Inhibition of the membrane repair protein annexin-A2 prevents tumor invasion and metastasis.

Cancer cells are exposed to major compressive and shearing forces during invasion and metastasis, leading to extensive plasma membrane damage. To survive this mechanical stress, they need to repair membrane injury efficiently. Targeting the membrane repair machinery is thus potentially a new way to prevent invasion and metastasis. We show here that annexin-A2 (ANXA2) is required for membrane repair in invasive breast and pancreatic cancer cells. Mechanistically, we show by fluorescence and electron microscopy that cells fail to reseal shear-stress damaged membrane when ANXA2 is silenced or the protein is inhibited with neutralizing antibody. Silencing of ANXA2 has no effect on proliferation in vitro, and may even accelerate migration in wound healing assays, but reduces tumor cell dissemination in both mice and zebrafish. We expect that inhibiting membrane repair will be particularly effective in aggressive, poor prognosis tumors because they rely on the membrane repair machinery to survive membrane damage during tumor invasion and metastasis. This could be achieved either with anti-ANXA2 antibodies, which have been shown to inhibit metastasis of breast and pancreatic cancer cells, or with small molecule drugs.

Transition from Saltation to Collisional Regime in Windblown Sand.

We report experiments on windblown sand that highlight a transition from saltation to collisional regime above a critical dimensionless mass flux or Shields number. The transition is first seen through the mass flow rate Q, which deviates from a linear trend with the Shields number and seems to follow a quadratic law. Other physical evidences confirm the change of the transport properties. In particular, the particle velocity and the height of the transport layer increases with increasing Shields number in the collisional regime while the latter are invariant with the wind strength in the saltation regime. Discrete numerical simulations support the experimental findings and ascertain that mid-air collisions are responsible for the change of transport regime.

Particle impact on a cohesive granular media.

We investigate numerically the impact process of a particle of diameter d and velocity V_{i} onto a cohesive granular packing made of similar particles via two-dimensional discrete element method simulations. The cohesion is ensured by liquid bridges between neighboring particles and described by short range attraction force based on capillary modeling. The outcome of the impact is analyzed through the production of ejected particles from the packing, referred to as the splash process. We quantify this production as a function of the impact velocity for various capillary strength Γ and liquid content Ω. The numerical data indicate that the splash process is modified when the dimensionless cohesion number Co=6Γ/ρ_{p}gd^{2} (where ρ_{p} is the particle density, d its diameter, and g the gravitational acceleration) exceeds a critical value of the order of the unity. Above this value, we highlight that the ejection process is triggered above a threshold impact Froude number, Fr=V_{i}/sqrt[gd], which depends both on Γ and Ω and scales as Γ^{ß}Ω^{δ}, where the values of the exponents are found close to 1/2 and 1/6, respectively, and can be derived from rational physical arguments. Importantly, we show that, above the threshold, the number of splashed particles follows a linear law with the impact Froude number as in the cohesionless case.

Defective membrane repair machinery impairs survival of invasive cancer cells.

Cancer cells are able to reach distant tissues by migration and invasion processes. Enhanced ability to cope with physical stresses leading to cell membrane damages may offer to cancer cells high survival rate during metastasis. Consequently, down-regulation of the membrane repair machinery may lead to metastasis inhibition. We show that migration of MDA-MB-231 cells on collagen I fibrils induces disruptions of plasma membrane and pullout of membrane fragments in the wake of cells. These cells are able to reseal membrane damages thanks to annexins (Anx) that are highly expressed in invasive cancer cells. In vitro membrane repair assays reveal that MDA-MB-231 cells respond heterogeneously to membrane injury and some of them possess a very efficient repair machinery. Finally, we show that silencing of AnxA5 and AnxA6 leads to the death of migrating MDA-MB-231 cells due to major defect of the membrane repair machinery. Disturbance of the membrane repair process may therefore provide a new avenue for inhibiting cancer metastasis.

Tunable High Spatio-Spectral Purity Undulator Radiation from a Transported Laser Plasma Accelerated Electron Beam.

Undulator based synchrotron light sources and Free Electron Lasers (FELs) are valuable modern probes of matter with high temporal and spatial resolution. Laser Plasma Accelerators (LPAs), delivering GeV electron beams in few centimeters, are good candidates for future compact light sources. However the barriers set by the large energy spread, divergence and shot-to-shot fluctuations require a specific transport line, to shape the electron beam phase space for achieving ultrashort undulator synchrotron radiation suitable for users and even for achieving FEL amplification. Proof-of-principle LPA based undulator emission, with strong electron focusing or transport, does not yet exhibit the full specific radiation properties. We report on the generation of undulator radiation with an LPA beam based manipulation in a dedicated transport line with versatile properties. After evidencing the specific spatio-spectral signature, we tune the resonant wavelength within 200-300 nm by modification of the electron beam energy and the undulator field. We achieve a wavelength stability of 2.6%. We demonstrate that we can control the spatio-spectral purity and spectral brightness by reducing the energy range inside the chicane. We have also observed the second harmonic emission of the undulator.

Control of laser plasma accelerated electrons for light sources.

With gigaelectron-volts per centimetre energy gains and femtosecond electron beams, laser wakefield acceleration (LWFA) is a promising candidate for applications, such as ultrafast electron diffraction, multistaged colliders and radiation sources (betatron, compton, undulator, free electron laser). However, for some of these applications, the beam performance, for example, energy spread, divergence and shot-to-shot fluctuations, need a drastic improvement. Here, we show that, using a dedicated transport line, we can mitigate these initial weaknesses. We demonstrate that we can manipulate the beam longitudinal and transverse phase-space of the presently available LWFA beams. Indeed, we separately correct orbit mis-steerings and minimise dispersion thanks to specially designed variable strength quadrupoles, and select the useful energy range passing through a slit in a magnetic chicane. Therefore, this matched electron beam leads to the successful observation of undulator synchrotron radiation after an 8 m transport path. These results pave the way to applications demanding in terms of beam quality.

Publisher Correction: Control of laser plasma accelerated electrons for light sources.

The original version of this Article contained an error in the last sentence of the first paragraph of the Introduction and incorrectly read 'A proper electron beam control is one of the main challenges towards the Graal of developing a compact alternative of X-ray free-electron lasers by coupling LWFA gigaelectron-volts per centimetre acceleration gradient with undulators in the amplification regime in equation 11, nx(n-ß) x ß: n the two times and beta the two times should be bold since they are vectorsin Eq. 12, ß should be bold as well.' The correct version is 'A proper electron beam control is one of the main challenges towards the Graal of developing a compact alternative of X-ray free-electron lasers by coupling LWFA gigaelectron-volts per centimetre acceleration gradient with undulators in the amplification regime.'This has been corrected in both the PDF and HTML versions of the Article.

[Anaesthetic-induced myocardial preconditioning: fundamental basis and clinical implications]. / Préconditionnement myocardique induit par les agents anesthésiques halogénés: bases fondamentales et implications cliniques.

OBJECTIVE: Volatile halogenated anaesthetics offer a myocardial protection when they are administrated before a myocardial ischaemia. Cellular mechanisms involved in anaesthetic preconditioning are now better understood. The objectives of this review are to understand the anaesthetic-induced preconditioning underlying mechanisms and to know the clinical implications. DATA SOURCES: References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: volatile anaesthetic, isoflurane, halothane, sevoflurane, desflurane, preconditioning, protection, myocardium. DATA SYNTHESIS: Ischaemic preconditioning (PC) is a myocardial endogenous protection against ischaemia. It has been described as one or several short ischaemia before a sustained ischemia. These short ischaemia trigger a protective signal against this longer ischaemia. An ischemic organ is able to precondition a remote organ. It is possible to replace the short ischaemia by a preadministration of halogenated volatile anaesthetic with the same protective effect, this is called anaesthetic PC (APC). APC and ischaemic PC share similar underlying biochemical mechanisms including protein kinase C, tyrosine kinase activation and mitochondrial and sarcolemnal K(ATP) channels opening. All halogenated anaesthetics can produce an anaesthetic PC effect. Myocardial protection during reperfusion, after the long ischaemia, has been shown by successive short ischaemia or volatile anaesthetic administration, this is called postconditioning. Ischaemic PC has been described in humans in 1993. Clinical studies in human cardiac surgery have shown the possibility of anaesthetic PC with volatile anaesthetics. These studies have shown a decrease of postoperative troponin in patient receiving halogenated anaesthetics.

Review: Annexin-A5 and cell membrane repair.

Annexins are soluble proteins that bind to biological membranes containing negatively charged phospholipids, principally phosphatidylserine, in a Ca(2+)-dependent manner. Annexin-A5 (AnxA5), the smallest member of the annexin family, presents unique properties of membrane binding and self-assembly into ordered two-dimensional (2D) arrays on membrane surfaces. We have previously reported that AnxA5 plays a central role in the machinery of membrane repair by enabling rapid resealing of plasma membrane disruption in murine perivascular cells. AnxA5 promotes membrane repair via the formation of a protective 2D bandage at membrane damaged site. Here, we review current knowledge on cell membrane repair and present recent findings on the role of AnxA5 in membrane resealing of human trophoblasts.

[Our operative strategy in the cure of genital prolapse by high approach]. / Notre tactique opératoire dans la cure des prolapsus génitaux par voie haute.

The work from the School of Broca has made it possible to specify simple techniques which at one and the same time deal with genital prolapse and stress incontinence. These results, which for a long time had been disappointing, seem now to have improved in the last few years. The authors describe a triple operation which is particularly indicated in cases of large cystoceles found in patients suffering from the clinical condition of prolapse.

[An index for induction of labour. A scheme based on Parzen's method (author's transl)]. / Indice de déclenchement du travail. Détermination selon la méthode de Parzen.

It would seem to be necessary to make a score for pre-induction which would give the highest success rate and which would be available to all members of the obstetrical team, since there has been such a constant increase in the number of indications for induction of labour. Following a study based on 255 inductions the authors have been able to work out a system for calculating the prognosis according to the different classical scores used up till now and they have, after treating the information available, been able to work out a score according to the analytical method of Parzen which allows discrimination. In 95 per cent of cases one can predict the successful outcome by considering just 6 parameters: consistency of the cervix, the height of the presenting part, the length of the cervix, the height of the uterine fundus, and an estimation of the fetal weight and the state of the membranes. A complete list of the group that failed is furnished by the computer which could coordinate each new case in two minutes. As the study concerned itself with only 18 variables, a new study should be carried out on 1,000 case histories which would include some extra parameters such as: tocolytics used in pregnancy, cerclage (Shirodkar's stitch), the psychological state of the mother...which might shift the relative importance of the six variable that have been kept on perhaps even show how a percentage could be worked out of the cases classified using a smaller number of parameters to be taken into account.

Randomised trial of preventive nasal ventilation in Duchenne muscular dystrophy. French Multicentre Cooperative Group on Home Mechanical Ventilation Assistance in Duchenne de Boulogne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in children. Paralysis of respiratory muscles causes a decrease in forced vital capacity (FVC) from age 12 years, and death occurs between 20 and 25 years old and is usually related to respiratory insufficiency. Uncontrolled studies suggest that early home use of nasal intermittent positive-pressure ventilation (NIPPV) in DMD patients free of respiratory failure could limit progression of the restrictive syndrome and therefore improve survival because efficacy of preventive NIPPV has not been demonstrated in a controlled trial, we undertook a randomised multicentre study in which 70 patients with DMD were included. Patients were free of daytime respiratory failure and FVC was between 20 and 50% of predicted values. At least 6 h of nocturnal NIPPV (n = 35) was compared with conventional treatment (n = 35). During a mean follow-up of 52 months, 10 patients died, 8 in the NIPPV group and 2 in the control group (p = 0.05, log-rank test). No differences were observed between the two groups for occurrence of hypercapnia, decrease of FVC below 20% of initial values, or use of necessary mechanical ventilation. Preventive NIPPV did not improve respiratory handicap and reduced survival of DMD patients. Use of NIPPV for preventive purposes should be avoided in patients with FVC between 20 and 50% of predicted values.

[Management of neuromuscular training and psychotherapy]. / Conduite de l'éducation neuro-musculaire et psychothérapie.

In 9 out of 10 cases it is a very simple matter to persuade children age 7 to 9 years to stop sucking their thumbs by means of very elementary and brief supportive psychotherapy. In the majority of cases it is possible, three months after interruption of the habit and after studying the morphologic improvement, to decide whether treatment should be completed by education of deglutition and of phonetic articulation, possible after previous mechanical treatment if this is justified by the residual vestibulolingual bite disorder.