3,233 research outputs found
NADPH-cytochrome P450 reductase is involved in flunitrazepam reductive metabolism in Hep G2 and Hep 3B cells.
No full textTargeting the neonatal Fc receptor for antigen delivery using engineered Fc fragments
No full textThe development of approaches for Ag delivery to the appropriate subcellular compartments of APCs and the optimization of Ag persistence are both of central relevance for the induction of protective immunity or tolerance. The expression of the neonatal Fc receptor, FcRn, in APCs and its localization to the endosomal system suggest that it might serve as a target for Ag delivery using engineered Fc fragment-epitope fusions. The impact of FcRn binding characteristics of an Fc fragment on in vivo persistence allows this property to also be modulated. We have therefore generated recombinant Fc (mouse IgG1-derived) fusions containing the N-terminal epitope of myelin basic protein that is associated with experimental autoimmune encephalomyelitis in H-2 u mice. The Fc fragments have distinct binding properties for FcRn that result in differences in intracellular trafficking and in vivo half-lives, allowing the impact of these characteristics on CD4+ T cell responses to be evaluated. To dissect the relative roles of FcRn and the "classical" FcγRs in Ag delivery, analogous aglycosylated Fc-MBP fusions have been generated. We show that engineered Fc fragments with increased affinities for FcRn at pH 6.0 -7.4 are more effective in delivering Ag to FcRn-expressing APCs in vitro relative to their lower affinity counterparts. However, higher affinity of the FcRn-Fc interaction at near neutral pH results in decreased in vivo persistence. The trade-off between improved FcRn targeting efficiency and lower half-life becomes apparent during analyses of T cell proliferative responses in mice, particularly when Fc-MBP fusions with both FcRn and FcγR binding activity are used.</p
The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies
Get PDFReproducibility 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
Predictive pulmonary function of school children in an area of low air pollution in Taiwan
No full textAbsenteeism due to respiratory morbidity in elementary schools with low level air pollution
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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
From sorting endosomes to exocytosis: Association of Rab4 and Rab11 GTPases with the Fc receptor, FcRn, during recycling
No full textA longstanding question in cell biology is how is the routing of intracellular organelles within cells regulated? Although data support the involvement of Rab4 and Rab11 GTPases in the recycling pathway, the function of Rab11 in particular is uncertain. Here we have analyzed the association of these two Rab GTPases with the Fc receptor, FcRn, during intracellular trafficking. This Fc receptor is both functionally and structurally distinct from the classical Fcγ receptors and transports immunoglobulin G (IgG) within cells. FcRn is therefore a recycling receptor that sorts bound IgG from unbound IgG in sorting endosomes. In the current study we have used dual color total internal reflection fluorescence microscopy (TIRFM) and wide-field imaging of live cells to analyze the events in human endothelial cells that are involved in the trafficking of FcRn positive (FcRn+) recycling compartments from sorting endosomes to exocytic sites at the plasma membrane. Our data are consistent with the following model for this pathway: FcRn leaves sorting endosomes in Rab4+Rab11+ or Rab11+ compartments. For Rab4+Rab11+ compartments, Rab4 depletion occurs by segregation of the two Rab proteins into discrete domains that can separate. The Rab11+FcRn+ vesicle or tubule subsequently fuses with the plasma membrane in an exocytic event. In contrast to Rab11, Rab4 is not involved in exocytosis.</p
The overall FC-SC relationships.
No full text<p>(A) The probability densities of FC strengths between structurally connected and unconnected regions pairs. When direct SC presents, higher FC strength appears than the case direct SC absents, indicating a robust relationship between FC and SC. (B) Scatter plot of SC strength against FC strength for the regions with direct SC. Further analysis showed significant coefficient between FC and SC strengths for all groups. Data are from group averaged functional connectivity matrix of AD, aMCI, and NC groups, at the high resolution (1024×1024).</p
Il10/fc fusion proteins useful as enhancers of immunotherapies
No full textThe present disclosure relates to new agents useful for anti-cancer therapy such as anti-cancer adoptive T-cell transfer (ACT) immunotherapy or immune check-point blockade therapy and related compositions, uses and methods thereof.AVP-R-TTOLBIAlternative title(s) : (de) Il10/fc-fusionsproteine als verstärker von immuntherapien (fr) Protéines de fusion il10/fc utiles pour améliorer les immunothérapie
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