104 research outputs found

    TEM4 is a junctional Rho GEF required for cell-cell adhesion, monolayer integrity and barrier function

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    Signaling events mediated by Rho family GTPases orchestrate cytoskeletal dynamics and cell junction formation. The activation of Rho GTPases is tightly regulated by guanine-nucleotide-exchange factors (GEFs). In this study, we identified a novel Rho-specific GEF called TEM4 (tumor endothelial marker 4) that associates with multiple members of the cadherin–catenin complex and with several cytoskeleton-associated proteins. Depending on confluence, TEM4 localized to either actin stress fibers or areas of cell–cell contact. The junctional localization of TEM4 was independent of actin binding. Depletion of endogenous TEM4 by shRNAs impaired Madin–Darby canine kidney (MDCK) and human umbilical vein endothelial cell (HUVEC) cell junctions, disrupted MDCK acini formation in 3D culture and negatively affected endothelial barrier function. Taken together, our findings implicate TEM4 as a novel and crucial junctional Rho GEF that regulates cell junction integrity and epithelial and endothelial cell function

    Spatial and seasonal variations of aerosols over China from two decades of multi-satellite observations – Part 2: AOD time series for 1995–2017 combined from ATSR ADV and MODIS C6.1 and AOD tendency estimations

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    Understanding long-term variations in aerosol loading is essential for evaluating the health and climate effects of airborne particulates as well as the effectiveness of pollution control policies. The expected satellite lifetime is about 10 to 15 years. Therefore, to study the variations of atmospheric constituents over longer periods information from different satellites must be utilized.Here we introduce a method to construct a combined annual and seasonal long time series of AOD at 550 nm using the Along-Track Scanning Radiometers (ATSR: ATSR-2 and AATSR combined) and the MODerate resolution Imaging Spectroradiometer on Terra (MODIS/Terra), which together cover the 1995–2017 period. The long-term (1995–2017) combined AOD time series are presented for all of mainland China, for southeastern (SE) China and for 10 selected regions in China. Linear regression was applied to the combined AOD time series constructed for individual L3 (1°&thinsp; × &thinsp;1°) pixels to estimate the AOD tendencies for two periods: 1995–2006 (P1) and 2011–2017 (P2), with respect to the changes in the emission reduction policies in China.During P1, the annually averaged AOD increased by 0.006 (or 2&thinsp;% of the AOD averaged over the corresponding period) per year across all of mainland China, reflecting increasing emissions due to rapid economic development. In SE China, the annual AOD positive tendency in 1995–2006 was 0.014 (3&thinsp;%) per year, reaching maxima (0.020, or 4&thinsp;%, per year) in Shanghai and the Pearl River Delta regions. After 2011, during P2, AOD tendencies reversed across most of China with the annually averaged AOD decreasing by −0.015 (−6&thinsp;%) per year in response to the effective reduction of the anthropogenic emissions of primary aerosols, SO2 and NOx. The strongest AOD decreases were observed in the Chengdu (−0.045, or −8&thinsp;%, per year) and Zhengzhou (−0.046, or −9&thinsp;%, per year) areas, while over the North China Plain and coastal areas the AOD decrease was lower than −0.03 (approximately −6&thinsp;%) per year. In the less populated areas the AOD decrease was small.The AOD tendency varied by both season and region. The increase in the annually averaged AOD during P1 was mainly due to an increase in summer and autumn in SE China (0.020, or 4&thinsp;%, and 0.016, or 4&thinsp;%, per year, respectively), while during winter and spring the AOD actually decreased over most of China. The AOD negative tendencies during the 2011–2017 period were larger in summer than in other seasons over the whole of China (ca. −0.021, or −7&thinsp;%, per year) and over SE China (ca. −0.048, or −9&thinsp;%, per year).The long-term AOD variations presented here show a gradual decrease in the AOD after 2011 with an average reduction of 30&thinsp;%–50&thinsp;% between 2011 and 2017. The effect is more visible in the highly populated and industrialized regions in SE China, as expected.</p

    Spatial and seasonal variations of aerosols over China from two decades of multi-satellite observations – Part 1: ATSR (1995–2011) and MODIS C6.1 (2000–2017)

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    Aerosol optical depth (AOD) patterns and interannual and seasonal variations over China are discussed based on the AOD retrieved from the Along-Track Scanning Radiometer (ATSR-2, 1995–2002), the Advanced ATSR (AATSR, 2002–2012) (together ATSR) and the MODerate resolution Imaging Spectroradiometer (MODIS) aboard the Terra satellite (2000–2017). The AOD products used were the ATSR Dual View (ADV) v2.31 AOD and the MODIS/Terra Collection 6.1 (C6.1) merged dark target (DT) and deep blue (DB) AOD product. Together these datasets provide an AOD time series for 23 years, from 1995 to 2017. The difference between the AOD values retrieved from ATSR-2 and AATSR is small, as shown by pixel-by-pixel and monthly aggregate comparisons as well as validation results. This allows for the combination of the ATSR-2 and AATSR AOD time series into one dataset without offset correction.ADV and MODIS AOD validation results show similar high correlations with the Aerosol Robotic Network (AERONET) AOD (0.88 and 0.92, respectively), while the corresponding bias is positive for MODIS (0.06) and negative for ADV (−0.07). Validation of the AOD products in similar conditions, when ATSR and MODIS/Terra overpasses are within 90&thinsp;min of each other and when both ADV and MODIS retrieve AOD around AERONET locations, show that ADV performs better than MODIS in autumn, while MODIS performs slightly better in spring and summer. In winter, both ADV and MODIS underestimate the AERONET AOD.Similar AOD patterns are observed by ADV and MODIS in annual and seasonal aggregates as well as in time series. ADV–MODIS difference maps show that MODIS AOD is generally higher than that from ADV. Both ADV and MODIS show similar seasonal AOD behavior. The AOD maxima shift from spring in the south to summer along the eastern coast further north.The agreement between sensors regarding year-to-year AOD changes is quite good. During the period from 1995 to 2006 AOD increased in the southeast (SE) of China. Between 2006 and 2011 AOD did not change much, showing minor minima in 2008–2009. From 2011 onward AOD decreased in the SE of China. Similar patterns exist in year-to-year ADV and MODIS annual AOD tendencies in the overlapping period. However, regional differences between the ATSR and MODIS AODs are quite large. The consistency between ATSR and MODIS with regards to the AOD tendencies in the overlapping period is rather strong in summer, autumn and overall for the yearly average; however, in winter and spring, when there is a difference in coverage between the two instruments, the agreement between ATSR and MODIS is lower.AOD tendencies in China during the 1995–2017 period will be discussed in more detail in Part 2 (a following paper: Sogacheva et al., 2018), where a method to combine AOD time series from ADV and MODIS is introduced, and combined AOD time series are analyzed.</p

    VEGF and Angiopoietin-1 Exert Opposing Effects on Cell Junctions by Regulating the Rho GEF Syx

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    Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoA-specific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was caused by PKD1 (protein kinase D1)-mediated phosphorylation of Syx at Ser806, which reduced Syx association to its junctional anchors. In support of the pivotal role of Syx in regulating EC junctions, syx−/− mice had defective junctions, resulting in vascular leakiness, edema, and impaired heart function

    Promoter Complexity and Tissue-Specific Expression of Stress Response Components in Mytilus galloprovincialis, a Sessile Marine Invertebrate Species

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    The mechanisms of stress tolerance in sessile animals, such as molluscs, can offer fundamental insights into the adaptation of organisms for a wide range of environmental challenges. One of the best studied processes at the molecular level relevant to stress tolerance is the heat shock response in the genus Mytilus. We focus on the upstream region of Mytilus galloprovincialis Hsp90 genes and their structural and functional associations, using comparative genomics and network inference. Sequence comparison of this region provides novel evidence that the transcription of Hsp90 is regulated via a dense region of transcription factor binding sites, also containing a region with similarity to the Gamera family of LINE-like repetitive sequences and a genus-specific element of unknown function. Furthermore, we infer a set of gene networks from tissue-specific expression data, and specifically extract an Hsp class-associated network, with 174 genes and 2,226 associations, exhibiting a complex pattern of expression across multiple tissue types. Our results (i) suggest that the heat shock response in the genus Mytilus is regulated by an unexpectedly complex upstream region, and (ii) provide new directions for the use of the heat shock process as a biosensor system for environmental monitoring

    The Molecular Identification of Organic Compounds in the Atmosphere: State of the Art and Challenges

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