ABSTRACT
Atmospheric aerosol types and characteristics have regional and seasonal characteristics mainly due spatial and temporal differences in emission sources and diffuse transport conditions. We explored regional three-dimensional spatial and temporal distribution characteristics of aerosol types in Central Asia from daytime to nighttime by using long-term (2007-2021) CALIPSO lidar measurements. The three results are as follows: (1) Average aerosol optical depth (AOD) values during the 14 years were 0.44 and 0.47 during daytime and nighttime, respectively, with an overall decreasing trend, among which the AOD in spring in the southern border region and in winter in the northern border region showed high values, 0.66 and 0.31 during daytime and 0.69 and 0.33 during nighttime, respectively, and nighttime AOD values were higher than those of daytime, possibly due to the lower signal-to-noise ratio of the CALIPSO during the daytime than during the nighttime. (2) The primary representative aerosol type in the Taklamakan Desert region being pure sand and dust, and more apparent winter-polluted sand and dust exist along the northern slope of the Tianshan Mountains in Xinjiang in winter than in other areas. High-altitude soot mainly existed below 4 km and was primarily concentrated in northern Central Asia, with the highest values (0.016 and 0.003) in summer and winter, respectively, which may be due to different diffusion and transport conditions. (3) Dust aerosols in spring were mainly concentrated in the region of 2-6 km in the Taklamakan Desert area; pure dust particles in summer and fall lifted height diffusion and gradually moved to the northern border region; polluted dust was mainly in northern Xinjiang in fall and winter and spread to northern Central Asia; and the average top height of aerosols in the transmission process reached the top of the troposphere, and transmission height was higher than source area.
ABSTRACT
Calmodulin (CaM) mutations are associated with congenital long QT (LQT) syndrome (LQTS), which may be related to the dysregulation of the cardiac-predominant Ca2+ channel isoform CaV1.2. Among various mutants, CaM-E141G was identified as a critical missense variant. However, the interaction of this CaM mutant with the CaV1.2 channel has not been determined. In this study, by utilizing a semiquantitative pull-down assay, we explored the interaction of CaM-E141G with CaM-binding peptide fragments of the CaV1.2 channel. Using the patch-clamp technique, we also investigated the electrophysiological effects of the mutant on CaV1.2 channel activity. We found that the maximum binding (Bmax) of CaM-E141G to the proximal COOH-terminal region, PreIQ-IQ, PreIQ, IQ, and NT (an NH2-terminal peptide) was decreased (by 17.71-59.26%) compared with that of wild-type CaM (CaM-WT). In particular, the Ca2+-dependent increase in Bmax became slower with the combination of CaM-E141G + PreIQ and IQ but faster in the case of NT. Functionally, CaM-WT and CaM-E141G at 500 nM Ca2+ decreased CaV1.2 channel activity to 24.88% and 55.99%, respectively, compared with 100 nM Ca2+, showing that the inhibitory effect was attenuated in CaM-E141G. The mean open time of the CaV1.2 channel was increased, and the number of blank traces with no channel opening was significantly decreased. Overall, CaM-E141G exhibits disrupted binding with the CaV1.2 channel and induces a flickering gating mode, which may result in the dysfunction of the CaV1.2 channel and, thus, the development of LQTS. The present study is the first to investigate the detailed binding properties and single-channel gating mode induced by the interaction of CaM-E141G with the CaV1.2 channel.
