Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict

About eight million animal species are estimated to live on Earth, and all except those belonging to one subphylum are invertebrates. Invertebrates are incredibly diverse in their morphologies, life histories, and in the range of the ecological niches that they occupy. A great variety of modes of reproduction and sex determination systems is also observed among them, and their mosaic-distribution across the phylogeny shows that transitions between them occur frequently and rapidly. Genetic conflict in its various forms is a long-standing theory to explain what drives those evolutionary transitions. Here, we review (1) the different modes of reproduction among invertebrate species, highlighting sexual reproduction as the probable ancestral state; (2) the paradoxical diversity of sex determination systems; (3) the different types of genetic conflicts that could drive the evolution of such different systems

Individualized Visits to Foster the Engagement and the re-visit in Museums

International audienceMuseums have become places that, besides conserving and storing artefacts, provide visitors with education and amusement. They now have to compete with the entertainment industry to attract visitors and expand their audience. The use of digital technology is emerging as a solution.While many studies focus on the visitor side, we are interested in tools for museum staff. To understand their needs and processes, we adopted a participatory and iterative design process, involving museum professionals as end-users at each step (i.e. user observation, design, prototyping, users tests). We conducted 7 meetings, 4 interviews studies and 2 experimental observations with 12 museum experts (communication, IT, public and content experts) from 5 institutions (Exhibition Centres, Science Centre, Archaeological Museum, Museum of Fine Arts).Our analysis revealed two issues faced by these museums. First, despite the recommendation of institutional documents, visitors service is almost never involved before the end of the exhibition design process. Thus, they have no mean to shape the scenography in order to adapt it to visitors. Second, we identified a strong need for encouraging local visitors’ engagement and revisit. Diversifying the visits is a solution considered by museums, but relying on temporary exhibits is too costly for small museums and creating thematic visits is not participatory enough.The creation of individualized visits, allowing visitors to explore existing exhibition on their own depending on their needs and desires, meets both challenges. We thus focus on the design of tools that empower museum professionals to create such visits. We identified that museums need, first, to collect more information about their visitors and, second, to be able to create, evolve and maintain the solutions on their own according to visitors needs. Our aim is to design a tool which respects these two key points and could enable the creation of personalized and dynamic museum visits

Totem de Personnalisation : Conception d'une Interface Tangible pour le Choix de Parcours de Visite dans les Musées

De nos jours, les musées doivent rivaliser avec le marché du divertissement pour attirer un large public. Une solution envisagée pour les rendre plus attractifs tient dans la personnalisation des parcours de visite en fonction des préférences des visiteurs. En se basant sur l'analyse des besoins réalisée auprès de cinq musées, nous avons conçu cinq storyboards d'interface permettant à un groupe de visi-teurs de choisir un parcours en fonction de leurs personnal-ités et envies. Nous avons également identifié grâce à cette analyse, ainsi que la littérature, douze exigences qui nous ont permis d'évaluer les solutions proposées. Enfin, nous avons conçu un prototype basse fidélité de "totem de per-sonnalisation", permettant à chaque membre du groupe de renseigner ses caractéristiques propres puis de collaborer dans le choix de caractéristiques communes.Museums today are competing with the entertainment industry to attract visitors. Personalizing museum visits, depending on visitors’ preferences, is one possible solution for making museums more attractive. Based on an analysis of the needs of museums professionals, we have designed five storyboards of interactions which allow a group of visitors to select a personalized tour based on their characteristics and desires. Based on this analysis and the related work, we have identified twelve requirements to evaluate these solutions. We then designed a low-fidelity prototype which we call "personalization totem", which allows members of the group to specify their individual characteristics and then collaboratively choose the characteristics common to the group

Sirt1 inhibits resistin expression in aortic stenosis

The development of human calcified aortic stenosis (AS) includes age-dependent processes that have been involved in atherosclerosis, such as infiltration of macrophages in aortic valves, which then promote production of many proinflammatory cytokines, including resistin. However, the molecular mechanisms contributing to these processes are not established. Since Sirt1 has been shown to modulate macrophage biology and inflammation, we examined its levels in human AS and tested its impact on resistin expression. Sirt1 mRNA (p = 0.01) and protein (p,0.05) levels were reduced in explanted valves from AS patients (n = 51) compared to those from control (n = 11) patients. Sirt1 mRNA levels were negatively associated with resistin mRNA levels quantified in AS valves (p = 0.02). Stimulation of Sirt1 by resveratrol or virusdriven overexpression robustly diminished resistin mRNA and protein expression in macrophages, whereas down-regulation of Sirt1 triggered a large increase in resistin expression. These effects were direct, as chromatin immunoprecipitation assays showed that Sirt1 physically interacted with the resistin promoter region at an AP-1 response element. Moreover, Sirt1 blocked c-jun-induced resistin transactivation in gene reporter assays. These findings demonstrate that, in calcified AS, levels of Sirt1 are reduced whereas those of resistin are increased within aortic valve leaflets. Our results also suggest that this loss of Sirt1 expression alleviates its inhibition of resistin transcription in macrophages. Although the overall contribution of this process to the underlying mechanisms for AS disease development remains unresolved, these observations suggest that modification of Sirt1 expression and/or activity could represent a novel approach against inflammation in AS

Crosstalk between alternatively spliced UGT1A isoforms and colon cancer cell metabolism

Alternative splicing at the human glucuronosyltransferase 1 gene locus (UGT1) produces alternate isoforms UGT1A_i2s that control glucuronidation activity through protein-protein interactions. Here, we hypothesized that UGT1A_i2s function into a complex protein network connecting other metabolic pathways with influence on cancer cell metabolism. This is based on a pathway enrichment analysis of proteomic data that identified several high-confidence candidate interaction proteins of UGT1A_i2 proteins in human tissues, namely the rate-limiting enzyme of glycolysis pyruvate kinase (PKM), which plays a critical role in cancer cell metabolism and tumor growth. The partnership of UGT1A_i2 and PKM2 was confirmed by co-immunoprecipitation in the HT115 colon cancer cells and was supported by a partial co-localization of these two proteins. In support of a functional role for this partnership, depletion of UGT1A_i2 proteins in HT115 cells enforced the Warburg effect with higher glycolytic rate at the expense of mitochondrial respiration, and led to lactate accumulation. Untargeted metabolomics further revealed a significantly altered cellular content of 58 metabolites including many intermediates derived from the glycolysis and TCA cycle pathways. These metabolic changes were associated with a greater migration potential. The potential relevance of our observations is supported by the down-regulation of UGT1A_i2s mRNA in colon tumors compared to normal tissues. Alternate UGT1A variants may thus be part of the expanding compendium of metabolic pathways involved in cancer biology directly contributing to the oncogenic phenotype of colon cancer cells. Findings uncover new aspects of UGT functions diverging from their transferase activity

The rare allele of DGKZ SNP rs10838599 is associated with variability in HDL-cholesterol levels among severely obese patients

Introduction: Diacylglycerol kinase-zeta, one of the ten isoforms of DGKs expressed in mammals is an important enzyme of lipid metabolism. It catalyzes the interconversion of diacylglycerol and phosphatidic acid, two major second messengers. Its gene DGKZ has been previously identified as being overexpressed and undermethylated in visceral adipose tissue of patients with (MetS+) versus without (MetS-) the metabolic syndrome (MetS). Objective: The aim of this study was to investigate the associations between DGKZ gene polymorphisms (SNPs) and phenotypes related to MetS (BMI, waist girth, CRP, fasting glucose, lipid profile (triglycerides, total-cholesterol, LDL-cholesterol and HDL-cholesterol (HDL-C)), resting systolic and diastolic blood pressures). Methods: The study sample included 1752 severely obese participants who underwent bariatric surgery. Associations between the five selected tSNPs of DGKZ and features of the MetS were tested. The effects of these SNPs on DGKZ methylation and expression levels were tested in subgroups of 32 and 14 obese subjects, respectively. Correlations between methylation and expression levels were also computed. Results: Homozygotes for the rare allele of rs10838599 displayed higher plasma HDL-C concentrations compared to the other genotype groups (p=0.03). For gene methylation, only a trend with the cg05412031 CpG site (p=0.09) was found for the single significantly phenotype-associated SNP. There was no significant correlation between DGKZ methylation at cg05412031 and expression levels. Conclusion: These results suggest that DGKZ SNP rs10838599 modulates plasma HDL-C levels thereby its gene contributes to the inter-individual variability observed in the cardiometabolic risk profile of patients with severe obesity

Genetic Background of Escherichia coli and Extended-spectrum β-Lactamase Type

ESBL-producing E. coli may arise from interactions between ESBL type, strain genetic background, and selective pressures in various ecologic niches

Build Your Own Hercules : une interface tangible de choix de parcours de visites personnalisées au musée

National audienceIn this demonstration we present “Build your own Hercules”. This tangible token+constraint system allows museum visitors to indicate their characteristics and desires in order to choose a personalized visit. We designed this system in collaboration with Musée Saint-Raymond in Toulouse, which hosted a pilot study of the prototype in-situ.Dans cette démonstration, nous présentons « Build your own Hercules ». Ce système tangible de type token+constraint permet aux visiteurs d’un musée d’indiquer leurs caractéristiques et leurs envies afin de choisir une visite personnalisée. Nous avons conçu ce système en collaboration avec le musée Saint-Raymond de Toulouse, qui a accueilli une étude pilote du prototype

Regulation of human CD4+ T cell differentiation

Naive CD4+ T cells differentiate into specific effector subsets—Th1, Th2, Th17, and T follicular helper (Tfh)—that provide immunity against pathogen infection. The signaling pathways involved in generating these effector cells are partially known. However, the effects of mutations underlying human primary immunodeficiencies on these processes, and how they compromise specific immune responses, remain unresolved. By studying individuals with mutations in key signaling pathways, we identified nonredundant pathways regulating human CD4+ T cell differentiation in vitro. IL12Rβ1/TYK2 and IFN-γR/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is required for Th17, Tfh, and IL-10–secreting cells. IL12Rβ1/TYK2 and NEMO are also required for Th17 induction. Strikingly, gain-of-function STAT1 mutations recapitulated the impact of dominant-negative STAT3 mutations on Tfh and Th17 cells, revealing a putative inhibitory effect of hypermorphic STAT1 over STAT3. These findings provide mechanistic insight into the requirements for human T cell effector function, and explain clinical manifestations of these immunodeficient conditions. Furthermore, they identify molecules that could be targeted to modulate CD4+ T cell effector function in the settings of infection, vaccination, or immune dysregulation