31 research outputs found

    Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

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    <p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) in learning, memory and long-term potentiation (LTP). However, previous studies have also shown that alpha-CaMKII (+/-) heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes.</p> <p>Results</p> <p>We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/-) heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression.</p> <p>Conclusion</p> <p>Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects aggressive behavior.</p

    Mental workload during endoscopic sinus surgery is associated with surgeons’ skill levels

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    IntroductionSurgeons’ mental workload during endoscopic sinus surgery (ESS) has not been fully evaluated. The assessment was challenging due to the great diversity of each patient’s anatomy and the consequence variety of surgical difficulties. In this study, we examined the mental workload of surgeons with various surgical skill levels during ESS under the standardized condition provided by novel-designed 3D sinus models.Materials and methodsForty-seven participants performed a high-fidelity ESS simulation with 3D-printed sinus models. Surgeons’ mental workload was assessed with the national aeronautics and space administration-task load index (NASA-TLX). Associations between the total and subscales score of NASA-TLX and surgical skill index, including the board certification status, the number of experienced ESS cases, and the objective structured assessment of technical skills (OSATS), were analyzed. In addition, 10 registrars repeated the simulation surgery, and their NASA-TLX score was compared before and after the repetitive training.ResultsThe total NASA-TLX score was significantly associated with OSATS score (p = 0.0001). Primary component analysis classified the surgeons’ mental burden into three different categories: (1) the skill-level-dependent factors (temporal demand, effort, and performance), (2) the skill-level-independent factors (mental and physical demand), and (3) frustration. After the repetitive training, the skill-level-dependent factors were alleviated (temporal demand; z = −2.3664, p = 0.0091, effort; z = −2.1704, p = 0.0346, and performance; z = −2.5992, p = 0.0017), the independent factors were increased (mental demand; z = −2.5992, p = 0.0023 and physical demand; z = −2.2509, p = 0.0213), and frustration did not change (p = 0.3625).ConclusionSome of the mental workload during ESS is associated with surgical skill level and alleviated with repetitive training. However, other aspects remain a burden or could worsen even when surgeons have gained surgical experience. Routine assessment of registrars’ mental burdens would be necessary during surgical training to sustain their mental health

    Spatiotemporal impact of COVID-19 on Taiwan air quality in the absence of a lockdown: Influence of urban public transportation use and meteorological conditions

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    The unprecedented outbreak of COVID-19 significantly improved the atmospheric environment for lockdown-imposed regions; however, scant evidence exists on its impacts on regions without lockdown. A novel research framework is proposed to evaluate the long-term monthly spatiotemporal impact of COVID-19 on Taiwan air quality through different statistical analyses, including geostatistical analysis, change detection analysis and identification of nonattainment pollutant occurrence between the average mean air pollutant concentrations from 2018–2019 and 2020, considering both meteorological and public transportation impacts. Contrary to lockdown-imposed regions, insignificant or worsened air quality conditions were observed at the beginning of COVID-19, but a delayed improvement occurred after April in Taiwan. The annual mean concentrations of PM10, PM2.5, SO2, NO2, CO and O3 in 2020 were reduced by 24%, 18%, 15%, 9.6%, 7.4% and 1.3%, respectively (relative to 2018–2019), and the overall occurrence frequency of nonattainment air pollutants declined by over 30%. Backward stepwise regression models for each air pollutant were successfully constructed utilizing 12 meteorological parameters (R2 > 0.8 except for SO2) to simulate the meteorological normalized business-as-usual concentration. The hybrid single-particle Lagrangian integrated trajectory (HYSPLIT) model simulated the fate of air pollutants (e.g., local emissions or transboundary pollution) for anomalous months. The changes in different public transportation usage volumes (e.g., roadway, railway, air, and waterway) moderately reduced air pollution, particularly CO and NO2. Reduced public transportation use had a more significant impact than meteorology on air quality improvement in Taiwan, highlighting the importance of proper public transportation management for air pollution control and paving a new path for sustainable air quality management even in the absence of a lockdown

    Mechanisms of translational regulation by a human eIF5-mimic protein

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    The translation factor eIF5 is an important partner of eIF2, directly modulating its function in several critical steps. First, eIF5 binds eIF2/GTP/Met-tRNAiMet ternary complex (TC), promoting its recruitment to 40S ribosomal subunits. Secondly, its GTPase activating function promotes eIF2 dissociation for ribosomal subunit joining. Finally, eIF5 GDP dissociation inhibition (GDI) activity can antagonize eIF2 reactivation by competing with the eIF2 guanine exchange factor (GEF), eIF2B. The C-terminal domain (CTD) of eIF5, a W2-type HEAT domain, mediates its interaction with eIF2. Here, we characterize a related human protein containing MA3- and W2-type HEAT domains, previously termed BZW2 and renamed here as eIF5-mimic protein 1 (5MP1). Human 5MP1 interacts with eIF2 and eIF3 and inhibits general and gene-specific translation in mammalian systems. We further test whether 5MP1 is a mimic or competitor of the GEF catalytic subunit eIF2Bε or eIF5, using yeast as a model. Our results suggest that 5MP1 interacts with yeast eIF2 and promotes TC formation, but inhibits TC binding to the ribosome. Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function

    Monte Carlo Simulation of D-D Neutron Emission Rate in NBI-Heated Deuterium Plasma of LHD

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    As the first step to analyze the orbit of the triton produced by the fusion reaction between the beam-injected deuteron and the deuteron in the bulk plasma, we developed the code to calculate the velocity and spatial profiles of the fusion products in the Large Helical Device (LHD) that properly treats the particle loss boundary and the velocity anisotropy of the triton at birth. The neutron emission and neutron counting rates calculated by the code were compared with experimental results. The experimental results are reproduced by the developed code when the bulk plasma density, including the impurity ion, was used
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