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41.
T Rispens J Meesters TH den Bleker P Ooijevaar-De Heer J Schuurman PW Parren A Labrijn RC Aalberse 《Molecular immunology》2013,53(1-2):35-42
Human IgG4 antibodies are remarkable not only because they can dynamically exchange half-molecules (Fab-arm exchange) but also for their ability to interact with the Fc part of IgG4 and other IgG subclasses. This rheumatoid factor-like binding of IgG4 does not appear to take place spontaneously, because it is only observed to solid-phase or antigen-bound IgG. We hypothesized that Fc-Fc interactions might involve (partial) dissociation of heavy chains. We investigated the molecular basis of these Fc-Fc interactions, and found that the structural features important for the exchange reaction also control the Fc binding activity. In particular, if arginine-409 in the CH(3)-CH(3) interface in IgG4 is mutated to lysine (the equivalent in IgG1), Fc-Fc interactions are formed 3 orders of magnitude less efficiently compared to the wild-type. This mutation was previously found to increase the CH(3)-CH(3) interaction strength in IgG4. Furthermore, of the two hinge isomers of IgG4, the intra-chain (non-covalently linked) form was found to form Fc-Fc interactions, but not the inter-chain form. Together, these results demonstrate that Fc-Fc interactions of IgG4 involve (partial or complete) dissociation of heavy chains. The promiscuity to other IgG subclasses suggests that IgG4 might act as scavenger to IgG molecules with impaired structural integrity. 相似文献
43.
Darab Ghadimi Michael de Vrese Michael Ebsen Christoph Röcken Sven Olaf Frahm Janine Zahlten Regina Fölster-Holst Knut J. Heller Wilhelm Bockelmann 《Immunobiology》2021,226(1):152028
Background and AimsPglyrp3 is a bactericidal innate immunity protein known to sustain the habitual gut microbiome and protect against experimental colitis. Intestinal inflammation and metaflammation are commonly associated with a marked reduction of commensal bifidobacteria. Whether Pglyrp3 and bifidobacteria interact synergistically or additively to alleviate metaflammation is unknown. We investigated the extent to which Pglyrp3 and bifidobacteria regulate metaflammation and gut bacterial dysbiosis in DSS-induced mouse models of intestinal inflammation.Material & Methods8–10 weeks old male mice were used. In both WT and Pglyrp3 ?/? experiments, the mice were randomly divided into three groups of 16 mice per group: (1) a control group receiving sterile tap water, (2) an experimental group receiving sterile tap water supplemented with only 5% DSS, and (3) an experimental group receiving sterile tap water supplemented with 5% DSS and 1 × 109 CFU/ml of Bifidobacterium adolescentis (B.a.) for 7 days. Wild-type (WT) littermates of the respective gene (i.e. Pglyrp3) were used as controls throughout the study. Clinical signs of general health and inflammation were monitored daily. Faecal pellet samples were analysed by qRT-PCR for microbial composition. Histology of relevant organs was carried out on day 8. Metabolic parameters and liver inflammation were determined in serum samples.ResultsIntestinal inflammation in mice of group 2 were significantly increased compared to those of control group 1. There was a significant difference in mean scores for inflammation severity between DSS-treated WT and DSS-treated Pglyrp3 ?/? mice. Buildup of key serum metabolic markers (cholesterol, triglyceride and glucose) was set off by colonic inflammation. qRT-PCR quantification showed that DSS significantly decreased the Clostridium coccoides and Bifidobacterium cell counts while increasing those of Bacteroides group in both WT and Pglyrp3 ?/? mice. These manifestations of DSS-induced dysbiosis were significantly attenuated by feeding B.a. Both the local and systemic ill-being of the mice alleviated when they received B.a.DiscussionThis study shows that Pglyrp3 facilitates recognition of bifidobacterial cell wall-derived peptidoglycan, thus leading additively to a reduction of metaflammation through an increase in the number of bifidobacteria, which were able to mitigate intestinal immunopathology in the context of Pglyrp3 blockade. 相似文献
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Feld Katharina Feld Dustin Karger Bernd Helmus Janine Schwimmer-Okike Nneka Pfeiffer Heidi Banaschak Sibylle Wittschieber Daniel 《International journal of legal medicine》2021,135(1):235-244
International Journal of Legal Medicine - The shaken baby syndrome (SBS) is a common variant of abusive head trauma (AHT) in infants and toddlers. Data on the legal outcome of such cases are still... 相似文献
46.
da Silva Barros Caio Csar de Souto Medeiros Maurlia Raquel de Azevedo Roberto Almeida da Costa Miguel Mrcia Cristina dos Santos Jean Nunes da Silveira ricka Janine Dantas 《Oral and maxillofacial surgery》2021,25(4):575-579
Oral and Maxillofacial Surgery - Peripheral dentinogenic ghost cell tumor (DGCT) is a rare and non-aggressive benign odontogenic tumor. They usually affect the elderly and are predominantly located... 相似文献
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Kasey G. Creswell Aidan G. C. Wright Wendy M. Troxel Robert E. Ferrell Janine D. Flory Stephen B. Manuck 《Social cognitive and affective neuroscience》2015,10(6):869-876
Humans have a fundamental need for strong interpersonal bonds, yet individuals differ appreciably in their degree of social integration. That these differences are also substantially heritable has spurred interest in biological mechanisms underlying the quality and quantity of individuals’ social relationships. We propose that polymorphic variation in the oxytocin receptor gene (OXTR) associates with complex social behaviors and social network composition through intermediate effects on negative affectivity and the psychological processing of socially relevant information. We tested a hypothesized social cascade from the molecular level (OXTR variation) to the social environment, through negative affectivity and inhibited sociality, in a sample of 1295 men and women of European American (N = 1081) and African American (N = 214) ancestry. Compared to European Americans having any T allele of rs1042778, individuals homozygous for the alternate G allele reported significantly lower levels of negative affectivity and inhibited sociality, which in turn predicted significantly higher levels of social support and a larger/more diverse social network. Moreover, the effect of rs1042778 variation on social support was fully accounted for by associated differences in negative affectivity and inhibited sociality. Results replicated in the African American sample. Findings suggest that OXTR variation modulates levels of social support via proximal impacts on individual temperament. 相似文献