Towards a full higher order AD-based continuation and bifurcation framework

International audienceSome of the theoretical aspects of continuation and bifurcation methods devoted to the solution for nonlinear parametric systems are presented in a higher-order automatic differentiation (HOAD) framework. Besides benefits in terms of generality and ease of use, HOAD is used to assess fold and simple bifurcations points. In particular, the formation of a geometric series in successive Taylor coefficients allows for the implementation of an efficient detection and branch switching method at simple bifurcation points. Some comparisons with the Auto and MatCont continuation software are proposed. Strengths are then exemplified on a classical case study in structural mechanics

Reconstitution of archaeal H/ACA small ribonucleoprotein complexes active in pseudouridylation

Pseudouridine (Ψ) are frequently modified residues in RNA. In Eukarya, their formation is catalyzed by enzymes or by ribonucleoprotein complexes (RNPs) containing H/ACA snoRNAs. H/ACA sRNA and putative ORFs for H/ACA sRNP proteins (L7Ae, aCBF5, aNOP10 and aGAR1) were found in Archaea. Here, by using Pyrococcus abyssi recombinant proteins and an in vitro transcribed P.abyssi H/ACA sRNA, we obtained the first complete in vitro reconstitution of an active H/ACA RNP. Both L7Ae and the aCBF5 RNA:Ψ synthase bind directly the sRNA; aCBF5 also interacts directly and independently with aNOP10 and aGAR1. Presence of aCBF5, aNOP10 and a U residue at the pseudouridylation site in the target RNA are required for RNA target recruitment. In agreement, we found that the aCBF5–aNOP10 pair is the minimal set of proteins needed for the formation of a particle active for pseudouridylation. However, particles more efficient in targeted pseudouridylation can be formed with the addition of proteins L7Ae and/or aGAR1. Although necessary for optimal activity, the conserved ACA motif in the sRNA was found to be not essential

Identification of determinants in the protein partners aCBF5 and aNOP10 necessary for the tRNA:Ψ55-synthase and RNA-guided RNA:Ψ-synthase activities

Protein aNOP10 has an essential scaffolding function in H/ACA sRNPs and its interaction with the pseudouridine(Ψ)-synthase aCBF5 is required for the RNA-guided RNA:Ψ-synthase activity. Recently, aCBF5 was shown to catalyze the isomerization of U55 in tRNAs without the help of a guide sRNA. Here we show that the stable anchoring of aCBF5 to tRNAs relies on its PUA domain and the tRNA CCA sequence. Nonetheless, interaction of aNOP10 with aCBF5 can counterbalance the absence of the PUA domain or the CCA sequence and more generally helps the aCBF5 tRNA:Ψ55-synthase activity. Whereas substitution of the aNOP10 residue Y14 by an alanine disturbs this activity, it only impairs mildly the RNA-guided activity. The opposite effect was observed for the aNOP10 variant H31A. Substitution K53A or R202A in aCBF5 impairs both the tRNA:Ψ55-synthase and the RNA-guided RNA:Ψ-synthase activities. Remarkably, the presence of aNOP10 compensates for the negative effect of these substitutions on the tRNA: Ψ55-synthase activity. Substitution of the aCBF5 conserved residue H77 that is expected to extrude the targeted U residue in tRNA strongly affects the efficiency of U55 modification but has no major effect on the RNA-guided activity. This negative effect can also be compensated by the presence of aNOP10

Lymphocyte Cell-Cycle Inhibition by HLA-G Is Mediated by Phosphatase SHP-2 and Acts on the mTOR Pathway

Human leukocyte antigen G (HLA-G) is involved in regulating T-cell responses through its interaction with inhibitory receptors belonging to the immunoglobulin-like transcript family (ILT). In this context, we investigated the pathways involved in the control of cell-cycle entry of T cells following HLA-G interaction with its inhibitory receptor. We show that HLA-G acts through its interaction with the LILRB1 receptor expressed on T lymphocytes. Both HLA-G and LILRB1 antibodies block the inhibitory effect of HLA-G and restore T-cell proliferation. The interaction of HLA-G with T lymphocytes is associated with phosphorylation of SHP-2 phosphatase, but not SHP-1. In addition, in activated T cells, their incubation with HLA-G is not associated with a decrease in the TCR or CD28 downstream pathways, but is associated with dephosphorylation of the mTOR molecule and p70S6K. In contrast, Akt, which acts upstream of mTOR, is not affected by HLA-G. The inhibition of SHP-2 by NSC-87877(5 µM), a chemical inhibitor of SHP-2, or the use of siRNA, abrogates dephosphorylation of mTOR and impairs the overexpression of p27kip in the presence of HLA-G. Together, these results indicate that HLA-G is associated with activation of phosphatase SHP-2, which inhibits the mTOR pathway and favors the inhibition of the cell-cycle entry of human-activated T cells

Differentiation Therapy: Targeting Human Renal Cancer Stem Cells with Interleukin 15

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Pengaruh Kesadaran Politik terhadap Pasrtisipasi Politik Masyarakat Kecamatan Tenayan Raya dalam Pemilihan Umum Walikota Pekanbaru Tahun 2017

One manifestation of political consciousness is political participation in the election of the mayor. Political participation based on political consciousness will encourage people to exercise their right to vote rationally and in accordance with the aspirations of the people. But in reality, the level of voter participation in the election mayor of Pekanbaru in 2017 is still lacking. Percentage of voters\u27 participation in sub district Tenayan Raya only reached 43.72%, which means there are still many voters who did not participate that reached 56.28%. This study aims to explain the effect of political awareness on political participation. This study uses quantitative descriptive by spreading questionnaires to 100 respondents in four urban villages in Tenayan Raya sub district, then the data is analyzed by using logistic regression. Based on the result of research, it can be concluded that there is a significant influence between political awareness on political participation because the value of p value Chi-Square 13,105 > Chi-Square table 3,841. In the Pseudo R Square table of 16.4% political awareness contribution to political participation, in other words 83.6% other factors from outside the model that explain the dependent variable. Based on the analysis of political awareness data of Tenayan Raya sub-district is low down to 68%, while the political participation of Tenayan Raya community in the election of mayor of Pekanbaru is also categorized as low by 94%

Guides optiques infrarouges pour la détection du CO2

session affiches A7 " Instrumentation, Caractérisation et Capteurs " [A7.1]National audienceL'équipe Verres et Céramiques développe des fibres optiques originales qui sont à la base de la réalisation de capteur optique opérant dans l'infrarouge. L'intérêt et le potentiel de ces capteurs ont été démontrés dans des domaines variés, notamment en biologie et en médecine. L'objet de ce travail consiste à exploiter ce savoir faire pour réaliser des guides optiques permettant la détection et le monitoring du CO2. Des premiers résultats ont été obtenus en transmission classique entre deux fibres infrarouges. Ils ont montré qu'il est possible de détecter jusqu'à 0.5% de CO2. L'objectif actuel est d'améliorer la sensibilité de détection au dioxyde de carbone par une augmentation de la surface de contact gaz-fibre, en utilisant des fibres microstructurées. Une autre voie consiste à fabriquer des guides planaires qui nous permettent d'envisager, à terme, la réalisation de micro-composants optiques en verre de chalcogénure avec une robustesse et une compacité accrue

human renal cancer cells express a novel membrane bound interleukin 15 that induces in response to the soluble interleukin 15 receptor α chain epithelial to mesenchymal transition

Although interleukin-15 (IL-15) is a powerful immunomodulatory factor that has been proposed for cancer immunotherapy, its intratumoral expression may be correlated with tumor progression and/or poor clinical outcome. Therefore, neoplasias potentially sensitive to immunotherapy should be checked for their IL-15 expression and function before choosing immunotherapy protocols. Primary human renal cancer cells (RCC) express a novel form of membrane-bound IL-15 (mb-IL-15), which displays three major original properties: (a) It is expressed as a functional membrane homodimer of 27 kDa, (b) it is shed in the extracellular environment by the metalloproteases ADAM17 and ADAM10, and (c) its stimulation by soluble IL-15 receptor α (s-IL-15Rα) chain triggers a complex reverse signal (mitogen-activated protein kinases, FAK, pMLC) necessary and sufficient to ~induce epithelial-mesenchymal transdifferentiation (EMT), a crucial process in tumor progression whose induction is unprecedented for IL-15. In these cells, complete EMT is characterized by a dynamic reorganization of the cytoskeleton with the subsequent generation of a mesenchymal/contractile phenotype (α-SMA and vimentin networks) and the loss of the epithelial markers E-cadherin and ZO-1. The retrosignaling functions are, however, hindered through an unprecedented cytokine/receptor interaction of mb-IL-15 with membrane-associated IL-15Rα subunit that tunes its signaling potential competing with low concentrations of the s-IL-15Rα chain. Thus, human RCC express an IL-15/IL-15R system, which displays unique biochemical and functional properties that seem to be directly involved in renal tumoral progression. [Cancer Res 2009;69(4):1561–9