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Agricultural residues burning as a means of land preparation commonly practiced in many Southeast Asian countries causes significant deterioration of ambient air quality and public health. In this study, WRF-CMAQ Atmospheric Chemical Transport Model was used to conduct a year-round simulation (1 January - 31 December 2019) of PM2.5 spatio-temporal variation over Southeast Asia. The model utilized the Fire emission Inventory from NCAR (FINNv1.5) from National Center for Atmospheric Research (NCAR) as a biomass burning emission input. The model performance was evaluated by comparing simulated values with observed values from monitoring stations in nine major cities. The model shows acceptable performance reproducing the PM2.5 concentration with 14.9% normalized mean bias (NMB) and correlation coefficient of 0.89. After that, the simulation was conducted again with emission from FINNv1.5 turned off. The results from FINNv1.5 on and off cases were then compared to evaluate contribution of biomass burning to PM2.5 concentration in two major cities of Thailand: Bangkok and Chiang Mai. The comparison shows that biomass burning contributes to 49.1% and 13.1% of PM2.5 annual average concentration in Chiang Mai and Bangkok respectively with highest month being April for Chiang Mai (70.7% contribution) and March for Bangkok (35.5% contribution).

Air pollution problems in East Asia are now critical. One issue attracting much attention is the high level of aerosol loading, so that, aerosol effects on climate and air quality are more significant than in other regions. These effects can substantially influence air quality prediction. Thus, it leads to a need to apply online models for climate and air quality simulations in this region. In this study, an online coupled meteorology and air quality modeling system composed of the Weather Research and Forecasting (WRF) model and the Community Multiscale Air Quality (CMAQ) model was applied for the purpose of evaluating the impacts of aerosol direct effects on meteorology and air quality in East Asia. Simulations were carried out in both one-way and two-way online (without and with the aerosol direct effects) for the whole historical year 2014 at a horizontal resolution of 45 km × 45 km. The model showed a good performance in reproducing the observations as well as capturing the spatial and temporal fluctuation of meteorological variables and air pollutant concentrations. On average, due to aerosol direct effects, shortwave radiation (SWR), temperature (T), planetary boundary layer height (PBLH), and wind speed (WS) were decreased by −7.71%, −0.42 °C, −8.13% and −1.00%, respectively; PM2.5, SO2, and NO2 concentrations were increased by +6.26%, +4.91%, +7.48%, respectively; while O3 concentration was decreased by −3.12% over China, Korea, and Japan for the entire year. Analyzing the cause-effect relationships among the responses of the above selected meteorological variables and air pollutants indicated that the reduction in SWR at ground surface caused by aerosol direct effects produces a decrease in T and PBLH, leading to an increase in PM2.5 concentration and a decrease in O3 concentration. Aerosol direct effects also affected long-range transport of PM2.5 from the continent to downwind area. Investigation of eastward response of PM2.5 to aerosol direct effects revealed that the amount of long-range transported PM2.5 was decreased in downwind area due to the impact of aerosol direct effects. It was mainly attributed to the increase in dry deposition of PM2.5 precursors and the decrease in WS in the continent. The results of study highlighted that the aerosol direct effects play an important role in the atmospheric dynamic and chemistry and cause considerable impacts on East Asia air quality.

A novel sample extraction method using an ISOLUTE PLD+ protein and phospholipid removal column was developed for simultaneous quantification of 20 psychoactive drugs, including antidepressants, antipsychotics, sedative-hypnotics, and amphetamines, in postmortem whole blood samples by liquid chromatography-tandem mass spectrometry. The method showed improvement in extract cleanliness compared with traditional protein precipitation and the QuEChERS extraction method. The method was validated for all analytes; the calibration curves showed good linearity, with r

The dynamics of dissolved oxygen in lake is a fundamental issue of comprehending the water environmental habitats of aquatic organisms. In recent years, the decrease in dissolved oxygen has been observed at the bottom of the northern part of Lake Biwa, Japan. In recent years, eutrophication and global warming caused the decrease in the dissolved oxygen in the deep layer. Under these circumstances, in order to preserve the ecosystem of Lake Biwa and to provide water resources, the environmental changes in Lake Biwa should be accurately grasped. In our present study, a water quality model considering the flow field from hydrodynamic model was developed in order to grasp the concentration of phytoplankton, zooplankton, nitrogen, phosphorus, dissolved oxygen and chemical oxygen demand in Lake Biwa. Numerical simulation was carried out for 3 years from 2007 to 2009. Comparisons of the simulations with the observations showed that the seasonal and interannual change of dissolved oxygen was well reproduced. The dissolved oxygen decreased during decomposingthe organic matter by bacteria in the bottom layer with little oxygen supply from the atmosphere and the photosynthesis from the phytoplankton under the thermocline from spring to autumn. The simulation confirmed that in each year, the dissolved oxygen was supplied in all layers by the overturning in winter.

Accurate spatial and temporal prediction of PM2.5 ambient concentration is crucial to appropriate exposure assessment. We develop a spatiotemporal land use regression model by integrating a random forests (RF) technique and the Community Multiscale Air Quality (CMAQ) modeling system to accurately estimate daily PM2.5 levels in the Kansai region of Japan, which is affected by long-range transport in the Asian continent and by local pollution. The most important advantage of RF is that it captures nonlinearity among the target air pollutants and the predictor variables including land-use variables, meteorological variables, and CMAQ-estimated PM2.5 concentration. We compare the predicting performances of the land use random forests (LURF) models with and without CMAQ variables to determine their effectiveness. A cross-validation (CV) technique that calculates the coefficient of determination (R2) and root mean square error (RMSE) is performed to evaluate their prediction performances through spatial and temporal CVs. The performance of the with-CMAQ LURF model was superior to that of the without-CMAQ LURF model. Moreover, we evaluated the PM2.5 prediction performances of the with-CMAQ LURF and the with-CMAQ land use linear regression (LULR) models via CV to determine the efficiency of the non-linear model. Accordingly, the with-CMAQ LURF model is preferable for PM2.5 estimation compared to that of the with-CMAQ LULR model. In addition, the with-CMAQ LURF model exhibits higher PM2.5 predictability than the CMAQ model, as indicated by the higher model-R2 and lower model-RMSE values. Our findings demonstrate that the CMAQ-simulated PM2.5 level integrated into the LURF is advantageous in accurately estimating PM2.5 concentration, which is influenced by long-range transport and local pollution.

Here we evaluated the effect of using water retentive pavement or WRP made from fly ash as material for main street in a real city block. We coupled computational fluid dynamics and pavement transport (CFD-PT) model to examine energy balance in the building canopies and ground surface. Two cases of 24 h unsteady analysis were simulated: case 1 where asphalt was used as the pavement material of all ground surfaces and case 2 where WRP was used as main street material. We aim to (1) predict diurnal variation in air temperature, wind speed, ground surface temperature and water content; and (2) compare ground surface energy fluxes. Using the coupled CFD-PT model it was proven that WRP as pavement material for main street can cause a decrease in ground surface temperature. The most significant decrease occurred at 1200 JST when solar radiation was most intense, surface temperature decreased by 13.8°C. This surface temperature decrease also led to cooling of air temperature at 1.5 m above street surface. During this time, air temperature in case 2 decreased by 0.28°C. As the radiation weakens from 1600 JST to 2000 JST, evaporative cooling had also been minimal. Shadow effect, higher albedo and lower thermal conductivity of WRP also contributed to surface temperature decrease. The cooling of ground surface eventually led to air temperature decrease. The degree of air temperature decrease was proportional to the surface temperature decrease. In terms of energy balance, WRP caused a maximum increase in latent heat flux by up to 255 W/m 2 and a decrease in sensible heat flux by up to 465 W/m 2 .

Air quality in future will change in response to anthropogenic emission change as well as climate change. In this study, an advanced online coupled Weather Research and Forecasting (WRF) and Community Multiscale Air Quality (CMAQ) model was applied to the Continental Southeast Asia. The targets were to investigate the impacts of projected change in future anthropogenic emissions and its impacts in combination with climate change impacts on future particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) and ozone (O3) air quality. Future anthropogenic emissions were produced by scaling Hemispheric Transport of Air Pollution (HTAP) emissions in year 2010 using ratios taken from the Evaluating the Climate and Air Quality Impacts of Short-Lived Pollutants (ECLIPSE) emission database in year 2050 and 2010 under current legislation (CLE) scenario. Future climate projections were obtained by implementing a dynamical downscaling method based on pseudo global warming (PGW) technique using future (2046-2055) climate conditions and present (2006-2015) climate conditions provided by the Coupled Model Intercomparison Experiment (CMIP5) Community Earth System Model (CESM) data and the 2014 meteorological conditions. Two Representative Concentration Pathway (RCP) climate scenarios, RCP4.5 and RCP8.5, were considered. Overall, anthropogenic emission change alone appears to cause higher PM2.5 and O3 levels in future period. Across four target countries namely Cambodia, Laos, Thailand, and Vietnam, on average, PM2.5 and O3 concentrations increase by +4.56 μg/m3 (+13.76%) and +5.12 ppb (+13.20%) during the dry season, +3.03 μg/m3 (+27.72%) and +5.89 ppb (+23.97%) during the wet season, respectively. PM2.5 increase is attributed to the emission growth of primary PM2.5 and PM2.5 precursors. Among PM2.5 species, while raising trend was mainly predicted for anthropogenic secondary organic aerosol (PM2.5 ASOA), sulfate ion (PM2.5 SO42−), nitrate ion (PM2.5 NO3−), and ammonium ion (PM2.5 NH4+) concentrations, reducing trend was mainly predicted for element carbon (PM2.5 EC) and primary organic aerosol (PM2.5 POA) concentrations due to the projected primary PM2.5 emission decrease in China. O3 increase is driven by high nitrogen oxides (NOx) emission increase rather than non-methane volatile organic compounds (NMVOCs) emission increase since NOx-limited regime mostly dominates over the region. Both future PM2.5 and O3 increases in Continental Southeast Asia are also contributed by pollutant emission growth in India. Driven by climate change and emission change in combination, the rise in PM2.5 and O3 concentrations is larger in RCP8.5 scenario than that in RCP4.5 scenario. Averagely, under RCP4.5 scenario, PM2.5 and O3 concentrations, across four target countries, were projected to increase by +3.43 μg/m3 (+10.36%) and +4.37 ppb (+11.27%) during the dry season, +2.20 μg/m3 (+20.15%) and +5.20 ppb (+21.16%) during the wet season. Under RCP8.5 scenario, they increase by +7.10 μg/m3 (+21.43%) and +6.35 ppb (+16.38%) during the dry season, +3.08 μg/m3 (+28.15%) and +6.20 ppb (+25.20%) during the wet season, respectively. The simulation results indicated that emission trend is a major factor in the variation in PM2.5 and O3 concentrations, while the climate change also plays an important role. Current legislations and pollution controls as in ECLIPSE CLE scenario are inadequate for better PM2.5 and O3 air quality in the region. A stronger emission control strategy will be required to cope with this PM2.5 and O3 air quality degradation, particularly under RCP8.5 scenario.

Climatic factors such as air temperature and wind speed can affect the structure of stratification in Lake Biwa. In general, the rise in air temperature and the decrease in wind speed weaken the vertical mixing and strengthen the structure of the stratification, which interrupts the transport of the substances. However, how much the change of each climate element can influence the structure of the stratification is not clarified. Therefore, it is important to evaluate the effects of each element on the stratification quantitatively. In the present study, we investigated the effect of the change in air temperature and wind speed on the seasonal change of stratification in Lake Biwa by using a three-dimensional hydrodynamic model. Numerical simulations were carried out for a baseline case using realistic meteorological data from 2007 to 2012 and hypothetical cases using meteorological data with modified air temperature or wind speed for sensitivity analysis. The analysis showed that the increase and decrease in air temperature changed the vertical water temperature uniformly in almost all layers. Thus, the strength of the stratification is hardly changed. The increase and decrease in wind speed, however, altered the water temperature near the surface of the lake, so that it significantly influenced the stratification. The increase in wind speed made the water parcels of the surface layer well mixed, and the decrease in wind speed made the mixed layer thinner.

Water temperature near the surface of a lake increases with increasing air temperature, whichresults in stratification. The strength of stratification substantially influences the transport of dissolved oxygenfrom the surface to the bottom water of a lake. In recent years, the decrease in dissolved oxygen at the bottom ofthe northern part of the Lake Biwa, the largest freshwater lake in Japan, has been observed. The main cause ofthis is considered to be the change in stratification, which depends on weather and climate conditions. In thepresent study, numerical simulations were carried out to investigate the effect of strong wind on the structure ofstratification in Lake Biwa. The baseline simulation was conducted using actual meteorological data, andexperimental simulations were conducted using meteorological data with modified wind speed and direction.The numerical experiments showed that if the magnitude of the wind is strong enough, the stratificationcollapses and the wind can enhance the vertical mixing in the bottom layer even in the summer season withstrong thermal stratification. In a stratified season, when the strong wind blows predominantly in one direction,the rate of the vertical mixing changes by the wind direction. Moreover, as the duration of the strong windextends, vertical mixing easily occurs.

This study evaluates the impact of solar photovoltaic (PV) cell on building surface temperature, urban-canyon air temperature and energy fluxes. Computational fluid dynamics (CFD) coupled with weather research forecasting (WRF) model and one-dimensional heat conduction model are employed. Under clear weather conditions, the installation of solar PV leads to cooling of building surface but specific warming may occur. During daytime, cooling effect is greater on the roof surface (2.1 °C) than on wall (0.8 °C) because of efficient thermal convection and greater sky view factor which leads to air circulation. During nighttime, cooling effect is greater on wall (4.3 °C) than on roof (1.4 °C) because of shading effect. Shading effect minimizes the heat absorption during daytime and hence minimizes heat release during nighttime. The reduced surface temperature leads to urban air cooling, up to 0.4 °C during nighttime. The installation of solar PV does not affect anthropogenic heat, however it can reduce sensible heat flux and increase net radiation as a consequence of surface temperature cooling. Roof PV produce power output 63.5% greater than wall PV and under the assumption that the power generated will be used for cooling, a decrease in energy consumption can be expected.

Information on concentration of contaminants is important for management of indoor air quality. Recently, data assimilation techniques are used in order to accurately estimate location and intensity of contamination source in addition to concentration field. In this study, the variational continuous assimilation (VCA) method, which was originally developed in meteorological simulations, was applied to estimates of indoor air quality. The method modifies the governing equations of computational fluid dynamics (CFD) model by adding a correction term which reduces the error between original CFD calculation and observed data. In the mass conservation equation, the correction term can be assumed to be a pseudo source term. The validity of VCA method was confirmed by numerical experiments for two-dimensional steady-state calculation with the following procedures: (i) “true” concentration field was produced by CFD calculations with “true” concentration source; (ii) “pseudo-observation” data were extracted from “true” concentration field; (iii) the VCA method was applied to “false” CFD calculations without contamination source to produce “corrected” concentration field using “pseudo-observation” data; (iv) “corrected” concentration field and contamination source were compared with “true” dataset. The numerical experiments revealed the following findings: the VCA method can identify the area where the contamination source was located; and the VCA method can also reduce errors between “true” and CFD-calculated concentration field although the peak concentration was not well-estimated. These results suggest that the VCA method is a utilizable method to estimate concentration field, and location and intensity of contamination source.

Water temperature near the surface of a lake increases with increasing air temperature, which results in stratification. The strength of stratification substantially influences the transport of water parcels from the surface to the bottom of a lake. In recent years, the stratification in Lake Biwa—the largest freshwater lake in Japan—has been stronger. However, it is difficult to reproduce the stratification well in the simulations. In the present study, we built a hydrodynamic model for the purpose of analyzing the structure of the stratification in detail. Using the model, we evaluated the reproducibility of the seasonal and annual changes of vertical water distribution and flow field in Lake Biwa from 2007 to 2011. The hydrodynamic model results show that the vertical water distribution approximately agrees with the field observations based on the statistical analysis. The seasonal change of thermal stratification is reasonably reproduced by the hydrodynamic model simulations. In the simulation, there are mainly two circulation flows at the surface layer of the lake. The first flows anticlockwise and the second flows clockwise in the northern part of Lake Biwa. In order to compensate for the surface water flow, the water under the thermocline sometimes flows in the opposite direction under each circulation flow.

An online coupled modeling system composed of Weather Research and Forecasting (WRF) model and Community Multiscale Air Quality (CMAQ) model was applied to assess aerosol direct effects on meteorology and air quality with the focus on particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) and ozone (O3) in Continental Southeast Asia. Comprehensive model evaluations demonstrated that the modeling system had the capacity to reproduce the observations, and could capture the temporal and spatial variations of temperature, radiation, humidity, wind speed, wind direction, PM2.5 concentration, and O3 concentration. The performance of the two-way online simulation was slightly better than that of the one-way online simulation. The aerosol direct effects on the meteorology and air quality were calculated by taking the differences between the results of the two-way online simulation and the one-way online simulation. Over four target countries, namely Laos, Cambodia, Thailand, and Vietnam, the aerosol direct effects moderately decreased the shortwave radiation, temperature, planetary boundary layer (PBL) height, and wind speed by −10.98 W/m2 (−5.17%), −0.21 °C (−0.85%), −27.25 m (−6.13%), and −0.03 m/s (−1.29%), respectively. These percentages were −17.80 W/m2 (−7.71%), −0.39 °C (−1.67%), −48.33 m (−8.89%), and −0.06 m/s (−2.01%) during the dry season, and −4.31 W/m2 (−2.22%), −0.03 °C (−0.12%), −6.71 m (−1.92%), and −0.01 m/s (−0.50%) during the wet season, respectively. Consequently, the meteorological response to direct effects led to changes in the ground-level PM2.5 and O3 concentrations. The PM2.5 concentration was found to increase by +1.21 μg/m3 (+5.36%) and the O3 concentration was found to decrease by −0.40 ppb (−1.26%) over the entire year. For each season, the PM2.5 concentration increased by +2.09 μg/m3 (+6.75%) during the dry season and +0.15 μg/m3 (+1.42%) during the wet season. The O3 concentration decreased by −0.96 ppb (−2.41%) during the dry season and slightly increased by +0.13 ppb (+0.55%) during the wet season. The direct effects were large during high PM2.5 polluted periods and locations. A correlation matrix clarified that the increasing effect of aerosol on the PM2.5 concentration was attributed to the decrease in the above-mentioned meteorological variables. The increase or decrease in the O3 concentration depended on the responses of the atmospheric dynamics as well as the photolysis rates.

Changing climate will impact future air quality. In this study, an online coupled meteorology and chemistry WRF-CMAQ model was applied to simulate such impacts on future O3 and PM2.5 air quality over Continental Southeast Asia. Simulations were conducted for present (2006–2015) and future (2046–2055) years under two climate scenarios, RCP4.5 and RCP8.5. Future climate projections were obtained by implementing a downscaling dynamical method based on pseudo global warming technique. In order to estimate the impacts of climate change alone, anthropogenic and biomass burning emissions were held constant at present level while biogenic emissions varying with climate were used. The model results indicated a future regional meteorology characterized by a warmer and more humid atmosphere, increased precipitation, and more stagnant condition. Affected by climate change, NOx and NMVOCs biogenic emissions increase which contribute to the increasing effects on O3 and PM2.5 precursors concentrations. Subsequently, the changes in meteorology and biogenic emission affect air quality. These influence on ground level O3 and PM2.5 are different between the two climate scenarios. Under RCP4.5 scenario, future atmosphere appears to be reduced in O3 and PM2.5 concentrations, suggesting a potential “climate benefit” for air quality. At four target countries, namely Cambodia, Laos, Thailand, and Vietnam, O3 concentration decreases by −0.76 ppb (−2.40%), PM2.5 concentration decreases by −0.95 μg/m3 (−4.32%) on average for the entire year. However, climate change worsen O3 and PM2.5 air pollution under RCP8.5 scenario. O3 concentration increases by +0.26 ppb (+0.84%), PM2.5 concentration increases by +0.92 μg/m3 (+4.20%) on average for the entire year. Significant increases were generally located in northern Vietnam (for O3) and southern Vietnam (for PM2.5) during the dry season. The analysis suggests that the decrease in O3 concentration is due to the dominancy of the negative effect of water vapor increase and the increase in O3 concentration is affected largely by the temperature increase, stagnant condition, and biogenic emission increase. The responses of PM2.5 to climate change depend on the physical and chemical characteristics of each PM2.5 species. The major climate change effect on PM2.5 is the physical effect, rather than the chemical effect.

Although mutations of autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), presenting a wide spectrum of many characteristic and non-characteristic clinical features, some patients lack AIRE gene mutations. Therefore, something other than a mutation, such as dysregulation of AIRE gene, may be a causal factor for APECED or its related diseases. However, regulatory mechanisms for AIRE gene expression and/or translation have still remained elusive. We found that IL-2-stimulated CD4(+) T (IL-2T) cells showed a high expression of AIRE gene, but very low AIRE protein production, while Epstein-Barr virus-transformed B (EBV-B) cells express both AIRE gene and AIRE protein. By using microarray analysis, we could identify miR-220b as a possible regulatory mechanism for AIRE gene translation in IL-2T cells. Here we report that miR-220b significantly reduced the expression of AIRE protein in AIRE gene with 3'UTR region transfected 293T cells, whereas no alteration of AIRE protein production was observed in the open reading frame of AIRE gene alone transfected cells. In addition, anti-miR-220b reversed the inhibitory function of miR-220b for the expression of AIRE protein in AIRE gene with 3'UTR region transfected cells. Moreover, when AIRE gene transfected cells with mutated 3'UTR were transfected with miR-220b, no reduction of AIRE protein production was observed. Taken together, it was concluded that miR-220b inhibited the AIRE gene translation through the 3'UTR region of AIRE gene, indicating that miR-220b could serve as a regulator for human AIRE gene translation.

Introduction: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by monogenic mutations in the autoimmune regulator (AIRE) gene. No attention has been paid to muscle manifestations in this disorder. We aimed to uncover whether progressive myopathy is a component of this disorder. Methods: A case description and literature search for APECED cases presenting with myopathy and analysis of AIRE gene expression in biopsied muscles from 4 healthy volunteers and the patient by reverse transcriptase polymerase chain reaction. Results: A 52-year-old woman with APECED caused by AIRE gene mutations developed progressive myopathy involving proximal limb and paraspinal muscles. Muscle biopsy specimens showed myopathic changes without inflammatory cell infiltrate. We detected AIRE gene expression in all muscle tissues examined. An extensive literature search uncovered 5 cases of APECED with myopathy, all of whom had similar features. Conclusions: Progressive myopathy involvement could be a hitherto unknown manifestation of APECED. Muscle Nerve 45: 904-908, 2012

A large size botulinum toxin complex (L-TC) is composed of a single neurotoxin (BoNT), a single nontoxic nonhaemagglutinin (NTNHA) and a haemagglutinin (HA) complex. The HA complex is comprised of three HA-70 molecules and three arm structures of HA-33/HA-17 that consist of two HA-33 and a single HA-17. In addition to the mature L-TC, smaller TCs are present in cultures: M-TC (BoNT/NTNHA), M-TC/HA-70 and immature L-TCs with fewer HA-33/HA-17 arms than mature L-TC. Because L-TC displays higher oral toxicity than pure BoNT, it was presumed that nontoxic proteins are critical for food poisoning. In this study, the absorption of TCs across intestinal epithelial cells was assessed by examining the cell binding and monolayer transport of serotype D toxins in the rat intestinal epithelial cell line IEC-6. All TCs, including pure BoNT, displayed binding and transport, with mature L-TC showing the greatest potency. Inhibition experiments using antibodies revealed that BoNT, HA-70 and HA-33 could be responsible for the binding and transport. The findings here indicate that all TCs can transport across the cell layer via a sialic acid-dependent process. Nonetheless, binding and transport markedly increased with number of HA-33/HA-17 arms in the TC. We therefore conclude that the HA-33/HA-17 arm is not necessarily required for, but facilitates, transport of botulinum toxin complexes.

Clostridium botulinum produces a large toxin complex (L-TC) composed of neurotoxin (BoNT) and non-toxic proteins. In animal botulism, BoNT or L-TC is absorbed via the intestinal epithelium. To establish the cellular mechanisms of botulinum toxin absorption, we used cultured rat intestinal epithelial cells to test the binding and transport of serotype C l BoNT and L-TC through the cell layers. BoNT and L-TC bound to and passed through the cell layers, with L-TC exhibiting larger binding and transport. Binding and transport of these toxins were inhibited by N-acetyl neuraminic acid or neuraminidase treatment of the cells. These results suggest that binding of serotype C1 BoNT and L-TC to sialic acid on the cells promoted their transport through intestinal epithelial cell layers.

The autoimmune regulator (AIRE) gene is a gene responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Here we show that AIRE is expressed in human peripheral CD4-positive T-cells, and most highly in antigen- and interleukin 2-stimulated T (IL-2T) cells. Mitogen-activated protein kinases (MAPKs), including MAPK kinase (MEK) 1/2 and p38 MAPK, were phosphorylated in IL-2T cells and the expression of the AIRE gene was inhibited by a specific p38 MAPK inhibitor (SB203580), thereby indicating that AIRE gene expression is controlled by the MAPK pathway in IL-2T cells. These data suggested the possible significance of the AIRE gene in the peripheral immune system.