Most members of the tumor-necrosis factor superfamily have been reported to mediate reverse signaling in T cells, macrophages, and/or dendritic cells. BAFF has been reported to have important functions in B-cell survival through forward signaling, but the presence of reverse signaling has not been explored. To investigate the possibility of BAFF-mediated reverse signaling, the expression patterns and functions of BAFF were analyzed in monocytic cell lines including the human macrophage-like cell line, THP-1. The expression of BAFF and its receptors was detected in monocytic cell lines, either before or after activation. The stimulation of BAFF induced the expression of matrix metalloproteinase (MMP)-9, interleukin -8, and transforming growth factor-b-induced gene product (big-h3) and the upregulation of intercellular adhesion molecule-1 in THP-1 cells. The activation of mitogen-activated protein kinase extracellular signal-regulated kinase1/2 and nuclear factor-jB was required for these responses. In addition to these stimulatory effects, BAFF-mediated signaling inhibited processes involving cytoskeletal movement such as phagocytosis and transmigration through blocking the activation of phosphatidylinositol 3-kinase/AKT and Rac-1. Furthermore, murine primary macrophage culture such as peritoneal macrophages expressed BAFF and stimulation of it induced the expression of MMP-9. These observations show that the reverse signaling initiated from BAFF induces the expression of inflammatory mediators while suppressing the cytoskeletal movements associated with phagocytosis and transmigration.
We have achieved very efficient high-harmonic generation in a two-color laser field using a long gas jet of He. With the optimization of laser parameters and target conditions, strong harmonics were produced at 2͑2n +1͒th orders in an orthogonally polarized two-color field. The strongest harmonic at the 38th order ͑21.6 nm͒ reached an energy of 0.6 J with a 6 mm gas jet, giving a conversion efficiency as high as 2 ϫ 10 −4 .
The polarization of high-harmonics from aligned N(2) molecules was measured by observing the visibility of spatial interference between two high-harmonics generated separately. The minimum visibility was observed at an angle of 60 degrees between the polarization of the harmonic generation laser field and the molecular orientation. In this case, the angular shift of harmonic polarization is 15 degrees from the molecular orientation. Our measurement of the visibility variation matches the theoretical prediction based on the harmonic field calculation for aligned N(2) molecules.
Characteristics of high harmonics generated from aligned N 2 molecules were investigated by rotating the molecules with respect to the polarization of harmonic generation pulses. The high harmonics in the plateau and the cutoff regions showed distinctive behaviour, which could be explained from the calculation of transition dipole moments between recolliding electron and multi-orbitals of N 2 molecule consisting of the highest occupied molecular orbital (HOMO) and the lower-lying orbital below HOMO (HOMO-1). It was also observed that the angular dependence of harmonics from aligned molecules with respect to the polarization of harmonic generation pulses was closely related to the geometrical structure of molecular orbitals, and that the harmonic in the transition region from the plateau to the cutoff was influenced comparably by both HOMO and HOMO-1. These results confirmed that high harmonic generation and molecular structure were closely linked.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and multiple inflammatory cytokines are involved in RA pathogenesis. Interleukin (IL)-18, in particular, has a significant positive correlation with RA. In this study, we investigated the effect of erythroid differentiation regulator 1 (Erdr1), which is negatively regulated by IL-18, in an animal model of inflammatory arthritis, collagen-induced arthritis (CIA) in DBA/1J mice. Treatment of mice with recombinant (r)Erdr1 significantly suppressed the severity of arthritis, histologic features of arthritic tissue, and serum levels of anti-collagen autoantibodies (IgG, IgG1, IgG2a and IgM) in CIA. In addition, IL-18 expression was reduced in the affected synovium of rErdr1-treated mice. Interestingly, Erdr1 treatment suppressed migration in contrast to the pro-migratory effect of IL-18, indicating the therapeutic effects of Erdr1 on CIA through inhibiting synovial fibroblast migration. In addition, Erdr1 inhibited activation of ERK1/2, a key signaling pathway in migration of various cell types. Taken together, these data show that rErdr1 exerts therapeutic effects on RA by inhibiting synovial fibroblast migration, suggesting that rErdr1 treatment might be an effective therapeutic approach for RA.
We have demonstrated ultrafast direct soft x-ray microscopy imaging. Microscopy images were acquired using an objective zone plate and a single strong high harmonic burst generated from He in a two-color laser field. This zone-plate-based microscopy system delivered real-space images directly without any data processing. The spatial resolution of the microscope was estimated to be about 140 nm from the image of nanoscale grating patterns.
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