Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties

Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway

: In this paper, we investigate the structural and biological features of G-quadruplex (G4) aptamers as promising antiproliferative compounds affecting the STAT3 signalling pathway. Targeting the STAT3 protein through high-affinity ligands to reduce its levels or activity in cancer has noteworthy therapeutic potential. T40214 (STAT) [(G3C)4] is a G4 aptamer that can influence STAT3 biological outcomes in an efficient manner in several cancer cells. To explore the effects of an extra cytidine in second position and/or of single site-specific replacements of loop residues in generating aptamers that can affect the STAT3 biochemical pathway, a series of STAT and STATB [GCG2(CG3)3C] analogues containing a thymidine residue instead of cytidines was prepared. NMR, CD, UV, and PAGE data suggested that all derivatives adopt dimeric G4 structures like that of unmodified T40214 endowed with higher thermal stability, keeping the resistance in biological environments substantially unchanged, as shown by the nuclease stability assay. The antiproliferative activity of these ODNs was tested on both human prostate (DU145) and breast (MDA-MB-231) cancer cells. All derivatives showed similar antiproliferative activities on both cell lines, revealing a marked inhibition of proliferation, particularly at 72 h at 30 µM. Transcriptomic analysis aimed to evaluate STAT's and STATB's influence on the expression of many genes in MDA-MB-231 cells, suggested their potential involvement in STAT3 pathway modulation, and thus their interference in different biological processes. These data provide new tools to affect an interesting biochemical pathway and to develop novel anticancer and anti-inflammatory drugs

The notion of core collocation : a corpus-based study with teaching applications

L'objet d'étude de la présente recherche est la notion de « collocation fondamentale ». Nous calquons ce terme sur celui de « vocabulaire fondamental », issu de la dénomination Français fondamental utilisée par Gougenheim et al. (1964) pour désigner le vocabulaire de base de la langue française. Dans la thèse, les collocations fondamentales sont envisagées comme des unités polylexicales significatives (unies par des liens collocationnels) fréquentes (dans l'usage) ou non fréquentes (lorsqu'elles sont pertinentes pour la communication) qui représentent pour les locuteurs natifs les contextes de cooccurrence les plus essentiels et les plus typiques d'un mot pivot donné. Les études descriptives ou acquisitionnelles sur les collocations sont assez récentes et, à notre connaissance, ne se sont pas encore intéressées à cette notion, qui devrait pourtant constituer une étape préliminaire cruciale dans toute approche didactique destinée aux apprenants de langue étrangère. La présente étude se veut une recherche qualitative et quantitative d'un échantillon de collocations fondamentales constitué à partir de dix substantifs pivots représentant des « événements sociaux ». Le corpus que nous avons analysé est frWac (Baroni et al., 2010), un très vaste corpus écrit issu du Web analysé à l'aide de scripts Perl développés par Olivier Kraif (2011). A partir des pivots choisis, nous avons extrait de ce corpus les associations candidates au statut de collocations fondamentales ; puis nous avons demandé à 90 locuteurs natifs du français de sélectionner celles qui leur apparaissaient essentielles pour la communication. L'objectif a été d'évaluer, à l'aide de l'intuition de locuteurs natifs, la validité de l'échantillon automatiquement constitué, et de comprendre de quoi dépendait l'assignation du caractère fondamental de la part des enquêtés. Nous avons obtenu deux résultats principaux : - En premier lieu, nous avons constaté l'existence d'une corrélation faiblement positive, mais non systématique, entre la fréquence des associations dans le corpus et le score obtenu pour les associations sélectionnées par les locuteurs natifs. - En second lieu, nous avons constaté que lorsque la fréquence ne jouait pas de rôle, pour les enquêtés, dans l'attribution du caractère fondamental, alors la cause était à chercher dans le figement. En effet, dans des cas singuliers, les associations peu fréquentes sont sélectionnées parce qu'elles comportent un certain degré de figement ; à l'inverse, les associations les plus fréquentes sont exclues parce qu'elles sont perçues comme libres. Enfin, nous avons présenté la notion de collocation fondamentale en vue d'une exploitation didactique : à travers l'analyse de la structuration du domaine sémantique des « événements sociaux » qui nous a servi d'exemple, nous avons montré l'importance du repérage des « collocations fondamentales » afin d'opérer la sélection du vocabulaire à enseigner en classe de FLE.The focus of the present study is the concept of core collocation. This term is defined with reference to the core vocabulary list produced by Gougenheim et al. (1964), Le Français Fondamental. Despite the fact that the importance of this list is broadly acknowledged, a critical point is that the analysis of the syntagmatic level was neglected. From this awareness, we develop the main focus of the present research and our basic assumption that the criteria applied to define core vocabulary, mainly frequency and availability, should be equally applied to define core collocations, a key concept in L2 teaching. We define core collocations as significative (the collocational relation), frequent (the usage) or available (essential for accomplishing basic communicative tasks) units representing the most basic co-occurrences of a word. This study aims to define core collocations through the investigation of a sample of collocations associated with ten basic nouns in a lexical area of interest for second language learners, the one of social relations. The corpus that we investigated is frWaC (Baroni et al., 2010), a lemmatized web-derived corpus assembled through automated procedures crawling the Web. The corpus was analyzed using a tool based on programming scripts Perl developed by Olivier Kraif (2011). The extraction tool makes use of frequency, dispersion and four associative measures (mutual information, log likelihood, t-score and z-score) and produces concordance lines. We chose the ten pivot nouns, we extracted the most frequent and available collocations and we evaluated the extracted sample through a comparison between 90 native speakers' intuitions about core collocations with statistical data. The results of the present research can be summarized as follows: - Since the most frequent collocations also received the highest number of votes by the tested subjects, we claim that frequency is a crucial feature in dictating the lexical choices made by speakers. However, some associations represent outliers: they are deviating points from the normal distribution of correlation between frequency and coreness attributed by native speakers. We might conclude that there is a certain linear correlation between the two variables but that this correlation is not systematic. - What is core is not only a matter of frequency, but it also depends on units' fixedness. Native speakers sometimes ignore frequent associations since they have a loose degree of fixedness, being rather free combinations; whereas other times they chose low frequent associations that they perceive as being very fixed. This study finally draws important pedagogical implications. The analysis of core collocations in the semantic area of “social relations” served us to explain which criteria can be adopted to run a filter across the wide set of phraseological units a given word produces, helping L2 teachers to find criteria to select the essential items to be taught first

Core vocabulary and core collocations: combining corpus analysis and native speaker judgement to inform selection of collocations in learner dictionaries

International audienceThis paper presents the concepts of “core vocabulary” and “core collocations” and discusses implications for the treatment of collocations in monolingual learner phraseological dictionaries. In the first section, we give an account of what the above concepts refer to by drawing on previous research. In the second part, we present the findings from a study (Benigno et al., 2015; Benigno et al., forthcoming) using L1 speaker judgements to validate a method to automatically extract core collocations from frWaC (Baroni et al., 2010), a very large web-corpus. The study aims to identify what features can be used to define and filter “core collocations” from a set of potential candidates – which were retrieved from the corpus by means of frequency, dispersion, and associative measures and then subjected to the evaluation of a group of native speakers who were asked to decide about the importance of collocations to communicate in everyday situations. Findings from the study showed that frequency is an appropriate but not sufficient measure to identify such central and nuclear units in language. In fact native speakers seem to attach importance (intended as usefulness in language use) to highly restricted and fixed units regardless of their frequency of occurrence - providing evidence of the fact that what is core is not systematically a matter of frequency. Based on these findings, the third part of the paper deals with phraseology from the lexicographical perspective and argues that in learner dictionaries both frequency and usefulness should serve as main organizing principles. Our discussion will be accompanied by practical examples extracted from the “Longman Collocations Dictionary and Thesaurus”, a learner dictionary informed by corpus data as well as by pedagogical judgements of expert lexicographers

Core vocabulary and core collocations: combining corpus analysis and native speaker judgement to inform selection of collocations in learner dictionaries

International audienceThis paper presents the concepts of “core vocabulary” and “core collocations” and discusses implications for the treatment of collocations in monolingual learner phraseological dictionaries. In the first section, we give an account of what the above concepts refer to by drawing on previous research. In the second part, we present the findings from a study (Benigno et al., 2015; Benigno et al., forthcoming) using L1 speaker judgements to validate a method to automatically extract core collocations from frWaC (Baroni et al., 2010), a very large web-corpus. The study aims to identify what features can be used to define and filter “core collocations” from a set of potential candidates – which were retrieved from the corpus by means of frequency, dispersion, and associative measures and then subjected to the evaluation of a group of native speakers who were asked to decide about the importance of collocations to communicate in everyday situations. Findings from the study showed that frequency is an appropriate but not sufficient measure to identify such central and nuclear units in language. In fact native speakers seem to attach importance (intended as usefulness in language use) to highly restricted and fixed units regardless of their frequency of occurrence - providing evidence of the fact that what is core is not systematically a matter of frequency. Based on these findings, the third part of the paper deals with phraseology from the lexicographical perspective and argues that in learner dictionaries both frequency and usefulness should serve as main organizing principles. Our discussion will be accompanied by practical examples extracted from the “Longman Collocations Dictionary and Thesaurus”, a learner dictionary informed by corpus data as well as by pedagogical judgements of expert lexicographers

La ricorrenza del lessico di base in produzioni scritte di italiano L2 e L1

This paper discusses the results of an experiment designed to analyze lexical richness, operationalized in terms of lexical frequency, in the written production of a group of L2 learners and native speakers of Italian. The data are derived from the CALC study (Communicative Adequacy and Linguistic Complexity in L2 writing; cfr. Kuiken / Vedder / Gilabert 2010; Vedder 2012), set up to investigate the relationship between communicative adequacy and linguistic complexity in L2 and L1 writing (Italian, Dutch, Spanish), in relation to the Common European Framework of References (CEFR; Council of Europe, 2001). The present study focuses on the data of the L2 learners and native speakers of Italian. The first research question discussed in the study concerns the relationship between lexical richness and the general proficiency level of L2 learners. The second question addresses lexical richness in the written texts of Dutch low-intermediate and intermediate learners of Italian, compared to that of native speakers of Italian and assessed by means of a lexical frequency profiling method (Laufer / Nation 1995). The participants are 39 Dutch university students of Italian, with a proficiency level ranging from A2 to B1, and 18 native speakers of Italian, enrolled in an Italian university. In the study the participants had to carry out two writing tasks, consisting of a short essay in which an opinion had to be reported about factual information. To establish the general language proficiency in L2 a C-test and the DIALANG placement test were administered. Results show that although a relationship between lexical richness and language proficiency in L2 could not be demonstrated, there appeared to be significant differences in lexical richness between the L2 and L1 writers. The paper concludes with a discussion of the development of lexical richness in Italian L2

Les collocations fondamentales : une piste pour l’apprentissage lexical.

International audienceLes listes de fréquence (listes de base, élémentaires, etc.) ont connu un certain succès pédagogique, notamment en France à la suite des travaux pionniers de Gougenheim. Cependant, les recherches étaient restées centrées sur l’unité-mot, sans prendre en compte les associations lexicales les plus fréquentes de la langue, associations qui fonctionnent comme de véritables unités lexico-grammaticales. Notre contribution vise à préciser la relation entre fréquence et jugement pour l’identification du caractère “fondamental” des unités polylexicales et avance l’hypothèse que le figement de ces unités joue un rôle dans le choix opéré par les locuteurs natifs. Nous proposons ensuite quelques pistes didactiques à partir d’une étude de corpus réalisée dans le domaine des “événements sociaux”

Les collocations fondamentales : une piste pour l’apprentissage lexical.

International audienceLes listes de fréquence (listes de base, élémentaires, etc.) ont connu un certain succès pédagogique, notamment en France à la suite des travaux pionniers de Gougenheim. Cependant, les recherches étaient restées centrées sur l’unité-mot, sans prendre en compte les associations lexicales les plus fréquentes de la langue, associations qui fonctionnent comme de véritables unités lexico-grammaticales. Notre contribution vise à préciser la relation entre fréquence et jugement pour l’identification du caractère “fondamental” des unités polylexicales et avance l’hypothèse que le figement de ces unités joue un rôle dans le choix opéré par les locuteurs natifs. Nous proposons ensuite quelques pistes didactiques à partir d’une étude de corpus réalisée dans le domaine des “événements sociaux”

La notion de collocation fondamentale : une étude de corpus

International audienceDans cette étude les « collocations fondamentales » sont envisagées comme des unités polylexicales significatives (unies par des liens collocationnels) fréquentes (dans l’usage) ou non fréquentes (lorsqu’elles sont pertinentes pour la communication) qui représentent pour les locuteurs natifs les contextes les plus essentiels d’un mot donné. Nous avons extrait du corpus frWaC (Baroni et al. 2010) environ 20 000 associations à partir de dix mots pivots issus du Dictionnaire Fondamental de Gougenheim (1971) ; puis, au moyen de la fréquence et de mesures d’association, nous avons sélectionné un échantillon d’environ 400 associations candidates au statut de collocations fondamentales et demandé à 90 locuteurs natifs du français de sélectionner celles qui leur apparaissaient essentielles pour la communication. L’objectif était : a) de développer une méthode pour le repérage automatique des collocations fondamentales ; et b) d’évaluer, à l’aide de l’intuition de locuteurs natifs, la validité de l’échantillon automatiquement constitué et de comprendre de quoi dépendait l’assignation du caractère fondamental de la part des enquêtés. Nous avons constaté que, lorsque la fréquence ne jouait pas de rôle, pour les enquêtés, dans l’attribution du caractère fondamental la cause était à chercher dans le figement. D’après les résultats obtenus, nous avons pu confirmer l’intuition gougenheimienne sur l’équation fondamental = fréquence et/ou utilité communicative