7,748 research outputs found
The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies
Full text linkReproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity
The Roles of Membrane Rafts in CD32A-Mediated Phagocytosis
Full text linkMembrane rafts are highly dynamic heterogeneous sterol- and sphingolipid-rich micro-domains on cell surfaces. They are generally believed to provide residency for cell surface molecules (e.g., adhesion and signaling molecules) and scaffolding to facilitate the functions of these molecules such as membrane trafficking, receptor transport, cell signaling, and endocytosis.
The governing, or overall hypothesis, for this project is that membrane rafts provide residency for Fc[gamma]RIIA (CD32A) on K562 cells, and that by doing so they provide a platform from which Fc[gamma]RIIA initiate or carry out their functions, which include migration, signaling, phagocytic synapse formation, and internalization of IgG opsonized targets.
Using immuno-fluorescent laser scanning confocal microscopy and reflection interference microscopy (RIM), we studied the spatial and temporal distributions of membrane rafts and surface receptors, signaling molecules, and cell organelles during the formation of phagocytic contact areas. K562 cells, which naturally express CD32A, a cell surface receptor for the Fc portion of Immuno-globulin G(IgG), was chosen as a model for neutrophils. An opsonized target was modeled using a glass supported lipid bilayer reconstituted with IgG. CD32A was found to cluster and co-localize with membrane rafts. Placing the K562 cells on the lipid bilayer triggered a process of contact area formation that includes binding between receptors and ligands, their recruitment to the contact area, a concurrent membrane raft movement to and concentration in the contact area, and transport of CD32A, IgG, and membrane rafts to the Golgi complex. Characterization of these processes was performed using agents known to disrupt detergent resistant membranes (DRMs), dissolve actin microfilaments, and inhibit myosin motor activity, which abolished the CD32A clusters and prevented the contact area formation. 
The relevance to phagocytosis of contact area formation between K562 cells and lipid bilayers was demonstrated using micro-beads coated with a lipid bilayer reconstituted with IgG as the opsonized target instead of the glass supported planar lipid bilayer. Disruption of membrane rafts, salvation of the actin cytoskeleton, and inhibition of myosin II activity were found to inhibit phagocytosis.
These data suggest membrane rafts play several important roles in CD32A mediated phagocytosis including pre-clustering CD32A, transport of CD32A to the phagocytic cup, and transport of the opsonized target towards the Golgi complex. Here we have provided evidence that membrane rafts serve as platforms which are used to cluster CD32A and transport CD32A along the actin cytoskeleton to the site of phagocytic synapse formation thus allowing for the quick assembly of a phagocytic synapse.

Fc-lectin binding profiles to <i>C</i>. <i>albicans</i> cell wall glycosylation mutants.
No full text(A) Indirect immunofluorescence images of Fc-conjugated CTL probes binding to C. albicans O-mannan and N-mannan cell wall mutants of C. albicans (as described in the text). 3D visualisation was performed using an UltraView VoX spinning disk confocal microscope and images are presented as extended focus reconstructions in the Volocity software (Quorum Technologies), which displays a single image created by making a brightest-point merge of all the Z-slices through a cell. Scale bars represent 4 μm.</p
Altered human neutrophil Fc gamma RI and Fc gamma RIII but not Fc gamma RII expression is associated with the acute coronary event in patients with coronary artery disease
No full textObjective Neutrophils enhancing atherosclerotic plaque instability have been observed in patients with acute coronary syndrome (ACS). Generally, activation of neutrophils in lesions depends on the interaction of Fc gamma receptors (Fc gamma Rs) with immunoglobulin G antibodies in immune complexes. However, altered Fc gamma R expression on neutrophils of patients with ACS is unknown. We aimed to evaluate changes in Fc gamma R expression on neutrophils of patients with ACS. Methods We enrolled 106 patients who were divided into four groups: acute myocardial infarction (AMI), unstable angina (UA), stable angina, and normal coronary arteries. The expressions of Fc gamma RI, Fc gamma RII, and Fc gamma RIII on neutrophils and related upstream ligand and downstream molecules were measured by flow cytometry and enzyme-linked immunosorbent assay. Results The expression of unbound Fc gamma RI was significantly decreased in AMI and UA patients and that of unbound Fc gamma RIII was significantly decreased in AMI patients, with no difference in the expression of unbound Fc gamma RII among the four groups. In contrast, plasma levels of antioxidized LDL antibody, myeloperoxidase, matrix metalloproteinase-9, and neutrophil gelatinase-associated lipocalin were significantly greater in AMI and UA than in stable angina and normal coronary arteries patients. Conclusion Unbound Fc gamma RI and Fc gamma RIII expression was decreased on neutrophils of patients with ACS, which reflects a potential role of disturbed Fc gamma RI and Fc gamma RIII expression in the destabilization of atherosclerotic plaque. Our findings may provide insight into the mechanism underlying culprit plaque-relevant activation of neutrophil Fc gamma Rs in ACS patients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.Project of Shaanxi Province Youth Science and Technology Star [2016KJXX-25]; National Nature Science Fund for Distinguished Young Scholars of China [81400181]SCI(E)PubMedARTICLE163-692
Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales
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In contrast to traditional strategies based on external driving forces, an internal path for intratumoral delivery is explored by degrading the tumor microenvironment component hyaluronan. Natural hyaluronidase PH20 and constructed long-acting PH20-Fc have been used to achieve this objective. It has been then evaluated how these agents facilitate the diffusion of the following typical therapeutic agents varying in nanoscales: doxorubicin (approximate to 1.5 x 1.0 x 0.7 nm) chemotherapy, trastuzumab (10-15 nm) biotherapy, and gold nanorod (approximate to 100 x 35 nm) thermotherapy. In traditional 2D cultures, PH20 and PH20-Fc have little influence on cytotoxicity due to lack of a tumor microenvironment. However, the cytotoxicities of the three therapeutic agents in 3D tumor spheroids are all enhanced by PH20 or PH20-Fc because hyaluronan degradation facilitates therapeutic penetration and accumulation. Furthermore, in vivo evaluations reveal that the significantly prolonged circulation time of PH20-Fc leads to accumulation in the tumor and subsequent hyaluronan degradation. Consequently, PH20-Fc coadministration further inhibits tumor growth. The performance of PH20-Fc varies for the three therapeutic agents due to their different nanoscales. Trastuzumab benefits most from combination with PH20-Fc. The results provide here novel insights that can aid in the development of more effective hyaluronidase-based therapeutic systems.</p
Le Corbeau et le Renard: 99 versions réinventées: Style d'exercices
No full textThis book represents a fascinating effort. At first I thought it was going to be a collection of various parodies of La Fontaine's FC. It is not that, but rather a creative presentation of some 97 different versions of La Fontaine created by the author. The first two versions are a French translation of the Greek prose of the most original FC text in the Aesopic manuscripts and then La Fontaine's verse. Thereafter the fun begins! The imagination and the execution of this project are both remarkable. Let me offer a sample of five approaches: (1) an acrostic, so that the opening letters of each verse spell "M Jean La Fontaine"; (2) a prose version after the manner of Balzac; (3) a scientific version needing more than a full page; (4) a tourist guide version; and (5) a rhyming version in English. T of C at the end. 136 pages. 5¼" x 8". Printed upon demand.Language note: FrenchNicolas Mille
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Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway
No full textBackground: The regulation of platelet function by pharmacological agents that modulate platelet signaling haspharmacolo proven a successful approach to the prevention of thrombosis. A variety of molecules present in the diet have been shown to inhibit platelet activation, including the antioxidant quercetin. Objectives: In this report we investigate the molecular mechanisms through which quercetin inhibits collagen-stimulated platelet aggregation. Methods: The effect of quercetin on platelet aggregation, intracellular calcium release, whole cell tyrosine phosphorylation and intracellular signaling events including tyrosine phosphorylation and kinase activity of proteins involved in the collagen-stimulated glycoprotein (GP) signaling pathway were investigated. Results: We report that quercetin inhibits collagen-stimulated whole cell protein tyrosine phosphorylation and intracellular mobilization of calcium, in a concentration-dependent manner. Quercetin was also found to inhibit various events in signaling generated by the collagen receptor GPVI. This includes collagen-stimulated tyrosine phosphorylation of the Fc receptor gamma-chain, Syk, LAT and phospholipase Cgamma2. Inhibition of phosphorylation of the Fc receptor gamma-chain suggests that quercetin inhibits early signaling events following stimulation of platelets with collagen. The activity of the kinases that phosphorylate the Fc receptor gamma-chain, Fyn and Lyn, as well as the tyrosine kinase Syk and phosphoinositide 3-kinase was also inhibited by quercetin in a concentration-dependent manner, both in whole cells and in isolation. Conclusions: The present results provide a molecular basis for the inhibition by quercetin of collagen-stimulated platelet activation, through inhibition of multiple components of the GPVI signaling pathway, and may begin to explain the proposed health benefits of high quercetin intake
Production of polyclonal antibodies against territrem B and detecion of territrem B in the conidia of Aspergullus terreus 23-1 by immunoelectron microscopy.
No full textNoninvasive tests for the prediction of significant hepatic fibrosis in hepatitis C virus carriers with persistently normal alanine aminotransferases.
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