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1.
Laura C. Burzynski Melanie Humphry Martin R. Bennett Murray C. H. Clarke 《The Journal of biological chemistry》2015,290(41):25188-25196
Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection. 相似文献
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An evaluation of semi‐automated methods for collecting ecosystem‐level data in temperate marine systems 下载免费PDF全文
Kingsley J. Griffin Luke H. Hedge Manuel González‐Rivero Ove I. Hoegh‐Guldberg Emma L. Johnston 《Ecology and evolution》2017,7(13):4640-4650
Historically, marine ecologists have lacked efficient tools that are capable of capturing detailed species distribution data over large areas. Emerging technologies such as high‐resolution imaging and associated machine‐learning image‐scoring software are providing new tools to map species over large areas in the ocean. Here, we combine a novel diver propulsion vehicle (DPV) imaging system with free‐to‐use machine‐learning software to semi‐automatically generate dense and widespread abundance records of a habitat‐forming algae over ~5,000 m2 of temperate reef. We employ replicable spatial techniques to test the effectiveness of traditional diver‐based sampling, and better understand the distribution and spatial arrangement of one key algal species. We found that the effectiveness of a traditional survey depended on the level of spatial structuring, and generally 10–20 transects (50 × 1 m) were required to obtain reliable results. This represents 2–20 times greater replication than have been collected in previous studies. Furthermore, we demonstrate the usefulness of fine‐resolution distribution modeling for understanding patterns in canopy algae cover at multiple spatial scales, and discuss applications to other marine habitats. Our analyses demonstrate that semi‐automated methods of data gathering and processing provide more accurate results than traditional methods for describing habitat structure at seascape scales, and therefore represent vastly improved techniques for understanding and managing marine seascapes. 相似文献
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Nonalcoholic fatty liver disease and measures of early brain health in middle‐aged adults: The CARDIA study 下载免费PDF全文
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David Dubbeldam Sofía Calero Donald E. Ellis Randall Q. Snurr 《Molecular simulation》2016,42(2):81-101
A new software package, RASPA, for simulating adsorption and diffusion of molecules in flexible nanoporous materials is presented. The code implements the latest state-of-the-art algorithms for molecular dynamics and Monte Carlo (MC) in various ensembles including symplectic/measure-preserving integrators, Ewald summation, configurational-bias MC, continuous fractional component MC, reactive MC and Baker's minimisation. We show example applications of RASPA in computing coexistence properties, adsorption isotherms for single and multiple components, self- and collective diffusivities, reaction systems and visualisation. The software is released under the GNU General Public License. 相似文献
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H. James Spooner 《CMAJ》1996,154(12):1875-1876