Effets de l’expérience sur la perception de mélanges odorants chez l’Homme adulte et le lapereau nouveau-né

 Prix du meilleur poster• L’organisme est exposé à un environnement chimique complexe (mélanges d’odorants) duquel il doit extraire l’information.• Un signal véhiculé par un mélange peut être perçu de façon analytique AB = A+B et/ou synthétique AB = M (mélange)• Homme ->perception d’un mélange AB de façon partiellement synthétique (Le Berre et al.,2008)• Lapereaux -> perception du mélange AB de façon synthétique et analytique (Coureaud et al., 2008, 2009)Objectifs : Comment l’expérience influence-t-elle la perception de ce mélange AB et de ses composants A et B?Qu’en est-il pour un mélange perçu initialement de façon analytique (AC ou CD)

New treatment options for lupus – a focus on belimumab

Belimumab is the first biologic approved for patients with systemic lupus erythematosus (SLE). Belimumab is the first of a new class of drug targeting B cell-stimulating factors or their receptors to reach the market. Its target, BLyS, also known as BAFF (B cell-activating factor from the tumor necrosis factor family), is a type II transmembrane protein that exists in both membrane-bound and soluble forms. Additionally to a robust rational from murine experiments conducted in lupus prone mice, BLyS circulating levels are increased in SLE patients. After the negative results of a Phase II trial, two Phase III trials met their primary endpoints. Some SLE patients are still refractory to the standard options of care or necessitate prolonged high-dose corticotherapy and/or long-term immunosuppressive regimens. However, some experts still feel that the effect of this biologic might not be clinically relevant and blame the use of the new systemic lupus response index as well as the discrepancies between both trials and the noninclusion of the severe form of the disease as nephritis. In this review, we aim to discuss the characteristics of belimumab, critically evaluate the different steps of its development, and consider its future place in the arsenal against SLE, taking into account the patients’ perspectives

The Role of Natural Killer Cells in Sepsis

Severe sepsis and septic shock are still deadly conditions urging to develop novel therapies. A better understanding of the complex modifications of the immune system of septic patients is needed for the development of innovative immunointerventions. Natural killer (NK) cells are characterized as CD3−NKp46+CD56+ cells that can be cytotoxic and/or produce high amounts of cytokines such as IFN-γ. NK cells are also engaged in crosstalks with other immune cells, such as dendritic cells, macrophages, and neutrophils. During the early stage of septic shock, NK cells may play a key role in the promotion of the systemic inflammation, as suggested in mice models. Alternatively, at a later stage, NK cells-acquired dysfunction could favor nosocomial infections and mortality. Standardized biological tools defining patients' NK cell status during the different stages of sepsis are mandatory to guide potential immuno-interventions. Herein, we review the potential role of NK cells during severe sepsis and septic shock

Genomic analysis of the secretion stress response in the enzyme-producing cell factory Aspergillus niger

<p>Abstract</p> <p>Background</p> <p>Filamentous fungi such as <it>Aspergillus niger </it>have a high capacity secretory system and are therefore widely exploited for the industrial production of native and heterologous proteins. However, in most cases the yields of non-fungal proteins are significantly lower than those obtained for fungal proteins. One well-studied bottleneck appears to be the result of mis-folding of heterologous proteins in the ER during early stages of secretion, with related stress responses in the host, including the unfolded protein response (UPR). This study aims at uncovering transcriptional and translational responses occurring in <it>A. niger </it>exposed to secretion stress.</p> <p>Results</p> <p>A genome-wide transcriptional analysis of protein secretion-related stress responses was determined using Affymetrix DNA GeneChips and independent verification for selected genes. Endoplasmic reticulum (ER)-associated stress was induced either by chemical treatment of the wild-type cells with dithiothreitol (DTT) or tunicamycin, or by expressing a human protein, tissue plasminogen activator (t-PA). All of these treatments triggered the UPR, as shown by the expression levels of several well-known UPR target genes. The predicted proteins encoded by most of the up-regulated genes function as part of the secretory system including chaperones, foldases, glycosylation enzymes, vesicle transport proteins, and ER-associated degradation proteins. Several genes were down-regulated under stress conditions and these included several genes that encode secreted enzymes. Moreover, translational regulation under ER stress was investigated by polysomal fractionation. This analysis confirmed the post-transcriptional control of <it>hacA </it>expression and highlighted that differential translation also occurs during ER stress, in particular for some genes encoding secreted proteins or proteins involved in ribosomal biogenesis and assembly.</p> <p>Conclusion</p> <p>This is first genome-wide analysis of both transcriptional and translational events following protein secretion stress. Insight has been gained into the molecular basis of protein secretion and secretion-related stress in an effective protein-secreting fungus, and provides an opportunity to identify target genes for manipulation in strain improvement strategies.</p

Responses to hydric stress in the seed-borne necrotrophic fungus Alternaria brassicicola

Alternaria brassicicola is a necrotrophic fungus causing black spot disease and is an economically important seed-borne pathogen of cultivated brassicas. Seed transmission is a crucial component of its parasitic cycle as it promotes long-term survival and dispersal. Recent studies, conducted with the Arabidopsis thaliana/A. brassicicola pathosystem, showed that the level of susceptibility of the fungus to water stress strongly influenced its seed transmission ability. In this study, we gained further insights into the mechanisms involved in the seed infection process by analyzing the transcriptomic and metabolomic responses of germinated spores of A. brassicicola exposed to water stress. Then, the repertoire of putative hydrophilins, a group of proteins that are assumed to be involved in cellular dehydration tolerance, was established in A. brassicicola based on the expression data and additional structural and biochemical criteria. Phenotyping of single deletion mutants deficient for fungal hydrophilin-like proteins showed that they were affected in their transmission to A. thaliana seeds, although their aggressiveness on host vegetative tissues remained intact

Analysis of a compartmental model of endogenous immunoglobulin G metabolism with application to multiple myeloma

Immunoglobulin G (IgG) metabolism has received much attention in the literature for two reasons: (i) IgG homeostasis is regulated by the neonatal Fc receptor (FcRn), by a pH-dependent and saturable recycling process, which presents an interesting biological system; (ii) the IgG-FcRn interaction may be exploitable as a means for extending the plasma half-life of therapeutic monoclonal antibodies, which are primarily IgG-based. A less-studied problem is the importance of endogenous IgG metabolism in IgG multiple myeloma. In multiple myeloma, quantification of serum monoclonal immunoglobulin plays an important role in diagnosis, monitoring and response assessment. In order to investigate the dynamics of IgG in this setting, a mathematical model characterizing the metabolism of endogenous IgG in humans is required. A number of authors have proposed a two-compartment nonlinear model of IgG metabolism in which saturable recycling is described using Michaelis-Menten kinetics; however it may be difficult to estimate the model parameters from the limited experimental data that are available. The purpose of this study is to analyse the model alongside the available data from experiments in humans and estimate the model parameters. In order to achieve this aim we linearize the model and use several methods of model and parameter validation: stability analysis, structural identifiability analysis, and sensitivity analysis based on traditional sensitivity functions and generalized sensitivity functions. We find that all model parameters are identifiable, structurally and taking into account parameter correlations, when several types of model output are used for parameter estimation. Based on these analyses we estimate parameter values from the limited available data and compare them with previously published parameter values. Finally we show how the model can be applied in future studies of treatment effectiveness in IgG multiple myeloma with simulations of serum monoclonal IgG responses during treatment

Anàlisi territorial de la preinscripció al sistema universitari públic de Catalunya. L’efecte distància–temps des del domicili habitual en l’elecció de centre i estudi.

[cat] La mobilitat obligada per raó d'estudi analitza els desplaçaments dels alumnes entre el seu lloc de residencia i el lloc d'estudi en qualsevol de les etapes educatives, des dels ensenyaments primaris obligatoris fins als superiors. En aquest sentit, doncs, el fenomen de la mobilitat es consubstancial a la mateixa universitat ja des dels seus inicis esdevenint avui un fenomen complex fent-se necessari, per entendre'I en tota la seva magnitud, identificar-ne tant els diferents actors que hi intervenen com les diferents escales geogràfiques que abasta, el mare formal en el que es desenvolupa i la seva direccionalitat. En aquest context, l'objectiu principal que persegueix aquesta recerca es el d'esbrinar els criteris i patrons que determinen l'elecció de centre i estudi per part dels estudiants residents a Catalunya que accedeixen per primer cop a l'oferta de titulacions de les universitats catalanes que participen del procés de preinscripció (UB, UAB, UPC, UPF, Udl, UdG, URV i UVic) tot confeccionant un mapa de fluxos de la mobilitat d'aquest col·lectiu al llarg del per1ode que abasta del curs 2000-01 al 2013-14 per a, tal vegada, obtenir orientacions sobre el seu comportament futur. D'aquesta manera, emprant com a font principal de dades els fitxers del sistema UNEIX sobre els estudiants matriculats de nou accés en cadascuna d'aquestes universitats per a cada any acadèmic analitzat i a partir de la comarca d'origen d'aquest estudiantat (aquella on tenen establert el seu domicili habitual, generalment el familiar) s'han determinat en primer lloc l'àrea d'influència i de captació d'aquestes institucions per tal d'esbrinar quina es la seva presencia i pes específic en el territori i, en segon terme, s'han identificat tres dinàmiques de comportament dels estudiant a l'hora d'escollir centre i estudi segons sigui la distancia que separa aquest domicili de la ubicació de l'oferta universitària. Tot plegat, pretén resoldre el problema que planteja el desconeixement existent en l'actualitat de les relacions complexes que s'estableixen entre la selecció d'estudis universitaris i centre amb les xarxes de transport i la mobilitat induïda dels estudiants del sistema universitari de Catalunya.[eng] Mobility forced by study reasons analyses the students' travels between their place of residence and the study location in any of the formative stages: from mandatory elementary studies to higher education. In this sense, the mobility phenomenon is consubstantial to university itself from the very start, currently growing up to be a complex phenomenon. In order to be able to understand it to its fullest, it is then necessary to identify the various actors participating in it, the different geographical scales reached, as well as the formal framework in which it is carried out, and its directionality.In this contex the main objective of this research is to find out the criteria and patterns that prompt the choice of centre and studies by the students residing in Catalonia accessing for the very first time the degree's offer from the Catalan universities taking part of the pre­ registration process (UB, UAB, UPC, UPF, Udl , UdG, URV and UVic), by composing a flow map of this collective's mobility within the period covering the academic years 2000/01 to 2013/ 14, so as to perhaps obtain orientations on their future behaviour.In this way, and by using as a primary source the data from the UNEIX system files on freshman students, sorted by each of the aforementioned universities and academic year, and based on the county of origin of this student body (the one where their permanent address is estabilshed, generally this being the home address), the following has been determined: first, these institutions' influence and acquisition area in order to find out their actual presence and specific weight within the territory; and, second, three students' behaviour dynamics regarding their centre and studies choice, depending on the distance separating their place of residence and the location of the university offer.All of that hopes to solve the problem resulting from the currently existing ignorance on the complex relations established vis a vis the university studies and centre selection, and the transport network and induced mobility of the Catalan university system's students

Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview

The breast tissue is the site of major metabolic conversions of estradiol (E(2)) mediated by specific cytochromes P450 hydroxylations and methylation by catechol-O-methytransferase. In addition to E(2 )itself, recent findings highlight the significance of 4-hydroxylated estrogen metabolites as chemical mediators and their link to breast cancer development and progression, whereas, in opposition, 2-methoxylated estrogens appear to be protective. Recent data also indicate that breast tissue possesses enzymatic machinery to inactivate and eliminate E(2 )and its oxidized and methoxylated metabolites through conjugation catalyzed by UDP-glucuronosyltransferases (UGTs), which involves the covalent addition of glucuronic acid. In opposition to other metabolic pathways of estrogen, the UGT-mediated process leads to the formation of glucuronides that are devoid of biologic activity and are readily excreted from the tissue into the circulation. This review addresses the most recent findings on the identification of UGT enzymes that are responsible for the glucuronidation of E(2 )and its metabolites, and evidence regarding their potential role in breast cancer

Jouer en bibliothèque

Le développement du jeu vidéo mais également l’engouement des jeunes adultes pour les jeux de plateau, l’utilisation de dispositifs ludiques comme outils de médiation ou associés aux apprentissages sont venus prolonger les services des ludothèques et conduisent les bibliothèques à se réinventer pour devenir les lieux naturels où permettre la pratique de l’expérience du jeu dans toutes ses dimensions. Le plan s’organise autour de quatre parties : connaître le contexte (les espaces, les équipes, le droit), acquérir/valoriser (les fonds, jouets et serious games), animer/créer (projet de service, partenariats, médiation), et participer (une approche orientée communauté)