Quand les données officielles dévoilent la vitalité des conflits sociaux

Issu de l'enquête « Relations professionnelles et négociations d'entreprise » (Réponse) menés par le ministère du travail, cet article réfléchit à la fabrication des outils de mesure de la conflictualité social

Nanorhéomètre pour l’étude des liquides confiné

International audienceNanorhéomètre pour la mesure des propriétés mécaniques sans contac

Multiple Infections by the Anther Smut Pathogen Are Frequent and Involve Related Strains

Population models of host–parasite interactions predict that when different parasite genotypes compete within a host for limited resources, those that exploit the host faster will be selected, leading to an increase in parasite virulence. When parasites sharing a host are related, however, kin selection should lead to more cooperative host exploitation that may involve slower rates of parasite reproduction. Despite their potential importance, studies that assess the prevalence of multiple genotype infections in natural populations remain rare, and studies quantifying the relatedness of parasites occurring together as natural multiple infections are particularly scarce. We investigated multiple infections in natural populations of the systemic fungal plant parasite Microbotryum violaceum, the anther smut of Caryophyllaceae, on its host, Silene latifolia. We found that multiple infections can be extremely frequent, with different fungal genotypes found in different stems of single plants. Multiple infections involved parasite genotypes more closely related than would be expected based upon their genetic diversity or due to spatial substructuring within the parasite populations. Together with previous sequential inoculation experiments, our results suggest that M. violaceum actively excludes divergent competitors while tolerating closely related genotypes. Such an exclusion mechanism might explain why multiple infections were less frequent in populations with the highest genetic diversity, which is at odds with intuitive expectations. Thus, these results demonstrate that genetic diversity can influence the prevalence of multiple infections in nature, which will have important consequences for their optimal levels of virulence. Measuring the occurrence of multiple infections and the relatedness among parasites within hosts in natural populations may be important for understanding the evolutionary dynamics of disease, the consequences of vaccine use, and forces driving the population genetic structure of parasites

Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of β-catenin in adrenocortical carcinoma

International audienceAdrenocortical cancer (ACC) is a very aggressive tumor, and genomics studies demonstrate that the most frequent alterations of driver genes in these cancers activate the Wnt/β-catenin signaling pathway. However, the adrenal-specific targets of oncogenic β-catenin-mediating tumorigenesis have not being established. A combined transcriptomic analysis from two series of human tumors and the human ACC cell line H295R harboring a spontaneous β-catenin activating mutation was done to identify the Wnt/β-catenin targets. Seven genes were consistently identified in the three studies. Among these genes, we found that AFF3 mediates the oncogenic effects of β-catenin in ACC. The Wnt response element site located at nucleotide position − 1408 of the AFF3 transcriptional start sites (TSS) mediates the regulation by the Wnt/β-catenin signaling pathway. AFF3 silencing decreases cell proliferation and increases apoptosis in the ACC cell line H295R. AFF3 is located in nuclear speckles, which play an important role in RNA splicing. AFF3 overexpression in adrenocortical cells interferes with the organization and/or biogenesis of these nuclear speckles and alters the distribution of CDK9 and cyclin T1 such that they accumulate at the sites of AFF3/speckles. We demonstrate that AFF3 is a new target of Wnt/β-catenin pathway involved in ACC, acting on transcription and RNA splicing

A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that, in particular, provokes functional alteration of CUG-binding proteins. As a consequence, several genes with misregulated alternative splicing have been linked to clinical symptoms. In our search for additional molecular mechanisms that would trigger functional defects in DM1, we took advantage of mutant gene-carrying human embryonic stem cell lines to identify differentially expressed genes. Among the different genes found to be misregulated by DM1 mutation, one strongly downregulated gene encodes a transcription factor, ZNF37A. In this paper, we show that this defect in expression, which derives from a loss of RNA stability, is controlled by the RNA-binding protein, CUGBP1, and is associated with impaired myogenesis—a functional defect reminiscent of that observed in DM1. Loss of the ZNF37A protein results in changes in the expression of the subunit α1 of the receptor for the interleukin 13. This suggests that the pathological molecular mechanisms linking ZNF37A and myogenesis may involve the signaling pathway that is known to promote myoblast recruitment during development and regeneratio

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

Une organisation confrontée à son institutionnalisation (Contribution à une sociologie du changement organisationnel)

A partir d'une enquête par entretiens et par observations, cette recherche, inspirée des sociologies de l'action, propose d'étudier les processus de changement de l'ANPE. Un premier regard est porté sur les transformations institutionnelles de ce service public. Aujourd'hui, l'ANPE n'est plus seulement une institution qui distingue les "vrais" des "faux" chômeurs comme elle pouvait le faire jusque dans les années 90. Elle est désormais une institution qui cherche à normaliser les demandeurs d'emploi afin qu'ils recouvrent une autonomie d'action. Cette nouvelle mission est la conséquence d'une rupture du rapport d'autorité que l'ANPE entretenait avec ses usagers. Alors que l'égalité de traitement organisait la relation à l'autre sur la base d'une indifférenciation, l'équité a ouvert la voie à une nouvelle représentation des demandeurs d'emploi, laissant penser que tous n'avaient pas la même capacité à retrouver un travail. Aussi, bien que limitée à l'ANPE, l'étude de l'institutionnalisation de cette agence montre que l'Etat social n'est pas en train de se déliter, mais d'acquérir une nouvelle logique pour gérer le social. Un deuxième regard est porté sur les transformations organisationnelles de l'ANPE. Car, sans elles, cette administration n'aurait pas pu modifier son visage institutionnel. Pour autant, l'enquête ne s'inscrit pas complètement dans la tradition de la sociologie des organisations dans la mesure où les conseillers pour l'emploi n'ont pas été des acteurs du changement. Parce qu'être acteurs a parfois un coût trop élevé, ils ont au contraire préféré se déterminer rationnellement comme des agents sociaux. Mieux, ils n'ont pas cherché à avoir une prise sur les transformations de l'ANPE car ils avaient de "bonnes raisons" de se désintéresser des changements opérés.LILLE1-BU (590092102) / SudocSudocFranceF

Les oxazaphosporines, nouvelles stratégies de développement (études de toxicité de l'ifosfamide et de ses analogues diméthyles)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Young's modulus of some SOFC materials as a function of temperature

International audienceSolid oxide fuel cells (SOFCs) have been under great consideration during this last decade and much effort has been dedicated to model their thermo-mechanical behavior, trying to take into account the different properties of the materials, such as their elasticity. In this paper, we report the elastic behavior of three classical materials used in SOFCs as a function of temperature: Yttria stabilized zirconia (YSZ), La0.8Sr0.2MnO3 (LSM) and Ni-YSZ. Both YSZ and LSM present unusual behaviors. The elastic modulus of YSZ first decreases slowly up to 150 ◦C, then dramatically up to 550 ◦C (certainly due to atomic motion) and finally increases probably because of an order-disorder transition (oxygen vacancies). The state of the art on zirconia was reviewed. For the LSM material, Young's modulus could not be determined below 600 ◦C. Above this temperature, samples with totally closed porosity present a continuously increasing modulus, while the other samples have a quite constant modulus