PTEN regulates normal signaling through the B cell receptor (BCR). In systemic lupus erythematosus (SLE), enhanced BCR signaling contributes to increased B cell activity, but the role of PTEN in human SLE has remained unclear. We performed fluorescence-activated cell sorting analysis in B cells from SLE patients and found that all SLE B cell subsets, except for memory B cells, showed decreased expression of PTEN compared with B cells from healthy controls. Moreover, the level of PTEN expression was inversely correlated with disease activity. We then explored the mechanisms governing PTEN regulation in SLE B cells. Notably, in normal but not SLE B cells, interleukin-21 (IL-21) induced PTEN expression and suppressed Akt phosphorylation induced by anti-immunoglobulin M and CD40L stimulation. However, this deficit was not primarily at the signaling or the transcriptional level, because IL-21-induced STAT3 (signal transducer and activator of transcription 3) phosphorylation was intact and IL-21 up-regulated PTEN mRNA in SLE B cells. Therefore, we examined the expression of candidate microRNAs (miRs) that could regulate PTEN: SLE B cells were found to express increased levels of miR-7, miR-21, and miR-22. These miRs down-regulated the expression of PTEN, and IL-21 stimulation increased the expression of miR-7 and miR-22 in both normal and SLE B cells. Indeed, a miR-7 antagomir corrected PTEN-related abnormalities in SLE B cells in a manner dependent on PTEN. Therefore, defective miR-7 regulation of PTEN contributes to B cell hyperresponsiveness in SLE and could be a new target of therapeutic intervention.
In this paper, the effect of the non-uniformity settlement of ground foundation on the upper frame structure is studied. It takes a four-story space frame structure with two spans as an example. The different pedestals are installed at the joint of column footing, which respectively form the fixed supported model and the elastic supported model. Basin shaped settlement is applied in each model. The result shows that the beams are principally suffered with the bending moment and the columns principally suffered with axial force, shear force and bending moment, and that the elastic support model has certain economy.
A series of pseudo-static tests were conducted with 4 coupling beams whose span-depth ratio 1.2. Common reinforced concrete and PVA fiber reinforced concrete were used for different specimens. In each of the specimens, there were longitudinal reinforcement, constructional reinforcement and stirrup, one of the specimens had crossed reinforcing bars. The failure mode of the coupling beams were studied, as well as hysteretic behavior. The test result indicated that using PVA fiber reinforced concrete could improve coupling beams carrying capacity, and could also reduce the amount of stirrup needed for seismic calculation; PVA members ductility was also improved.
Comparative analyses of twenty-eight finite element structures with filler walls were established to study dynamic characteristics of RC frame structures under seismic waves. The results of these analyses show that filler walls have little influence on vibration modes of the structure. But as a result of soft storey in the bottom of building caused by reduction of the filler walls, vibration modes have a great influence. As the stiffness of filler wall decrease, the stiffness of soft storey decrease shapely, vibration mode curve becomes much smoother. Considering the filler wall has influence on the vibration periods of framework, the reduction factor of 0.7 should be taken. The influence of filler wall to the value of lateral drift and storey displacement angle of frame can not be ignored. The main effect factors to the dynamic characteristics of framework are included quantity, location, material of the fill wall and the selection of seismic waves.
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