The complete ectodomain of integrin αIIbβ3 reveals a bent, closed, low-affinity conformation, the β-knee, and a mechanism for linking cytoskeleton attachment to high affinity for ligand. Ca and Mg ions in the recognition site, including the synergistic metal ion binding site (SyMBS), are loaded prior to ligand binding. Electrophilicity of the ligand-binding Mg ion is increased in the open conformation. The β3 knee passes between the β3-PSI and αIIb-knob to bury the lower β-leg in a cleft, from which it is released for extension. Different integrin molecules in crystals and EM reveal breathing that appears on pathway to extension. Tensile force applied to the extended ligand-receptor complex stabilizes the closed, low-affinity conformation. By contrast, an additional lateral force applied to the β subunit to mimic attachment to moving actin filaments stabilizes the open, high-affinity conformation. This mechanism propagates allostery over long distances and couples cytoskeleton attachment of integrins to their high affinity state.

Background: Systemic lupus erythematous (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against various autoantigens. But the expression profiles and functions of circular RNAs (circRNAs) in SLE are still scarce. Objectives: To explore the roles of circRNA in SLE and its potential diagnostic potential in SLE. Methods: SLE patients and healthy control subjects were recruited. CD4+ T cells were isolated, circRNA microarray analysis were used to screen for circRNA candidate in CD4+ T cells. Expression of DNMT1, CD11a and CD70, and methylation level of CD11a and CD70 were detected after transfecting hsa_circ_0012919-targetted siRNA. The network analysis of hsa_circ_0012919 was used by bioinformatics. Luciferase reporter assay and fluorescence in situ hybridization (FISH) assay were used for screening for which miRNAs could bind with hsa_circ_0012919. Results: Twelve circRNAs were up-regulated and two circRNAs were down-regulated in SLE patients group after circRNA microarray analysis. Hsa_circ_0012919 was further confirmed to be significantly different between healthy control and SLE patients (P<0.05) and associated with SLE characters (P<0.05). Down-regulation of hsa_circ_0012919 (i) increased the expression of DNMT1 and reduced the expression of CD70, CD11a, (ii) reversed the DNA hypomethylation of CD11a and CD70 in CD4+ T cells of SLE, but it could be reversed by down-regulation of DNMT1. Hsa_circ_0012919 regulated KLF13 and RANTES by miR-125a. Conclusion: Hsa_circ_0012919 could be regarded as a biomarker for SLE and hsa_circ_0012919 was the competitive endogenous RNA (ceRNA) for miR-125a-3p.

BackgroundSystemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease involving the dysfunction of lymphocytes. Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with a covalently closed loop structure, with abnormal expression in various human diseases may participate in the pathogenesis, while further study is needed in SLE. In this study, we aimed to find the circRNAs abnormally expressed in SLE and explore the function of circRNAs in SLE.MethodsCircRNA sequencing was used to find the abnormally expressed circRNA and qRT-PCR was used to detect the expression. Correlation analysis was used to analyze the correlation between circIBTK or miR-29b and clinicopathological variables in patients with SLE. Cell culture, nuclear-cytoplasmic fractionation, qRT-PCR, transfection, luciferase reporter assay, western blot analysis, DNA extraction and global methylation analysis were used to explain the function of circIBTK and miR-29b in the progression of SLE. SPSS 18.0 software was used to perform statistics.ResultsWe found that the expression of circIBTK was downregulated in SLE and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds)DNA and complement C3 level in patients with SLE. Then miR-29b expression was upregulated in SLE and correlated with SLEDAI score, anti-dsDNA and complement C3 level in patients with SLE. Mechanistic investigations indicated that miR-29b could induce DNA demethylation and activate the AKT signaling pathway and circIBTK might reverse the DNA demethylation and activation of the AKT signaling pathway induced by miR-29b via binding to miR-29b in SLE.ConclusionsCircIBTK was downregulated in SLE and might regulate DNA demethylation and the AKT signaling pathway via binding to miR-29b in SLE. CircIBTK and miR-29 could also act as biomarkers and therapeutic targets for SLE.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1618-8) contains supplementary material, which is available to authorized users.

To describe the prevalence of human papillomavirus (HPV) and its genotype distribution among females in the suburb of Shanghai. A total of 33 562 participants were enrolled in this study from January to December 2016. HPV GenoArray test kit was used to perform HPV genotyping and was also used in DNA amplification and HybriBio's proprietary flow-through hybridization technique. The overall prevalence of HPV was 18.98% and the top ten genotypes of HPV infection were HPV 16 (3

Hefei Doppler radar observation data over the downstream region of the Yangtze River during the Meiyu period from 2001 to 2003, were analyzed in order to reveal the predominant structural characteristics of meso-b-scale convective systems (MbCSs) around the Meiyu front. Convective and stratiform portions were separated from MbCSs using the bright-band fraction (BBF) method. The daily and yearly mean vertical profiles of radar reflectivity for the convective portion were calculated.Results showed that the vertical profile of the convective portion of MbCSs for 3 years was characterized by low altitude of radar reflectivity peaks (around 3 km), and large decrease of reflectivity with height above the melting level. To understand these characteristics of MbCSs, the convection of medium depth (CMD) is defined as a group of convective cells whose echo top height, with the reflectivity of 15 dBZ, is equal to or less than 8 km, and in which the reflectivity peak is below 4 km throughout their lifetime.To investigate the structural characteristics of MbCSs around the Meiyu front, observed MbCSs were categorized into slow-moving (a 3 m s À1 ) and south-of-front (SSF) type, slow-moving and along-the-front (SAF) type, fast-moving (b 7 m s À1 ) and along-the-front (FAF) type, and slow-moving and north-of-front (SNF) type; according to their movement speed, and their locations relative to the surface front. The predominant convection in the SSF type was the CMD, and it covered 51% of the convective area. The CMD and deep convections (DC) coexisted in the SAF, with the CMD covering 34% of convective area. TheCorresponding author: Cheng-Zhong Zhang, Hydrospheric Atmospheric Research Center, Nagoya University, Nagoya 464-8601, Japan. E-mail: zhang@rain.hyarc.nagoya-u.ac.jp ( 2006, Meteorological Society of Japan FAF type was organized from the DC, and the SNF type primarily consisted of the CMD. The environmental conditions under which the SSF type formed were characterized by a weak wind convergence (<2 Â 10 À5 s À1 ) near the surface, a low level of neutral buoyancy and humid atmosphere below the middle level. The large contribution of the CMD to convective rainfall amount in the SSF type, and its unnegligible contribution in the SAF type, indicate that the CMD has one of the main structures of the Meiyu frontal convective precipitation systems.