347,295 research outputs found

    RNA-dependent association with myosin IIA promotes F-actin-guided trafficking of the ELAV-like protein HuR to polysomes

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    The role of the mRNA-binding protein human antigen R (HuR) in stabilization and translation of AU-rich elements (ARE) containing mRNAs is well established. However, the trafficking of HuR and bound mRNA cargo, which comprises a fundamental requirement for the aforementioned HuR functions is only poorly understood. By administering different cytoskeletal inhibitors, we found that the protein kinase Cδ (PKCδ)-triggered accumulation of cytoplasmic HuR by Angiotensin II (AngII) is an actin-myosin driven process functionally relevant for stabilization of ARE-bearing mRNAs. Furthermore, we show that the AngII-induced recruitment of HuR and its bound mRNA from ribonucleoprotein particles to free and cytoskeleton bound polysomes strongly depended on an intact actomyosin cytoskeleton. In addition, HuR allocation to free and cytoskeletal bound polysomes is highly sensitive toward RNase and PPtase and structurally depends on serine 318 (S318) located within the C-terminal RNA recognition motif (RRM3). Conversely, the trafficking of the phosphomimetic HuRS318D, mimicking HuR phosphorylation at S318 by the PKCδ remained PPtase resistant. Co-immunoprecipitation experiments with truncated HuR proteins revealed that the stimulus-induced association of HuR with myosin IIA is strictly RNA dependent and mediated via the RRM3. Our data implicate a microfilament dependent transport of HuR, which is relevant for stimulus-induced targeting of ARE-bearing mRNAs from translational inactive ribonucleoprotein particles to polysomes

    New monophyletic branches of the teloschistaceae (lichen-forming ascproved by three gene phylogenyomycota)

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    Seventeen robust monophyletic branches newly discovered in the phylogenetic tree of the Teloschistaceae after separate nrITS, nrLSU and mtSSU, as well as combined phylogenetic analysis are proposed to consider as the following separate genera: Dijigiella S. Y. Kondr. et L. Lo′kös gen. nov. for the D. kaernefeltiana group, Elixjohnia S. Y. Kondr. et J.-S. Hur gen. nov. for the Sirenophila jackelixii group, Fominiella S. Y. Kondr., D. Upreti et J.-S. Hur gen. nov. for the F. tenerifensis group; Gintarasiella S. Y. Kondr. et J.-S. Hur gen. nov. for Caloplaca aggregata, Hanstrassia S. Y. Kondr. gen. nov. for the Elenkiniana lenae group, Harusavskia S. Y. Kondr. gen. nov. for H. elenkinianoides sp. n., Huriella S. Y. Kondr. et D. Upreti gen. nov. for H. loekoesiana sp. n., Ikaeria S. Y. Kondr., D. Upreti et J.-S. Hur gen. nov. for Caloplaca aurantiellina, Klauderuiella S. Y. Kondr. et J.-S. Hur gen. nov. for the Variospora thallincola group, Laundonia S. Y. Kondr., L. Lo′kös et J.-S. Hur gen. nov. for the Gyalolechia flavovirescens group, Lazarenkoiopsis S. Y. Kondr., L. Lo′kös et J.-S. Hur gen. nov. for Caloplaca ussuriensis, Nevilleiella S. Y. Kondr. et J.-S. Hur gen. nov. for the Caloplaca marchantii group, Opeltia S. Y. Kondr. et L. Lo′kös gen. nov. for the Caloplaca neobaltistanica group, Oxneriopsis S. Y. Kondr., D. Upreti et J.-S. Hur gen. nov. for the Caloplaca oxneri group, Teuvoahtiana S. Y. Kondr. et J.-S. Hur gen. nov. for the Caloplaca rugulosa group, Tomnashia S. Y. Kondr. et J.-S. Hur gen. nov. for the Polycauliona rosei group, and Xanthaptychia S. Y. Kondr. et S. Ravera gen. nov. for the Seirophora orientalis group. Hitherto missing molecular data on three gene sequences of the type species of the genera Seirophora and Sirenophila are completed within this study. Six new to science species (Dijigiella kaernefeltiana S. Y. Kondr. sp. n., D. subaggregata S. Y. Kondr. et Kärnefelt sp. n., Fominiella tenerifensis S. Y. Kondr., Kärnefelt, A. Thell et T. Feuerer sp. n., Hanstrassia jaeseounhurii S. Y. Kondr., Ch.-H. Park et L. Lo′kös sp. n., Harusavskia elenkinianoides S. Y. Kondr., X. Y. Wang, S.-O. Oh et J.-S. Hur sp. n., Huriella loekoesiana S. Y. Kondr. et D. Upreti sp. n.) are described, compared with closely related taxa. A total of 34 new combinations for genera mentioned above are proposed

    Hur, S

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    Kaposin-B enhances the PROX1 mRNA stability during lymphatic reprogramming of vascular endothelial cells by Kaposi's sarcoma herpes virus.

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    Kaposi's sarcoma (KS) is the most common cancer among HIV-positive patients. Histogenetic origin of KS has long been elusive due to a mixed expression of both blood and lymphatic endothelial markers in KS tumor cells. However, we and others discovered that Kaposi's sarcoma herpes virus (KSHV) induces lymphatic reprogramming of blood vascular endothelial cells by upregulating PROX1, which functions as the master regulator for lymphatic endothelial differentiation. Here, we demonstrate that the KSHV latent gene kaposin-B enhances the PROX1 mRNA stability and plays an important role in KSHV-mediated PROX1 upregulation. We found that PROX1 mRNA contains a canonical AU-rich element (ARE) in its 3'-untranslated region that promotes PROX1 mRNA turnover and that kaposin-B stimulates cytoplasmic accumulation of the ARE-binding protein HuR through activation of the p38/MK2 pathway. Moreover, HuR binds to and stabilizes PROX1 mRNA through its ARE and is necessary for KSHV-mediated PROX1 mRNA stabilization. Together, our study demonstrates that kaposin-B plays a key role in PROX1 upregulation during lymphatic reprogramming of blood vascular endothelial cells by KSHV

    Diffusive author(s), cohesive author: Analysis of S/N (1994)

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    This study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    An SMT Encoding of LLVM’s Memory Model for Bounded Translation Validation

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    © 2021, The Author(s).Several automatic verification tools have been recently developed to verify subsets of LLVMs optimizations. However, none of these tools has robust support to verify memory optimizations. In this paper, we present the first SMT encoding of LLVMs memory model that 1) is sufficiently precise to validate all of LLVMs intra-procedural memory optimizations, and 2) enables bounded translation validation of programs with up to hundreds of thousands of lines of code. We implemented our new encoding in Alive2, a bounded translation validation tool, and used it to uncover 21 new bugs in LLVM memory optimizations, 10 of which have been already fixed. We also found several inconsistencies in LLVM IRs official specification document (LangRef) and fixed LLVMs code and the document so they are in agreement.Y

    Biomarkers in emergency medicine

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    Researchers navigate the ocean of biomarkers searching for proper targets and optimal utilization of them. Emergency medicine builds up the front line to maximize the utility of clinically validated biomarkers and is the cutting edge field to test the applicability of promising biomarkers emerging from thorough translational researches. The role of biomarkers in clinical decision making would be of greater significance for identification, risk stratification, monitoring, and prognostication of the patients in the critical- and acute-care settings. No doubt basic research to explore novel biomarkers in relation to the pathogenesis is as important as its clinical counterpart. This special issue includes five selected research papers that cover a variety of biomarker- and disease-related topics

    LRRK2 and membrane trafficking: nexus of Parkinson's disease

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    Recent evidence from genetics, animal model systems and biochemical studies suggests that defects in membrane trafficking play an important part in the pathophysiology of Parkinson's disease (PD). Mutations in leucine-rich repeat kinase 2 (LRRK2) constitute the most frequent genetic cause of both familial and sporadic PD, and LRRK2 has been suggested as a druggable target for PD. Although the precise physiological function of LRRK2 remains largely unknown, mounting evidence suggests that LRRK2 controls membrane trafficking by interacting with key regulators of the endosomal-lysosomal pathway and synaptic recycling. In this review, we discuss the genetic, biochemical and functional links between LRRK2 and membrane trafficking. Understanding the mechanism by which LRRK2 influences such processes may contribute to the development of disease-modifying therapies for PD.OAIID:RECH_ACHV_DSTSH_NO:T201912980RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080672CITE_RATE:3.085FILENAME:2019_BMB_LRRK2.pdfDEPT_NM:수의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/05f9710e-4c31-4d16-ab9c-7c379b86ccb2/linkN
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