3,200 research outputs found

    Functional characterization of the HuR:CD83 mRNA interaction.

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    Maturation of dendritic cells (DC) is characterized by expression of CD83, a surface protein that appears to be necessary for the effective activation of naïve T-cells and T-helper cells by DC. Lately it was shown that CD83 expression is regulated on the posttranscriptional level by interaction of the shuttle protein HuR with a novel posttranscriptional regulatory RNA element (PRE), which is located in the coding region of the CD83 transcript. Interestingly, this interaction commits the CD83 mRNA to efficient nuclear export via the CRM1 pathway. To date, however, the structural basis of this interaction, which potentially involves three distinct RNA recognition motifs (RRM1-3) in HuR and a complex three-pronged RNA stem-loop element in CD83 mRNA, has not been investigated in detail. In the present work we analyzed this interaction in vitro and in vivo using various HuR- and CD83 mRNA mutants. We are able to demonstrate that both, RRM1 and RRM2 are crucial for binding, whereas RRM3 as well as the HuR hinge region contributed only marginally to this protein:RNA interaction. Furthermore, mutation of uridine rich patches within the PRE did not disturb HuR:CD83 mRNA complex formation while, in contrast, the deletion of specific PRE subfragments from the CD83 mRNA prevented HuR binding in vitro and in vivo. Interestingly, the observed inhibition of HuR binding to CD83 mRNA does not lead to a nuclear trapping of the transcript but rather redirected this transcript from the CRM1- towards the NXF1/TAP-specific nuclear export pathway. Thus, the presence of a functional PRE permits nucleocytoplasmic trafficking of the CD83 transcript via the CRM1 pathway

    Letter from Alexander T. Vogelsang to Mr. Snyder regarding the Havasupai reservation with draft of proposed bill

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    Letter from Alexander Vogelsang to Homer P. Snyder regarding land allocation for the Havasupai Tribe

    The poetical works of Alexander Pope, esq., to which is prefixed the life of the author,

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    Includes his translations of Homer, and Parnell's translation of The battle of the frogs and mice (Batrachomyomachia) corrected by Pope.Added t.-p., engr.: The poetical works of Alexander Pope, esq. Including his translation of Homer.Mode of access: Internet

    Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.

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    IFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells

    Expression of CD83 Is Regulated by HuR via a Novel cis-Active Coding Region RNA Element

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    Dendritic cells are the most potent of the antigen-presenting cells and are characterized by surface expression of CD83. Here, we show that the coding region of CD83 mRNA contains a novel cis-acting structured RNA element that binds to HuR, a member of the ELAV family of AU-rich element RNA-binding proteins. Transient transfection of mammalian cells demonstrated that this CD83 mRNA-derived element acts as a post-transcriptional regulatory element in cells over-expressing HuR. Notably, binding of HuR to the CD83 post-transcriptional regulatory element did not affect mRNA stability. Using RNA interference, we show that HuR mediated efficient expression of CD83. In particular, HuR was required for cytoplasmic accumulation of CD83 transcripts. Likewise, inhibition of the CRM1 nuclear export pathway by leptomycin B or overexpression of a defective form of the nucleoporin Nup214/CAN diminished cytoplasmic CD83 mRNA levels. In summary, the data presented demonstrate that the HuR-CRM1 axis affects the nucleocytoplasmic translocation of CD83 mRNA under regular physiological conditions

    An introduction to clinical pharmaceutics / Alexander T. Florence.

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    Book fair2012xiii, 179 pages:This textbook describes a variety of dosage forms and their clinical importance and use. The use and behaviour of dosage forms in different age groups and patient groups will also be considered along with recent developments such as personalised therapies and genomics. It contains relevant examples and clinical case studie

    Odoardo Fialetti (1573-c.1638): the interrelation of Venetian art and anatomy, and his importance in England

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    Bolognese artist Odoardo Fialetti (1573 – c.1638) is a fascinating figure upon which curiously little work has been done. Though he is a rarely discussed pupil of Tintoretto, Fialetti’s oeuvre is vast (some 55 known paintings and approximately 450 prints) and incredibly diverse. His work encompasses religious subjects, portraits, books on drawing and sport, maps, and illustration for treatises on city defences, literary texts, and anatomy. His work was influential for several hundred years after his death, not only in Venice and northern Italy, but also in France where his designs were used as decoration on faïence produced at Nevers, and England, where his paintings were much admired at court. Fialetti’s close association with Sir Henry Wotton, and the careful copy of his drawing book made by Alexander Browne in the mid-seventeenth century, attest to his impact on the formation of an Italianate sensibility in the appreciation of the visual arts in Early Modern England. In the realm of science, Fialetti’s influence can be deduced from his drawings of curiously animated cadavers in detailed landscapes to those of future generations of anatomists and illustrators throughout Europe. Because of the diverse associations and projects throughout his career, the study of Fialetti is inherently interdisciplinary, encompassing the history of art, history of science and history of the Venetian book trade, as well as crossing geographical boundaries in linking Venetian art and English tastes of the late renaissance and early baroque. Through examination of his extant oeuvre, as well as discussion of lost work, I aim to recognise Fialetti’s status as an artist responding to contemporary artistic debates (disegno versus colorito), a changing cultural climate and the burgeoning importance of the printed medium

    Fundamental group and twisted Alexander polynomial of link complement in 3-torus

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    We consider a diagrammatic approach to investigate tame knots and links in three dimensional torus T3T^3. We obtain a finite set of generalised Reidemeister moves for equivalent links up to ambient isotopy. We give a presentation for fundamental group of link complement in 3-torus T3T^3 and the first homology group. We also compute Alexander polynomial and twisted Alexander polynomials of this class of links.Comment: 21 pages. arXiv admin note: text overlap with arXiv:1209.6532, arXiv:1606.03224 by other author
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