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

An Mdo-Compatible Method for Robust Design of Vehicles, Systems, and Components

A CAE simulation process was developed to quantify the variability of vehicle attributes such as safety, durability, vehicle dynamics, NVH and weight. The process was integrated with the Ford multi-function optimization (MFO) tool — MOVE (Multi-Function Optimization Visualization Environments) in order to facilitate the robust design of vehicles, systems and components. The statistics of vehicle attribute responses are computed given the statistics of the design parameters. The response surface approximation was used to simplify the input and output relationships. A variety of statistical distributions can be selected to match the statistics of the design parameters which are continuous or discrete. In addition to parametric statistical analysis methods, nonparametric statistical analysis approaches were also available. To achieve robust design, a series of robust targets were used in the search for the optimized design. The method also ranks the contribution of individual design parameter variability to a specific vehicle attribute variability. The ranking was used to set up a tolerance strategy for reducing the variability and the total cost of the product. The integrated MFO/robust design process has been applied in several Ford vehicle programs for robust and reliable optimized design. A couple of applications are described here

Age composition, growth, and reproduction of koi carp (Cyprinus carpio L.) in the lower Waikato, New Zealand

A total of 566 koi carp (Cyprinus carpio) from the lower Waikato region were aged from scales and opercular bones, and growth was modelled with the von Bertalanffy growth function. There was no difference in growth rate between male and female carp. Growth of koi carp between zero and 3 years of age was lower than that of common carp in Europe and Australia. However, after 5 years of age the growth of koi carp was higher than that of common carp in Europe, but still below that of carp in Australia. Males rarely lived in excess of 8 years, whereas females lived to 12 years. Mean total fecundity calculated from 44 running-ripe females was 299 000 oocytes (±195 600 SD) (range 29 800–771 000). Relative fecundity ranged from 19 300 to 216 000 oocytes kg–1 total body weight, with a mean of 97 200 (±35 000 SD) oocytes kg–1. Feral koi carp in the Waikato are capable of multiple spawnings within their lifetimes. Within a spawning season, Waikato populations of feral koi carp contained females that spawned once, and females that had the potential to have spawned repeatedly. Female gonadosomatic index (GSI) varied with season and was negatively related to water temperature

Creation of Skyrmions in a Spinor Bose-Einstein Condensate

We propose a scheme for the creation of skyrmions (coreless vortices) in a Bose-Einstein condensate with hyperfine spin F=1. In this scheme, four traveling-wave laser beams, with Gaussian or Laguerre-Gaussian transverse profiles, induce Raman transitions with an anomalous dependence on the laser polarization, thereby generating the optical potential required for producing skyrmions.Comment: 5 pages, 2 figures, RevTe

WIPP panel simulations with gas generation

An important issue in nuclear waste repository performance is the potential for fracture development resulting in pathways for release of radionuclides beyond the confines of the repository. A series of demonstration calculations using structural finite element analyses are presented here to examine the effect of internal gas generation on the response of a sealed repository. From the calculated stress fields, the most probable location for a fracture to develop was determined to be within the pillars interior to the repository for the range of parameter values considered. If a fracture interconnects the rooms and panels of the repository, fracture opening produces significant additional void volume to limit the excess gas pressure to less than 1.0 MPa above the overburden pressure. Consequently, the potential for additional fracture development into the barrier pillar is greatly reduced, which provides further confidence that the waste will be contained within the repository

SALT DAMAGE CRITERION PROOF-OF-CONCEPT RESEARCH

The purpose of this study was to conduct a field-scale application demonstrating the use of continuum damage mechanics to determine the minimum allowable operating pressure of compressed natural gas storage caverns in salt formations. A geomechanical study was performed of two natural gas storage caverns (one existing and one planned) utilizing state-of-the-art salt mechanics to assess the potential for cavern instability and collapse. The geomechanical study consisted primarily of laboratory testing, theoretical development, and analytical/numerical tasks. A total of 50 laboratory tests was performed on salt specimens to aid in the development and definition of the material model used to predict the behavior of rock salt. Material model refinement was performed that improved the predictive capability of modeling salt during damage healing, recovery of work-hardened salt, and the behavior of salt at stress states other than triaxial compression. Results of this study showed that the working gas capacity of the existing cavern could be increased by 18 percent and the planned cavern could be increased by 8 percent using the proposed method compared to a conventional stress-based method. Further refinement of the continuum damage model is recommended to account for known behavior of salt at stress conditions other than triaxial compression that is not characterized accurately by the existing model

Use of Radio-Telemetry to Test for Investigator Effects on Nesting Mallards, Anas platyrhynchos

We examined the effects of investigator activity on hatching rates of radio-marked wild female Mallards (Anas platyrhynchos), and evaluated the efficacy of radio-telemetry to minimize nest disturbance, characterize vegetation at nest sites, and mark nests for later relocation. Differences in hatching rates between birds that were flushed once (experimental) and those never flushed (control) approached significance (P = 0.086). However, hatching rates did not differ (P = 0.588) between the two groups when nests where investigator activity caused abandonment (30% of experimental nests) were removed from analysis. If the nest remained active, flushing the bird and visiting the nest once did not appear to increase the likelihood of the nest being depredated. We were able to locate 92% of radio-telemetry marked nests (control) after the female was no longer tending the nest. Radio-telemetry provides a technique to collect relatively unbiased nesting data for Mallards without disturbing the female

Violence against children perpetrated by peers: A cross-sectional school-based survey in Uganda

Violence against children by peers is a global public health problem. We aimed to assess factors associated with peer violence victimization among primary school children in Uganda. We conducted multilevel multivariable logistic regression analyses of cross-sectional data from 3706 primary students in 42 Ugandan primary schools. Among primary school students, 29% and 34% had ever experienced physical and emotional violence perpetrated by their peers, respectively. Factors strongly associated with both physical and emotional violence were similar and overlapping, and included exposure to interparental violence, having an attitude supportive of violence against children from school staff, not living with biological parents, working for payment, and higher SDQ score. However, we found that younger age, sharing sleeping area with an adult and achieving a higher educational performance score, were specifically associated with physical violence. On the other hand, being female, walking to school, reporting disability and eating one meal on the previous day, were particularly associated with emotional violence. Interventions to reduce peer violence should focus on family contexts, school environments and those with poor socio-economic status may need extra support