Spin-nematic interaction in the multiferroic compound Ba2CoGe2O7.

We demonstrate the existence of the spin-nematic interactions in an easy-plane type antiferromagnet Ba2CoGe2O7 by exploring the magnetic anisotropy and spin dynamics. The combination of neutron scattering and magnetic susceptibility measurements reveals that the origin of the in-plane anisotropy is an antiferro-type interaction of the spin-nematic operator. The relation between the nematic operator and the electric polarization in the ligand symmetry of this compound is presented. The introduction of the spin-nematic interaction is useful to understand the physics of spin and electric dipole in multiferroic compounds.

Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules.

To maintain various T cell responses and immune equilibrium, activation signals triggered by T cell antigen receptor (TCR) must be regulated by inhibitory signals. Gab2, an adaptor protein of the insulin receptor substrate-1 family, has been shown to be involved in the downstream signaling from cytokine receptors. We investigated the functional role of Gab2 in TCR-mediated signal transduction. Gab2 was phosphorylated by ZAP-70 and co-precipitated with phosphoproteins, such as ZAP-70, LAT, and CD3zeta, upon TCR stimulation. Overexpression of Gab2 in Jurkat cells or antigen-specific T cell hybridomas resulted in the inhibition of NF-AT activation, interleukin-2 production, and tyrosine phosphorylation. The structure-function relationship of Gab2 was analyzed by mutants of Gab2. The Gab2 mutants lacking SHP-2-binding sites mostly abrogated the inhibitory activity of Gab2, but its inhibitory function was restored by fusing to active SHP-2 as a chimeric protein. A mutant with defective phosphatidylinositol 3-kinase binding capacity also impaired the inhibitory activity, and the pleckstrin homology domain-deletion mutant revealed a crucial function of the pleckstrin homology domain for localization to the plasma membrane. These results suggest that Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transduction by mediating the recruitment of inhibitory molecules to the TCR signaling complex.

Strong coupling between local moments and superconducting 'heavy' electrons in UPd2Al3.

The electronic structure of heavy-fermion compounds arises from the interaction of nearly localized 4f- or 5f-shell electrons (with atomic magnetic moments) with the free-electron-like itinerant conduction-band electrons. In actinide or rare-earth heavy-fermion materials, this interaction yields itinerant electrons having an effective mass about 100 times (or more) the bare electron mass. Moreover, the itinerant electrons in UPd2Al3 are found to be superconducting well below the magnetic ordering temperature of this compound, whereas magnetism generally suppresses superconductivity in conventional metals. Here we report the detection of a dispersive excitation of the ordered f-electron moments, which shows a strong interaction with the heavy superconducting electrons. This 'magnetic exciton' is a localized excitation which moves through the lattice as a result of exchange forces between the magnetic moments. By combining this observation with previous tunnelling measurements on this material, we argue that these magnetic excitons may produce effective interactions between the itinerant electrons, and so be responsible for superconductivity in a manner analogous to the role played by phonons in conventional superconductors.

Negative regulation of expression and function of Fc gamma RIII by CD3 zeta in murine NK cells.

Fc gamma RIII is involved in Ab-dependent cell-mediated cytotoxicity (ADCC) and cytokine production by NK cells. Signaling and expression of Fc gamma RIII are dependent on FcR gamma. Although NK cells express not only FcR gamma but also CD3 zeta, the role of CD3 zeta in NK cell function remains unclear. Here, we found that the expression of Fc gamma RIII on NK cells from CD3 zeta-deficient mice is unexpectedly up-regulated compared with that on cells from normal mice. Furthermore, ADCC and IFN-gamma production upon Fc gamma RIII-cross-linking by NK cells from CD3 zeta-deficient mice were also up-regulated. Up-regulation of the surface expression of Fc gamma RIII on CD3 zeta-deficient NK cells is not mediated by transcriptional augmentation of either Fc gamma RIII or FcR gamma gene because there was no significant difference in the expression of mRNA for Fc gamma RIII and FcR gamma. Transfection of CD3 zeta into a cell line expressing Fc gamma RIII and FcR gamma induced a decrease in the cell surface expression of Fc gamma RIII. These findings reveal a negative regulatory role of CD3 zeta in Fc gamma RIII-mediated function of murine NK cells.

Activity of anthocyanins from fruit extract of Ribes nigrum L. against influenza A and B viruses.

Earlier, we have detected antiviral activity in an extract from Ribes nigrum L. fruits ("Kurokarin", name of the one species of black currant in Japanese) against influenza A and B viruses, and herpes simplex virus 1 (Knox et al., Food Processing 33, 21-23, 1998). In the present study, the antiviral activity of constituents of a Kurokarin extract and the mechanism of its antiviral action were examined. Kurokarin extracts were separated to fractions A to D by column chromatography. The major constituents of the fraction D were estimated as anthocyanins. The fraction D was further fractionated by thin-layer chromatography (TLC) to fractions A' to G'. The fraction E' consisted of 3-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranosyl-cyanidin and 3-O-beta-D-glucopyranosyl-cyanidin, and the fraction F' consisted of 3-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranosyl-delphinidin and 3-O-beta-D-glucopyranosyl-delphinidin, identified by high performance liquid chromatography (HPLC) with standards and by high resolution mass spectrometry. The fractions D' to G' showed potent antiviral activity against influenza viruses A and B. The additive antiviral effect of a combination of the fractions E' and F' was assessed. Anthocyanins in the fraction F' did not directly inactivate influenza viruses A and B, but they inhibited virus adsorption to cells and also virus release from infected cells.

Orbitally degenerate spin-1 model for insulating V2O3

Motivated by recent neutron, x-ray absorption, and resonant scattering experiments, we revisit the electronic structure of V2O3. We propose a model in which S = 1 V3+ ions are coupled in the vertical V-V pairs forming twofold orbitally degenerate configurations with S = 2. Ferro-orbital ordering of the V-V pairs gives a description which is consistent with all experiments in the antiferromagnetic insulating phase.

Role of transforming growth factor-beta pathway in the mechanism of wound healing by saponin from Ginseng Radix rubra.

1. The effects of saponin from Ginseng Radix rubra on extracellular matrix metabolism, the activation and synthesis of TGF-beta1, and the modification of TGF-beta receptor in fibroblasts were examined to elucidate the contribution of the TGF-beta pathway to the mechanism of wound healing by saponin. 2. Fibronectin synthesis was analysed by the immunoprecipitation method. Activation and synthesis of TGF-beta1 were measured by ELISA. The expressions of TGF-beta receptors in fibroblasts were examined at protein and mRNA levels by the cross-linking method and Northern blot analysis, respectively. 3. The fibronectin synthesis increased 2.3- and 3.9-fold at fibroblasts treated with 1 and 10 microg ml(-1) of saponin, respectively, compared with that in non-treated cells. Fibronectin synthesis stimulated with 10 microg ml(-1) of saponin was inhibited with 69% by 5 microg ml(-1) of an anti-TGF-beta1 antibody. mRNA of TGF-beta type I receptor increased 4.8- and 4.4-fold at fibroblasts treated with 1 and 10 microg ml(-1) of saponin, respectively, and that of TGF-beta type II receptor also increased 3.4- and 3.2-fold at fibroblasts treated with 1 and 10 microg ml(-1) of saponin, respectively. The significant increases of TGF-beta type I and II receptors and of fibronectin synthesis were observed at the same concentrations of saponin. TGF-beta content increased 1.74- and 1.87-fold at conditioned medium of fibroblasts treated with 100 and 250 microg ml(-1) of saponin, respectively, higher concentrations than those which accelerated fibronectin synthesis. Furthermore, the active TGF-beta content was below 10% of total TGF-beta at each concentration of saponin. 4. These results indicate that saponin stimulates fibronectin synthesis through the changes of TGF-beta receptor expressions in fibroblasts.

Role of latent TGF-beta 1 binding protein in vascular remodeling.

Transforming growth factor-beta (TGF-beta) is secreted as a latent, high molecular weight complex, which is composed of TGF-beta, a latency associated peptide (LAP) and a latent TGF-beta binding protein (LTBP). In this study, we report on the role of LTBP in vascular remodeling. 0.01-5 ng/ml of LTBP stimulated the migration activities of cultured rat arterial smooth muscle cells (SMC) about 4-7 fold compared with control in vitro. The maximal activity of SMC migration by LTBP was 75% of that by 10 ng/ml of PDGF-BB. A checker board analysis showed that the migration by LTBP was chemotactic, not chemokinetic. By cross-linking experiment, LTBP associated with 80-120 kd cell surface protein of SMC, suggesting that a part of LTBP can bind with SMC. Furthermore, LTBP was more strongly expressed in the intimal layer than in the medial layer of BCI artery. These results suggest that LTBP plays an important role in the initial stage of arterial intimal thickening through the acceleration of SMC migration from the medial to intimal layer and is one of the essential factors influencing vascular remodeling.

Transforming growth factor-beta receptor and fibronectin expressions in aortic smooth muscle cells in diabetic rats.

Smooth muscle cells in arteries of diabetic rats and rabbits have unique properties including the overexpression of platelet-derived growth factor (PDGF) beta-receptor compared with controls. Fibronectin, one of the increased components of extra-cellular matrices in diabetic arteries, plays an important role in the phenotypic change of smooth muscle cells from the contractile to the synthetic type with the expression of the PDGF beta-receptor. Moreover, fibronectin synthesis is regulated by transforming growth factor-beta (TGF-beta). In this study, we report on the expression of TGF-beta receptors in diabetic smooth muscle cells, by immunohistochemistry, cross-linking of 125I-TGF-beta 1 to cells and quantitative reverse transcription-polymerase chain reaction. We also report on the effects of TGF-beta 1 on fibronectin synthesis of diabetic smooth muscle cells by use of ELISA and immunoprecipitation, in order to clarify the role of TGF-beta-fibronectin pathway in forming characteristic changes of diabetic smooth muscle cells. Cultured aortic smooth muscle cells of diabetic rats expressed TGF-beta type II receptor about 8.7 times that of controls at the protein level and 5.7 times at the mRNA level, whereas the expression of the type I receptor did not differ between the two types of smooth muscle cells. These changes were accompanied by increased fibronectin synthesis in diabetic smooth muscle cells in response to TGF-beta 1. Furthermore, protein expression of fibronectin, and mRNA and protein of TGF-beta type II receptor were increased in the diabetic aorta compared with the control aorta in vivo, implying the importance of the TGF-beta-fibronectin pathway for the unique biology of smooth muscle cells in the diabetic artery.

Specific inhibition of vascular cell adhesion molecule-1 expression by type IV collagen in endothelial cells.

The effects of matrices on the expression of adhesion molecules were studied in cultured human umbilical cord vein endothelial cells(HUVEC). The expression of vascular cell adhesion molecule-1 (VCAM-1) but not of intercellular adhesion molecule-1 stimulated with various substances was remarkably low in HUVEC cultured on type IV collagen, the major component of the basement membrane, compared with that on type I collagen. This inhibition was observed not only at the protein level but also at the mRNA level. These data suggested that VCAM-1 expression in endothelial cells is strictly regulated by the underlying basement membrane.

Mechanism of angiogenic effects of saponin from ginseng Radix rubra in human umbilical vein endothelial cells.

1. The effects of saponin from Ginseng Radix rubra on angiogenesis (tube formation) and its key steps (protease secretion, proliferation and migration) in human umbilical vein endothelial cells (HUVEC) were examined to elucidate the mechanism of the tissue repairing effects of Ginseng Radix rubra. The effect on a wound healing model was also studied. 2. Tube formation was measured by an in vitro system. The activity and immunoreactivity of tissue-type plasminogen activator (tPA) as a protease for angiogenesis and the immunoreactivity of its inhibitor, plasminogen activator inhibitor-1 (PAI-1), were measured in conditioned medium of HUVEC stimulated for 24 h with saponin. Cell proliferation was measured by counting the cell numbers at 2-7 days after seeding. Migration was measured by Boyden's chamber method. The effect on wound healing was studied in the skin of diabetic rats. 3. Saponin at 10-100 micrograms ml-1 significantly stimulated tube formation by HUVEC in a dose-dependent manner. Saponin in a similar concentration-range increased the secretion of tPA from HUVEC as estimated by immunoreactivity and enzyme activity. On the other hand, PAI-1 immunoreactivity was slightly increased at 10 micrograms ml-1 of saponin, but then was significantly decreased at 50 and 100 micrograms ml-1. Cell proliferation was only slightly enhanced by 1-100 micrograms ml-1 of saponin, but migration was significantly enhanced by 10-100 micrograms ml-1 in a dose-dependent manner. Moreover, saponin stimulated wound healing with enhanced angiogenesis in vivo. 4. These results indicate that saponin stimulates tube formation mainly by modifying the balance of protease/protease inhibitor secretion from HUVEC and enhancing the migration of HUVEC, and that it is effective in vivo.

Platelet-derived growth factor is a potent stimulator of expression of intercellular adhesion molecule-1 in human arterial smooth muscle cells.

The effects of platelet-derived growth factor (PDGF) on the expression of intercellular adhesion molecule-1 (ICAM-1) as an indicator of cell activation were investigated in cultured human arterial smooth muscle cells (SMC). PDGF-BB and -AB but not -AA at 2-10 ng/ml stimulated ICAM-1 expression at a subconfluent but not a confluent state in a dose-dependent manner. ICAM-1 expression was induced at 2h, reached a plateau at 4h, and continued for at least 24h after stimulation with PDGF. The maximal stimulatory effect of PDGF-BB at 10 ng/ml was comparable to that by optimal concentrations of other cytokines and inflammatory agents. These data suggested that PDGF was a potent stimulator of ICAM-1.