Spontaneous migration of cellular aggregates from giant keratocytes to running spheroids

Despite extensive knowledge on the mechanisms that drive singlecell migration, those governing the migration of cell clusters, as occurring during embryonic development and cancer metastasis,remain poorly understood. Here, we investigate the collective migration of cell on adhesive gels with variable rigidity, using 3D cellular aggregates as a model system. After initial adhesion to the substrate, aggregates spread by expanding outward a cell monolayer, whose dynamics is optimal in a narrowrange of rigidities. Fast expansion gives rise to the accumulation of mechanical tension that leads to the rupture of cell–cell contacts and the nucleation of holes within the monolayer, which becomes unstable and undergoes dewetting like a liquid film. This leads to a symmetry breaking and causes the entire aggregate to move as a single entity. Varying the substrate rigidity modulates the extent of dewetting and induces different modes of aggregate motion: “giant keratocytes,” where the lamellipodium is a cell monolayer that expands at the front and retracts at the back; “penguins,” characterized by bipedal locomotion; and “running spheroids,” for nonspreading aggregates. We characterize these diverse modes of collectivemigration by quantifying the flows and forces that drive them, andwe unveil the fundamental physical principles that govern these behaviors, which underscore the biological predisposition of living material to migrate, independent of length scale

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality

The benefit of combining curcumin, bromelain and harpagophytum to reduce inflammation in osteoarthritic synovial cells

International audienceBackground: Osteoarthritis (OA) is the most common form of arthritis, affecting millions of people worldwide and characterised by joint pain and inflammation. It is a complex disease involving inflammatory factors and affecting the whole joint, including the synovial membrane. Since drug combination is widely used to treat chronic inflammatory diseases, a similar strategy of designing plant-derived natural products to reduce inflammation in OA joints may be of interest. In this study, we characterised the response of OA synovial cells to lipopolysaccharide (LPS) and investigated the biological action of the combination of curcumin, bromelain and harpagophytum in this original in vitro model of osteoarthritis.Methods: Firstly, human synovial cells from OA patients were stimulated with LPS and proteomic analysis was performed. Bioinformatics analyses were performed using Cytoscape App and SkeletalVis databases. Additionally, cells were treated with curcumin, bromelain and harpagophytum alone or with the three vegetal compounds together. The gene expression involved in inflammation, pain or catabolism was determined by RT-PCR. The release of the encoded proteins by these genes and of prostaglandin E2 (PGE2) were also assayed by ELISA.Results: Proteomic analysis demonstrated that LPS induces the expression of numerous proteins involved in the OA process in human OA synovial cells. In particular, it stimulates inflammation through the production of pro-inflammatory cytokines (Interleukin-6, IL-6), catabolism through an increase of metalloproteases (MMP-1, MMP-3, MMP-13), and the production of pain-mediating neurotrophins (Nerve Growth Factor, NGF). These increases were observed in terms of mRNA levels and protein release. LPS also increases the amount of PGE2, another inflammation and pain mediator. At the doses tested, vegetal extracts had little effect: only curcumin slightly counteracted the effects of LPS on NGF and MMP-13 mRNA, and PGE2, IL-6 and MMP-13 release. In contrast, the combination of curcumin with bromelain and harpagophytum reversed lots of effects of LPS in human OA synovial cells. It significantly reduced the gene expression and/or the release of proteins involved in catabolism (MMP-3 and -13), inflammation (IL-6) and pain (PGE2 and NGF).Conclusion: We have shown that the stimulation of human OA synovial cells with LPS can induce protein changes similar to inflamed OA synovial tissues. In addition, using this model, we demonstrated that the combination of three vegetal compounds, namely curcumin, bromelain and harpagophytum, have anti-inflammatory and anti-catabolic effects in synovial cells and may thus reduce OA progression and related pain

An investigation of the potential of optical computed tomography for imaging of synchrotron-generated x-rays at high spatial resolution

X-ray microbeam radiation therapy (MRT) is a novel form of treatment, currently in its preclinical stage, which uses microplanar x-ray beams from a synchrotron radiation source. It is important to perform accurate dosimetry on these microbeams, but, to date, there has been no accurate enough method available for making 3D dose measurements with isotropic, high spatial resolution to verify the results of Monte Carlo dose simulations. Here, we investigate the potential of optical computed tomography for satisfying these requirements. The construction of a simple optical CT microscopy (optical projection tomography) system from standard commercially available hardware is described. The measurement of optical densities in projection data is shown to be highly linear (r2=0.999). The depth-of-field (DOF) of the imaging system is calculated based on the previous literature and measured experimentally using a commercial DOF target. It is shown that high quality images can be acquired despite the evident lack of telecentricity and despite DOF of the system being much lower than the sample diameter. Possible reasons for this are discussed. Results are presented for a complex irradiation of a 22 mm diameter cylinder of the radiochromic polymer PRESAGE, demonstrating the exquisite 'dose-painting' abilities available in the MRT hutch of beamline ID-17 at the European Synchrotron Radiation Facility. Dose distributions in this initial experiment are equally well resolved on both an optical CT scan and a corresponding transmission image of radiochromic film, down to a line width of 83 microm (6 lp mm(-1)) with an MTF value of 0.40. A group of 33 microm wide lines was poorly resolved on both the optical CT and film images, and this is attributed to an incorrect exposure time calculation, leading to under-delivery of dose. Image artefacts in the optical CT scan are discussed. PRESAGE irradiated using the microbeam facility is proposed as a suitable material for producing phantom samples for quantitative characterization of optical CT microscopy systems

The Girders System for the New ESRF Storage Ring

International audienceThe ESRF is proceeding with the design and procurement of its new low emittance storage ring (Extremely Brilliant Source project). This completely new storage ring requires a high performance support system, providing high stability (first resonance frequency about 50Hz) and a precise alignment capability (50μm, manual in transverse direction and motorized in the vertical one). In order to meet these requirements we decided to support the magnets of each of the 32 cells of the synchrotron with four identical girders that was considered the best compromise between cost, complexity and performances. Each of the resulting 128 girders is 5.1m long, carries about seven tons of magnets, and its weight including fixed basement and adjusting system is six tons. The adjustment system relies on modified commercial wedges; their stiffness was evaluated through laboratory tests. The FEA calculations carried out to optimize the design will be presented, together with the results obtained on a complete prototype girder system which was built and extensively tested and confirmed the modal calculations

OCARI: an energy-efficient WSN

International audienceEnergy efficiency is the main concern of applications supported by WSNs where some nodes are battery operated and it is difficult, expensive or even impossible to renew their energy. In the literature, four classes of energy-efficient techniques have been distinguished in WSNs: (1) topology control where the transmitter adapts its transmission power, depending on the receiver (2) energy-efficient routing where the energy consumed by an end-to-end transmission is minimized and nodes with low residual energy are avoided, (3) node activity scheduling where nodes come back to the sleep mode to save energy and finally (4) optimization of transfers in order to avoid useless transfers. The OCARI WSN has been designed for industrial applications where energy efficiency matters. OCARI targets applications such as monitoring of industrial equipments or civil engineering, performance testing of equipments, radioprotection of site maintenance and state control of some devices. Such applications require determinism in the medium access and low energy consumption. OCARI is based on the 802.15.4 physical layer and supports the application objects defined by ZigBee. It differs from other protocols like ZigBee, WirelessHART and ISA100.11a by its unique characteristics: - An energy efficient deterministic medium access supporting relaying of time-constrained packets, called MaCARI. - A proactive routing taking into account the residual energy of nodes, minimizing energy consumption and supporting nomadism, called EOLSR. The residual energy of a node is estimated by a model that provides an accuracy better than the linear model, especially in the case of a low duty cycle. - A node activity scheduling based on node coloring, reducing interferences and thus optimizing energy efficiency, called SERENA. The OCARI topology consists in a mesh of stars, each star is ruled by a coordinator node. Coordinator nodes are able to route packets whereas simple sensor nodes are not, they are only able to communicate with their coordinators. In OCARI, both types of nodes can sleep, while maintaining network connectivity. In conclusion, OCARI optimizes transfers with collision avoidance, reduction of interferences, and broadcasts optimization. Cross-layering is used to reduce the routing overhead by maintaining only useful routes. Moreover, it allows OCARI to optimize data gathering delays and data freshness