Background: IgA1-producing cells of IgA nephropathy patients secrete IgA1 with galactose-deficient O-glycans; these IgA1 molecules form nephritogenic immune complexes.Results: Cytokines IL-6 and IL-4 accentuate IgA1 galactose deficiency via modulation of key glycosyltransferases.Conclusion: Some cytokines alter IgA1 O-glycosylation and increase production of nephritogenic IgA1 glycoforms.Significance: These data provide a mechanism explaining increased immune-complex formation in IgA nephropathy patients.

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Background. Patients with IgA nephropathy (IgAN) have an increased amount of abnormally O-glycosylated IgA1 in circulation, in glomerular deposits and produced by tissue cells in vitro. Although increased production of Th2 cytokines by peripheral blood lymphocytes and a functional abnormality of core 1 β1,3-galactosyltransferase (C1β3Gal-T) have been proposed as mechanisms underlying pathogenesis of IgAN, they are still obscure and are not connected.Methods. To clarify the effect of T-cell cytokines, we analysed the mRNA levels of C1β3Gal-T and its molecular chaperone Cosmc, C1β3Gal-T activity and subsequent O-glycosylation of IgA1 in a human B-cell line stimulated with these cytokines. The surface IgA1-positive human B-cell line was cultured with recombinant human IFN-γ, IL-2, IL-4 or IL-5. The production and glycosylation of IgA1 were determined by sandwich ELISA and enzyme-linked lectin binding assay, respectively. The mRNA levels of C1β3Gal-T and Cosmc were quantitatively measured by real-time PCR. C1β3Gal-T activity was analysed using high-performance liquid chromatography.Results. IgA1 production by IL-4-stimulated cells was significantly higher than controls or after IFN-γ or IL-5. The terminal glycosylation of secreted IgA1 was altered in response to IL-4. IL-4 stimulation significantly decreased the mRNA levels of both C1β3Gal-T and Cosmc and of C1β3Gal-T activity. IL-4 stimulation was clearly blocked by recombinant human IL-4 soluble receptor.Conclusions. It appears that Th2 cytokine IL-4 may play a key role in controlling glycosylation of the IgA1 hinge region.

IntroductionIgA nephropathy is a chronic renal disease characterized by mesangial immunodeposits that contain autoantigen, which is aberrantly glycosylated IgA1 with some hinge-region O-glycans deficient in galactose. Macroscopic hematuria during an upper respiratory tract infection is common among patients with IgA nephropathy, which suggests a connection between inflammation and disease activity. Interleukin-6 (IL-6) is an inflammatory cytokine involved in IgA immune response. We previously showed that IL-6 selectively increases production of galactose-deficient IgA1 in IgA1-secreting cells from patients with IgA nephropathy.MethodsWe characterized IL-6 signaling pathways involved in the overproduction of galactose-deficient IgA1. To understand molecular mechanisms, IL-6 signaling was analyzed by kinomic activity profiling and Western blotting, followed by confirmation assays using siRNA knock-down and small-molecule inhibitors.ResultsSTAT3 was differentially activated by IL-6 in IgA1-secreting cells from patients with IgA nephropathy compared with those from healthy control subjects. Specifically, IL-6 induced enhanced and prolonged phosphorylation of STAT3 in the cells from patients with IgA nephropathy, which resulted in overproduction of galactose-deficient IgA1. This IL-6−mediated overproduction of galactose-deficient IgA1 could be blocked by small molecule inhibitors of JAK/STAT signaling.DiscussionOur results revealed that IL-6−induced aberrant activation of STAT3-mediated overproduction of galactose-deficient IgA1. STAT3 signaling pathway may thus represent a new target for disease-specific therapy of IgA nephropathy.

The current study proposes a novel approach that improves the conventional performance analysis in table tennis by introducing the concept of frequency, or the number of shots, of each shot number. The improvements over the conventional method are as follows: better accuracy of the evaluation of skills and tactics of players, additional insights into scoring and returning skills and ease of understanding the results with a single criterion. The performance analysis of matches played at the 2012 Summer Olympics in London was conducted using the proposed method. The results showed some effects of the shot number and gender differences in table tennis. Furthermore, comparisons were made between Chinese players and players from other countries, what threw light on the skills and tactics of the Chinese players. The present findings demonstrate that the proposed method provides useful information and has some advantages over the conventional method.

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The official material used in table tennis balls was changed from celluloid to plastic, a material free of celluloid, in 2014. The purpose of this study was to understand the differences and similarities in the two types of ball materials by comparing their behavior upon collision with a table. The behavior of the balls before and after collision with a table, at various initial speeds ranging from 15 to 115 km/h, was captured using high-speed cameras. Velocities and spin rates before collision and velocities after collision were computed to calculate the coefficients of restitution and friction. Based on the computed variables, the post-collision trajectories of both balls were calculated by integrating the equation of motion of the ball for simulated service, smash and drive conditions with respect to time. The coefficients of restitution were higher for the plastic balls than the celluloid ones when the initial vertical velocities were higher. The coefficients of friction were higher for plastic balls when the initial horizontal contact point velocities were slower. Because of the differences in the material characteristics, the plastic ball trajectories of services with backspin and drives with great topspin were expected to be different from those of celluloid balls. Since the extent of differences between the two ball types varied depending on the initial conditions, testing at various initial conditions was suggested for comparing and understanding the characteristics of the balls.

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