Study information about proportion of Tregs in RA patients or control subjects

<p>Study information about proportion of Tregs in RA patients or control subjects</p

Flow diagram of study selection.

<p>Flow diagram of study selection.</p

Forest plots of the proportion of Tregs in peripheral blood of different diseases activity and synovial fluid.

<p>(A) Standardized mean difference (the proportion of Tregs among CD4⁺ T cells in PB of active RA patients minus that of remission RA patients) was estimated by meta-analysis. Tregs, which were defined by “CD25 and FOXP3 double positive”, were selected for meta-analysis. (B) Standardized mean difference (the proportion of Tregs among CD4⁺ T cells in SF of RA patients minus that in PB of control subjects) was estimated by meta-analysis. Tregs, which were defined by “CD25 and FOXP3 double positive”, were selected for meta-analysis.</p

Forest plot for sub-group meta-analysis of the proportion of Tregs defined by CD25 and FOXP3 double positive.

<p>Standardized mean difference (the proportion of Tregs among CD4⁺ T cells in PB of RA patients minus that of control subjects) was estimated by meta-analysis. Tregs, which were defined by “CD25 and FOXP3 double positive”, were selected for sub-analysis.</p

Additional file 1 of Automatic evaluation of atlantoaxial subluxation in rheumatoid arthritis by a deep learning model

Additional file 1: Sup Fig. 1. Distribution of ADI and SAC. a Atlantodental interval (ADI, mm). b Space available for the spinal cord (SAC, mm)

Structure of the Plexin Ectodomain Bound by Semaphorin-Mimicking Antibodies

<div><p>Semaphorin family proteins act on cells to mediate both repulsive and attractive guidance via binding to plexin family receptors, thereby playing fundamental roles in the morphogenesis and homeostasis of various tissues. Although semaphorin-plexin signaling is implicated in various diseases and is thus a target of intensive research, our mechanistic understanding of how semaphorins activate plexins on the cell surface is limited. Here, we describe unique anti-plexin-A1 antibodies that can induce a collapsed morphology in mouse dendritic cells as efficiently as the semaphorin 3A (Sema3A) ligand. Precise epitope analysis indicates that these “semaphorin-mimicking” antibodies dimerize cell-surface plexin-A1 by binding to the N-terminal sema domain of the plexin at sites away from the interface used by the Sema3A ligand. Structural analysis of plexin-A1 fragments using negative stain electron microscopy further revealed that this agonistic capacity is closely linked to the location and orientation of antibody binding. In addition, the full-length plexin-A1 ectodomain exhibited a highly curved “C” shape, reinforcing the very unusual dimeric receptor conformation of this protein at the cell surface when engaged with Sema3A or agonistic antibodies.</p></div

Anti-mouse plexin A1 antibodies.

<p>Anti-mouse plexin A1 antibodies.</p

Docking models of the Fab-PlxnA1 complex.

<p>(A-D) A representative 2D projection average was derived for each PlxnA1_1-6-Fab complex by the further refinement of the images shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156719#pone.0156719.g003" target="_blank">Fig 3</a>. Bar: 100 Å. (E-H) Cartoon representation of the modeled PlxnA1_1-6 protein (gray) upon simulated Fab binding. The viewing orientation for the complex models was arbitrarily chosen to maximize shape similarity with the EM images.</p

Visualization of the mouse PlxnA1_1-6-Fab complex using negative-stain EM.

<p>Purified PlxnA1_1-6 protein alone (A) or in complex with Fab fragments derived from PXB361b (B), PXB693 (C), and PXB727 (D) were separated by size exclusion chromatography on a Superdex 200 column. The upper subpanels show the overlaid chromatograms of PlxnA1_1-6 protein (blue line), PlxnA1_1-6 mixed with Fab (red line), and Fab alone (gray dotted line). SDS-PAGE gel profiles of the collected fractions (thick horizontal bars) are shown in the <i>insets</i>. The peak fraction (asterisk) was subjected to negative-stain EM and image analysis. The molecular size of the collected peak calculated using the positions of standard marker proteins is indicated in the chromatogram, together with the theoretical value in parenthesis. The lower subpanels present a gallery of 20 class averages obtained from ~1,000 selected particles. The number of individual particles represented by each average is shown at the bottom left corner in either white (clockwise) or yellow (counter-clockwise) to indicate their tail curvature orientation. Bar: 100 Å.</p

Estrogen-Dependent Proteolytic Cleavage of Semaphorin 4D and Plexin-B1 Enhances Semaphorin 4D-Induced Apoptosis during Postnatal Vaginal Remodeling in Pubescent Mice

<div><p>Around the fifth week after birth, the vaginal cavity in female mouse pups opens to the overlaying skin. This postnatal tissue remodeling of the genital tract occurs during puberty, and it largely depends upon hormonally induced apoptosis that mainly occurs in the epithelium at the lower part of the mouse vaginal cavity. Previously, we showed that most BALB/c mice lacking the class IV Semaphorin (Sema4D) develop imperforate vagina and hydrometrocolpos; therefore, we reasoned that the absence of Sema4D-induced apoptosis in vaginal epithelial cells may cause the imperforate vagina. Sema4D signals via the Plexin-B1 receptor; nevertheless detailed mechanisms mediating this hormonally triggered apoptosis are not fully documented. To investigate the estrogen-dependent control of Sema4D signaling during the apoptosis responsible for mouse vaginal opening, we examined structural and functional modulation of Sema4D, Plexin-B1, and signaling molecules by analyzing both wild-type and Sema4D−/− mice with or without ovariectomy. Both the release of soluble Sema4D and the conversion of Plexin-B1 by proteolytic processing in vaginal tissue peaked 5 weeks after birth of wild-type BALB/c mice at the time of vaginal opening. Estrogen supplementation of ovariectomized wild-type mice revealed that both the release of soluble Sema4D and the conversion of Plexin-B1 into an active form were estrogen-dependent and concordant with apoptosis. Estrogen supplementation of ovariectomized Sema4D−/− mice did not induce massive vaginal apoptosis in 5-week-old mice; therefore, Sema4D may be an essential apoptosis-inducing ligand that acts downstream of estrogen action in vaginal epithelium during this postnatal tissue remodeling. Analysis of ovariectomized mice also indicated that Sema4D contributed to estrogen-dependent dephosphorylation of Akt and ERK at the time of vaginal opening. Based on our results, we propose that apoptosis in vaginal epithelium during postnatal vaginal opening is induced by enhanced Sema4D signaling that is caused by estrogen-dependent structural changes of Sema4D and Plexin-B1.</p></div