The local linear functional kNN estimator of the conditional expectile: uniform consistency in number of neighbors

International audienc

2D versus 3D Convolutional Spiking Neural Networks Trained with Unsupervised STDP for Human Action Recognition

International audienc

Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling

Abstract The heterogenous and dynamic constitution of the membrane fine-tunes signal transduction. In particular, the polyunsaturated fatty acid (PUFA) tails of phospholipids influence the biophysical properties of the membrane, production of second messengers, or membrane partitioning. Few evidence mostly originating from studies of rhodopsin suggest that PUFAs directly modulate the conformational dynamic of transmembrane proteins. However, whether such properties translate to other G protein-coupled receptors remains unclear. We focused on the dopamine D2 receptor (D2R), a main target of antipsychotics. Membrane enrichment in n-3, but not n-6, PUFAs potentiates ligand binding. Molecular dynamics simulations show that the D2R preferentially interacts with n-3 over n-6 PUFAs. Furthermore, even though this mildly affects signalling in heterologous systems, in vivo n-3 PUFA deficiency blunts the effects of D2R ligands. These results suggest that n-3 PUFAs act as allosteric modulators of the D2R and provide a putative mechanism for their potentiating effect on antipsychotic efficacy

18F]FDG PET/CT for predicting triple-negative breast cancer outcomes after neoadjuvant chemotherapy with or without pembrolizuma

International audiencePurpose: To determine if pretreatment [18F]FDG PET/CT could contribute to predicting complete pathological complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy with or without pembrolizumab. Methods: In this retrospective bicentric study, we included TNBC patients who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy (NAC) or chemo-immunotherapy (NACI) between March 2017 and August 2022. Clinical, biological, and pathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from the PET images. Cut-off values were determined using ROC curves and a multivariable model was developed using logistic regression to predict pCR. Results: N = 191 patients were included. pCR rates were 53 and 70% in patients treated with NAC (N = 91) and NACI (N = 100), respectively (p 12.3), and low TMTV (≤ 3.0 cm3) were predictors of pCR in the NAC cohort while tumor staging classification ( 17.2), and low TMTV (≤ 7.3 cm3) correlated with pCR in the NACI cohort. In multivariable analysis, only high tumor SUVmax (NAC: OR 8.8, p < 0.01; NACI: OR 3.7, p = 0.02) and low TMTV (NAC: OR 6.6, p < 0.01; NACI: OR 3.5, p = 0.03) were independent factors for pCR in both cohorts, albeit at different thresholds. Conclusion: High tumor metabolism (SUVmax) and low tumor burden (TMTV) could predict pCR after NAC regardless of the addition of pembrolizumab. Further studies are warranted to validate such findings and determine how these biomarkers could be used to guide neoadjuvant therapy in TNBC patients

Les cahiers de la SFSIC -18- EDITO

International audienceLe présent numéro, loin d’échapper au questionnement des grands enjeux et efets du numérique, met l’accent sur denouvelles recherches ou projets pédagogiques menés par des collègues dans le champ des sciences de l’information et de la communication. Il se structure en 4 grands volets : Questions de recherches,Formation, Mondes professionnels, Carte blanche aux doctorant

Toward the use of proxies for efficient learning manipulation and locomotion strategies on soft robots.

International audienceSoft robots are naturally designed to perform safe interactions with their environment, like locomotion and manipulation. In the literature, there are now many concepts, often bio-inspired, to propose new modes of locomotion or grasping. However, a methodology for implementing motion planning of these tasks, as exists for rigid robots, is still lacking. One of the difficulties comes from the modeling of these robots, which is very different, as it is based on the mechanics of deformable bodies. These models, whose dimension is often very large, make learning and optimization methods very costly. In this paper, we propose a proxy approach, as exists for humanoid robotics. This proxy is a simplified model of the robot that enables frugal learning of a motion strategy. This strategy is then transferred to the complete model to obtain the corresponding actuation inputs. Our methodology is illustrated and analyzed on two classical designs of soft robots doing manipulation and locomotion tasks

Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro

International audiencePancreatic Ductal Adenocarcinoma (PDAC) is characterized by an acidic microenvironment, which contributes to therapeutic failure. So far there is a lack of knowledge with respect to the role of the acidic microenvironment in the invasive process. This work aimed to study the phenotypic and genetic response of PDAC cells to acidic stress along the different stages of selection. To this end, we subjected the cells to short- and long-term acidic pressure and recovery to pHe 7.4. This treatment aimed at mimicking PDAC edges and consequent cancer cell escape from the tumor. The impact of acidosis was assessed for cell morphology, proliferation, adhesion, migration, invasion, and epithelial–mesenchymal transition (EMT) via functional in vitro assays and RNA sequencing. Our results indicate that short acidic treatment limits growth, adhesion, invasion, and viability of PDAC cells. As the acid treatment progresses, it selects cancer cells with enhanced migration and invasion abilities induced by EMT, potentiating their metastatic potential when re-exposed to pHe 7.4. The RNA-seq analysis of PANC-1 cells exposed to short-term acidosis and pHe-selected recovered to pHe 7.4 revealed distinct transcriptome rewiring. We describe an enrichment of genes relevant to proliferation, migration, EMT, and invasion in acid-selected cells. Our work clearly demonstrates that upon acidosis stress, PDAC cells acquire more invasive cell phenotypes by promoting EMT and thus paving the way for more aggressive cell phenotypes

NALCN ‐mediated sodium influx confers metastatic prostate cancer cell invasiveness

International audienceThere is growing evidence that ion channels are critically involved in cancer cell invasiveness and metastasis. However, the molecular mechanisms of ion signaling promoting cancer behavior are poorly understood and the complexity of the underlying remodeling during metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques, we show that metastatic prostate cancer cells acquire a specific Na+ /Ca2+ signature required for persistent invasion. We identify the Na+ leak channel, NALCN, which is overexpressed in metastatic prostate cancer, as a major initiator and regulator of Ca2+ oscillations required for invadopodia formation. Indeed, NALCN-mediated Na+ influx into cancer cells maintains intracellular Ca2+ oscillations via a specific chain of ion transport proteins including plasmalemmal and mitochondrial Na+ /Ca2+ exchangers, SERCA and store-operated channels. This signaling cascade promotes activity of the NACLN-colocalized proto-oncogene Src kinase, actin remodeling and secretion of proteolytic enzymes, thus increasing cancer cell invasive potential and metastatic lesions in vivo. Overall, our findings provide new insights into an ion signaling pathway specific for metastatic cells where NALCN acts as persistent invasion controller

Widening exposome exploration by means of complementary HRMS analytical platforms: use case on pesticide exposure

International audienceHuman exposure to food and environmental contaminants (such as pesticides) is generally estimated by indirect methods. Targeted bio-monitoring is a way to assess the internal exposure on a limited number of substances, needing large sample amounts for analyses as rigorous and sensitive as possible. Thus, the human health risks associated with multi-exposure to complex mixtures currently remain under-explored.In this context, the SCREENPEST project aims at providing a unified methodology for large-scale characterisation of human internal exposure to pesticides, via a "suspect profiling" approach, using urine

De Parthénos à Mèter : considérations archéologiques sur les fonctions d'Athéna dans le champ des maternités

International audienceDans la religion grecque antique Athéna est, au même titre qu’Artémis et Hestia, la déesse vierge par excellence. Conçue en dehors de toute matrice féminine, née du crâne de Zeus, Athéna s’inscrit en marge du schéma reproductif habituel. En outre, la déesse échappe au destin traditionnel de la femme dans les sociétés anciennes en refusant le mariage et, de fait, la « douloureuse obligation de la maternité » . Athéna apparaît ainsi comme une figure « déviante » en tant que déesse sans mère, fille de Zeus et éternelle parthenos (vierge), écartée de facto de toute fonction maternelle. Toutefois, si elle est biologiquement inapte à être mère, Athéna joue un rôle dans l’éducation de certains individus ; c’est une déesse kourotrophe (kourotrophos), soit une divinité qui accompagne les jeunes gens du berceau jusqu’à l’âge adulte et préside à certains rites de passages. leMèter), tandis qu’à Athènes elle est la « mère » (matèr) de tous les Athéniens. La déesse est également associée à d’autres puissances divines qui interviennent lors de la grossesse, l’accouchement et/ou la petite enfance. Par conséquent, Athéna agit, à sa manière, dans le champ de la maternité.L’objectif de cette communication est de mettre en évidence l’ambiguïté de la figure d’Athéna en tant que figure maternelle et maternante à travers un ensemble de réflexions sur la maternité des déesses grecques. Il s’agit, surtout, de comprendre quelles sont les capacités d’actions d’Athéna dans le champ des maternités, qu’elles soient réelles et symboliques.Le corpus permettant d’envisager Athéna au prisme de la maternité est réduit. Pour cette raison, nous travaillerons sur l’ensemble du monde grec du VIIIe s. av. J.-C. au Ve s. apr. J.-C. Notre perspective sera pluridisciplinaire et prendra en compte une grande variété de sources, qu’elles soient littéraires, épigraphiques, archéologiques et onomastiques.Par l’analyse de cet ensemble, nous souhaitons mettre en évidence le rapport ambivalent d’Athéna vis-à-vis de la maternité : d’une part, en tant que figure en marge de toute capacité reproductive, puisqu’elle est parthenos ; d’autre part, comme divinité avec des compétences qui touchent à la maternité, mais avec des modes d’action qui lui sont propres. De par ses configurations avec d’autres puissances divines, comme Ilithyie liée à l’accouchement, son lien avec le domaine de la maternité est plus net. Pourtant, Athéna agit avant tout sur la protection et l’intégrité du corps civique, plutôt que sur le corps maternel. En tant que kourotrophos, elle protège le devenir de la cité en préservant et en éduquant ses futurs citoyens