Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette transporters (ABC transporters) associated with MDR, as well as epithelial–mesenchymal transition (EMT) markers, selectively in invasive breast cancer cells, but not in immortalized or non-invasive cells. Interestingly, the mere induction of an EMT in immortalized and non-invasive cell lines increased their expression of ABC transporters, migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive cells by downregulating EMT-inducing transcription factors reduced their expression of ABC transporters, invasion, and rendered them more chemosensitive. Mechanistically, we demonstrate that the promoters of ABC transporters carry several binding sites for EMT-inducing transcription factors, and overexpression of Twist, Snail, and FOXC2 increases the promoter activity of ABC transporters. Furthermore, chromatin immunoprecipitation studies revealed that Twist binds directly to the E-box elements of ABC transporters. Thus, our study identifies EMT inducers as novel regulators of ABC transporters, thereby providing molecular insights into the long-standing association between invasiveness and MDR. Targeting EMT transcription factors could hence serve as novel strategies to curb both metastasis and the associated drug resistance.

<p><strong>Abstract.</strong> Improving the accuracy of regional aerosol climate impact assessment calls for an improvement in the accuracy of regional aerosol radiative effects (ARE) estimation. One of the most important means of achieving this is to use spatially homogeneous and temporally continuous datasets of critical aerosol properties, such as spectral aerosol optical depth (AOD) and single scattering albedo (SSA), which are the most important parameters for estimating aerosol radiative effects. However, observations do not provide the above; the space-borne observations though provide wide spatial coverage, are temporally snapshots and suffer from possible sensor degradation over extended periods. On the other hand, the ground-based measurements provide more accurate and temporally continuous data, but are spatially near-point observations. Realizing the need for spatially homogeneous and temporally continuous datasets on one hand and the near-non-existence of such data over the south Asian region (which is one of the regions where aerosols show large heterogeneity in most of their properties), construction of accurate gridded aerosol products by synthesizing the long-term space-borne and ground-based data, has been taken up as an important objective of the South West Asian Aerosol Monsoon Interactions (SWAAMI), a joint Indo-UK field campaign, aiming at characterizing aerosol-monsoon links and their variabilities over the Indian region.</p> <p>In the Part-1 of this two-part paper, we present spatially homogeneous gridded datasets of AOD and absorption AOD (AAOD), generated for the first time over this region. These data products are developed by merging the highly accurate aerosol measurements from the dense networks of 44 (for AOD) and 34 (for AAOD) ground-based observatories of Aerosol Radiative Forcing NETwork (ARFINET) and AErosol RObotic NETwork (AERONET) spread across the Indian region, with satellite-retrieved AOD and AAOD, following statistical assimilation schemes. The satellite data used for AOD assimilation includes AODs retrieved from MODerate Imaging Spectroradiometer (MODIS) and Multiangle Imaging SpectroRadiometer (MISR) over the same domain. For AAOD, the ground-based Black Carbon (BC) mass concentration measurements from the network of 34 ARFINET observatories and satellite-based (Kalpana-1, INSAT-3A) infrared (IR) radiance measurements, are blended with gridded AAODs (500 nm, monthly mean) derived from Ozone Monitoring Instrument (OMI)-retrieved AAODs (at 354 nm and 388 nm). The details of the assimilation methods and the gridded datasets generated are presented in this paper. </p> <p>The merged, gridded AOD and AAOD products thus generated, are validated against the data from independent ground-based observatories, which were not used for the assimilation process, but are representative of different subregions of the complex domain. This validation exercise revealed that the independent ground-based measurements are better confirmed by merged datasets than the respective satellite products. As ensured by assimilation techniques employed, the uncertainties in merged AODs and AAODs are significantly less than those in corresponding satellite products. These merged products also exhibit all important, large-scale spatial and temporal features which are already reported for this region. Nonetheless, the merged AODs and AAODs are significantly different in magnitude, from the respective satellite products. On the background of above mentioned quality enhancements demonstrated by merged products, we have employed them for deriving the columnar SSA and analysed its spatio-temporal characteristics. The columnar SSA thus derived has demonstrated distinct seasonal variation, over various representative subregions of the study domain. The uncertainties in the derived SSA are observed to be substantially less than those in OMI SSA. On the backdrop of these benefits, the merged datasets are employed for the estimation of regional aerosol radiative effects (direct), the results of which would be presented in a companion paper; Part-2 of this two-part paper.</p>

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Abstract. The vertical structure of atmospheric aerosols over the Indian mainland and the surrounding oceans and its spatial distinctiveness and resultant atmospheric heating are characterised using long-term (2007–2020) satellite observations, assimilated aerosol single scattering albedo, and radiative transfer calculations. The results show strong, seasonally varying zonal gradients in the concentration and vertical extent of aerosols over the study region. Compared to the surrounding oceans, where the vertical extent of aerosols is confined within 3 km, the aerosol extinction coefficients extend to considerably higher altitudes over the mainland, reaching as high as 6 km during pre-monsoon and monsoon seasons. Longitudinally, the vertical extent is highest around 75∘ E and decreasing gradually towards either side of the study region, particularly over peninsular India. Particulate depolarisation ratio profiles affirm the ubiquity of dust aerosols in western India from the surface to nearly 6 km. While the presence of low-altitude dust aerosols decreases further east, the high-altitude (above 4 km) dust layers remain aloft throughout the year with seasonal variations in the zonal distribution over north-western India. High-altitude (around 4 km) dust aerosols are observed over southern peninsular India and the surrounding oceans during the monsoon season. Radiative transfer calculations show that these changes in the vertical distribution of aerosols result in enhanced atmospheric heating at the lower altitudes during the pre-monsoon, especially in the 2–3 km altitude range throughout the Indian region. These results have strong implications for aerosol–radiation interactions in regional climate simulations.

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Abstract. The vertical structure of atmospheric aerosols over the Indian mainland and the surrounding oceans and its spatial distinctiveness are characterized using long-term (2007–2020) spaceborne lidar observations, satellite-retrieved aerosol optical depths and assimilated aerosol single scattering albedo. The consequence of these on the spatial distribution of aerosol-induced atmospheric heating is estimated using radiative transfer calculations. The results show strong, seasonally varying zonal gradients in the concentrations and vertical extent of aerosols over the study region. In general, while over the oceans, aerosol concentrations decrease rather monotonically with increase in altitude (from its highest value near the surface), over the mainland, the concentrations initially increase from the surface to about 1 km before decreasing towards higher altitudes, in all seasons over Central India and during summer monsoon season in northern India. This is attributed to the seasonal variations in the source strengths and the atmospheric boundary layer dynamics. Compared to the surrounding oceans, where the vertical extent of aerosols is confined within 3 km, the aerosol extinction coefficients extend to considerably higher altitudes over the mainland, reaching as high as 6 km during pre-monsoon and monsoon seasons. Longitudinally, the vertical extent is highest around 75° E and decreasing gradually on either side over the peninsular India. In the west, the concentrations and vertical extent of aerosols are highest during summer/monsoon due to the lofting and strong advection of mineral dust and sea salt aerosols. Particulate depolarization ratio profiles affirm the ubiquity of dust aerosols in western India during monsoon. Dust aerosols are distributed all the way from surface to 6 km over the north-western semi-arid regions. While the presence of low-altitude dust aerosols decreases further east, the high-altitude (above 4 km) dust layers are observed to remain aloft throughout the year with seasonal variations in its zonal distribution over north-western India. Southern peninsular India and its surrounding oceans are marked with high-altitude (around 4 km) dust aerosols during the monsoon season. Radiative transfer calculations show that these changes in vertical distribution of aerosol loading and types result in enhanced atmospheric heating at the lower altitudes during pre-monsoon, with prominent heating within 2–3 km throughout the Indian region. These results will have large implications for aerosol-radiation interactions in regional climate simulations.

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