3,747 research outputs found
APOPTOTIC SIGNALING THROUGH CD95 (FAS/APO-1) ACTIVATES AN ACIDIC SPHINGOMYELINASE
No full textAbstract: Intracellular pathways leading from membrane receptor engagement to apoptotic cell death are still poorly characterized. We investigated the intracellular signaling generated after cross-linking of CD95 (Fas/Apo-1 antigen), a broadly expressed cell surface receptor whose engagement results in triggering of cellular apoptotic programs. DX2, a new functional anti-CD95 monoclonal antibody was produced by immunizing mice with human CD95-transfected L cells. Crosslinking of CD95 with DX2 resulted in the activation of a sphingomyelinase (SMase) in promyelocytic U937 cells, as well as in other human tumor cell lines and in CD95-transfected murine cells, as demonstrated by induction of in vivo sphingomyelin (SM) hydrolysis and generation of ceramide. Direct in vitro measurement of enzymatic activity within CD95-stimulated U937 cell extracts, using labeled SM vesicles as substrates, showed strong SMase activity, which required pH 5.0 for optimal substrate hydrolysis. Finally, all CD95-sensitive cell lines tested could be induced to undergo apoptosis after exposure to cell-permeant C-2-ceramide. These data indicate that CD95 cross-linking induces SM breakdown and ceramide production through an acidic SMase, thus providing the first information regarding early signal generation from CD95, and may be relevant in defining the biochemical nature of intracellular messengers leading to apoptotic cell death
Natalia LL - artystka neoawangardowa
No full textThe paper shows Natalia Lach-Lachowicz (Natalia LL) as a neo avant-garde artist whose works in a specific maximalistic way are very close to the main currents of avant-garde trends: new mediality (photography), minimalism, conceptualism, performance, bodyart, pop-art, and feminist art. The author of the article concentrates mainly on the mutual influences of conceptualism, consumptionism, and feminism in Natalia LL’s works and pays attention to the emancipatory potential of her works of the seventies and the eighties
KLRK1 (killer cell lectin-like receptor subfamily K, member 1)
No full textReview on KLRK1 (killer cell lectin-like receptor subfamily K, member 1), with data on DNA, on the protein encoded, and where the gene is implicated
KLRK1 (killer cell lectin-like receptor subfamily K, member 1)
No full textReview on KLRK1 (killer cell lectin-like receptor subfamily K, member 1), with data on DNA, on the protein encoded, and where the gene is implicated
Energy flux in isotropic turbulence under large variations of external forcing
No full textWe investigate the response of energy flux in isotropic turbulence to step-function like perturbation in external forcing at large length scales. From both physical experiments and direct numerical simulations, we measured the evolution of the Eulerian velocity structure functions, such as , , before and after the perturbation in forcing. In both cases, we observed the cascade of the energy excess at large scales cascade through scales to the dissipative range, which can be used to study the dynamics of the cascade, and in particular, to estimate the relevant time scales
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Some rhetorical strategies in later nineteenth-century laboring-class poetry
No full textStructural and functional analysis of the pro-domain of human cathelicidin, LL-37
No full textCathelicidins form a family of small host defense peptides distinct from another class of cationic antimicrobial peptides, the defensins. They are expressed as large precursor molecules with a highly conserved pro-domain known as the cathelin-like domain (CLD). CLDs have high degrees of sequence homology to cathelin, a protein isolated from pig leukocytes and belonging to the cystatin family of cysteine protease inhibitors. In this report, we describe for the first time the X-ray crystal structure of the human CLD (hCLD) of the sole human cathelicidin, LL-37. The structure of hCLD, determined at 1.93 Å resolution, shows the cystatin-like fold and is highly similar to the structure of the CLD of the pig cathelicidin, protegrin-3. We assayed the in vitro antibacterial activities of hCLD, LL-37 and the precursor form, pro-cathelicidin (also known as hCAP18), and we found that the unprocessed protein inhibited the growth of Gramnegative bacteria with efficiencies comparable to the mature peptide, LL-37. In addition, the antibacterial activity of LL-37 was not inhibited by hCLD intermolecularly, since exogenously added hCLD had no effect on the bactericidal activity of the mature peptide. hCLD itself lacked antimicrobial function and did not inhibit the cysteine protease, cathepsin L. Our results contrast with previous reports of hCLD activity. A comparative structural analysis between hCLD and the cysteine protease inhibitor stefin A showed why hCLD is unable to function as an inhibitor of cysteine proteases. In this respect, the cystatin scaffold represents an ancestral structural platform from which proteins evolved divergently, with some losing inhibitory functions
The modulatory effect of TLR2 on LL-37-induced human mast cells activation
No full textThe sole and endogenous anti-microbial peptide LL-37 is a significant effector molecule in the innate host defense system. Apart from its broadly direct anti-microbial activity, the peptide also activates mast cell in respect of allergic diseases and inflammation. On the other hand, mast cell can be activated by Toll-like receptors (TLRs) which are at the center of innate immunity. It was the aim of the study to illustrate the modulatory effect of TLR2 ligands peptidoglycan (PGN) and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4) on LL-37 induced LAD2 cells (a human mast cell line) activation. LL-37 induced LAD2 cells degranulation and the release of IL-8. TLR2 ligands didn't induce LAD2 cells degranulation, but triggered the release of IL-8. Incubation with PGN or Pam3CSK4 significantly suppressed LL-37-induced degranulation through inhibition of calcium mobilization from LAD2 cells. Similarly, the release of IL-8 was inhibited when LAD2 cells were co-stimulated with TLR2 ligands and LL-37. Studies with inhibitors of key enzymes involved in mast cell signaling indicated that the release of IL-8 induced by TLR2 ligands and LL-37 involved the activation of the PI3K, ERK, JNK and calcineurin signaling pathways. In contrast, p38 activation down-regulated the release of IL-8 induced by TLR2 ligands and LL-37. Taken together, these observations suggest that activation of human mast cells by LL-37 could be modified by TLR2 ligands and the function of human mast cells could be switched from allergic reactions to innate immune response. (C) 2016 Elsevier Inc. All rights reserved.National Natural Science Foundation of China [81271755, 81371737]; Guangdong Natural Science Foundation [2014A030313708]; Shenzhen Research Grant [CXZZ20140416144209739, JCYJ20130329110752142, KQCX20120803145850990]SCI(E)[email protected]; [email protected]
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