sample of stars with photometric data of a quality that has heretofore been only available for our Sun. It provides the first opportunity to compare the irradiance variations of our Sun to a large cohort of stars ranging from vary similar to rather different stellar properties, at a wide variety of ages. Although Kepler data is in an early phase of maturity, and we only analyze the first month of coverage, it is sufficient to garner the first meaningful measurements of our Sun's variability in the context of a large cohort of main sequence stars in the solar neighborhood. We find that nearly half of the full sample is more active than the active Sun, although most of them are not more than twice as active. The active fraction is closer to a third for the stars most similar to the Sun, and rises to well more than half for stars cooler than mid K spectral types.Comment: 13 pages, 4 figures, accepted to ApJ Letter