Human umbilical cord mesenchymal cells from 4 donors cultured from P1 or P2 to replicative senescence
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE119987 | GEO | 2019/09/03
REPOSITORIES: GEO
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Project description:Human umbilical cord mesenchymal cells from 4 donors cultured from P1 or P2 to replicative senescence
| PRJNA490899 | ENA
Project description:Malaria remains one the most infectious and destructive protozoan diseases worldwide. Plasmodium falciparum, a protozoan parasite with a complex life cycle and high genetic variability responsible for the difficulties in vaccine development, is implicated in most malaria-related deaths. In the course of study, we prepared a set of antigens based on P-proteins from P. falciparum and determined their immunogenicity in an in vivo assay on a mouse model. The pentameric complex P0-(P1-P2)2 was prepared along with individual P1, P2, and P0 antigens. We determined the level of cellular- and humoral-type immunological response followed by development of specific immunological memory. We have shown that the number of Tc cells increased significantly after the first immunization with P2 and after the second immunization with P1 and P0-(P1-P2)2, which highly correlated with the number of Th1 cells. P0 appeared as a poor inducer of cellular response. After the third boost with P1, P2, or P0-(P1-P2)2, the initially high cellular response dropped to the control level accompanied by elevation of the number of activated Treg cells and a high level of suppressive TGF-β. Subsequently, the humoral response against the examined antigens was activated. Although the titers of specific IgG were increasing during the course of immunization for all antigens used, P2 and P0-(P1-P2)2 were found to be significantly stronger than P1 and P0. A positive correlation between the Th2 cell abundance and the level of IL-10 was observed exclusively after immunization with P0-(P1-P2)2. An in vitro exposure of spleen lymphocytes from the immunized mice especially to the P1, P2, and P0-(P1-P2)2 protein caused 2-3-fold higher cell proliferation than that in the case of lymphocytes from the nonimmunized animals, suggesting development of immune memory. Our results demonstrate for the first time that the native-like P-protein pentameric complex represents much stronger immune potential than individual P-antigens.
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2021-12-01 | GSE160239 | GEO
Project description:Riboswitches regulate genes by adopting different structures in responds to metabolite binding. The guanidine-II riboswitch is the smallest representative of the ykkC class with the mechanism of its function being centred on the idea that its two stem loops P1 and P2 form a kissing hairpin interaction upon binding of guanidinium (Gdm+). This mechanism is based on in-line probing experiments with the full-length riboswitch and crystal structures of the truncated stem loops P1 and P2. However, the crystal structures reveal only the formation of the homodimers P1 | P1 and P2 | P2 but not of the proposed heterodimer P1 | P2. Here, site-directed spin labeling (SDSL) in combination with Pulsed Electron-Electron Double Resonance (PELDOR or DEER) is used to study their structures in solution and how they change upon binding of Gdm+. It is found that both hairpins adopt different structures in solution and that binding of Gdm+ does indeed lead to the formation of the heterodimer but alongside the homodimers in a statistical 1:2:1 fashion. These results do thus support the proposed switching mechanism.
| S-EPMC7544219 | biostudies-literature
Project description:The eukaryotic P-stalk contains two P1-P2 protein dimers with a conserved C- terminal domain (CTD) critical for the interaction with external factors. To understand the role of the individual CTD of human P1/P2 proteins, we examined the interaction of reconstituted human P-protein complexes and C-terminally truncated forms with ricin A chain (RTA), which binds to the stalk to depurinate the sarcin/ricin loop (SRL). The interaction between P-protein complexes and RTA was examined by surface plasmon resonance, isothermal titration calorimetry, microscale thermophoresis and bio-layer interferometry. The P1-P2 heterodimer missing a CTD on P2 was able to bind RTA. In contrast, the P1-P2 heterodimer missing the CTD of P1 protein displayed almost no binding toward RTA. Very low interaction was detected between RTA and the non-truncated P2-P2 homodimer, suggesting that the structural architecture of the P1-P2 heterodimer is critical for binding RTA. The reconstituted pentameric human stalk complex had higher affinity for RTA than the P1-P2 dimer. Deletion of P1 CTD, but not P2 CTD reduced the affinity of the pentamer for RTA. These results highlight the importance of the heterodimeric organization of P1-P2 in the human stalk pentamer and functional non-equivalence of the individual P-protein CTDs in the interaction with RTA.
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Project description:A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings between a nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to the respective unsaturated derivatives. Compound containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity.
| S-EPMC4133278 | biostudies-literature
Project description:Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.
| S-EPMC4027635 | biostudies-literature
Project description:Serum- and xeno-free cryopreservation is suitable for cells to be used in clinical applications. However, dimethyl sulfoxide (DMSO), which is often used in conventional cryoprotectant medium, has been shown to be toxic to many cell types and can induce morphological and gene expression changes that can lead to changes in cell function when they are cultured. In order to evaluate this issue in depth, we examined the efficiency of a DMSO-free/serum-free/xeno-free chemically defined cryoprotectant media, STEM-CELLBANKER DMSO-Free, when culturing human mesenchymal stem cells (MSCs) and chondrocytes. Interestingly, the cells cryopreserved in STEM-CELLBANKER DMSO-Free had a similar growth rate, morphology, and global gene expression profile compared to that observed for cells preserved in conventional freezing medium, which contains 10% DMSO and 20% fetal bovine serum. From these data, we therefore propose that STEM-CELLBANKER DMSO-Free may be an effective tool for maintaining the cellular characteristics of MSCs and chondrocytes during cryo-storage prior to clinical application.
2019-03-22 | GSE79496 | GEO
Project description:BackgroundSec18p/N-ethylmaleimide-sensitive factor (NSF) is a conserved eukaryotic ATPase, which primarily functions in vesicle membrane fusion from yeast to human. However, the function of the OsSec18 gene, a homologue of NSF in rice, remains unknown.ResultsIn the present study, we investigated the function of OsSec18 in rice and found that OsSec18 complements the temperature-sensitive phenotype and interferes with vacuolar morphogenesis in yeast. Overexpression of OsSec18 in rice decreased the plant height and 1000-grain weight and altered the morphology of the protein bodies. Further examination revealed that OsSec18 presented as a 290-kDa complex in rice endosperm cells. Moreover, Os60sP0 was identified a component of this complex, demonstrating that the OsSec18 complex contains another complex of P0(P1-P2)2 in rice endosperm cells. Furthermore, we determined that the N-terminus of OsSec18 can interact with the N- and C-termini of Os60sP0, whereas the C-terminus of OsSec18 can only interact with the C-terminus of Os60sP0.ConclusionOur results revealed that the OsSec18 regulates vacuolar morphology in both yeast and rice endosperm cell and the OsSec18 interacts with P0(P1-P2)2 complex in rice endosperm cell.
| S-EPMC4340293 | biostudies-literature
Project description:In this study, we sought to examine whether an extracellular matrix (ECM)-based xeno-free culture system that we recently established could be used together with a microRNA-enhanced mRNA reprogramming method for the generation of clinically safe iPS cells. The notable features of this method are (1) the use of a xeno-free/feeder-free culture system for the generation and expansion of iPS cells rather than the conventional labor-intensive culture systems using human feeder cells or human feeder-conditioned medium and (2) the enhancement of mRNA-mediated reprogramming via the delivery of microRNAs. Strikingly, we observed the early appearance of iPS cell colonies (~11 days), substantial reprogramming efficiency (~0.2-0.3%), and a high percentage of ESC-like colonies among the total colonies (~87.5%), indicating enhanced kinetics and reprogramming efficiency. Therefore, the combined method established in this study provides a valuable platform for the generation and expansion of clinically safe (i.e., integration- and xeno-free) iPS cells, facilitating immune-matched cell therapy in the near future.
2016-04-21 | GSE68035 | GEO