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

Researchers need to better address time-of-day as a critical biological variable

No abstrac

Characteristics of hypervelocity impact craters on LDEF experiment S1003 and implications of small particle impacts on reflective surfaces

The Ion Beam textured and coated surfaces EXperiment (IBEX), designated S1003, was flown on LDEF at a location 98 deg in a north facing direction relative to the ram direction. Thirty-six diverse materials were exposed to the micrometeoroid (and some debris) environment for 5.8 years. Optical property measurements indicated no changes for almost all of the materials except S-13G, Kapton, and Kapton-coated surfaces, and these changes can be explained by other environmental effects. From the predicted micrometeoroid flux of NASA SP-8013, no significant changes in optical properties of the surfaces due to micrometeoroids were expected. There were hypervelocity impacts on the various diverse materials flown on IBEX, and the characteristics of these craters were documented using scanning electron microscopy (SEM). The S1003 alumigold-coated aluminum cover tray was sectioned into 2 cm x 2 cm pieces for crater documentation. The flux curve generated from this crater data fits well between the 1969 micrometeoroid model and the Kessler debris model for particles less than 10(exp -9) gm which were corrected for the S1003 positions (98 deg to ram). As the particle mass increases, the S1003 impact data is greater than that predicted by even the debris model. This, however, is consistent with data taken on intercostal F07 by the Micrometeoroid/Debris Special Investigating Group (M/D SIG). The mirrored surface micrometeoroid detector flown on IBEX showed no change in solar reflectance and corroborated the S1003 flux curve, as well as results of this surface flown on SERT 2 and OSO 3 for as long as 21 years

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

Remote sensing applications to resource problems in South Dakota

The author has identified the following significant results. Change in the vegetative structure was taking place in the Black Hills. Temporal analysis of the areal extent of open meadows was accomplished using black and white and color infrared aerial photography. A reduction of nearly 1100 hectares of open meadows was determined using photointerpretation. Techniques were developed for the management of meandering lakes, including use of LANDSAT imagery for continuous monitoring, classification of hydrophytes on low altitude CIR imagery, and planning and evaluation of improvements and multiple uses on aerial photography and photo mosaics. LANDSAT data were analyzed statistically from small and entire study scene areas to determine the effect of soils stratifications of corn signatures. Band 5 early season and band 7 later season recorded the strongest evidence of the influence of soils on corn signatures. Significant strata were determined by a multiple range test

Disruptions of Circadian Rhythms and Thrombolytic Therapy During Ischemic Stroke Intervention

Several endogenous and exogenous factors interact to influence stroke occurrence, in turn contributing to discernable daily distribution patterns in the frequency and severity of cerebrovascular events. Specifically, strokes that occur during the morning tend to be more severe and are associated with elevated diastolic blood pressure, increased hospital stay, and worse outcomes, including mortality, compared to strokes that occur later in the day. Furthermore, disrupted circadian rhythms are linked to higher risk for stroke and play a role in stroke outcome. In this review, we discuss the interrelation among core clock genes and several factors contributing to ischemic outcomes, sources of disrupted circadian rhythms, the implications of disrupted circadian rhythms in foundational stroke scientific literature, followed by a review of clinical implications. In addition to highlighting the distinct daily pattern of onset, several aspects of physiology including immune response, endothelial/vascular and blood brain barrier function, and fibrinolysis are under circadian clock regulation; disrupted core clock gene expression patterns can adversely affect these physiological processes, leading to a prothrombotic state. Lastly, we discuss how the timing of ischemic onset increases morning resistance to thrombolytic therapy and the risk of hemorrhagic transformation

Analytical approximation for the sphere-sphere Coulomb potential

A simple analytical expression, which closely approximates the Coulomb potential between two uniformly charged spheres, is presented. This expression can be used in the optical potential semiclassical analyses which require that the interaction be analytic on and near the real r-axis.Comment: 4 pages including 3 figures and 1 tabl

A new approximation scheme in quantum mechanics

An approximation method which combines the perturbation theory with the variational calculation is constructed for quantum mechanical problems. Using the anharmonic oscillator and the He atom as examples, we show that the present method provides an efficient scheme in estimating both the ground and the excited states. We also discuss the limitations of the present method.Comment: 14pages, to be published in Eur. J. Phy

Impact of early seed quality selection on maize inbreds and hybrids

Seed composition, genetic background, and environment influence seed quality. Plant breeders selecting for improved seed composition seldom select their inbreds for improved seed quality traits. The standard germination test evaluates seed viability, but it often overestimates field performance. Therefore, seed vigor tests are used to predict seed germination under stressful environments. There is little information on the possible genetic improvement of seed selected for both, improved seed composition and vigor. The objectives of this study were 1) to evaluate the seed quality attributes of a group of maize (Zea mays L.) inbreds selected for high protein content; 2) to assess whether early selection improves the seed quality and decreases the phenotypic variability of seed vigor in a group of inbreds; and 3) to calculate the breeding parameters of general (GCA) and specific combining ability (SCA). During summer 2002 and 2003, related sets of inbred lines were grown in replicated nurseries near Clinton, IL, and Ames, IA. Seed from each inbred was produced by self pollination. Some of the inbred lines grown in 2002 and all grown in 2003 were high-protein white lines that also had been selected for germination cold tolerance and high post-accelerated aging field emergence. In 2002, the mean percentage of standard germination test, saturated cold test, accelerated aging test, soak test, and fast green test for the group of selected high-protein white inbreds were significantly (P ≤ 0.05) higher than the corresponding average values of the yellow inbred checks. There was genetic variability for seed quality in these sets of high protein white inbreds even after a very intense selection process for improved seed quality traits. GCA effects for seed quality were more important than the SCA effects, indicating that the additive effect of the inbreds was more important than the dominant effect to the final seed quality of the hybrids. Selecting inbreds for high seed quality early in the breeding program is beneficial and important for improving germination and field performance