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

The effect of vacuum polarisation on muon-proton scattering at small energies and angles

We give a compact expression for the unpolarised differential cross section for muon-proton scattering in the one photon exchange approximation. The effect of adding the vacuum polarisation amplitude to the no-spin-flip amplitude for one photon exchange is calculated at small energies and scattering angles and is found to be negligible for present experiments.Comment: 6 pages, one figur

Suspected Canine Zinc Toxicosis Caused by Ingestion of Pennies

A 21 pound, nine year old spayed female Shih Tzu was presented to the Oradell Animal Hospital at 3 a.m. on Sunday morning with a complaint of anorexia, lethargy and vomiting for the past two days. The dog\u27s previous medical history was unremarkable, except for being hit by a car in November 1983. A right ilial fracture sustained at that time had been plated. The animal was current on all routine vaccinations

Stocking Threadfin Shad: Consequences for Young-of-Year Fishes

Threadfin shad Dorosoma petenense are commonly introduced into reservoirs to supplement prey available to piscivorous fishes. To determine how early life stages of threadfin shad and their potential competitors and predators interact, we introduced this species into two Ohio lakes—Clark and Stonelick—and evaluated how its young of year influenced young-of-year bluegills Lepomis macrochirus and largemouth bass Micropterus salmoides. After adults were stocked in April, peak abundance of young-of-year threadfin shad occurred in August in both lakes. Bluegills generally spawned earlier than threadfin shad, which apparently reduced competition between young of these species. In Clark Lake, young-of-year threadfin shad did not reduce zooplankton populations, but in Stonelick Lake, peak abundance of young-of-year threadfin shad was followed by a precipitous decline in zooplankton. Data on cladoceran birth rates indicated this decline was due to increased predation by threadfin shad. Survival of bluegills to a size at which they move into the littoral zone also declined in Stonelick Lake, perhaps because of the virtual elimination of zooplankton. Limited survival of bluegills in turn contributed to reduced growth of young-of-year largemouth bass dependent on them as prey. Given that zooplankton declined in one but not the other lake, interactions among young-of-year fishes due to annually introduced threadfin shad will likely vary among systems and years. Nonetheless, introduced threadfin shad could, in some systems in some years, negatively affect growth and recruitment of the very species they were meant to enhance.This work was funded in part by National Science Foundation grants NSF BSR-8705518 to R. A. Stein and NSF BSR-8715730 to G. G. Mittelbach, and by Federal Aid in Fish Restoration Project F-57-R awarded to R. A. Stein and administered through the Ohio Division of Wildlife

COMPTEL solar flare observations

COMPTEL as part of a solar target of opportunity campaign observed the sun during the period of high solar activity from 7-15 Jun. 1991. Major flares were observed on 9 and 11 Jun. Although both flares were large GOES events (greater than or = X10), they were not extraordinary in terms of gamma-ray emission. Only the decay phase of the 15 Jun. flare was observed by COMPTEL. We report the preliminary analysis of data from these flares, including the first spectroscopic measurement of solar flare neutrons. The deuterium formation line at 2.223 MeV was present in both events and for at least the 9 Jun. event, was comparable to the flux in the nuclear line region of 4-8 MeV, consistent with Solar-Maximum Mission (SSM) Observations. A clear neutron signal was present in the flare of 9 Jun. with the spectrum extending up to 80 MeV and consistent in time with the emission of gamma-rays, confirming the utility of COMPTEL in measuring the solar neutron flux at low energies. The neutron flux below 100 MeV appears to be lower than that of the 3 Jun. 1982 flare by more than an order of magnitude. The neutron signal of the 11 Jun. event is under study. Severe dead time effects resulting from the intense thermal x-rays require significant corrections to the measured flux which increase the magnitude of the associated systematic uncertainties

Energetic Adaptations along a Broad Latitudinal Gradient: Implications for Widely Distributed Assemblages

Most community-based models in ecology assume that all individuals within a species respond similarly to environmental conditions and thereby exert identical effects as consumers or prey. Rather, individuals differ among systems, with important implications for population demographics and community interactions. For widely distributed assemblages made up of poikilotherms with high first-year mortality, species-specific differences in growth reaction norms as affected by both temperature and genotype will influence biotic interactions. For a broadly distributed fish assemblage, first-year growth does not vary with latitude for a planktivorous prey species, but declines with increasing latitude for a terminal piscivore. Size-based competitive interactions between these species are likely to be more intense at high latitudes, as they spend an extended time sharing resources during early life. Such patterns probably are pervasive and must be considered when seeking to understand species interactions. Improving our knowledge of how temperature and local adaptations affect size-based interactions should enhance our ability to manage and conserve widespread assemblages

Remote sensing applications to resource problems in South Dakota

Cooperative projects between RSI and numerous South Dakota agencies have provided a means of incorporating remote sensing techniques into operational programs. Eight projects discussed in detail are: (1) detection of high moisture zones near interstate 90; (2) thermal infrared census of Canada geese in South Dakota; (3) dutch elm disease detection in urban environment; (4) a feasibility study for monitoring effective precipitation in South Dakota using TIROS-N; (5) open and abandoned dump sites in Spink county; (6) the influence of soil reflectance on LANDSAT signatures of crops; (7) A model implementation program for Lake Herman watershed; and (8) the Six-Mile Creek investigation follow-on