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International audience; Simple Summary: Stress Granules (SGs) were discovered in 1999 and while the first decade of research has focused on some fundamental questions, the field is now investigating their role in human pathogenesis. Since then, evidences of a link between SGs and cancerology are accumulating in vitro and in vivo. In this work we summarized the role of SGs proteins in cancer development and their prognostic values. We find that level of expression of protein involved in SGs formation (and not mRNA level) could serve a prognostic marker in cancer. With this review we strongly suggest that SGs (proteins) could be targets of choice to block cancer development and counteract resistance to improve patients care. Abstract: Cancer treatments are constantly evolving with new approaches to improve patient outcomes. Despite progresses, too many patients remain refractory to treatment due to either the development of resistance to therapeutic drugs and/or metastasis occurrence. Growing evidence suggests that these two barriers are due to transient survival mechanisms that are similar to those observed during stress response. We review the literature and current available open databases to study the potential role of stress response and, most particularly, the involvement of Stress Granules (proteins) in cancer. We propose that Stress Granule proteins may have prognostic value for patients. According to the World Health Organization, cancer is the second leading cause of death worldwide. In most cases, mortality is not due to the primary tumor itself, but to the occurrence of metastasis. At diagnosis, non-metastatic diseases are treated with first line systemic adjuvant (post-operative) and/or neoadjuvant (pre-operative) treatments in order to avoid tumor relapse by eradicating potential residual or micro-metastatic foci. In case of metastatic disease, the aim of systemic treatment is to achieve clinical remissions as durable as possible, which remains a palliative situation for most of solid cancers. In both situations, if the therapy does not eliminate all malignant cells, residual cancer cells may acquire migratory properties and develop drug resistance mechanisms, further contributing to difficult-to-treat metastasis [1].

International audience; Macrophages are an integral part of all organs in the body, where they contribute to immune surveillance, protection, and tissue-specific homeostatic functions. This is facilitated by so-called niches composed of macrophages and their surrounding stroma. These niches structurally anchor macrophages and provide them with survival factors and tissue-specific signals that imprint their functional identity. In turn, macrophages ensure appropriate functioning of the niches they reside in. Macrophages thus form reciprocal, mutually beneficial circuits with their cellular niches. In this review, we explore how this concept applies to the spleen, a large secondary lymphoid organ whose primary functions are to filter the blood and regulate immunity. We first outline the splenic micro-anatomy, the different populations of splenic fibroblasts and macrophages and their respective contribution to protection of and key physiological processes occurring in the spleen. We then discuss firmly established and potential cellular circuits formed by splenic macrophages and fibroblasts, with an emphasis on the molecular cues underlying their crosstalk and their relevance to splenic functionality. Lastly, we conclude by considering how these macrophage-fibroblast circuits might be impaired by aging, and how understanding these changes might help identify novel therapeutic avenues with the potential of restoring splenic functions in the elderly.

International audience; Among primates, humans are special in their ability to create and manipulate highly elaborate structures of language, mathematics, and music. Here we show that this sensitivity to abstract structure is already present in a much simpler domain: the visual perception of regular geometric shapes such as squares, rectangles, and parallelograms. We asked human subjects to detect an intruder shape among six quadrilaterals. Although the intruder was always defined by an identical amount of displacement of a single vertex, the results revealed a geometric regularity effect: detection was considerably easier when either the base shape or the intruder was a regular figure comprising right angles, parallelism, or symmetry rather than a more irregular shape. This effect was replicated in several tasks and in all human populations tested, including uneducated Himba adults and French kindergartners. Baboons, however, showed no such geometric regularity effect, even after extensive training. Baboon behavior was captured by convolutional neural networks (CNNs), but neither CNNs nor a variational autoencoder captured the human geometric regularity effect. However, a symbolic model, based on exact properties of Euclidean geometry, closely fitted human behavior. Our results indicate that the human propensity for symbolic abstraction permeates even elementary shape perception. They suggest a putative signature of human singularity and provide a challenge for nonsymbolic models of human shape perception.

Presentation Dernier rejeton d'une longue lignee d'homme de lettres, le jeune Zhang Dai 張岱 (1597-1681) connut l'opulence d'un riche lettre oisif, s'adonnant tout a loisir a sa passion pour la litterature et a son gout tres marque pour le theâtre avant de tout perdre au moment de la chute des Ming 明 (1644). Reste fidele a la defunte dynastie, il brava les interdits en en redigeant l'histoire. Depouille et traque, il eprouva la misere et la clandestinite, ce qui explique que la plupart de ses e...

International audience; Proper circulation of white blood cells (WBCs) in the pulmonary vascular bed is crucial for an effective immune response. In this branched vascular network, WBCs have to strongly deform to pass through the narrowest capillaries and bifurcations. Although it is known that this process depends on the cell mechanical properties, it is still poorly understood due to the lack of a comprehensive model of cell mechanics and of physiologically relevant experiments. Here, using an in-house microfluidic device mimicking the pulmonary capillary bed we show that the dynamics of THP1 monocytes evolves along successive capillary-like channels, from a non-stationary slow motion with hops to a fast and smooth efficient one. We used actin cytoskeleton drugs to modify the traffic dynamics. This led us to propose a simple mechanical model that shows that a very-finely tuned cortical tension combined with a high cell viscosity govern the fast transit through the network while preserving cell integrity. We finally highlight that the cortical tension controls the steady-state cell velocity via the viscous friction between the cell and the channel walls.

12 pages; International audience; Human leukocyte antigen (HLA)-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelium cells (HBEC). Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation. Studies reported both higher and equivalent soluble HLA-G (sHLA-G) expression in different cohorts of asthmatic patients. In particular, we recently described impaired local expression of HLA-G and abnormal profiles for alternatively spliced isoforms in HBEC from asthmatic patients. sHLA-G dosage is challenging because of its many levels of polymorphism (dimerization, association with β2-microglobulin, and alternative splicing), thus many clinical studies focused on HLA-G single-nucleotide polymorphisms as predictive biomarkers, but few analyzed HLA-G haplotypes. Here, we aimed to characterize HLA-G haplotypes and describe their association with asthmatic clinical features and sHLA-G peripheral expression and to describe variations in transcription factor (TF) binding sites and alternative splicing sites. HLA-G haplotypes were differentially distributed in 330 healthy and 580 asthmatic individuals. Furthermore, HLA-G haplotypes were associated with asthmatic clinical features showed. However, we did not confirm an association between sHLA-G and genetic, biological, or clinical parameters. HLA-G haplotypes were phylogenetically split into distinct groups, with each group displaying particular variations in TF binding or RNA splicing sites that could reflect differential HLA-G qualitative or quantitative expression, with tissue-dependent specificities. Our results, based on a multicenter cohort, thus support the pertinence of HLA-G haplotypes as predictive genetic markers for asthma.

Use of a multi-sensor approach can provide citizens with holistic insights into the air quality of their immediate surroundings and their personal exposure to urban stressors. Our work, as part of the ICARUS H2020 project, which included over 600 participants from seven European cities, discusses the data fusion and harmonization of a diverse set of multi-sensor data streams to provide a comprehensive and understandable report for participants. Harmonizing the data streams identified issues with the sensor devices and protocols, such as non-uniform timestamps, data gaps, difficult data retrieval from commercial devices, and coarse activity data logging. Our process of data fusion and harmonization allowed us to automate visualizations and reports, and consequently provide each participant with a detailed individualized report. Results showed that a key solution was to streamline the code and speed up the process, which necessitated certain compromises in visualizing the data. A thought-out process of data fusion and harmonization of a diverse set of multi-sensor data streams considerably improved the quality and quantity of distilled data that a research participant received. Though automation considerably accelerated the production of the reports, manual and structured double checks are strongly recommended. This work has received funding from the European Union’s Horizon 2020 Programme for Research, Technological Development, and Demonstration, under grant agreement No. 690105 (Integrated Climate forcing and Air Pollution Reduction in Urban Systems (ICARUS)). This work reflects only the authors’ views, and the European Commission is not responsible for any use that may be made of the information it contains. Funding was received from the Young Researchers Program and the P1-0143 program “Cycling of substances in the environment, mass balances, modelling of environmental processes and risk assessment“, both funded by the Slovenian Research Agency. The authors thank RECETOX Research Infrastructure (No. LM2018121) and ACTRIS-CZ Research Infrastructure (No. LM2018122) financed by the Ministry of Education, Youth and Sports and the Operational Programme Research, Development and Innovation (CZ.02.1.01/0.0/0.0/16_013/0001315 and CZ.02.1.01/0.0/0.0/16_013/0001761), as well as the CETOCOEN Excellence Project, supported by the Teaming Action of the EU Horizon 2020 programme (857560) and the Operational Programme Research, Development and Innovation (No. CZ.02.1.01/0.0/0.0/17_043/0009632). Sí