FXR: un récepteur aux acides biliaires comme cible pour le traitement du cancer de la prostate - Étude des effets de FXR en lignées cellulaires

FXR est un récepteur nucléaire qui s’est démontré avoir des effets ambivalents dans le contexte de différents cancers. Son effet dans le cancer de la prostate (PCa) est peu documenté. Nous avons observé une répression des enzymes UGT2B15 et 2B17, les enzymes d’élimination des hormones androgènes; ces dernières ont un rôle prépondérant dans la croissance du PCa, suggérant que l’activation de FXR pourrait avoir un effet pro-prolifératif dans le PCa. Ce projet vise à évaluer le potentiel de trois agonistes (6-ECDCA, CDCA, GW4064) dans des lignées de PCa androgéno-dépendantes (LNCaP, LAPC-4) et androgéno-indépendantes (DU-145, VCaP et LN95). À l’opposé des résultats attendus, un effet antiprolifératif fut observé caractérisé par un arrêt du cycle cellulaire et une induction de l’apoptose. Une inhibition transcriptionelle du récepteur aux androgènes fut obtenue, exposant un avantage de FXR sur les traitements actuels du PCa. Les résultats recueillis ici proposent FXR comme nouvelle cible thérapeutique pour le PCa.FXR is a nuclear receptor that exerts ambivalent effects in multiple cancers. FXR signaling in prostate cancer (PCa) is not yet defined, but recent observations indicate that its activation represses two major androgen-metabolizing enzymes, namely UGT2B15 and 2B17. Based on this observation, we proposed that FXR acts as a pro-carcinogenic agent that may promote the development of androgen-dependent PCa tumors. The aim of this project is to evaluate the potential of three FXR agonist’s (6-ECDCA, CDCA, GW4064) in androgen-dependent (LNCaP, LAPC-4) and androgen-independent (DU-145, VCaP, LN95) PCa cell lines. Unexpectedly, anti-proliferative effects were observed, characterized by a cell cycle blockade and an induction of apotosis. Furthermore, a negative transcriptional regulation of the androgen receptor was observed, exposing an advantage of FXR over the actual PCa treatment. Results collected here propose FXR as a new target to medicate PCa

A Type System for Privacy Properties (Technical Report)

Mature push button tools have emerged for checking trace properties (e.g. secrecy or authentication) of security protocols. The case of indistinguishability-based privacy properties (e.g. ballot privacy or anonymity) is more complex and constitutes an active research topic with several recent propositions of techniques and tools. We explore a novel approach based on type systems and provide a (sound) type system for proving equivalence of protocols, for a bounded or an unbounded number of sessions. The resulting prototype implementation has been tested on various protocols of the literature. It provides a significant speed-up (by orders of magnitude) compared to tools for a bounded number of sessions and complements in terms of expressiveness other state-of-the-art tools, such as ProVerif and Tamarin: e.g., we show that our analysis technique is the first one to handle a faithful encoding of the Helios e-voting protocol in the context of an untrusted ballot box

The role of parental achievement goals in predicting autonomy-supportive and controlling parenting

Although autonomy-supportive and controlling parenting are linked to numerous positive and negative child outcomes respectively, fewer studies have focused on their determinants. Drawing on achievement goal theory and self-determination theory, we propose that parental achievement goals (i.e., achievement goals that parents have for their children) can be mastery, performance-approach or performance-avoidance oriented and that types of goals predict mothers' tendency to adopt autonomy-supportive and controlling behaviors. A total of 67 mothers (aged 30-53 years) reported their goals for their adolescent (aged 13-16 years; 19.4 % girls), while their adolescent evaluated their mothers' behaviors. Hierarchical regression analyses showed that parental performance-approach goals predict more controlling parenting and prevent acknowledgement of feelings, one autonomy-supportive behavior. In addition, mothers who have mastery goals and who endorse performance-avoidance goals are less likely to use guilt-inducing criticisms. These findings were observed while controlling for the effect of maternal anxiety

Population Projections and Demographic Knowledge in France and Great Britain in the Postwar Period

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111965/1/padr47.pd

Des routes et des hommes : la construction des échanges par les itinéraires et les transports

Les circulations humaines façonnent le paysage montagnard, traçant les routes qui permettent de franchir les obstacles, de créer un lien avec la plaine, de développer les activités économiques. Portant sur une diversité de territoires, cet ouvrage nous invite à mieux comprendre comment l’homme a ouvert des passages pour dépasser les frontières naturelles et culturelles des montagnes. La présentation de découvertes archéologiques, l’analyse de sources méconnues, l’étude du rôle de la technique et de la cartographie en dressent un panorama allant de l’Antiquité au xxe siècle. Le Congrès national des sociétés historiques et scientifiques rassemble chaque année universitaires, membres de sociétés savantes et jeunes chercheurs. Ce recueil est issu de travaux présentés lors du 142e Congrès sur le thème « Circulations montagnardes, circulations européennes »

Missing data in craniometrics: a simulation study

International audienceCraniometric measurements represent a useful tool for studying the differentiation of mammal populations. However, the fragility of skulls often leads to incomplete data matrices. Damaged specimens or incomplete sets of measurements are usually discarded prior to statistical analysis. We assessed the performance of two strategies that avoid elimination of observations: (1) pairwise deletion of missing cells, and (2) estimation of missing data using available measurements. The effect of these distinct approaches on the computation of inter-individual distances and population differentiation analyses were evaluated using craniometric measurements obtained from insular populations of deer mice Peromyscus maniculatus (Wagner, 1845). In our simulations, Euclidean distances were greatly altered by pairwise deletion, whereas Gower's distance coefficient corrected for missing data provided accurate results. Among the different estimation methods compared in this paper, the regression-based approximations weighted by coefficients of determination (r(2)) outperformed the competing approaches. We further show that incomplete sets of craniometric measurements can be used to compute distance matrices, provided that an appropriate coefficient is selected. However, the application of estimation procedures provides a flexible approach that allows researchers to analyse incomplete data sets

Le depistage de la tuberculose par l'epreuve a la cuti-bcg et les rayons-X

Une campagne spéciale et systématique de dépistage de la tuberculose, lancée à Arvida, en 1960, a permis de radiographier 75% de la population de plus de 10 ans, et d'éprouver l'allergie de 67$ de la population totale (14,500 habitants). Au cours de cette même année, 42 cas de tuberculose pulmonaire active ont été trouvés en circulation dans Arvida, soit 1 personne sur 347. Près de la moitié de ces cas furent dépistés au cours de la campagne. Au moyen de l'épreuve allergique quantitative appelée Cuti-BCG, employée parallèlement à la radiographie, le taux de prévalence de l'infection tube5rculeuse a été établi chez les non vaccinés à 6 ans, 10 ans, #4 ans et 25-29 ans. Ces taux sont respectivement de 7.1%, de 20.4%, 40.5% et 63.6% à 3 mm et plus, et de 3.86, 11.7, 29.4 et 43.8 à 4 mm et plus, et de 0.6, 2.5, 12.2 et 16.5 à 8-10 mm et plus. L'étude comparative de l'image radiologique et de l'intensité de la réaction à la Cuti-BCG montre que le risque de maladie active augmente avec l'intensité de la réaction. L'application systématique et rationalisée de cette épreuve dans une population pourrait permettre de faire converger économiquement le dépistage radiologique vers les catégories d'individus dans lesquelles les chances sont les plus grandes de trouver la maladie.</p

The identity of Argyria lacteella (Fabricius, 1794) (Lepidoptera, Pyraloidea, Crambinae), synonyms, and related species revealed by morphology and DNA capture in type specimens

In this study the aim was to resolve the taxonomy of several species of Argyria Hübner (Pyraloidea, Crambinae) with previously unrecognised morphological variation. By analysing the DNA barcode (COI-5P) in numerous specimens, the aim was to reconstruct phylogenetic relationships between species, to provide better evidence for synonymies, and to circumscribe their geographical distribution. Using an innovative DNA hybridisation capture protocol, the DNA barcode of the lectotype of Argyria lacteella (Fabricius, 1794) was partially recovered for comparison with the 229 DNA barcode sequences of Argyria specimens available in the Barcode of Life Datasystems, and this firmly establishes the identity of the species. The same protocol was used for the following type specimens: the Argyria abronalis (Walker, 1859) holotype, thus confirming the synonymy of this name with A. lacteella, the holotype of A. lusella (Zeller, 1863), syn. rev., the holotype of A. multifacta Dyar, 1914, syn. nov. newly synonymised with A. lacteella, and a specimen of Argyria diplomochalis Dyar, 1913, collected in 1992. In addition, nine specimens of A. lacteella, A. diplomochalis, A. centrifugens Dyar, 1914 and A. gonogramma Dyar, 1915, from North to South America were sampled using classical COI amplification and Sanger sequencing. Argyria gonogramma Dyar, described from Bermuda, is the name to be applied to the more widespread North American species formerly identified as A. lacteella. Following morphological study of its holotype, Argyria vestalis Butler, 1878, syn. nov. is also synonymised with A. lacteella. The name A. pusillalis Hübner, 1818, is considered a nomen dubium associated with A. gonogramma. The adult morphology is diagnosed and illustrated, and distributions are plotted for A. lacteella, A. diplomochalis, A. centrifugens, and A. gonogramma based on slightly more than 800 specimens. For the first time, DNA barcode sequences are provided for the Antillean A. diplomochalis. This work provides a modified, improved protocol for the efficient hybrid capture enrichment of DNA barcodes from 18th and 19th century type specimens in order to solve taxonomic issues in Lepidoptera