Sehestedburris5055

Enteric pathogen-host interactions occur at multiple interfaces, including the intestinal epithelium and deeper organs of the immune system. Microbial ligands and activities are detected by host sensors that elicit a range of immune responses. Membrane-bound toll-like receptors and cytosolic inflammasome pathways are key signal transducers that trigger the production of pro-inflammatory molecules, such as cytokines and chemokines, and regulate cell death in response to infection. In recent years, the inflammasomes have emerged as a key frontier in the tussle between bacterial pathogens and the host. Inflammasomes are complexes that activate caspase-1 and are regulated by related caspases, such as caspase-11, -4, -5 and -8. Importantly, enteric bacterial pathogens can actively engage or evade inflammasome signalling systems. Extracellular, vacuolar and cytosolic bacteria have developed divergent strategies to subvert inflammasomes. While some pathogens take advantage of inflammasome activation (e.g. Listeria monocytogenes, Helicobacter pylori), others (e.g. E. coli, Salmonella, Shigella, Yersinia sp.) deploy a range of virulence factors, mainly type 3 secretion system effectors, that subvert or inhibit inflammasomes. In this review we focus on inflammasome pathways and their immune functions, and discuss how enteric bacterial pathogens interact with them. These studies have not only shed light on inflammasome-mediated immunity, but also the exciting area of mammalian cytosolic immune surveillance. © 2020 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.BACKGROUND Working adults spend most of their leisure time watching TV. In this paper, we seek to clarify how experiences of psychological need fulfillment and well-being differ when watching TV and engaging in other leisure activities. We suggest that, compared to other leisure activities, watching TV is equally conducive to fulfilling needs for (a) relaxation and detachment from stress and (b) autonomy, but is less conducive to fulfilling needs for (c) meaning, (d) mastery, and (e) affiliation and thus also less conducive to promoting subjective wellbeing. METHODS We tested our predictions in two day reconstruction studies and a daily diary study. RESULTS People experienced similar levels of detachment and relaxation when watching TV and engaging in other types of leisure. However, they experienced less fulfillment of other needs, and lower levels of satisfaction and some aspects of affective well-being, when watching TV compared to other activities. Further, unlike time spent watching TV, daily time spent in physical activities was positively associated with positive activated affect. CONCLUSIONS Given that watching TV tends to be associated with lower levels of need fulfillment and well-being than other leisure activities, leisure choices may be an important target for improving employee well-being. © 2020 The International Association of Applied Psychology.HLA-DRB3*0339 differs from HLA-DRB3*030101 by a single nucleotide substitution in codon 22 (Glutamic acid to Lysine). © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.HLA-B*07387 differs from HLA-B*07050101 by a single nucleotide substitution in codon 91 (Glycine to Tryptophan). JM-8 © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Exhaustion of T cells limits their ability to clear chronic infections or eradicate tumors. Here, in the context of transplantation, we investigated whether T-cell exhaustion occurs and has a role in determining transplant outcome. A peptide/MHC tetramer-based approach was used to track exhausted CD8+ T cells in a male-to-female skin transplantation model. Transplantation of large-size whole-tail skins, but not small-size tail skins (0.8 cm x 0.8 cm), led to exhaustion of anti-male tetramer+ CD8+ T cells and subsequently the acceptance of skin grafts. To study CD4+ T-cell exhaustion, we used the TCR-transgenic B6 TEa cells that recognize a major transplant antigen I-Eα from Balb/c mice. TEa cells were adoptively transferred either into B6 recipients that received Balb/c donor skins, or into CB6F1 mice that contained an excessive amount of I-Eα antigen. Adoptively transferred TEa cells in skin-graft recipients were not exhausted. By contrast, virtually all adoptively transferred TEa cells were exhausted in CB6F1 mice. Those exhausted TEa cells lost ability to reject Balb/c skins upon further transfer into lymphopenic B6.Rag1-/- mice. Hence, T-cell exhaustion develops in the presence of abundant antigen and promotes transplant acceptance. These findings are essential for better understanding the nature of transplant tolerance. This article is protected by copyright. All rights reserved.Angelica sinensis (AS; Dang Gui), a traditional Chinese herb, has for centuries been used for the treatment of bone diseases, including osteoporosis and osteonecrosis. However, the effective ingredient and underlying mechanisms remain elusive. Here, we identified guaiacol as the active component of AS by two-dimensional cell membrane chromatography/C18 column/time-of-flight mass spectrometry (2D CMC/C18 column/TOFMS). Guaiacol suppressed osteoclastogenesis and osteoclast function in bone marrow monocytes (BMMCs) and RAW264.7 cells in vitro in a dose-dependent manner. Co-immunoprecipitation indicated that guaiacol blocked RANK-TRAF6 association and RANK-C-Src association. Moreover, guaiacol prevented phosphorylation of p65, p50, IκB (NF-κB pathway), ERK, JNK, c-fos, p38 (MAPK pathway) and Akt (AKT pathway), and reduced the expression levels of Cathepsin K, CTR, MMP-9 and TRAP. Guaiacol also suppressed the expression of nuclear factor of activated T-cells cytoplasmic 1(NFATc1) and the RANKL-induced Ca2+ oscillation. In vivo, it ameliorated ovariectomy-induced bone loss by suppressing excessive osteoclastogenesis. Taken together, our findings suggest that guaiacol inhibits RANKL-induced osteoclastogenesis by blocking the interactions of RANK with TRAF6 and C-Src, and by suppressing the NF-κB, MAPK and AKT signalling pathways. Therefore, this compound shows therapeutic potential for osteoclastogenesis-related bone diseases, including postmenopausal osteoporosis. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.