35 research outputs found

    Pro-invasive stimuli and the interacting protein Hsp70 favour the route of alpha-enolase to the cell surface

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    Cell surface expression of alpha-enolase, a glycolytic enzyme displaying moonlighting activities, has been shown to contribute to the motility and invasiveness of cancer cells through the protein non-enzymatic function of binding plasminogen and enhancing plasmin formation. Although a few recent records indicate the involvement of protein partners in the localization of alpha-enolase to the plasma membrane, the cellular mechanisms underlying surface exposure remain largely elusive. Searching for novel interactors and signalling pathways, we used low-metastatic breast cancer cells, a doxorubicin-resistant counterpart and a non-tumourigenic mammary epithelial cell line. Here, we demonstrate by a combination of experimental approaches that epidermal growth factor (EGF) exposure, like lipopolysaccharide (LPS) exposure, promotes the surface expression of alpha-enolase. We also establish Heat shock protein 70 (Hsp70), a multifunctional chaperone distributed in intracellular, plasma membrane and extracellular compartments, as a novel alpha-enolase interactor and demonstrate a functional involvement of Hsp70 in the surface localization of alpha-enolase. Our results contribute to shedding light on the control of surface expression of alpha-enolase in non-tumourigenic and cancer cells and suggest novel targets to counteract the metastatic potential of tumours

    Detecting significant features in modeling microRNA-target interactions

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    MicroRNAs (miRNAs) are small non-coding RNA molecules mediating the translational repression and degradation of target mRNAs in the cell. Mature miRNAs are used as a template by the RNA-induced silencing complex (RISC) to recognize the complementary mRNAs to be regulated. Up to 60% of human genes are putative targets of one or more miRNAs. Several prediction tools are available to suggest putative miRNA targets, however, only a small part of the interaction pairs has been validated by experimental approaches. The analysis of the expression profile of the RNA fraction immunoprecipitated (IP) with the RISC proteins is an established method to detect which genes are actually regulated by the RISC machinery. In fact, genes that result over-expressed in the IP sample with respect to the whole cell lysate RNA, are considered as involved in the RISC complex, then miRNA targets. Here, we aim to find the features useful to predict which genes are overexpressed in IP, i.e. miRNA targets, without actually performing the IP experiments. To this purpose, we compiled and analyzed a novel high throughput data set suitable to unravel the features involved in the miRNA regulatory activities. We analyzed IP samples obtained by the immunoprecipitation of two RISC proteins, AGO2 and GW182. The two proteins shows different behaviors, in terms of enriched genes and features characterizing the immunoprecipitated RNA fractio. Further analysis is needed to unravel the reason of such different behavior

    On the Multi-Language Construction

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    Modern software is no more developed in a single programming language. Instead, programmers tend to exploit cross-language interoperability mechanisms to combine code stemming from different languages, and thus yielding fully-fledged multi-language programs. Whilst this approach enables developers to benefit from the strengths of each single-language, on the other hand it complicates the semantics of such programs. Indeed, the resulting multi-language does not meet any of the semantics of the combined languages. In this paper, we broaden the boundary functions-based approach a la Matthews and Findler to propose an algebraic framework that provides a constructive mathematical notion of multi-language able to determine its semantics. The aim of this work is to overcome the lack of a formal method (resp., model) to design (resp., represent) a multi-language, regardless of the inherent nature of the underlying languages. We show that our construction ensures the uniqueness of the semantic function (i.e., the multi-language semantics induced by the combined languages) by proving the initiality of the term model (i.e., the abstract syntax of the multi-language) in its category

    Le schématisme linguistique chez K.L. Reinhold

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    abstract : In this paper, I propose to reconsider the philosophy of language of K.L. Reinhold (1757-1823). The matter has not been explored so far, since, usually, Reinhold's work is only considered as a bridge between Kant's philosophy and the nature idealism of Fichte, Schelling and Hegel. However, Reinhold doesn't pave the way for subjectivism and absolute idealism. On the contrary, his theory is based on the perceptive and linguistic systems. According to Reinhold's idea, many cognitive functions that idealism assigns to the absolute Subject are in fact perceptive competences. In this view, oral language is considered as the faculty of the (metaphoric) connection between perception and the mental structure. In this paper, I shall try to show how the role assigned to language is based on a linguistic interpretation of Kant's transcendental schematism.resume : En dĂ©pit de son image courante, la philosophie du langage de K.L. Reinhold (1757-1823) — visĂ©e par cet article — ne prĂ©pare pas le terrain au subjectivisme et Ă  l'idĂ©alisme. Bien au contraire, elle consiste dans un examen de la facultĂ© cognitive humaine tenant compte des dispositifs de mĂ©diation perceptive et linguistique. FondĂ©e sur une thĂ©orie de la sensibilitĂ© d'inspiration empiriste, elle dĂ©place au niveau perceptif plusieurs des fonctions que l'idĂ©alisme va attribuer au sujet absolu. Dans une telle perspective, le langage est conçu en tant que facteur de mĂ©diation (mĂ©taphorique) entre la sensibilitĂ© et le reste de l'articulation cognitive supĂ©rieure, l'auteur suggĂšre, Ă  la base de cette fonction, l'existence d'une interprĂ©tation linguistique du schĂ©matisme transcendantal de Kant.Perconti Pietro, Palancher J.-P. Le schĂ©matisme linguistique chez K.L. Reinhold. In: Histoire ÉpistĂ©mologie Langage, tome 18, fascicule 2, 1996. L'esprit et le langage. pp. 29-43

    Introduction

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    The book is devoted to three key questions concerning the relationship between complexity and natural language. Briefly, such questions are: (a) What kind of complexity for natural language? (b) Which theory of language in the perspective of complexity? (c) What sorts of methods and models in the analysis of the observed phenomena? All the essays in this volume show the reference to complexity as a constant element. However, the use of the singular may not be entirely appropriate
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