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Human brain Dynamics Underlying Psychological Freedom Through the Lifespan.
The latter revealed novel patterns that were not identified by previous analyses. TREEasy represents a reliable and simple tool to accelerate research in systematic biology (https//github.com/MaoYafei/TREEasy). This article is protected by copyright. All rights reserved.BACKGROUND Defective complement inhibition can lead to the formation of membrane attack complexes (MAC; C5b-9) on the plasma membranes of vascular endothelial cells, resulting in injury that drives the progression of thrombotic microangiopathy (TMA), a key pathology in kidney disease. OBJECTIVE/METHODS We examined the response of human endothelial cells to complement-mediated damage using blood outgrowth endothelial cells (BOECs) derived from healthy donors. BOECs were sensitized to complement factors present in normal human serum to induce the formation of C5b-9 on their plasma membranes. RESULTS This triggered an expected abrupt rise in intracellular Ca2+ reflecting membrane leakage. Remarkably, while intracellular Ca2+ remained elevated, membrane leakage ceased within 30 min, and cells did not show significant death. Extensive mobilization of Weibel-Palade bodies (WPBs) was observed along with secretion of von Willebrand Factor (VWF). click here The potential role of WPBs and VWF in mitigating complement-mediated damage was examined by comparing the effects of C5b-9 on BOECs derived from von Willebrand Disease (VWD) patients expressing reduced amounts of VWF, lacking expression of functional VWF, or lacking both VWF and WPBs. BOECs lacking WPBs were not resistant to complement-mediated damage, but became resistant when transfected to express VWF (and thus WPBs). CONCLUSION We conclude that BOECs exposed to C5b-9 attack respond by mobilizing WPBs, which mitigate and repair damage by fusing with the plasma membrane. We propose that a similar cell-specific response may protect the vascular endothelium from complement-mediated damage in vivo. This article is protected by copyright. All rights reserved.It is challenging to design metal catalysts for in situ transformation of endogenous biomolecules with good performance inside living cells. Herein, we report a multifunctional metal catalyst, ruthenium-coordinated oligo(p-phenylenevinylene) (OPV-Ru), for intracellular catalysis of transfer hydrogenation of nicotinamide adenine dinucleotide (NAD+ ) to its reduced format (NADH). Owing to its amphiphilic characteristic, OPV-Ru possesses good self-assembly capability in water to form nanoparticles through hydrophobic interaction and π-π stacking, and numerous positive charges on the surface of nanoparticles displayed a strong electrostatic interaction with negatively charged substrate molecules, creating a local microenvironment for enhancing the catalysis efficiency in comparison to dispersed catalytic center molecule (TOF value was enhanced by about 15 fold). OPV-Ru could selectively accumulate in the mitochondria of living cells. Benefiting from its inherent fluorescence, the dynamic distribution in cells and uptake behavior of OPV-Ru could be visualized under fluorescence microscopy. This work represents the first demonstration of a multifunctional organometallic complex catalyzing natural hydrogenation transformation in specific subcellular compartments of living cells with excellent performance, fluorescent imaging ability, specific mitochondria targeting and good chemoselectivity with high catalysis efficiency. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Endometrial cancer is one of the most common gynaecological malignancies and the sixth most common cause of cancer-related death among women. Here, we define the role and molecular mechanism of circ_0000043 (hereafter referred to as circ_PUM1) in the development and progression of endometrial carcinoma. QRT-PCR was used to detect the expression of circ_PUM1 in normal endometrial tissue and endometrial carcinoma tissues. Changes in cell function and tumorigenicity in nude mice were examined after circ_PUM1 overexpression or knockdown. Bioinformatic analysis and dual-luciferase reporter assay were used to predict and analyse the miRNAs that circ_PUM1 binds. Gene expression changes were analysed using Western blot. Circ_PUM1 was expressed at significantly higher levels in endometrial cancer tissues than in normal tissues. Up-regulation of circ_PUM1 promoted the proliferation, migration and invasion of endometrial carcinoma cells. Opposite results were observed with circ_PUM1 knockdown, and the tumorigenic ability of endometrial cancer cells after circ_PUM1 knockdown was reduced compared to control cells. Circ_PUM1 is capable of binding to miR-136, and up-regulating its target gene NOTCH3, which can be reversed by overexpression of miR-136. Circ_PUM1 can compete with miR-136, leading to up-regulation of NOTCH3, and thereby promote the development of endometrial cancer. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.To investigate the structural impact of phosphorylation in human H1.0 C-terminal domain, we performed NMR structural studies of model peptides containing a single phosphorylation site T118-H1.0 (T118PKK motif) and T140-H1.0 (T140PVK motif). Both model peptides are mainly disordered in aqueous solution in their non-phosphorylated and phosphorylated forms, but become structured in the presence of trifluoroethanol (TFE). The peptides T118-H1.0 and pT118-H1.0 contain two helical regions a long amphipathic α-helix spanning residues 104-115 and a short α/310 helix(residues 119-123), which are almost perpendicular in T118-H1.0, but their orientation is poorly defined in pT118-H1.0. Peptides T140-H1.0 and pT140-H1.0 form very similar α-helices between residues 141-147. The TPKK and TPVK motifs show the same backbone conformation, but differ in side-chain contacts; Thr and pThr side-chains interact with the i+2 Lys side-chain in the TPKK motif, and with the i+3 Lys side-chain in the TPVK motif. The pT phosphate group in pT118-H1.0 and pT140-H1.0 has pKa values below the intrinsic one that can be explained by non-specific charge-charge interactions with nearby Lys. The non-polar Val in the TPVK motif accounts for the pT140 pKa being closer to the intrinsic than the pT118 pKa. Altogeher, these results validate minimalist strategies using model peptides that can provide structural details difficult to get in short-lived intrinsically disordered proteins (IDPs) and domains. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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