Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL).Bio-organic Synthesi

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones

© 2021 National Academy of Sciences. All rights reserved.The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL)

Light and electron microscopic findings in five cases of cryoglobulinemic glomerulonephritis

Renal tissue from five patients with cryoglobulinemia was studied by light and electron microscopy and immunofluorescence. None of the histologic features observed at the light microscopic level seems to be specific for cryoglobulinemia. Electron microscopic investigations have shown very large electron dense deposits in almost every examined lobule in all cases. The deposits displayed two main patterns; a homogeneous texture in two cases and tubular or annular structures in three cases. The patients with typically structured deposits had IgG-IgM cryoglobulinemia (2 cases) or monoclonal IgM cryoglobulinemia (1 case). The presence of IgM in cryoglobulinemia may be the cause of the peculiar structure of the deposits

Triangulação entre métodos na administração: gerando conversações paradigmáticas ou meras validações "convergentes"?

O objetivo deste artigo é buscar responder à seguinte questão: a triangulação como método tem sido utilizada nas pesquisas em administração de uma perspectiva multiparadigmática, gerando conversações entre paradigmas? Ou tem sido utilizada simplesmente no intuito de se realizar uma validação "convergente" entre os métodos na pesquisa? Para responder à questão, utilizou-se o banco de dados referente a 174 artigos que utilizaram a triangulação em três anais do EnAnpad. Esses artigos foram analisados qualitativamente para verificar de que forma a triangulação foi conduzida, a fim de investigar se a combinação se ateve apenas no nível do método, ou se atingiu o âmbito paradigmático. O posicionamento adotado pelos pesquisadores neste estudo é o de defender a importância da conversação paradigmática para lidar com os fenômenos sociais característicos das pesquisas em administração. Os resultados demonstraram que a combinação de métodos tem sido adotada principalmente no intuito de validação convergente, não implicando necessariamente conversações efetivas entre diferentes visões de mundo e de conhecimento científico. O que se observa é sua aplicação principalmente em estudos nos quais predomina, em termos epistemológicos, uma visão positivista e, em termos metodológicos, uma postura nomotética

Dietary lipids modify the cytokine response to bacteria lipopolysaccharide in mice

To investigate the effect of dietary lipids with different fatty acid compositions upon the in vivo cytokine response to bacterial lipopolysaccharide (LPS), mice were fed for 5 weeks on a low-fat diet or on one of four high-fat diets that contained 20%, by weight, of coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO). The mice were injected intraperitoneally with a non-lethal dose of Escherichia coli LPS (100 ?g/20 g body weight) and killed 90 or 180 min later. Plasma tumour necrosis factor-? (TNF-?), interleukin (IL)-1?, IL-6 and IL-10 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Plasma TNF-? and IL-10 concentrations were higher 90 min postinjection than after 180 min, whereas plasma IL-1? and IL-6 concentrations were higher 180 min postinjection than after 90 min. Peak plasma TNF-?, IL-1? and IL-6 concentrations were lower in the CO- and FO-fed mice than in those fed the SO diet. Peak plasma IL-10 concentrations were higher in CO-fed mice than in those fed some of the other diets. These observations suggest that, relative to the n-6 polyunsaturated fatty acid-rich SO diet, CO and FO diminish production of proinflammatory cytokines in vivo. This indicates that these fatty acids might be useful therapies in acute and chronic inflammatory diseases. The enhanced production of IL-10 following CO feeding appears to be an additional antiinflammatory effect of this oil, which could give added benefit in various clinical conditions.<br/