Pentraxin-3 is a PI3K signaling target that promotes stem cell–like traits in basal-like breast cancers

Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics. Using transcriptomic analysis of activated PIK3CA-expressing BLBC cells, we identified the gene encoding the humoral pattern recognition molecule pentraxin-3 (PTX3) as a critical target of oncogenic PI3K signaling. We found that PTX3 abundance is stimulated, in part, through AKT- and nuclear factor κB (NF-κB)-dependent pathways and that presence of PTX3 is necessary for PI3K-induced stem cell-like traits. We further showed that PTX3 expression is greater in tumor samples from patients with BLBC and that it is prognostic of poor patient survival. Our results thus reveal PTX3 as a newly identified PI3K-regulated biomarker and a potential therapeutic target in BLBC

Meneco, a Topology-Based Gap-Filling Tool Applicable to Degraded Genome-Wide Metabolic Networks

International audienceIncreasing amounts of sequence data are becoming available for a wide range of non-model organisms. Investigating and modelling the metabolic behaviour of those organisms is highly relevant to understand their biology and ecology. As sequences are often incomplete and poorly annotated, draft networks of their metabolism largely suffer from incompleteness. Appropriate gap-filling methods to identify and add missing reactions are therefore required to address this issue. However, current tools rely on phenotypic or taxonomic information, or are very sensitive to the stoichiometric balance of metabolic reactions, especially concerning the co-factors. This type of information is often not available or at least prone to errors for newly-explored organisms. Here we introduce Meneco, a tool dedicated to the topological gap-filling of genome-scale draft metabolic networks. Meneco reformulates gap-filling as a qualitative combinatorial optimization problem, omitting constraints raised by the stoichiometry of a metabolic network considered in other methods, and solves this problem using Answer Set Programming. Run on several artificial test sets gathering 10,800 degraded Escherichia coli networks Meneco was able to efficiently identify essential reactions missing in networks at high degradation rates, outperforming the stoichiometry-based tools in scalability. To demonstrate the utility of Meneco we applied it to two case studies. Its application to recent metabolic networks reconstructed for the brown algal model Ectocarpus siliculosus and an associated bacterium Candidatus Phaeomarinobacter ectocarpi revealed several candidate metabolic pathways for algal-bacterial interactions. Then Meneco was used to reconstruct, from transcriptomic and metabolomic data, the first metabolic network for the microalga Euglena mutabilis. These two case studies show that Meneco is a versatile tool to complete draft genome-scale metabolic networks produced from heterogeneous data, and to suggest relevant reactions that explain the metabolic capacity of a biological system

Detecting horses' sickness: In search of visible signs

International audienceAssessing sickness in animals, by which we refer to non-specific states involving both physical discomfort and negative emotional states, is a real challenge. In this review, we demonstrate the need for clear and simple indicators of sickness in horses, a species in which suffering is largely underestimated. We provide a critical review of existing tools available to assess sickness in equids, which include composite pain scales and scores and welfare assessment scoring. Many such scales and scoring systems involve subjective assessments and lack of clear definitions. We discuss possible objective, visible indicators (qualitative and quantitative behavioural modifications and some postures) associated with sickness in horses, highlighting the two predominant modalities of expression (becoming unresponsive to environmental stimuli and “lethargic”, or becoming aggressive and hostile). Much work is still needed before an agreement can be achieved on the indicators of sickness in horses; there are however signs that, even if non-specific, should attract the owners’ attention on the horses’ welfare state

ETUDE DE L'IMPLICATION DES TRANSPORTEURS DE SUCRES DANS LE PHOTOCONTROLE DU DEBOURREMENT CHEZ LE ROSIER BUISSON (Rosa hybrida L.)

Bud break is a key developmental process controlling plant architecture. Buds are sink organs which require to import sugars to outgrowth. Very little is known about the way this sugars are imported and the role of sugar transporters in this process. In rosebush (Rosa hybrida), bud break requires light to occur, even in the absence of correlative inhibitions such as apical dominance. Bud break photocontrol involves a stimulation of sugar metabolism under light, indicating a mobilization of sucrose from the stem. The main goal of this work was to determine the role of sugar transporters in rose bud break photocontrol. In vitro experiments showed that rose buds need to import metabolisable sugars (sucrose, glucose or fructose) to outgrowth under light. Supplying buds with these sugars also promote bud break under total darkness (inhibitory condition). After beheading (apical dominance release), assays with radiolabelled sugars showed that bud break photocontrol is correlated with an uptake of hexose and then of sucrose. Furthermore, these uptake require both passive and active components. They could therefore involve symplasmic connections and sugar transporter activity. Phloem sap labelling with a fluorescent tracer demonstrated that dormant bud are not symplasmically connected to the surrounding stem and that connections take place at late stages of bud break. To study the role of sugar transporters into bud break photocontrol we isolated 10 putative sugar transporters (3 for sucrose and 7 for hexose). RT-QPCR analysis suggest that the high a nity sucrose/H+ symporter RhSUC2, as well the putative hexose transporters RhSTP1 and RhTMT2 are involved in bud break photocontrol. Functional validation of RhSUC2 in yeast expression system confirmed it is a sucrose/H+ symporter. All together, results allowed us to get insights of the mechanisms involved in bud break photocontrol by sugar metabolism.Le débourrement des bourgeons végétatifs, étape clé de la mise en place de l'architecture d'une plante, est sous le contrôle de facteurs endogènes et des facteurs de l'environnement. Les bourgeons sont des organes puits qui nécessitent d' importer des sucres pour débourrer. Peu de données sont cependant disponibles sur cette importation et sur le rôle des transporteurs de sucres dans ce processus. Chez le rosier buisson (Rosa hybrida), des résultats précédents à cette étude ont montré que les bourgeons ont un besoin absolu de lumière pour débourrer, même en l'absence d'inhibitions corrélatives telles que la dominance apicale. Le photocontrôle du débourrement implique une stimulation du métabolisme carboné à la lumière, indiquant une mobilisation du saccharose en provenance de la tige. Le principal objectif de cette thèse a été de déterminer le rôle des transporteurs de sucres dans le photocontrôle du débourrement des bourgeons de rosier. Des expériences de culture in vitro ont montré que les bourgeons de rosiers ont besoin d'importer des sucres métabolisables (saccharose, glucose ou fructose) pour débourrer à la lumière. Un apport exogène de ces di érents sucres stimule également leur débourrement à l'obscurité (condition inhibitrice). Après décapitation (levée de dominance apicale), l'utilisation de sucres radiomarqués a permis de montrer que le photocontrôle du débourrement est concomitant à une accumulation d'hexoses puis de saccharose, faisant intervenir à la fois un transport passif et actif des sucres. Cette accumulation pourrait donc impliquer des connexions symplasmiques ainsi que l'activité de transporteurs de sucres. Des marquages de la sève phloémienne à l'aide d'un traceur fluorescent ont montré que les bourgeons dormants sont isolés de la portion de tige adjacente et que des connexions s'établissent lors des stades tardifs du débourrement. Afin d'étudier le rôle des transporteurs de sucres dans le photocontrôle du débourrement, nous avons isolé 10 transporteurs potentiels de glucides (3 de saccharose et 7 d'hexoses). Les analyses d'expression des di érents gènes codant ces transporteurs par RT-QPCR suggèrent que le co-transporteur de saccharose/H+ RhSUC2, ainsi que les transporteurs d'hexoses potentiels RhSTP1 et RhTMT2 sont impliqués dans le photocontrôle du débourrement. La validation fonctionnelle de RhSUC2 a été e ffectuée chez la levure et confirme sa fonction de co-transporteur de saccharose/H+. L'ensemble des résultats obtenus permettent de progresser dans la compréhension des mécanismes impliquant le métabolisme glucidique dans le photocontrôle du débourrement

Detecting Welfare in a Non-Verbal Species: Social/Cultural Biases and Difficulties in Horse Welfare Assessment

International audienceHorses were domesticated for more than 5000 years and have been one of the most emblematic species living alongside humans. This long-shared history would suggest that horses are well known and well understood, but scientific data raise many concerns about the welfare state of most domestic horses suggesting that many aspects have been largely misunderstood. In the present review, we will examine some of the possible human factors that may explain the huge prevalence of welfare problems, despite horses being of special importance to humans. First of all, as horses are non-verbal, current management practices rely upon what one thinks is good for them, which opens the way to subjective interpretations and projections, based on one’s own subjective experience but probably still more on cultural/social norms and influences, traditions and beliefs. The lack of recognition, identification, or even the misinterpretation of signals are other potential reasons for welfare issues. Lastly, the over-exposure to animals with expressions of compromised welfare may lead to lower sensitivity of owners/professionals. That is why we lastly suggest that instead of simply providing information on what to do, we should promote validated visible indicators that leave less room for personal interpretation

Could snorts inform us on how horses perceive riding?

International audienceSeveral previous studies have shown that working conditions (including riding) can induce stress in horses. Riders’ actions and postures, when inappropriate, induce stress and conflict behaviours during riding and welfare impairment and negative emotional states outside work. Optimistic biases have been found in leisure horses, which, amongst positive management factors, were ridden with loose reins and low hands. Thus, one can wonder whether horses may positively perceive work or parts of it. Indicators of positive emotions are poorly known yet but we recently found that, out of the working context, a non-vocal acoustic signal, snorts, could reflect mild positive emotions in horses. We hypothesized that snorts could help identifying the working phases and actions appreciated by horses. An overview of snort production in 127 horses spread over 16 riding schools was first conducted to highlight a potential site effect. Results show a great difference in snorts frequency between facilities which may be due to different riding techniques. In order to test this hypothesis, we then focused on 37 horse-rider dyads by scoring horses’ postures (neck) and riders’ positions (hand, reins) during, but also out of the context of snort production. Results show that snorts were particularly associated with phases when the rider technique, i.e. long and loose reins, allowed more comfort for the horse, especially while walking. Results were more mitigated for higher paces since the association of snorts with signs of comfort was less clear-cut. Snorts could therefore be useful tools for identifying better practices, especially at slower gaits. However, care has to be taken at higher paces

Wide-eyed glare scares raptors: From laboratory evidence to applied management.

Raptors are one of the most important causes of fatalities due to their collisions with aircrafts as well as being the main victims of collisions with constructions. They are difficult to deter because they are not influenced by other airspace users or ground predators. Because vision is the primary sensory mode of many diurnal raptors, we evaluated the reactions of captive raptors to a "superstimulus" (a "paradoxical effect whereby animals show greater responsiveness to an exaggerated stimulus than to the natural stimulus") that combined an "eye shape" stimulus (as many species have an aversion for this type of stimulus) and a looming movement (LE). This looming stimulus mimics an impending collision and induces avoidance in a wide range of species. In captivity, raptors showed a clear aversion for this LE stimulus. We then tested it in a real life setting: at an airport where raptors are abundant. This study is the first to show the efficiency of a visual non-invasive repellent system developed on the basis of both captive and field studies. This system deterred birds of prey and corvids through aversion, and did not induce habituation. These findings suggest applications for human security as well as bird conservation, and further research on avian visual perception and sensitivity to signals