167,132 research outputs found
Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation
No full textCellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1 beta production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIPL is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1 beta. Hemizygotic deletion of c-FLIP impaired ATP-and monosodium uric acid (MSU)-induced IL-1 beta production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1 beta expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-alpha was not affected by downregulation in c-FLIP. c-FLIPL interacted with NLRP3 or procaspase-1. c-FLIP is required for the full NLRP3 inflammasome assembly and NLRP3 mitochondrial localization, and c-FLIP is associated with NLRP3 inflammasome. c-FLIP downregulation also reduced AIM2 inflammasome activation. In contrast, c-FLIP inhibited SMAC mimetic-, FasL-, or Dectin-1-induced IL-1 beta generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIPL in the optimal activation of the NLRP3 and AIM2 inflammasomes, and suggest that c-FLIP could be a valid target for treatment of inflammatory diseases caused by over-activation of inflammasomes
Enhancement of random lasing based on the composite consisting of nanospheres embedded in nanorods template
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A Rosary of Rubies: The Chronicle of the Gur-rigs mDo-chen Tradition from South-Western Tibet
Full text linkThe mDo-chen bKa’-brgyud-pa school represents a little known Buddhist tradition from Mang-yul Gung-thang in south-western Tibet. It goes back to a Buddhist yogin known as Ma-bdun-pa or Ma-bdun ras-chen (12th/13th c.) and was later mainly spread by members of the Gur family. Although belonging to the “Upper ’Brug” (stod ’brug) branch of the ’Brug-pa bKa’-brgyud-pa school, the mDo-chen tradition has always been deeply infused with the “spoken teachings” (bka’ ma) and “treasure teachings” (gter ma) of the rNying-ma-pa school, and the cult of the “Seven Ma-mo Sisters” (ma mo mched bdun) was particularly practised and transmitted by its members. This book presents a critical edition, an annotated translation and a photographic reproduction of a manuscript copy of a rare chronicle of the Gur-rigs mDo-chen tradition written by Brag-dkar rta-so sPrul-sku Chos-kyi dbang-phyug (1775–1837). The text provides us with an overview of the tradition’s development mainly through biographical accounts but also through prophecies, prayers and praises for individual masters. The study concludes with two appendices based on the mDo chen bka’ brgyud gser ’phreng, a lineage history composed in the 15th century, and the “records of teachings received” (thob yig) of three important members of the Gur family, thus allowing us to gain an insight into the transmissions of the mDo-chen bKa’-brgyud-pa school and the interactions of its representatives with other important Buddhist teachers up to the 18th century. The present work is a further outcome of the author’s investigations into the cultural and religious traditions of south-western Tibet and the neighbouring Himalayan valleys
A Novel Benzoxazole-Containing Poly(N-isopropylacrylamide) Copolymer as a Multifunctional Sensing Material
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