Assisting Nova SBE in developing an international placement strategic action plan: how to approach the French, Swiss and Italian job markets

Benefits of an international work experience are widely recognized. As students’ desire in pursuing an international career increases, it is of the universities’ interest to provide students with tools to accomplish this. The purpose of this work project is to develop placement recommendations for the French, Italian and Swiss job markets. The objective is to expand Nova’s placement range. Conclusions were achieved through the study of career services best practices from business schools present in three different rankings. Lastly, attractive job opportunities in these markets were assessed and practical recommendations on students’ curriculum and school practices were made

Together Beyond Accession: Turkey as the EU’s Indispensable Partner. College of Europe Policy Brief #15.18, November 2018

> Following turbulent years in European Union-Turkey relations, the June 2018 elections in Turkey and the prospective appointment of a new European Commission following the 2019 European Parliament elections provide a window of opportunity to take stock of the deadlock in Turkey’s EU bid. > Incoming European leaders should engage in a profound rethinking of EU-Turkey relations, beyond the accession perspective. > Concretely, the incoming Commission and especially High Representative should push for a renewal of EU strategic engagement with Turkey to ensure ‘togetherness’ in addressing changing geopolitical, economic and security equilibria. This engagement should rely on a four-pillar, multidimensional approach: > Amid growing economic instability in Turkey, we suggest advancing towards an updated Customs Union, while seizing on Turkey’s potential as a central hub in the Southern Energy Corridor. > This strong economic asset could leverage further EU engagement on human rights, rule of law and democracy and enable the Union to adopt innovative measures in support of Turkish civil society. > International developments have positioned Turkey as a crucial, albeit ambivalent, foreign policy partner, especially in the Middle East. For this reason, the EU should promote active foreign policy coordination and cooperation with Turkey. > Migration has been a rare, yet sensitive area of cooperation. In this domain, emphasis should be placed on enhancing the implementation of the 2016 EU-Turkey Statement

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I–related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes. Analysis of NOD mice that were deficient in MR1, and therefore lacked MAIT cells, revealed a loss of gut integrity and increased anti-islet responses associated with exacerbated diabetes. Together our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. Monitoring of MAIT cells might represent a new biomarker of T1D, while manipulation of these cells might open new therapeutic strategies

Masculinization of the X Chromosome in the Pea Aphid

International audienceEvolutionary theory predicts that sexually antagonistic mutations accumulate differentially on the X chromosome and autosomes in species with an XY sex-determination system, with effects (masculinization or feminization of the X) depending on the dominance of mutations. Organisms with alternative modes of inheritance of sex chromosomes offer interesting opportunities for studying sexual conflicts and their resolution, because expectations for the preferred genomic location of sexually antagonistic alleles may differ from standard systems. Aphids display an XX/X0 system and combine an unusual inheritance of the X chromosome with the alternation of sexual and asexual reproduction. In this study, we first investigated theoretically the accumulation of sexually antagonistic mutations on the aphid X chromosome. Our results show that i) the X is always more favourable to the spread of male-beneficial alleles than autosomes, and should thus be enriched in sexually antagonistic alleles beneficial for males, ii) sexually antagonistic mutations beneficial for asexual females accumulate preferentially on autosomes, iii) in contrast to predictions for standard systems, these qualitative results are not affected by the dominance of mutations. Under the assumption that sex-biased gene expression evolves to solve conflicts raised by the spread of sexually antagonistic alleles, one expects that male-biased genes should be enriched on the X while asexual female-biased genes should be enriched on autosomes. Using gene expression data (RNA-Seq) in males, sexual females and asexual females of the pea aphid, we confirm these theoretical predictions. Although other mechanisms than the resolution of sexual antagonism may lead to sex-biased gene expression, we argue that they could hardly explain the observed difference between X and autosomes. On top of reporting a strong masculinization of the aphid X chromosome, our study highlights the relevance of organisms displaying an alternative mode of sex chromosome inheritance to understanding the forces shaping chromosome evolution

Self-Reported Body Awareness: Validation of the Postural Awareness Scale and the Multidimensional Assessment of Interoceptive Awareness (Version 2) in a Non-clinical Adult French-Speaking Sample

Body awareness refers to the individual ability to process signals originating from within the body, which provide a mapping of the body’s internal landscape (interoception) and its relation with space and movement (proprioception). The present study aims to evaluate psychometric properties and validate in French two self-report measures of body awareness: the Postural Awareness Scale (PAS), and the last version of the Multidimensional Assessment of Interoceptive Awareness questionnaire (version 2, MAIA-2). We collected data in a non-clinical, adult sample (N = 308; 61% women, mean age 35 ± 12 years) using online survey, and a subset of the original sample (n = 122; 62% women, mean age 44 ± 11 years) also completed the retest control. Factor analyses and reliability analyses were conducted. Construct validity of the PAS and the MAIA-2 were examined by testing their association with each other, and with self-report measures of personality (Big Five Inventory), alexithymia (Toronto Alexithymia Scale) and dispositional trait mindfulness (Freiburg Mindfulness Inventory). Factor analyses of the PAS supported the same two-factor structure as previously published versions (in other languages). For the MAIA-2, factor analyses suggested that a six-factor structure, excluding Not-Worrying and Not-Distracting factors, could successfully account for a common general factor of self-reported interoception. We found satisfactory internal consistency, construct validity, and reliability over time for both the PAS and the MAIA-2. Altogether, our findings suggest that the French version of the PAS and the MAIA-2 are reliable self-report tools to assess both components of body awareness (proprioception and interoception dimension, respectively)

The activation of the cannabinoid receptor type 2 reduces neutrophilic protease-mediated vulnerability in atherosclerotic plaques

Aims The activation of cannabinoid receptor type 2 (CB2)-mediated pathways might represent a promising anti-atherosclerotic treatment. Here, we investigated the expression of the endocannabinoid system in human carotid plaques and the impact of CB2 pharmacological activation on markers of plaque vulnerability in vivo and in vitro. Methods and results The study was conducted using all available residual human carotid tissues (upstream and downstream the blood flow) from our cohort of patients symptomatic (n = 13) or asymptomatic (n = 27) for ischaemic stroke. Intraplaque levels of 2-arachidonoylglycerol, anandamide N-arachidonoylethanolamine, N-palmitoylethanolamine, N-oleoylethanolamine, and their degrading enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) were not different in human plaque portions. In the majority of human samples, CB1 (both mRNA and protein levels) was undetectable. In downstream symptomatic plaques, CB2 protein expression was reduced when compared with asymptomatic patients. In these portions, CB2 levels were inversely correlated (r = −0.4008, P = 0.0170) with matrix metalloprotease (MMP)-9 content and positively (r = 0.3997, P = 0.0174) with collagen. In mouse plaques, CB2 co-localized with neutrophils and MMP-9. Treatment with the selective CB2 agonist JWH-133 was associated with the reduction in MMP-9 content in aortic root and carotid plaques. In vitro, pre-incubation with JWH-133 reduced tumour necrosis factor (TNF)-α-mediated release of MMP-9. This effect was associated with the reduction in TNF-α-induced ERK1/2 phosphorylation in human neutrophils. Conclusion Cannabinoid receptor type 2 receptor is down-regulated in unstable human carotid plaques. Since CB2 activation prevents neutrophil release of MMP-9 in vivo and in vitro, this treatment strategy might selectively reduce carotid vulnerability in human

Interlaboratory Coverage Test on Plant Food Bioactive Compounds and their Metabolites by Mass Spectrometry-Based Untargeted Metabolomics.

Bioactive compounds present in plant-based foods, and their metabolites derived from gut microbiota and endogenous metabolism, represent thousands of chemical structures of potential interest for human nutrition and health. State-of-the-art analytical methodologies, including untargeted metabolomics based on high-resolution mass spectrometry, are required for the profiling of these compounds in complex matrices, including plant food materials and biofluids. The aim of this project was to compare the analytical coverage of untargeted metabolomics methods independently developed and employed in various European platforms. In total, 56 chemical standards representing the most common classes of bioactive compounds spread over a wide chemical space were selected and analyzed by the participating platforms (n = 13) using their preferred untargeted method. The results were used to define analytical criteria for a successful analysis of plant food bioactives. Furthermore, they will serve as a basis for an optimized consensus method

MAIT cells altered phenotype and cytotoxicity in lupus patients are linked to renal disease severity and outcome

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease in which circulating immune complexes can cause different types of glomerulonephritis, according to immune deposits and to the type of glomerular cell injury. Proliferative lesions represent the most severe form of lupus nephritis (LN) and often lead to kidney failure and death. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that recognize microbial-derived ligands from the riboflavin synthesis pathway. Although abundant in peripheral blood, MAIT cells are enriched in mucosal and inflamed tissues. While previous studies have reported concordant results concerning lower MAIT cell frequencies in the blood of SLE patients, no information is known about MAIT cell function and LN severity and outcome.MethodsIn the current study, we analyzed the baseline phenotype and function of peripheral blood MAIT cells by flow cytometry in 26 patients with LN and in a control group of 16 healthy individuals.ResultsWe observe that MAIT cell frequencies are markedly reduced in blood of LN patients. MAIT cells from patients have an altered phenotype in terms of migration, proliferation and differentiation markers, notably in most severe forms of LN. Frequencies of PMA/ionomycin stimulated MAIT cells secreting effector molecules, such as proinflammatory IL-17 and cytotoxic protein granzyme B, are higher in LN patients. Patients undergoing a complete renal remission after immunosuppressive therapy had higher MAIT cell frequency, lower expression of proliferation marker Ki-67 and granzyme B (GzB) at inclusion. Remarkably, GzB production defines a predictive model for complete remission.DiscussionWe report here that blood MAIT cells display proinflammatory and cytotoxic function in severe lupus nephritis which may play a pathogenesis role, but without association with systemic lupus activity. Finally, low cytotoxic profile of MAIT cells may represent a promising prognostic factor of lupus nephritis remission one year after induction therapy

Data-Driven Phenotyping of Central Disorders of Hypersomnolence With Unsupervised Clustering.

BACKGROUND AND OBJECTIVES Recent studies fueled doubts as to whether all currently defined central disorders of hypersomnolence are stable entities, especially narcolepsy type 2 and idiopathic hypersomnia. New reliable biomarkers are needed and the question arises whether current diagnostic criteria of hypersomnolence disorders should be reassessed. The main aim of this data-driven observational study was to see if data-driven algorithms would segregate narcolepsy type 1 and identify more reliable subgrouping of individuals without cataplexy with new clinical biomarkers. METHODS We used agglomerative hierarchical clustering, an unsupervised machine learning algorithm, to identify distinct hypersomnolence clusters in the large-scale European Narcolepsy Network database. We included 97 variables, covering all aspects of central hypersomnolence disorders such as symptoms, demographics, objective and subjective sleep measures, and laboratory biomarkers. We specifically focused on subgrouping of patients without cataplexy. The number of clusters was chosen to be the minimal number for which patients without cataplexy were put in distinct groups. RESULTS We included 1078 unmedicated adolescents and adults. Seven clusters were identified, of which four clusters included predominantly individuals with cataplexy. The two most distinct clusters consisted of 158 and 157 patients respectively, were dominated by those without cataplexy and, amongst other variables, significantly differed in presence of sleep drunkenness, subjective difficulty awakening and weekend-week sleep length difference. Patients formally diagnosed as narcolepsy type 2 and idiopathic hypersomnia were evenly mixed in these two clusters. DISCUSSION Using a data-driven approach in the largest study on central disorders of hypersomnolence to date, our study identified distinct patient subgroups within the central disorders of hypersomnolence population. Our results contest inclusion of sleep-onset rapid eye moment periods (SOREMPs) in diagnostic criteria for people without cataplexy and provide promising new variables for reliable diagnostic categories that better resemble different patient phenotypes. Cluster-guided classification will result in a more solid hypersomnolence classification system that is less vulnerable to instability of single features