1,006 research outputs found

    La SCOP, l'institution, et la culture comme compromis(sion)

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    International audienceWhat is happening when an institution hires an “educational cooperative” for its participative expertise to redefine both its cultural policy, its mediation methods and its internal management ? Our contribution aims at restoring collaboration between two organizations which, although they are driven by the same desire (and the same imperative) to produce “participatory”, do not share either its definition or its issues. For one, participatory should be a way to reform the common methods of cultural environment; for the other, it must lead to a political turmoil. From our scientific residence, we would like to describe the divisions and affinities between the two approaches that try to investigate together what "participate" means.Que se passe-t-il, lorsqu’une institution municipale en appelle à l’expertise « participative » d’une Scop d’éducation populaire pour redéfinir à la fois sa politique culturelle, ses méthodes de médiation et sa gestion interne de la prise de décision ? Notre contribution vise à restituer le parcours d’une collaboration entre deux structures qui, quoiqu’étant mues par la même volonté (et par le même impératif) de faire participation, n’en partagent ni la définition, ni les enjeux. Pour l’une, le participatif doit conduire à une réforme des méthodes ordinaires du milieu culturel ; pour l’autre, il doit conduire à un renouveau global de l’ordre politique. A partir d’une résidence scientifique commune dans un Centre consacré aux questions mémorielles, nous aimerions restituer les clivages et les affinités entre deux démarches qui s’emploient à explorer ensemble ce que « participer » veut dire

    A new paradigm in the Gulf abstract

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    [Extract] On June 5th2017 Saudi Arabia, United Arab Emirates, Bahrain and Egypt (the “Quartet”) cut their relations with Qatar. The Quartet decided to withdraw their ambassadors and impose a travel and trade ban. This has caught Qatar by surprise, which did not expect such drastic steps to be taken. Due to the Quartet actions the financial outflows and the costs have been massive for Qatar, but the system can absorb great shocks because of accumulated reserves and the income from the export of gas. The financial burden is nevertheless hitting the state hard, and it will be more and more difficult to sustain the current level of expenditure. So far Qatar has managed to adjust to the new reality mainly thanks to the financial reserves accumulated in the last two decades, the use of networks and an effective PR/lobbying campaign

    Editorial: Prion and prion-like proteins in neurodegenerative diseases

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    Des associations de femmes migrantes au sein de la société civile

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    Si la féminisation est une des grandes tendances des phénomènes migratoires depuis les années 1990, les femmes migrantes restent relativement invisibles dans les espaces publics des sociétés d’accueil, où elles demeurent la cible de représentations stéréotypées. L’invisibilité sociale de ces femmes se nourrit aussi des rôles qu’on leur fixe et des discours attendus auxquels elles doivent correspondre. Ce type d’assignations culturelles ou identitaires se retrouve dans les échanges entre les associations de femmes migrantes et d’autres acteurs associatifs

    Modelling the positioning of single needle electrodes for the treatment of breast cancer in a clinical case

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    Background: Breast cancer is the most common cancer in women worldwide and is the second most common cause of cancer death in women. Electrochemotherapy (ECT) used in early-phase clinical trials for the treatment of primary breast cancer resulted in a not complete tumor necrosis in most cases. The present study was undertaken to analyze the feasibility to use ECT to treat patients with histologically proven unifocal ductal breast cancer. In particular, results of ECT treatment in a clinical case are compared with the ones of a simplified 3D dosimetric model. Methods: This clinical study was conducted with the pulse generator Cliniporator Vitae (IGEA, Carpi, Italy). ECT procedures were performed according to ESOPE standard operating procedures. Five single needle electrodes were used with one positioned in the center of the tumor, and the other four distributed around the nodule. Histological images of the resected tumor are compared with the maps of the electric field obtained with a simplified 3D model in Comsol Multiphysics v 4.3. Results: The results of the clinical case demonstrated a reduced efficacy of the ECT treatment described. The proposed simple numerical model of the breast tumor located in a low conductive tissue suggests that this is due to the reduced electric field induced inside the tumor with such 5 electrodes placement. However, where the electric field is predicted higher than the reversible electroporation threshold (E > 400 V/cm), also the histological images confirm the necrosis of the target with a good agreement between the modeled and clinical results. Conclusions: The results suggest the dependence of the effectiveness of the treatment on the careful placement of the electrodes. A detailed planned procedure for the tumor analysis after the treatment is also needed in order to better correlate the single electrode positions and the histological images. Simulation models could be used to identify better electrodes configuration in planning the experimental protocol for ECT treatment of breast tumors

    Binding to DPF-motif by the POB1 EH domain is responsible for POB1-Eps15 interaction

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    <p>Abstract</p> <p>Background</p> <p>Eps15 homology (EH) domains are protein interaction modules binding to peptides containing Asn-Pro-Phe (NPF) motifs and mediating critical events during endocytosis and signal transduction. The EH domain of POB1 associates with Eps15, a protein characterized by a striking string of DPF triplets, 15 in human and 13 in mouse Eps15, at the C-terminus and lacking the typical EH-binding NPF motif.</p> <p>Results</p> <p>By screening a multivalent nonapeptide phage display library we have demonstrated that the EH domain of POB1 has a different recognition specificity since it binds to both NPF and DPF motifs. The region of mouse Eps15 responsible for the interaction with the EH domain of POB1 maps within a 18 amino acid peptide (residues 623–640) that includes three DPF repeats. Finally, mutational analysis in the EH domain of POB1, revealed that several solvent exposed residues, while distal to the binding pocket, mediate specific recognition of binding partners through both hydrophobic and electrostatic contacts.</p> <p>Conclusion</p> <p>In the present study we have analysed the binding specificity of the POB1 EH domain. We show that it differs from other EH domains since it interacts with both NPF- and DPF-containing sequences. These unusual binding properties could be attributed to a different conformation of the binding pocket that allows to accommodate negative charges; moreover, we identified a cluster of solvent exposed Lys residues, which are only found in the EH domain of POB1, and influence binding to both NPF and DPF motifs. The characterization of structures of the DPF ligands described in this study and the POB1 EH domain will clearly determine the involvement of the positive patch and the rationalization of our findings.</p

    A multifactorial \u2018Consensus Signature\u2019 by in silico analysis to predict response to neoadjuvant anthracycline-based chemotherapy in triple-negative breast cancer

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    BACKGROUND: Owing to the complex processes required for anthracycline-induced cytotoxicity, a prospectively defined multifactorial Consensus Signature (ConSig) might improve prediction of anthracycline response in triple-negative breast cancer (TNBC) patients, whose only standard systemic treatment option is chemotherapy. AIMS: We aimed to construct and evaluate a multifactorial signature, comprising measures of each function required for anthracycline sensitivity in TNBC. METHODS: ConSigs were constructed based on five steps required for anthracycline function: drug penetration, nuclear topoisomerase II\u3b1 (topoII\u3b1) protein location, increased topoII\u3b1 messenger RNA (mRNA) expression, apoptosis induction, and immune activation measured by, respectively, HIF1\u3b1 or SHARP1 signature, LAPTM4B mRNA, topoII\u3b1 mRNA, Minimal Gene signature or YWHAZ mRNA, and STAT1 signature. TNBC patients treated with neoadjuvant anthracycline-based chemotherapy without taxane were identified from publicly available gene expression data derived with Affymetrix HG-U133 arrays (training set). In silico analyses of correlation between gene expression data and pathological complete response (pCR) were performed using receiver-operating characteristic curves. To determine anthracycline specificity, ConSigs were assessed in patients treated with anthracycline plus taxane. Specificity, sensitivity, positive and negative predictive value, and odds ratio (OR) were calculated for ConSigs. Analyses were repeated in two validation gene expression data sets derived using different microarray platforms. RESULTS: In the training set, 29 of 147 patients had pCR after anthracycline-based chemotherapy. Various combinations of components were evaluated, with the most powerful anthracycline response predictors being ConSig1: (STAT1+topoII\u3b1 mRNA +LAPTM4B) and ConSig2: (STAT1+topoII\u3b1 mRNA+HIF1\u3b1). ConSig1 demonstrated high negative predictive value (85%) and high OR for no pCR (3.18) and outperformed ConSig2 in validation sets for anthracycline specificity. CONCLUSIONS: With further validation, ConSig1 may help refine selection of TNBC patients for anthracycline chemotherapy

    p53-sensitive epileptic behavior and inflammation in Ft1 hypomorphic mice

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    Epilepsy is a complex clinical condition characterized by repeated spontaneous seizures. Seizures have been linked to multiple drivers including DNA damage accumulation. Investigation of epilepsy physiopathology in humans imposes ethical and practical limitations, for this reason model systems are mostly preferred. Among animal models, mouse mutants are particularly valuable since they allow conjoint behavioral, organismal, and genetic analyses. Along with this, since aging has been associated with higher frequency of seizures, prematurely aging mice, simulating human progeroid diseases, offer a further useful modeling element as they recapitulate aging over a short time-window. Here we report on a mouse mutant with progeroid traits that displays repeated spontaneous seizures. Mutant mice were produced by reducing the expression of the gene Ft1 (AKTIP in humans). In vitro, AKTIP/Ft1 depletion causes telomere aberrations, DNA damage, and cell senescence. AKTIP/Ft1 interacts with lamins, which control nuclear architecture and DNA function. Premature aging defects of Ft1 mutant mice include skeletal alterations and lipodystrophy. The epileptic behavior of Ft1 mutant animals was age and sex linked. Seizures were observed in 18 mutant mice (23.6% of aged ≥ 21 weeks), at an average frequency of 2.33 events/mouse. Time distribution of seizures indicated non-random enrichment of seizures over the follow-up period, with 75% of seizures happening in consecutive weeks. The analysis of epileptic brains did not reveal overt brain morphological alterations or severe neurodegeneration, however, Ft1 reduction induced expression of the inflammatory markers IL-6 and TGF-β. Importantly, Ft1 mutant mice with concomitant genetic reduction of the guardian of the genome, p53, showed no seizures or inflammatory marker activation, implicating the DNA damage response into these phenotypes. This work adds insights into the connection among DNA damage, brain function, and aging. In addition, it further underscores the importance of model organisms for studying specific phenotypes, along with permitting the analysis of genetic interactions at the organismal level

    Influence of Myeloperoxidase Levels on Periodontal Disease: An Applied Clinical Study

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    In this trial, we evaluated the influence on plasma and salivary myeloperoxidase (MPO) levels of periodontal health, coronary heart disease (CHD), periodontitis, or both periodontitis and CHD. Clinical and periodontal parameters were collected from periodontitis patients (n = 31), CHD patients (n = 31), patients with both periodontitis and CHD (n = 31), and from healthy patients (n = 31) together with saliva and plasma samples. The median concentrations of salivary and plasma MPO were statistically higher in the CHD patients [plasma: 26.2 (18.2–34.4) ng/mg; saliva 83.2 (77.4–101.5) ng/mL, p < 0.01] and in the periodontitis plus CHD patients [plasma: 27.8 (22.5–35.7) ng/mg; saliva 85.6 (76.5–106.7) ng/mL, p < 0.001] with respect to periodontitis and control patients. Through a univariate regression analysis, c-reactive protein (CRP) and CHD (both p < 0.001) and periodontitis (p = 0.024) were statistically correlated with MPO in plasma. The multivariate regression analysis demonstrated that only CRP was statistically the predictor of MPO in plasma (p < 0.001). The multivariate regression analysis in saliva demonstrated that, regarding MPO levels the only predictors were CRP (p < 0.001) and total cholesterol (p = 0.035). The present study evidenced that subjects with CHD and periodontitis plus CHD had higher plasma and salivary levels of MPO compared to subjects with periodontitis and healthy controls
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