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This study examined the statistics of aviation turbulence that occurred in Japan between 2006 and 2018 by analyzing pilot reports (PIREP). In total, 81 639 turbulence events, with moderate or greater intensity, were reported over this period. The monthly number of turbulence cases has an annual periodic variation as observed in different regions by previous studies. The number of turbulence cases is high from March to June and low in July and August. Higher numbers of turbulence cases are experienced along the major flight routes in Japan, especially around Tokyo, for the active period between 0900 and 2000 local time. The number of cases of turbulence peaks when the flight reaches an altitude of 33 000 ft (FL330; 1000 ft ≈ 300 m), whereas it decreases when the flight altitude is above FL380 and below FL280. The statistical features are not largely different among the four seasons; however, there are some exceptions. For instance, the number of turbulence cases is large in high altitudes in summer and small in low altitudes in winter. Considering the number of flights, it is evident that the frequency of turbulence is higher in altitudes between FL200 and FL350, although the number of flights is low in this altitude region. The number of convectively induced turbulence cases is relatively large during the daytime in summer in comparison with the other seasons. A large amount of mountain-wave turbulence is observed around the mountainous region in autumn and winter when the jet stream flows over Japan. Significance Statement This study examines the statistics of aviation turbulence reported over Japan from 2008 to 2018.

We examined the sensitivity of the formation of moist convection to the number of aerosols that serve as cloud condensation nuclei (CCN) based on a set of numerical experiments using a nonhydrostatic model with a bin cloud microphysics model. Additionally, a linear stability analysis for an air parcel incorporating effects of the CCN number concentration (NCCN) has been conducted to further demonstrate the findings in numerical experiments. The results of the numerical experiments show that moist convection does not form when NCCN ≤ 10 cm−3. The sensitivity to NCCN can be divided into three regimes: when NCCN ≤ 10 cm−3, convection does not form or not fully develop; when 1 ≤ NCCN ≤ 102 cm−3, maximum vertical velocity increases with NCCN; and when NCCN ≥ 102 cm−3, the intensity of convection does not largely depend on NCCN. We demonstrate that the main reason convection does not form under environments with a small NCCN is that the time scale for condensation is longer than that to change environmental conditions. Given a supersaturated environment, fewer droplets form when NCCN is small and the size of droplets is potentially large. Consequently, the amount of latent heating is limited and the air parcel cannot obtain buoyancy within a reasonable time scale. Linear stability analysis using a parcel model considering the effect of NCCN without ice-phase processes shows unstable and stable regimes as a function of the number of droplets. The analytically obtained critical droplet number for the convection formation well corresponds to the minimum NCCN beyond which convection forms in the present numerical experiments.

Treatment of severe and critical cases of coronavirus disease 2019 (COVID-19) is still a top priority in public health. Previously, we reported distinct Th1 cytokines related to the pathophysiology of severe COVID-19 condition. In the present study, we investigated the association of Th1 and Th2 cytokine/chemokine endotypes with cell-mediated immunity via multiplex immunophenotyping, single-cell RNA-Seq analysis of peripheral blood mononuclear cells, and analysis of the clinical features of COVID-19 patients. Based on serum cytokine and systemic inflammatory markers, COVID-19 cases were classified into four clusters of increasing (I-IV) severity. Two prominent clusters were of interest and could be used as prognostic reference for a targeted treatment of severe COVID-19 cases. Cluster III reflected severe/critical pathology and was characterized by decreased in CCL17 levels and increase in IL-6, C-reactive protein CXCL9, IL-18, and IL-10 levels. The second cluster (Cluster II) showed mild to moderate pathology and was characterized by predominated CXCL9 and IL-18 levels, levels of IL-6 and CRP were relatively low. Cluster II patients received anti-inflammatory treatment in early-stage, which may have led prevent disease prognosis which is accompanied to IL-6 and CRP induction. In Cluster III, a decrease in the proportion of effector T cells with signs of T cell exhaustion was observed. This study highlights the mechanisms of endotype clustering based on specific inflammatory markers in related the clinical outcome of COVID-19.

The dependence of lightning frequency on the life cycle of an idealized tropical cyclone (TC) was investigated using a three-dimensional meteorological model coupled with an explicit lightning model. To investigate this dependence, an idealized numerical simulation covering the initial state to the steady state (SS) of an idealized TC was conducted. The simulation was consistent with the temporal evolution of lightning frequency reported by previous observational studies. Our analyses showed that the dependence originates from changes in the types of convective cloud with lightning over the life cycle of the TC. Before rapid intensification (RI) and in the early stage of RI, convective cloud cells that form under high-convective available potential energy (CAPE) conditions are the main contributors to lightning. As the TC reaches the late stage of RI and approaches SS, the secondary circulation becomes prominent and convective clouds in the eyewall region alongside the secondary circulation gradually become the main contributors to the lightning. In the convective cloud cells formed under high-CAPE conditions, upward velocity is strong and large charge density is provided through noninductive charge separation induced by graupel collisions. This large charge density frequently induces lightning in the clouds. On the other hand, the vertical velocity in the eyewall is weak, and it tends to contribute to lightning only when the TC reaches the mature stage. Our analyses imply that the maximum lightning frequency that occurs before the maximum intensity of a TC corresponds to the stage of a TC’s life cycle in which convective cloud cells are generated most frequently and moisten the upper troposphere.

This study examines the relationship between frozen hydrometeors and latent heating in model simulations and evaluates the capability of the Weather Research and Forecasting (WRF) Model to reproduce the observed frozen hydrometeors and their relationship to tropical cyclone (TC) intensification. Previous modeling studies have emphasized the importance of both the amount and location of latent heating in modulating the evolution of TC intensity. However, the lack of observations limits a full understanding of its importance in the real atmosphere. Idealized simulations using WRF indicate that latent heating is strongly correlated to the amount of ice water content, suggesting that ice water content can serve as an observable proxy for latent heat release in the mid- to upper troposphere. Based on this result, satellite observations are used to create storm-centered composites of ice water path as a function of TC intensity. The model reasonably captures the vertical and horizontal distribution of ice water content and its dependence upon TC intensity, with differences typically less than 20%. The model also captures the signature of increased ice water content for intensifying TCs, suggesting that observations of ice water content provide a useful diagnostic for understanding and evaluating model simulations of TC intensification.

Piccolo, a presynaptic cytomatrix protein, plays a role in synaptic vesicle trafficking in the presynaptic active zone. Certain single-nucleotide polymorphisms of the Piccolo-encoding gene PCLO are reported to be associated with mental disorders. However, a few studies have evaluated the relationship between Piccolo dysfunction and psychotic symptoms. Therefore, we investigated the neurophysiological and behavioral phenotypes in mice with Piccolo suppression in the medial prefrontal cortex (mPFC). Downregulation of Piccolo in the mPFC reduced regional synaptic proteins, accompanied with electrophysiological impairments. The Piccolo-suppressed mice showed an enhanced locomotor activity, impaired auditory prepulse inhibition, and cognitive dysfunction. These abnormal behaviors were partially ameliorated by the antipsychotic drug risperidone. Piccolo-suppressed mice received mild social defeat stress showed additional behavioral despair. Furthermore, the responses of these mice to extracellular glutamate and dopamine levels induced by the optical activation of mPFC projection in the dorsal striatum (dSTR) were inhibited. Similarly, the Piccolo-suppressed mice showed decreased depolarization-evoked glutamate and -aminobutyric acid elevations and increased depolarization-evoked dopamine elevation in the dSTR. These suggest that Piccolo regulates neurotransmission at the synaptic terminal of the projection site. Reduced neuronal connectivity in the mPFC-dSTR pathway via suppression of Piccolo in the mPFC may induce behavioral impairments observed in schizophrenia.

This study statistically investigates the characteristics of tropical cyclones (TCs) undergoing rapid intensification (RI) in the western North Pacific in the 37 years from 1979 to 2015 and the relevant atmospheric and oceanic environments. Among 900 TCs, 201 TCs undergoing RI (RI-TCs) are detected by our definition as a wind speed increase of 30 kt (15.4 m s−1) or more in a 24-h period. RI-TCs potentially occur throughout the year, with low variation in RI-TC occurrence rate among the seasons. Conversely, the annual occurrence of RI-TC varies widely. In El Niño years, TCs tend to undergo RI mainly as a result of average locations at the time of tropical storm formation (TSF) being farther east and south, whereas TCs experience RI less frequently in La Niña years. The occurrence rates of RI-TC increased from the 1990s to the late 2000s. The RI onset time is typically 0–66 h after the TSF and the duration that satisfies the criteria of RI is 1–2 days. RI frequently occurs over the zonally elongated area around the eastern Philippine Sea. The development stage and life-span are longer in RI-TCs than in TCs that do not undergo RI. RI-TCs are small at the time of TSF and tend to develop as intense TCs as a result of environmental conditions favorable for TC development, weak vertical wind shear, high convective available potential energy, and tropical cyclone heat potential. The occurrence rates of RI-TCs that make landfall in Japan and the Philippines are higher than in China and Vietnam.

This study proposes that secondary eyewall formation (SEF) of tropical cyclones (TCs) can be attributed to an instability of flow in the free atmosphere coupled with Ekman pumping. Unstable solutions of a 1.5-layer shallow-water system are obtained under fast–wind speed conditions in the free atmosphere. The instability condition derived in the linear model indicates the importance of the ratio of angular velocity to vorticity, and the condition is more likely to be satisfied when the ratio is large and its radial gradient is positive. Thus, fast angular velocity, low absolute vertical vorticity, small negative radial gradient of angular velocity, and large negative gradient of vertical vorticity are favorable. Eigenvalue analyses are performed over a wide range of parameters using a vorticity profile with an infinitesimal secondary maximum. The growth rate increases with vorticity outside the radius of maximum wind (RMW), the radius of the secondary vorticity maximum, its magnitude, and the Rossby number defined by maximum tangential velocity, the RMW, and the Coriolis parameter. Furthermore, the growth rate is positive only between 2 and 7 times the RMW, and it is negative close to or far outside the RMW. These features are consistent with previous studies on SEF. A dimensionless quantity obtained from the unstable condition in the linear theory is applied to SEF events simulated by two different full-physics numerical models; increases several hours before a secondary peak of tangential velocity forms, suggesting that the initial process of SEF can be attributed to the proposed mechanism.

Background Several clinical studies have suggested that N-acetylaspartate and N-acetylaspartylglutamate levels in the human brain are associated with various psychiatric disorders, including major depressive disorder. We have previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. Shati/Nat8l synthesizes N-acetylaspartate from L-aspartate and acetyl-coenzyme A. Further, N-acetylaspartate is converted into N-acetylaspartylglutamate, a neurotransmitter for metabotropic glutamate receptor 3. Methods Because Shati/Nat8l mRNA levels were increased in the dorsal striatum of mice following the exposure to forced swimming stress, Shati/Nat8l was overexpressed in mice by the microinjection of adeno-associated virus vectors containing Shati/Nat8l gene into the dorsal striatum (dS-Shati/Nat8l mice). The dS-Shati/Nat8l mice were further assessed using behavioral and neurochemical tests. Results The dS-Shati/Nat8l mice exhibited behavioral despair in the forced swimming and tail suspension tests and social withdrawal in the 3-chamber social interaction test. These depression-like behaviors were attenuated by the administration of a metabotropic glutamate receptor 2/3 antagonist and a selective serotonin reuptake inhibitor. Furthermore, the metabolism of N-acetylaspartate to N-acetylaspartylglutamate was decreased in the dorsal striatum of the dS-Shati/Nat8l mice. This finding corresponded with the increased expression of glutamate carboxypeptidase II, an enzyme that metabolizes N-acetylaspartylglutamate present in the extracellular space. Extracellular serotonin levels were lower in the dorsal striatum of the dS-Shati/Nat8l and normal mice that were repeatedly administered a selective glutamate carboxypeptidase II inhibitor. Conclusions Our findings indicate that the striatal expression of N-acetylaspartate synthetase Shati/Nat8l plays a role in major depressive disorder via the metabotropic glutamate receptor 3-mediated functional control of the serotonergic neuronal system.

An analytical model of maximum potential intensity (PI) for tropical cyclones (TCs) incorporating wind-induced ocean cooling is developed on the basis of Emanuel's PI theory. The model consists of a one-dimensional ocean and an axisymmetric TC vortex that is translating at a constant speed. The model advances upon previous approaches by accounting for TC size and shape. The PI is determined at the radius of maximum winds by radially integrating the effect of ocean mixing using a specified wind profile. The resulting analytic ocean cooling agrees well with numerical solutions, and the new PI model better captures maximum intensities of observed TCs compared with Emanuel's original PI. It is also shown that the degree of cooling (i.e., ocean's feedback to atmosphere) can be quantified by a dimensionless parameter, representing the ratio of atmospheric forcing to ocean stability.

The relationship of tropical cyclone (TC) future intensity change to current intensity and current axisymmetricity deduced from hourly Global Satellite Mapping of Precipitation (GSMaP) data was investigated. Axisymmetricity is a metric that correlates positively with the magnitude of the axisymmetric component of the rainfall rate and negatively with the magnitude of the asymmetric component. The samples used were all of the TCs that existed in the western North Pacific basin during the years 2000–15. The results showed that, during the development stage, the intensification rate at the current time, and 6 and 12 h after the current time was strongly related to both the current intensity and axisymmetricity. On average, the higher the axisymmetricity, the larger the intensity change in the next 24 h for TCs with a current central pressure (maximum sustained wind) between 945 and 995 hPa (85 and 40 kt). The mean value of the axisymmetricity for TCs experiencing rapid intensification (RI) was much higher than that for non-RI TCs for current intensities of 960–990 hPa. The new observational evidence for the intensification process presented here is consistent with the findings of previous theoretical studies emphasizing the role of the axisymmetric component of diabatic heating.

The environmental conditions for tropical cyclone genesis are examined by numerical experiment. We focus on the case of a non-developing disturbance showed features for tropical cyclone genesis in the Pacific Area Long-term Atmospheric observation for Understanding climate change in 2010 (PALAU2010) observation campaign over the western North Pacific. We clarify the importance of the presence of abundant moisture around the disturbance for continuous convection and demonstrate that the collocation of a mid-level vortex and a low-level vortex, i.e., the persistence of an upright structure of vortices, is important in tropical cyclone genesis. We conduct two numerical experiments using the Weather Research and Forecasting Model Advanced Research WRF model in double nested domains with a horizontal grid space of 27 km and 9 km for the outer domain and the inner domain, respectively. The first experiment is based on reanalysis data (a control experiment) and the second includes increased water vapor content over the northwestern dry area of the disturbance. In the control experiment, the disturbance did not develop into a tropical cyclone in spite of the existence of the mid-level and low-level vortices. In contrast, the sensitivity experiment shows that a tropical cyclone was formed from the disturbance with increased water vapor content. The presence of persistent upright vortices was supported by continuous convection until the genesis of the tropical cyclone.

The impacts of aerosols on the charge distribution of hydrometeors and lightning flash density in a tropical cyclone (TC) were investigated using a meteorological model coupled with an explicit lightning model. The meteorological model successfully simulated the tripole structure of charge density distribution in a TC, as reported by previous studies. The impacts of aerosols were investigated through a sensitivity experiment with changing the aerosol number concentration. The tripole structure became unclear with increasing aerosol number concentrations. The positive charge distribution located in the lower layer was not seen, and raindrops with negative charge distribution reached the surface. As a result, the vertical structure of the charge density was dipolar in the polluted case. As the tripole structure shifted to dipole, the magnitude of the electric field tended to be large, and the flash number was large. By contrast, in the pristine case, the tripole structure was dominant, and the flash number was much smaller than in the polluted case.

Intracellular Ca2+ levels are changed by influx from extracellular medium and release from intracellular stores. In the central nervous systems, Ca2+ release is involved in various physiological events, such as neuronal excitability and transmitter release. Although stable Ca2+ release in response to stimulus is critical for proper functions of the nervous systems, regulatory mechanisms relating to Ca2+ release are not fully understood in central neurons. Here, we demonstrate that ShcB, an adaptor protein expressed in central neurons, has an essential role in functional maintenance of Ca2+ store in cerebellar Purkinje cells (PCs). ShcB-knockout (KO)mice showed defects in cerebellar-dependent motor function and long-term depression (LTD) at cerebellar synapse. The reduced LTD was accompanied with an impairment of intracellular Ca2+ release. Although the expression of Ca2+ release channels and morphology of Ca2+ store looked intact, content of intracellular Ca2+ store and activity of sarco/endoplasmic reticular Ca2+-ATPase (SERCA) were largely decreased in the ShcB-deficient cerebellum. Furthermore, when ShcB was ectopically expressed in the ShcB-KO PCs, the Ca2+ release and its SERCA-dependent component were restored. These data indicate that ShcB plays a key role in the functional maintenance of ER Ca2+ store in central neurons through regulation of SERCA activity., Scientific Reports, 10(1), art.no.14475; 2020

Shati/Nat8l was originally isolated as a methamphetamine-related-molecule from the nucleus accumbens of mice. Since then, Shati/Nat8l has been characterized as an N-acetyltransferase-8-like protein (Nat8l) that catalyzes N-acetylaspartate (NAA) synthesis from aspartate and acetyl-coenzyme A. It has been shown that elevated NAA levels detected by proton magnetic resonance spectroscopy (1H-MRS) brain imaging indicates increased neuronal activity. Our group produced Shati/Nat8l knock out mice (Shati/Nat8l KO mice), which exhibit hyper locomotion, anxiety behaviors, and social dysfunction. These mice have a high sensitivity to methamphetamine, as evidenced by their results in assessments of locomotor activity and conditioned place preference, as well as their elevated dopamine levels. We used an adeno-associated virus (AAV) vector containing Shati/Nat8l (AAV-Shati/Nat8l) to overexpress the protein in different brain regions such as the striatum and the nucleus accumbens, in order to investigate their involvement in methamphetamine-induced behavioral and pharmacological changes. We showed that overexpression of accumbal Shati/Nat8l attenuates methamphetamine-induced behaviors.

We examine the influence of the grid aspect ratio of horizontal to vertical grid spacing on turbulence in the planetary boundary layer (PBL) in a large-eddy simulation (LES). In order to distinguish them as much as possible from other artificial effects caused by numerical schemes, we used a fully compressible meteorological LES model with a fully explicit scheme of temporal integration. The influences are investigated with a series of sensitivity tests with parameter sweeps of spatial resolution and grid aspect ratio. We confirmed that the mixing length of the eddy viscosity and diffusion due to sub-grid scale turbulence plays an essential role in reproducing the theoretical −5/3 slope of the energy spectrum. If we define the filter length in LES modeling based on consideration of the numerical scheme, and introduce a corrective factor for the grid aspect ratio into the mixing length, the theoretical slope of the energy spectrum can be obtained; otherwise, spurious energy piling appears at high wavenumbers. We also found that the grid aspect ratio has influence on the turbulent statistics, especially the skewness of the vertical velocity near the top of the PBL, which becomes spuriously large with large aspect ratio, even if a reasonable spectrum is obtained.

A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens of mice repeatedly treated with methamphetamine (METH). Shati/Nat8l has been reported to inhibit the pharmacological action induced by METH. Shati/Nat8l produces N-acetylaspartate from aspartate and acetyl-CoA. Previously, we reported that overexpression of Shati/Nat8l in nucleus accumbens attenuates the response to METH by N-acetylaspartylglutamate (which is derived from N-acetylaspartate)-mGluR3 signaling in the mice brain. In the present study, to clarify the type of cells that produce Shati/Nat8l, we carried out in-situ hybridization for the detection of Shati/Nat8l mRNA along with immunohistochemical studies using serial sections of mice brain. Shati/Nat8l mRNA was detected in neuronal cells, but not in astrocytes or microglia cells. Next, we investigated the function of Shati/Nat8l in the neuronal cells in mice brain; then, we used an adeno-associated virus vector containing Shati/Nat8l for transfection and overexpression of Shati/Nat8l protein into the primary cultured neurons to investigate the contribution toward the neuronal activity of Shati/Nat8l. Overexpression of Shati/Nat8l in the mice primary cultured neurons induced axonal growth, but not dendrite elongation at day 1.5 (DIV). This finding indicated that Shati/Nat8l contributes toward neuronal development. LY341495, a selective group II mGluRs antagonist, did not abolish this axonal growth, and N-acetylaspartylglutamate itself did not abolish axon outgrowth in the same cultured system. The cultured neurons overexpressing Shati/Nat8l contained high ATP, suggesting that axon outgrowth is dependent on energy metabolism. This study shows that Shati/Nat8l in the neuron may induce axon outgrowth by ATP synthesis and not through mGluR3 signaling.

Multi-frequency radars offer enhanced detection of clouds and precipitation compared to single-frequency systems, and are able to make more accurate retrievals when several frequencies are available simultaneously. An evaluation of a spaceborne three-frequency Ku/Ka/W-band radar system is presented in this study, based on modeling radar reflectivities from the results of a global cloud-resolving model with a 875 m grid spacing. To produce the reflectivities, a scattering model has been developed for each of the hydrometeor types produced by the model, as well as for melting snow. The effects of attenuation and multiple scattering on the radar signal are modeled using a radiative transfer model, while nonuniform beam filling is reproduced with spatial averaging. The combined effects of these are then quantified both globally and in five localized case studies. Two different orbital scenarios using the same radar are compared. Overall, based on the results, it is expected that the proposed radar would detect a high-quality signal in most clouds and precipitation. The main exceptions are the thinnest clouds that are below the detection threshold of the W-band channel, and at the opposite end of the scale, heavy convective rainfall where a combination of attenuation, multiple scattering and nonuniform beam filling commonly cause significant deterioration of the signal; thus, while the latter can be generally detected, the quality of the retrievals is likely to be degraded.

The effects of discretization on the equations, and their solutions, describing Rayleigh–Benard convection are studied through linear stability analysis and numerical integration of the discretized equations. Linear stability analyses of the discretized equations were conducted in the usual manner except that the assumed solution contained discretized components (e.g., spatial grid interval in the x direction, \({\Delta x}\)). As the resolution became infinitely high (\({\Delta x \rightarrow 0}\)), the solutions approached those obtained from the continuous equations. The wavenumber of the maximum growth rate increased with increasing \({\Delta x}\) until the wavenumber reached a minimum resolvable resolution, \({\pi \Delta x^{-1}}\). Therefore, the discretization of equations tends to reproduce higher-wavenumber structures than those predicted by the continuous equations. This behavior is counter intuitive and opposed to the expectation of \({\Delta x}\) leading to blurred simulated convection structures. However, when the analysis is conducted for discretized equations that are not combined into a single equation, as is the case for practically solved numerical models, the maximum growing wavenumber rather tends to decrease with increasing \({\Delta x}\) as intuitively expected. The degree of the decrease depends on the discretization accuracy of the first-order differentials. When the accuracy of the discretization scheme is of low order, the wavenumber monotonically decreases with increasing \({\Delta x}\). On the other hand, when higher-order schemes are used for the discretization, the wavenumber does increase with increasing \({\Delta x}\), a similar trend to that in the case of the single-discretized equation for smaller \({\Delta x}\).

Deep moist convection is an element of cloud disturbances such as Madden-Julian oscillation (MJO), tropical cyclones (TCs), mid-latitudinal low depressions (MDL), and fronts (FRT). However, differences in convection characteristics in disturbances remain unclear. We first clarified the statistical features of the convection (structure, intensity, and environmental parameters) in various disturbances simulated by a global simulation with a sub-kilometre grid spacing. The convection in MJO (TC) was tall with a strong (weak) upward motion, and was driven by large convective available potential energy (strong low-level convergence). The convection in MDL and FRT was shorter and characterized by a strong vertical wind shear.

We developed silicon micro-mirrors with two asymmetric axes for electrostatic field distribution measurements using a single external piezoelectric ceramic vibrating element. The 2D asymmetric silicon micro-mirrors were fabricated by using an SOI-MEMS process. The vibration transmissibility of the proposed mirror under a vacuum atmosphere was evaluated by dynamic analysis. We obtained the resonant frequency in the low-speed axis of 23.3 Hz and in the high-speed axis of 556.8 Hz respectively. To prevent a reduction in the amplitude width, we induced a 90° phase shift between the lowand high-speed axes at the resonance frequency. The ratio of the deformation between the low-speed axis of 30 Hz and the high-speed axis of 604 Hz was simulated to be 4.04. In measurement, the ratio of the deformation between the low-speed axis of 23.3 Hz and the high-speed axis of 556.8 Hz was 6.48. The difference between the calculated and experiment values were apparently due to the fabrication errors and frequency characteristics of piezoelectric ceramic vibrating element. A Lissajous pattern projected onto the screen. The scanning angle was a degree of 7.6 (total angle) in the lowand high-speed axis. We subsequently measured the electrostatic field distribution using the 2D asymmetric silicon micro-mirrors by means of the optical level method.

Transmembrane protein 168 (TMEM168) comprises 697 amino acid residues, including some putative transmembrane domains. It is reported that TMEM168 controls methamphetamine (METH) dependence in the nucleus accumbens (NAc) of mice. Moreover, a strong link between METH dependence-induced adaptive changes in the brain and mood disorders has been evaluated. In the present study, we investigated the effects of accumbal TMEM168 in a battery of behavioral paradigms. The adeno-associated virus (AAV) Tmem168 vector was injected into the NAc of C57BL/6J mice (NAc-TMEM mice). Subsequently, the accumbal TMEM168 mRNA was increased approximately by seven-fold when compared with the NAc-Mock mice (controls). The NAc-TMEM mice reported no change in the locomotor activity, cognitive ability, social interaction, and depression-like behaviors; however, TMEM168 overexpression enhanced anxiety in the elevated-plus maze and light/dark box test. The increased anxiety was reversed by pretreatment with the antianxiety drug diazepam (0.3 mg/kg i.p.). Moreover, the NAc-TMEM mice exhibited decreased prepulse inhibition (PPI) in the startle response test, and the induced schizophrenia-like behavior was reversed by pretreatment with the antipsychotic drug risperidone (0.01 mg/kg i.p.). Furthermore, accumbal TMEM168 overexpression decreased the basal levels of extracellular GABA in the NAc and the high K+ (100 mM)-stimulated GABA elevation; however, the total contents of GABA in the NAc remained unaffected. These results suggest that the TMEM168-regulated GABAergic neuronal system in the NAc might become a novel target while studying the etiology of anxiety and sensorimotor gating deficits.

We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati−/−) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati−/− mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati−/− mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.