Search

Abstract Metabolic rewiring offers novel therapeutic opportunities in cancer. Until recently, there was scant information regarding soft tissue sarcomas, due to their heterogeneous tissue origin, histological definition and underlying genetic history. Novel large-scale genomic and metabolomics approaches are now helping stratify their physiopathology. In this review, we show how various genetic alterations skew activation pathways and orient metabolic rewiring in sarcomas. We provide an update on the contribution of newly described mechanisms of metabolic regulation. We underscore mechanisms that are relevant to sarcomagenesis or shared with other cancers. We then discuss how diverse metabolic landscapes condition the tumor microenvironment, anti-sarcoma immune responses and prognosis. Finally, we review current attempts to control sarcoma growth using metabolite-targeting drugs.

While anxiety as a category is often used to designate a bodily sensation of discomfort peculiar to the individual, this issue of Tracés proposes to look at anxiety as a regime of experience in the face of uncertainty, no longer using the tools of psychoanalysis but those of the human and social sciences. The articles in the issue thus address the logics underlying the modes of manifestation of anxiety, taking into account their dimensions, which are at once corporeal, discursive and aesthetic, in original articles, an interview and a graphic work. The editorial returns in particular to the question of the socially situated nature of the expression of anguish, depending both on an institutional context and individual dispositions, but also their gendered aspect. However, analysing the manifestations of anxiety implies first of all questioning the conditions of its objectivation in medical discourse but also by the human and social sciences in all their diversity. If psychoanalytical discourse has imposed itself throughout the 20th century as the main vector for thinking of anguish as ontological and in this respect fundamentally different from fear (which is always linked to an object), the contribution of existentialist philosophy (Kierkegaard, in particular) allows us to think of anguish as man’s experimentation with the infinity of possibilities. As a learned category, anguish is also an ordinary category designating an emotion that can be considered as founding as much of a social group as of political modes of action. While anguish tends to be reduced to a process specific to the subject, the bias of our issue has therefore been to rethink this emotion in the light of the collective, that is to say, to make it the sign of a shared emotional regime in a given space and at a given time. If “experiencing anguish” comes out more from the body and the incorporated, to call oneself anguished would be to benefit from categories of understanding of the social world, notably those coming from psychoanalysis, which contribute not only to qualify its relationship to the world as pathological, but rather to affirm in the public space (after the private space) the legitimacy of the tortuous and painful singularity of this relationship.

Despite a large body of research on response properties of neurons in the inferior temporal (IT) cortex, studies to date have not yet produced quantitative feature descriptions that can predict responses to arbitrary objects. This deficit in the research prevents a thorough understanding of object representation in the IT cortex. Here we propose a fragment-based approach for finding quantitative feature descriptions of face neurons in the IT cortex. The development of the proposed method was driven by the assumption that it is possible to recover features from a set of natural image fragments if the set is sufficiently large. To find the feature from the set, we compared object responses predicted from each fragment and responses of neurons to these objects, and search for the fragment that revealed the highest correlation with neural object responses. Prediction of object responses of each fragment was made by normalizing Euclidian distance between the fragment and each object to 0 to 1 such that the smaller distance gives the higher value. The distance was calculated at the space where images were transformed to a local orientation space by a Gabor filter and a local max operation. The method allowed us to find features with a correlation coefficient between predicted and neural responses of 0.68 on average (number of object stimuli, 104) from among 560,000 feature candidates, reliably explaining differential responses among faces as well as a general preference for faces over to non-face objects. Furthermore, predicted responses of the resulting features to novel object images were significantly correlated with neural responses to these images. Identification of features comprising specific, moderately complex combinations of local orientations and colors enabled us to predict responses to upright and inverted faces, which provided a possible mechanism of face inversion effects. (292/300).

A honeybee colony, part of an apiary of nine, showed abnormalities in brood pattern and was thus presented for study. A classic veterinary medicine approach has allowed the diagnosis of a severe case of sacbrood virus (SBV) confirmed by a high viral load in affected larvae. SBV is known to infect larvae of the honeybee (Apis mellifera), resulting in failure to pupate and ultimately death of infected larvae. Several contributing factors combined, among them the parasite Varroa destructor, have been identified in this particular affected colony to explain the clinical outbreak of the disease whereas, in the majority of cases, infected colonies remain asymptomatic. As no specific cure of honeybee viruses is available, the management of these contributing factors is essential, including feeding of colonies and control of the Varroa parasite. After implementation of management solutions, the colony rapidly recovered in six weeks, but did not recommence honey production and remained at higher risk of a winter collapse. An earlier control management would have been more effective: regular visits of the colonies by the beekeepers should be the rule in order to detect abnormalities and also to detect and eliminate as early as possible the combination of factors that contribute to the proliferation of the virus.

Les conflictualités ont modifié les pacifismes et les humanitaires. Avant comme après la Grande Guerre, des acteurs, individuels et collectifs, ont cherché non seulement à penser l’humanité, mais encore à intervenir au nom des droits de l’homme. Il s’agit, singulièrement pour la Ligue des droits de l’homme (LDH) comme pour la Fédération internationale des droits de l’homme (FIDH), de protéger les individus, mais aussi de reconnaître leurs droits d’hommes, quelle que soit leur appartenance nationale, religieuse, politique, et sans oublier le droit des peuples. Face aux États souverains forts et à une organisation internationale, la SDN, faible dans un ordre westphalien, le projet de généralisation des droits, porté autant par des juristes que par des militants, révèle l’avènement de sociétés civiles analysant la communauté internationale et va plus loin que l’urgence humanitaire, avec tous les silences et les absences d’une inscription en politique.

This article relates the commitment and actions of prominent French figures of the League for Human Rights – most of whom had been previously involved in the defence of Captain Dreyfus – in favour of Ottoman Armenians, from the late 19th century to the early 20th century.

This article focuses on the regulation of the tests of professionalism. Faced with complexity and uncertainty, these regulations are mostly decentralized, procedural and collegiate. They generate contingent, flexible and reversible norms and rules with weak legitimacy. Although they are insufficient to guide action, they do allow professionals to avoid what is obviously beyond the pale and encourage them to discuss the limits of acceptable practice.

This paper presents an investigation of the notion of reaction time in some synchronous systems. A state-based description of such systems is given, and the reaction time of such systems under some classic composition primitives is studied. Reaction time is shown to be non-compositional in general. Possible solutions are proposed, and applications to verification are discussed. This framework is illustrated by some examples issued from studies on real-time embedded systems.

We present time-constrained automata (TCA), a model for hard real-time computation in which agents behaviors are modeled by automata and constrained by time intervals. TCA actions can have multiple start time and deadlines, can be aperiodic, and are selected dynamically following a graph, the time-constrained automaton. This allows expressing much more precise time constraints than classical periodic or sporadic model, while preserving the ease of scheduling and analysis. We provide some properties of this model as well as their scheduling semantics. We show that TCA can be automatically derived from source-code, and optimally scheduled on single processors using a variant of EDF. We explain how time constraints can be used to guarantee communication determinism by construction, and to study when possible agent interactions happen.

La tutelle et la curatelle sont des mesures destinées à protéger les biens des personnes vulnérables. En général imposées par le juge, ces mesures ne dépendent pas du consentement de leurs destinataires. Or, le droit tutélaire tend à faire aujourd’hui une place importante au consentement pour deux raisons principales : son recueil garantit en effet la dignité de la personne « incapable » ; le consentement obtenu est par ailleurs un indicateur positif dans les trajectoires d’autonomisation des personnes. En s’appuyant sur deux études de cas, traitées sur un mode ethnographique, les auteurs dégagent différentes facettes du consentement, dont une part inaccessible : le consentement « intime » ou « incertain », qu’ils analysent comme une marge de liberté à préserver chez ceux dont les capacités à consentir ont été juridiquement disqualifiées.

Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

This article explores the issue of asymmetry in the caring relationship towards vulnerable people. It assumes that if protection and welfare policies can reduce inequalities by assessing and addressing needs of individuals defined as “generic”, it is not the same when the issue is not only equality but also the singularity of "what matters" to the embodied person. In this case, the arbitrary nature of acts or decisions in the relationship seems irreducible on at least two levels: firstly, the deficit in rationality when neither career nor the person being cared for can successfully identify exactly "what matters"; secondly, the instability of feelings involved in care which remains largely aleatory. From a case study, we examine how the power of contestability can make the arbitrary nature of care acceptable.

Perception of stereoscopic depth requires that visual systems solve a correspondence problem: find parts of the left-eye view of the visual scene that correspond to parts of the right-eye view. The standard model of binocular matching implies that similarity of left and right images is computed by inter-ocular correlation. But the left and right images of the same object are normally distorted relative to one another by the binocular projection, in particular when slanted surfaces are viewed from close distance. Correlation often fails to detect correct correspondences between such image parts. We investigate a measure of inter-ocular similarity that takes advantage of spatially invariant computations similar to the computations performed by complex cells in biological visual systems. This measure tolerates distortions of corresponding image parts and yields excellent performance over a much larger range of surface slants than the standard model. The results suggest that, rather than serving as disparity detectors, multiple binocular complex cells take part in the computation of inter-ocular similarity, and that visual systems are likely to postpone commitment to particular binocular disparities until later stages in the visual process.

Les politiques psychiatriques et les politiques sociales se rejoignent aujourd’hui autour d’un principe qui consiste à mettre la personne et son projet de vie au centre des interventions dans une perspective de « rétablissement ». L’article interroge la manière dont ce principe est appliqué dans des programmes d’intervention en direction de personnes ayant des troubles psychiques graves. À partir de l’analyse d’une étude de cas, nous tirons des enseignements épistémologiques et politiques quant au rôle de la notion de « projet de vie » dans les recompositions du champ de la santé mentale.

Invading bacteria are recognized, captured and killed by a specialized form of autophagy, called xenophagy. Recently, defects in xenophagy in Crohn's disease (CD) have been implicated in the pathogenesis of human chronic inflammatory diseases of uncertain etiology of the gastrointestinal tract. We show here that pathogenic adherent-invasive Escherichia coli (AIEC) isolated from CD patients are able to adhere and invade neutrophils, which represent the first line of defense against bacteria. Of particular interest, AIEC infection of neutrophil-like PLB-985 cells blocked autophagy at the autolysosomal step, which allowed intracellular survival of bacteria and exacerbated interleukin-8 (IL-8) production. Interestingly, this block in autophagy correlated with the induction of autophagic cell death. Likewise, stimulation of autophagy by nutrient starvation or rapamycin treatment reduced intracellular AIEC survival and IL-8 production. Finally, treatment with an inhibitor of autophagy decreased cell death of AIEC-infected neutrophil-like PLB-985 cells. In conclusion, excessive autophagy in AIEC infection triggered cell death of neutrophils.

Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans.

Fatal neurodegenerative prion diseases are caused by the transmissible PrP(Sc) prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. However, prion replication also occurs in lymphoid cells. To assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic C57/BL6J background, by bone marrow replacement with hematopoietic cells expressing different levels of PrP protein. Nine different types of chimeric mice were inoculated intraperitoneally either with the lymphotropic Rocky Mountain Laboratory (RML) strain or the non lymphotropic ME-7 scrapie strain, at different doses. Here, we clearly demonstrate that overexpression of PrP by the hematopoietic system, or the lack of PrP expression by the bone marrow derived cells, does not change the incubation time period of the disease, even when the mice are infected at limiting doses. We conclude that the hematopoietic compartment is more or less permissive to prion replication, both for RML and ME-7, but does not play a role in neuroinvasion.

Copyright of Clio. Femmes, Genre, Histoire is the property of Belin Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)