Matrix-Bound PAI-1 Supports Cell Blebbing via RhoA/ROCK1 Signaling

The microenvironment of a tumor can influence both the morphology and the behavior of cancer cells which, in turn, can rapidly adapt to environmental changes. Increasing evidence points to the involvement of amoeboid cell migration and thus of cell blebbing in the metastatic process; however, the cues that promote amoeboid cell behavior in physiological and pathological conditions have not yet been clearly identified. Plasminogen Activator Inhibitor type-1 (PAI-1) is found in high amount in the microenvironment of aggressive tumors and is considered as an independent marker of bad prognosis. Here we show by immunoblotting, activity assay and immunofluorescence that, in SW620 human colorectal cancer cells, matrix-associated PAI-1 plays a role in the cell behavior needed for amoeboid migration by maintaining cell blebbing, localizing PDK1 and ROCK1 at the cell membrane and maintaining the RhoA/ROCK1/MLC-P pathway activation. The results obtained by modeling PAI-1 deposition around tumors indicate that matrix-bound PAI-1 is heterogeneously distributed at the tumor periphery and that, at certain spots, the elevated concentrations of matrix-bound PAI-1 needed for cancer cells to undergo the mesenchymal-amoeboid transition can be observed. Matrix-bound PAI-1, as a matricellular protein, could thus represent one of the physiopathological requirements to support metastatic formation

La baraque militaire dans les hôpitaux américains de la Grande Guerre: Stratégies économiques et choix socio-culturels

National audienceRecent archaeological research conducted on American logistics during the Great War and more particularly on the American Expeditionary Forces (AEF) hospitals raises many questions. The US military has demonstrated real logistical prowess to operationalize dozens of large medical facilities at the cutting edge of technology to accommodate hundreds of thousands of wounded. These huge camps built in a few months in the heart of the French countryside are structured from a prefabricated module: the military barracks. This construction method became the nerve of American military strategy, foreshadowing the major operations of the 20th and 21st centuries. Infrastructures, medical (operating rooms, pharmacies, morgues, laboratories, etc.) or not (supply, neighbourhoods, leisure, storage, etc.) are characterized by a prefabricated framework made of a recurring assembly of panels and trusses. This nomadic architecture inherited from a nineteenth-century design is also a reflection of socio-economic, cultural and architectural practices. Beyond the simple military barracks, these structures become the living and working place for soldiers and medical personnel, thousands of kilometres from their homes, in a foreign country and at war.Les récentes recherches archéologiques menées sur la logistique américaine durant la Grande Guerre et plus particulièrement sur les hôpitaux de l’American Expeditionary Forces (AEF) soulèvent de nombreux questionnements. L’armée américaine fait preuve de réelles prouesses logistiques pour rendre opérationnelles plusieurs dizaines de structures médicales d’envergure et à la pointe de la technologie afin d’accueillir des centaines de milliers de blessés. Ces immenses camps édifiés en quelques mois au cœur des campagnes françaises se structurent à partir d’un module préfabriqué : la baraque militaire. Ce mode de construction devient le nerf de la stratégie militaire américaine, préfigurant les grandes opérations des XXe et XXIe siècles. Les infrastructures, médicales (salles opératoires, pharmacies, morgues, laboratoires, etc.) ou non (approvisionnement, quartiers, loisir, stockages, etc.) se caractérisent par une charpente préfabriquée faite d’un assemblage répétitif de panneaux et de fermes. Cette architecture nomade héritée d’une conception du XIXe siècle est également le reflet des pratiques socio-économiques, culturelles et architecturales. Au-delà de la simple baraque militaire, ces structures deviennent le lieu de vie et de travail des soldats et du personnel soignant, à des milliers de kilomètres de leur foyer, dans un pays étranger et en guerre

Taking advantage of electric field induced bacterial aggregation for the study of interactions between bacteria and macromolecules by capillary electrophoresis

International audienceThe quantification of interaction stoechiometry and binding constant between bacteria (or other microorganism) and(macro)molecules remains a challenging issue for which only a few adapted methods are available. In this paper, a new methodologywas developed for the determination of the interaction stoichiometry and binding constant between bacteria and (macro)molecules. The originality of this work is to take advantage of the bacterial aggregation phenomenon to directly quantify the freeligand concentration in equilibrated bacteria-ligand mixtures using frontal analysis continuous capillary electrophoresis. The describedmethodology does not require any sample preparation such as filtration step or centrifugation. It was applied to the study ofinteractions between Erwinia carotovora and different generations of dendrigraft poly-L-lysines leading to quantitative informations(i.e. stoichiometry and binding site constant). High stoichiometries in the order of 106-107 were determined between nanometricdendrimer-like ligands and the rod-shaped micrometric bacteria. The effect of the dendrimer generation on the binding constantand the stoichiometry is discussed. Stoichiometries were compared with those obtained by replacing the bacteria by polystyrenemicrobeads to demonstrate the internalization of the ligands inside the bacteria and the increase of the specific surface via theformation of vesicles

Preadipocyte conversion to macrophage. Evidence of plasticity

Preadipocytes are present throughout adult life in adipose tissues and can proliferate and differentiate into mature adipocytes according to the energy balance. An increasing number of reports demonstrate that cells from adipose lineages (preadipocytes and adipocytes) and macrophages share numerous functional or antigenic properties. No large scale comparison reflecting the phenotype complexity has been performed between these different cell types until now. We used profiling analysis to define the common features shared by preadipocyte, adipocyte, and macrophage populations. Our analysis showed that the preadipocyte profile is surprisingly closer to the macrophage than to the adipocyte profile. From these data, we hypothesized that in a macrophage environment preadipocytes could effectively be converted into macrophages. We injected labeled stroma-vascular cells isolated from mouse white adipose tissue or 3T3-L1 preadipocyte cell line into the peritoneal cavity of nude mice and investigated changes in their phenotype. Preadipocytes rapidly and massively acquired high phagocytic activity and index. 60– 70% of preadipocytes also expressed five macrophagespecific antigens: F4/80, Mac-1, CD80, CD86, and CD45. These values were similar to those observed for peritoneal macrophages. In vitro experiments showed that cell-to-cell contact between preadipocytes and peritoneal macrophages partially induced this preadipocyte phenotype conversion. Overall, these results suggest that preadipocyte and macrophage phenotypes are very similar and that preadipocytes have the potential to be very efficiently and rapidly converted into macrophages. This work emphasizes the great cellular plasticity of adipose precursors and reinforces the link between adipose tissue and innate immunity processes

Diversity and functional specialization of oyster immune cells uncovered by integrative single cell level investigations

Mollusks are a major component of animal biodiversity and play a critical role in ecosystems and global food security. The Pacific oyster,Crassostrea (Magallana) gigas, is the most farmed bivalve mollusk in the world and is becoming a model species for invertebrate biology. Despite the extensive research on hemocytes, the immune cells of bivalves, their characterization remains elusive. Here we were able to extensively characterize the diverse hemocytes and identified at least seven functionally distinct cell types and three hematopoietic lineages. A combination of single-cell RNA sequencing, quantitative cytology, cell sorting, functional assays and pseudo-time analyses was used to deliver a comprehensive view of the distinct hemocyte types. This integrative analysis enabled us to reconcile molecular and cellular data and identify distinct cell types performing specialized immune functions, such as phagocytosis, reactive oxygen species production, copper accumulation, and expression of antimicrobial peptides. This study emphasized the need for more in depth studies of cellular immunity in mollusks and non-model invertebrates and set the ground for further comparative immunology studies at the cellular level

Vibrio–bivalve interactions in health and disease

none7In the marine environment, bivalve mollusks constitute habitats for bacteria of the Vibrionaceae family. Vibrios belong to the microbiota of healthy oysters and mussels, which have the ability to concentrate bacteria in their tissues and body fluids, including the hemolymph. Remarkably, these important aquaculture species respond differently to infectious diseases. While oysters are the subject of recurrent mass mortalities at different life stages, mussels appear rather resistant to infections. Thus, Vibrio species are associated with the main diseases affecting the worldwide oyster production. Here, we review the current knowledge on Vibrio–bivalve interaction in oysters (Crassostrea sp.) and mussels (Mytilus sp.). We discuss the transient versus stable associations of vibrios with their bivalve hosts as well as technical issues limiting the monitoring of these bacteria in bivalve health and disease. Based on the current knowledge of oyster/mussel immunity and their interactions with Vibrio species pathogenic for oyster, we discuss how differences in immune effectors could contribute to the higher resistance of mussels to infections. Finally, we review the multiple strategies evolved by pathogenic vibrios to circumvent the potent immune defences of bivalves and how key virulence mechanisms could have been positively or negatively selected in the marine environment through interactions with predators.mixedDestoumieux-Garzon D.; Canesi L.; Oyanedel D.; Travers M.-A.; Charriere G.M.; Pruzzo C.; Vezzulli L.Destoumieux-Garzon, D.; Canesi, L.; Oyanedel, D.; Travers, M. -A.; Charriere, G. M.; Pruzzo, C.; Vezzulli, L

Traits of a mussel transmissible cancer are reminiscent of a parasitic life style

Some cancers have evolved the ability to spread from host to host by transmission of cancerous cells. These rare biological entities can be considered parasites with a host-related genome. Still, we know little about their specific adaptation to a parasitic lifestyle. MtrBTN2 is one of the few lineages of transmissible cancers known in the animal kingdom. Reported worldwide, MtrBTN2 infects marine mussels. We isolated MtrBTN2 cells circulating in the hemolymph of cancerous mussels and investigated their phenotypic traits. We found that MtrBTN2 cells had remarkable survival capacities in seawater, much higher than normal hemocytes. With almost 100% cell survival over three days, they increase significantly their chances to infect neighboring hosts. MtrBTN2 also triggered an aggressive cancerous process: proliferation in mussels was ~ 17 times higher than normal hemocytes (mean doubling time of ~ 3 days), thereby favoring a rapid increase of intra-host population size. MtrBTN2 appears to induce host castration, thereby favoring resources re-allocation to the parasites and increasing the host carrying capacity. Altogether, our results highlight a series of traits of MtrBTN2 consistent with a marine parasitic lifestyle that may have contributed to the success of its persistence and dissemination in different mussel populations across the globe

Découverte d’une nouvelle faune d’âge cénomanien dans la région de Forthassa (Atlas saharien occidental, Algérie) : Implications biostratigraphiques et paléoenvironnementales

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Cross-talk and mutual shaping between the immune system and the microbiota during an oyster's life

The Pacific oyster Crassostrea gigas lives in microbe-rich marine coastal systems subjected to rapid environmental changes. It harbours a diversified and fluctuating microbiota that cohabits with immune cells expressing a diversified immune gene repertoire. In the early stages of oyster development, just after fertilization, the microbiota plays a key role in educating the immune system. Exposure to a rich microbial environment at the larval stage leads to an increase in immune competence throughout the life of the oyster, conferring a better protection against pathogenic infections at later juvenile/adult stages. This beneficial effect, which is intergenerational, is associated with epigenetic remodelling. At juvenile stages, the educated immune system participates in the control of the homeostasis. In particular, the microbiota is fine-tuned by oyster antimicrobial peptides acting through specific and synergistic effects. However, this balance is fragile, as illustrated by the Pacific Oyster Mortality Syndrome, a disease causing mass mortalities in oysters worldwide. In this disease, the weakening of oyster immune defences by OsHV-1 µVar virus induces a dysbiosis leading to fatal sepsis. This review illustrates the continuous interaction between the highly diversified oyster immune system and its dynamic microbiota throughout its life, and the importance of this cross-talk for oyster health. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’

New fossiliferous sites from the mid-Cretaceous Tendrara dome (High Plateaus, Morocco): biostratigraphical, paleoenvironmental and paleogeographical implications

International audienc