The CAN Protein: A Mediator of Nuc1eocytoplasmic Transport with Oncogenic Properties

The starting point of the work described in tius thesis was a novel gene, CAN, that had been cloned by virtue of its involvement in translocation (6;9) (von Lindern, 1990), a recurrent chromosomal aberration defining a specific subtype of acute myeloid leukemia. Tills gene's predicted amino acid sequence showed no homology to known proteins (chapter 3), and therefore its cellular function was unknown. The protein encoded by CANIs fusion partner in the (6;9) translocation, DEK, also had no significant homology to proteins in the database. Consequently, the role of the chimeric DEK-CAN fusion protein in t(6;9)-associated leukemogenesis was a complete mystery. In addition, illl'itl'o studies to show the oncogenic function ofDEK-CAN consistently proved unsuccessful (M. von Lindem, J. Boer, G. Grosveld, unpublished results). To gain understanding of the possible function ofDEK-CAN, as well as the normal cellular functions ofDEK and CAN, we analyzed their primary amino acid stmctures (chapter 3 and 4), studied their subcellular localization (chapter 3), and looked for interacting proteins (chapter 5 and 6). In these studies, we focused on the CAN protein, since this protein had also been found in another leukemia-related fusion protein, SET-CAN (von Lindem, 1992), which suggests that it could playa more general role in leukemogenesis. In view of the difficulty reproducing the oncogenic effect of the DEK-CAN gene in vitro, and toxic effects caused by overexpression of DEK-CAN, we also set out to create an ill vivo system to mimic translocation (6;9) in transgenic mice using Cre-mediated recombination (chapter 8)

Bibliothèque dans la cuisine : l\u27atelier "bonne recette et apprendre" de la médiathèque Monnaie (Une)

Regard sur les ateliers de cuisine organisés par la médiathèque Monnaie des pays de Romans

Anti-idiotype RNAs that mimic the leucine-rich nuclear export signal and specifically bind to CRM1/exportin 1

AbstractBackground: Anti-idiotype approaches are based on the assumption that an antibody recognising a ligand can be structurally related to the receptor. Recently we have generated anti-idiotype RNA aptamers designed to mimic the human immunodeficiency virus-1 (HIV-1) Rev nuclear export signal (NES). Nuclear injection of either NES–peptide conjugates or aptamer causes the inhibition of Rev-mediated export. This implied that NES mimics and export substrate might compete for binding to the NES receptor. The mechanism of inhibition, however, is unknown.Results: The interaction between the export aptamer and CRM1 was characterised in vitro. The aptamer binds specifically to CRM1 and this interaction is sensitive to competition by Rev NES–peptide conjugates. The recognition domain of CRM1 has been mapped and includes residues found previously to affect binding of leptomycin B, a fungicide interfering with nuclear export.Conclusions: Inhibition of Rev-mediated export in vivo by export aptamers appears to result from the binding of the aptamers to the NES-recognition domain of CRM1. This observation demonstrates that anti-idiotype RNA can mimic faithfully structural and functional properties of a protein and can be used to map ligand-binding domains of receptors

Microfluidics of binary liquid mixtures with temperature-dependent miscibility

Liquid–liquid microfluidic systems rely on the intricate control over the fluid properties of either miscible or immiscible mixtures. Herein, we report on the use of partially miscible binary liquid mixtures that lend their microfluidic properties from a highly temperature-sensitive mixing and phase separation behaviour. For a blend composed of the thermotropic liquid crystal 4-cyano-4′-pentylbiphenyl (5CB) and methanol, mixing at temperatures above the upper critical solution temperature (UCST; 24.4 °C) leads to a uniform single phase while partial mixing can be achieved at temperatures below the UCST. Thermally-driven phase separation inside the microfluidic channels results in the spontaneous formation of very regular phase arrangements, namely in droplets, plug, slug and annular flow. We map different flow regimes and relate findings to the role of interfacial tension and viscosity and their temperature dependence. Importantly, different flow regimes can be achieved at constant channel architecture and flow rate by varying the temperature of the blend. A consistent behaviour is observed for a binary liquid mixture with lower critical solution temperature, namely 2,6-lutidine and water. This temperature-responsive approach to microfluidics is an interesting candidate for multi-stage processes, selective extraction and sensing applications

Chromatin organization in relation to the nuclear periphery

AbstractIn the limited space of the nucleus, chromatin is organized in a dynamic and non-random manner. Three ways of chromatin organization are compaction, formation of loops and localization within the nucleus. To study chromatin localization it is most convenient to use the nuclear envelope as a fixed viewpoint. Peripheral chromatin has both been described as silent chromatin, interacting with the nuclear lamina, and active chromatin, interacting with nuclear pore proteins. Current data indicate that the nuclear envelope is a reader as well as a writer of chromatin state, and that its influence is not limited to the nuclear periphery

Le refuge des gens d’Église catholiques à Genève (1600‑1620)

Cette étude examine les modalités concrètes à travers lesquelles s’opère le changement de foi d’ex-membres du clergé catholique réfugiés à Genève. Si la Compagnie des pasteurs se soucie étroitement de l’instruction religieuse de ces migrants, c’est à travers leur capacité à s’insérer dans l’ordre social régi par la discipline ecclésiastique et à s’y conformer qu’elle éprouve la sincérité de leur conversion. Au centre du rapport qui unit le prosélyte à l’institution intervient la question de l’attestation, qui témoigne de la qualité de la relation et en constitue un enjeu principal. L’expérience de la conversion ne peut donc être envisagée qu’une fois replacée dans le cadre d’une confrontation entre un individu et les institutions qui définissent les modèles religieux et les normes censées encadrer et contrôler tout parcours de foi.This study examines the concrete modalities through which a change of faith occurred in former Catholic clergymen who moved to Geneva. While the Company of Pastors took great care with the religious instruction of these migrants, the sincerity of their conversion was tested through their capacity to fit into the social order governed by ecclesiastical discipline and to conform to it. At the centre of the relationship that joined the proselyte to the institution was the delivery of a certificate, which reflected the good quality of this relationship and was its main object. The experience of conversion should thus be reconsidered within the context of a confrontation between an individual and the institutions that define religious models and norms intended to supervise, direct and control every journey of faith

Introduction

Dans la plupart des pays européens, le patrimoine culturel religieux, immobilier et mobilier, constitue une part significative de l’héritage historique et artistique. Ces monuments familiers du paysage européen, tant rural qu’urbain, offrent un double visage, à la fois culturel et spirituel, qui renvoie à deux corpus de règles juridiques. En effet, le statut de biens utilisés à des fins de pratiques religieuses fait l’objet d’un encadrement légal spécifique, fondé sur la protection de la libe..

Jours fériés et fêtes religieuses

Historiquement, les jours fériés reconnus par la loi correspondent pour un certain nombre d’entre eux à des fêtes religieuses chrétiennes. Sous l’effet de la sécularisation, ces jours ont perdu une grande partie et pour certains la totalité de leur lien avec une pratique cultuelle. Or, la pluralisation des courants religieux se traduit par des demandes qui renvoient au contraire à un lien étroit entre fêtes et pratiques religieuses. C’est ce qu’illustre la question des autorisations d’absence pour fêtes religieuses tant pour les agents publics que les employés du secteur privé.Historically, the law enshrines public holidays that correspond to Christian feasts. As a result of secularization, these days have lost a large part and for some of them their entire link with religious practice. However, at the same time, the pluralization of religious currents is reflected in requests that refer to a close link between holidays and religious practices. This is illustrated by the issue of leave of absence for religious holidays for both public and private sector employees

Les édifices cultuels et la liberté de culte pendant l’état d’urgence sanitaire

La législation adoptée en France pendant l’état d’urgence sanitaire est synonyme de limitation voire de suppression des libertés, les contraintes et interdictions ayant porté principalement sur les droits et libertés liés à la dimension corporelle des individus, tandis que sont préservés les droits et libertés de l’esprit. Cette distinction découlerait de la scission de « l’unité de notre expérience vitale, qui est toujours inséparablement corporelle et spirituelle en même temps, en une entit..

Menus de substitution dans les cantines scolaires : de la laïcité à l’intérêt supérieur de l’enfant

Dans un jugement du 28 août 2017, le tribunal administratif de Dijon s’est à nouveau prononcé sur la décision prise par le maire de Chalon-sur-Saône de ne plus proposer de menus de substitution dès lors qu’un plat contenant du porc serait servi dans les cantines scolaires de la ville. Précédemment, dans une ordonnance du 12 août 2015, le tribunal administratif de Dijon, saisi cette fois dans le cadre d’un référé suspension, avait rejeté la requête de la Ligue de défense judiciaire des musulma..