The MHC class I peptide repertoire is molded by the transcriptome

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells

Interactive procedural simulation of paper tearing with sound

International audienceWe present a phenomenological model for the real-time simulation of paper tearing and sound. The model uses as input rotations of the hand along with the index and thumb of left and right hands to drive the position and orientation of two regions of a sheet of paper. The motion of the hands produces a cone shaped deformation of the paper and guides the formation and growth of the tear. We create a model for the direction of the tear based on empirical observation, and add detail to the tear with a directed noise model. Furthermore, we present a procedural sound synthesis method to produce tearing sounds during interaction. We show a variety of paper tearing examples and discuss applications and limitations

Mouse genetic background impacts both on iron and non-iron metals parameters and on their relationships

International audienceIron is reported to interact with other metals. In addition, it has been shown that genetic background may impact iron metabolism. Our objective was to characterize, in mice of three genetic backgrounds, the links between iron and several non-iron metals. Thirty normal mice (C57BL/6, Balb/c and DBA/2; n = 10 for each group), fed with the same diet, were studied. Quantification of iron, zinc, cobalt, copper, manganese, magnesium and rubidium was performed by ICP/MS in plasma, erythrocytes, liver and spleen. Transferrin saturation was determined. Hepatic hepcidin1 mRNA level was evaluated by quantitative RT-PCR. As previously reported, iron parameters were modulated by genetic background with significantly higher values for plasma iron parameters and liver iron concentration in DBA/2 and Balb/c strains. Hepatic hepcidin1 mRNA level was lower in DBA/2 mice. No iron parameter was correlated with hepcidin1 mRNA levels. Principal component analysis of the data obtained for non-iron metals indicated that metals parameters stratified the mice according to their genetic background. Plasma and tissue metals parameters that are dependent or independent of genetic background were identified. Moreover, relationships were found between plasma and tissue content of iron and some other metals parameters. Our data: (i) confirms the impact of the genetic background on iron parameters, (ii) shows that genetic background may also play a role in the metabolism of non-iron metals, (iii) identifies links between iron and other metals parameters which may have implications in the understanding and, potentially, the modulation of iron metabolis

Development of a multivariate prediction model for nocturia, based on urinary tract etiologies

Purpose: The main objective of our study was to determine which combination of modifiable and non-modifiable parameters that could discriminate patients with nocturia from those without nocturia. This was a post-hoc analysis of 3 prospective, observational studies conducted in Ghent University. Participants completed frequency volume chart (FVC) to compare characteristics between patients with and without nocturia. Method: This was a post hoc analysis of three prospective, observational studies conducted in Ghent University. Participants completed frequency volume chart (FVC) to compare characteristics between adults with and without nocturia. Study 1: adults with and without nocturia (n = 148); Study 2: patients >= 65 years with and without nocturnal LUTS (n = 54); Study 3: menopausal women before and after hormone replacement therapy (n = 43). All eligible patients (n = 183) completed a FVC during 24 hours (n = 13), 48 hours (n = 30) or 72 hours (n = 140). The combination of algorithms and number of determinants obtaining the best average area under the receiver operating curve (AUC-ROC) led to the final model. Differences between groups were assessed using the AUC-ROC and Mann- Whitney-Wilcoxon tests. Holm corrections were applied for multiple statistical testing. Also, the stability of the feature selection was evaluated. Results: The best discrimination was obtained when 13 determinants were included. However, a logistic regression model based on seven determinants selected with random forest had comparable discrimination including an optimal signature stability. It was able to discriminate almost perfectly between nights with and without nocturia. Conclusion: Relevant information to accomplish the excellent predictability of the model is; functional bladder capacity, 24 hours urine output, nocturnal output, age, BMI. The multivariate model used in this analysis provides new insights into combination therapy as it allows simulating the effect of different available treatment modalities and its combinations

Efficacy of First-Line Chemotherapy in Patients with Advanced Lung Sarcomatoid Carcinoma

Background:Sarcomatoid carcinomas (SCs) are rare tumors that may arise in the lung, accounting for 0.4% of non–small-cell lung cancers; the prognosis is poor. Only few retrospective small-size series have studied the efficacy of chemotherapy (CT) for metastatic SC.Methods:Multicenter study of patients with advanced or metastatic SC who received first-line CT. Clinical characteristics at baseline, response to first-line CT (Response Evaluation Criteria in Solid Tumors version 1.1), progression-free survival (PFS), and overall survival (OS) were retrospectively collected.Results:Ninety-seven patients were included. Median age was 62 (54–72) years. The majority of patients were men (70%), white (84%), and smokers (84%). Overall, 73% of patients received first-line platinum-based CT. At first tumor evaluation, 69% of patients experienced progression, 31% had disease control, and 16.5% had partial response. Partial response was observed in 20% of patients receiving platinum-based CT, and in none of those receiving non–platinum-based CT (p = 0.018). Median PFS was 2.0 months (confidence interval [CI] 95%: 1.8–2.3). PFS was not statistically different between patients receiving or not receiving a platinum-based CT. Median OS was 6.3 months (CI 95%: 4.7–7.8). There was a trend toward better OS for patients treated with platinum-based CT (7.0 months [CI 95%: 4.9–9.0] versus 5.3 months [CI 95%: 2.8–7.6]; p = 0.096). In multivariate analysis, disease control at first evaluation (hazard ratio = 0.38 [CI 95%: 0.21–0.59]) and at platinum-based CT (hazard ratio = 0.92 [CI 95%: 0.85–0.99]) was associated with better OS.Conclusion:SC is associated with poor prognosis and high rate of resistance to conventional first-line CT. New therapeutic strategies are needed, based on better knowledge of the carcinogenesis of SC

Functionalized artificial bidomain proteins based on an α-solenoid protein repeat scaffold : a new class of artificial diels-alderases

This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.αRep is a family of entirely artificial repeat proteins. Within the previously described αRep library, some variants are homodimers displaying interdomain cavities. Taking advantage of these properties, one of these homodimers called αRep A3 was converted into entirely artificial single chain bidomain metalloenzymes. A nonmutated A3 domain was covalently linked with an A3' domain bearing a unique cysteine on a chosen mutated position (F119C or Y26C). This single mutation ensured the covalent coupling of a 1:1 copper(II)/phenanthroline or copper(II)/terpyridine complex as a catalytic center within the interdomain cavity which was maintained large enough to accommodate two substrates of the Diels-Alder (D-A) reaction. This allowed us to obtain four new artificial Diels-Alderases that were fully characterized by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, UV-vis spectroscopy, and size exclusion chromatography analyses and were then further used for the catalysis of the D-A reaction. They were found to be able to catalyze the enantioselective D-A reaction of azachalcone with cyclopentadiene with up to 38% yield and 52% enantiomeric excess, which validates the proposed strategy. Moreover, the data were rationalized with a computational strategy suggesting the key factors of the selectivity. These results suggest that artificial metalloenzymes based on bidomain A3-A3 proteins modified with nitrogen donor ligands may be suitable for further catalyst optimization and may constitute valuable tools toward more efficient and selective artificial biocatalysts

Livret pédagogique : Apprendre à programmer Poppy Ergo Jr en Snap!

Un livret composé d'activités pédagogiques pour apprendre les bases de la programmation (programmation séquentielles, boucles, conditions, variables etc.) et des idées de défis et de projets pour appliquer les connaissancesCe livret propose des activités et des petits défis à réaliser pour se familiariser avec le robot Poppy Ergo Jr et le langage de programmation Snap!

Études sur la société grecque moderne et contemporaine

Yannis Tsiomis, directeur d’études (*)Pierre Chabard, maître de conférences à l’ENSA Marne-la-ValléeIsabelle Grudet, ingénieure de recherche à l’ENSAPLVCristiana Mazzoni, professeur à l’ENSA StrasbourgEstelle Thibault, maître de conférences à l’ENSAPB Villes, capitales, métropoles : Le Corbusier, les écrits Dans le cadre de ce séminaire qui étudie les théories et doctrines urbaines des XIXe et XXe siècles, nous nous sommes penchés cette année sur la prise de conscience, parfois lente et contr..