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PDF file - 3848K, Figure S1. Pathological doses of cl-CD95L trigger cell migration of TNBC cells. Figure S2. Cl-CD95L induces migration of TNBC cells through a PI3K(p110β)/c-yesdriven signaling pathway. Figure S3. NOX-3-dependent ROS production is instrumental in CD95-mediated cell motility in TNBC cells. Figure S4. Cl-CD95L induces co-localization of CD95 with EGFR. Figure S5. cl-CD95L promotes migration of TNBC cells via EGFR-dependent and EGFindependent signaling pathways.

Sphingonotus is a genus of grasshoppers that contains species groups with several closely related species, among which Sphingonotus caerulans and an unnamed Sphingonotus that are found in continental France. The exact distribution of both species is still under investigation, but it is believed that S. caerulans might be restricted to the northern part of the country, and that Sphingonotus sp. occurs in the southern half and might reach the north east. We explored the genetic identity of Sphingonotus grasshoppers in the upper Rhine Valley of Alsace (northeastern France) using combined fragments of mtDNA ND5 and cytb genes included with other available samples in ML and Bayesian phylogenetic analyses. The results indicate that the five specimens sampled within this region belong to S. caerulans. The actual distribution of Sphingonotus sp. in France remains to be investigated with wider sampling, especially to get a better knowledge on its northern limit.

Even though reptiles are threatened worldwide, few studies address their conservation, especially snakes. The goal of our study was to measure the genetic structure of a widely distributed temperate reptile, the smooth snake Coronella austriaca using eight microsatellite markers in two different areas at the core (Alsace, north-eastern France) and at the edge (Wallonia, southern Belgium) of its range. We sampled 506 individuals in 38 localities (respectively 10 and 28). Analysis of genetic structure conducted with a clustering method detected three clusters in Alsace, one group gathering all populations but two. In Wallonia, differentiation was observed on both sides of the Meuse river and in the Southern Ardenne region (southernmost sampling sites). Spatial autocorrelation analysis showed that individuals share parental relationship up to a distance of 2.8 km in Alsace and up to 10 km in Wallonia. Isolation by distance was detected in Wallonia but the distance explained a very limited part of the differentiation (r = 0.033), whereas no isolation-by-distance pattern was detected in Alsace. Even though genetic differentiation between populations separated by large rivers, highways, or crop fields was detected, dispersal between populations seem currently sufficient to avoid any kind of genetic drift in both regions. These results are strongly contrasting with a previous study in England, suggesting sharp local variation of genetic structuring and diversification between location within the same species, probably related to the position in the distribution area and different densities.

Les recommandations de gestion d’habitat en faveur des Squamates terrestres s’intéressent principalement aux éléments bordiers et délaissent souvent les habitats ouverts comme les prairies. L’observation visuelle et la surveillance régulière d’un réseau de plaques refuges positionnées sur les lisières et le centre d’une prairie permanente non pâturée ont permis de suivre une communauté de Squamates pendant une année au sein du département de la Loire-Atlantique. Nos résultats montrent qu’il existe des différences dans l’exploration de la prairie permanente non pâturée selon les espèces, le mode de thermorégulation, l’âge des individus et le moment de l’année. Les Lacertidae tendent à rester près des lisières, alors que les Serpents et les Orvets fragiles s’aventurent plus loin dans la prairie au cours du temps. Néanmoins, la richesse spécifique diminue lorsque la distance à la lisière augmente. Cette étude nous éclaire sur l’importance de la prise en compte des prairies permanentes non pâturées pour la conservation des Squamates en milieu bocager.

In intrapulmonary arteries (IPAs), mechanical forces due to blood flow control vessel tone, and these forces change during pulmonary hypertension (PH). Piezo1, a stretch-activated calcium channel, is a sensor of mechanical stress present in both endothelial cells (ECs) and smooth muscle cells (SMCs). The present study investigated the role of Piezo1 on IPA in the chronic hypoxia model of PH. Rats were raised in chronically hypoxic conditions for 1 (1W-CH, early stage) or 3 weeks (3W-CH, late-stage) of PH or in normoxic conditions (Nx). Immunofluorescence labeling and patch-clamping revealed the presence of Piezo1 in both ECs and SMCs. The Piezo1 agonist, Yoda1, induced an IPA contraction in Nx and 3W-CH. Conversely, Yoda1 induced an endothelial nitric oxide (eNOS) dependent relaxation in 1W-CH. In ECs, the Yoda1-mediated intracellular calcium concentration ([Ca

Expression of the nerve growth factor NGF is increased in pulmonary hypertension (PH). We have here studied whether oxidative stress and inflammation, two pathological conditions associated with transforming growth factor-β1 (TGF-β1) in PH, may trigger NGF secretion by pulmonary arterial (PA) cells. Effects of hydrogen peroxide (H2O2) and interleukin-1β (IL-1β) were investigated ex vivo on rat pulmonary arteries, as well as in vitro on human PA smooth muscle (hPASMC) or endothelial cells (hPAEC). TβRI expression was assessed by Western blotting. NGF PA secretion was assessed by ELISA after TGF-β1 blockade (anti-TGF-β1 siRNA, TGF-β1 blocking antibodies, TβRI kinase, p38 or Smad3 inhibitors). TβRI PA expression was evidenced by Western blotting both ex vivo and in vitro. H2O2 or IL-1β significantly increased NGF secretion by hPASMC and hPAEC, and this effect was significantly reduced when blocking TGF-β1 expression, binding to TβRI, TβRI activity, or signaling pathways. In conclusion, oxidative stress and inflammation may trigger TGF-β1 secretion by hPASMC and hPAEC. TGF-β1 may then act as an autocrine factor on these cells, increasing NGF secretion via TβRI activation. Since NGF and TGF-β1 are relevant growth factors involved in PA remodeling, such mechanisms may therefore be relevant to PH pathophysiology.

International audience; Although CD95L (also known as FasL) is still predominantly considered as a death ligand that induces apoptosis in infected and transformed cells, substantial evidence indicate that it can also trigger non-apoptotic signaling pathways whose pathophysiological roles remain to be fully elucidated. The transmembrane ligand CD95L belongs to the tumor necrosis factor (TNF) superfamily. After cleavage by metalloprotease, its soluble form (s-CD95L) fails to trigger the apoptotic program but instead induces signaling pathways promoting the aggressiveness of certain inflammatory disorders such as autoimmune diseases and cancers. We propose to evaluate the various pathologies in which the metalloprotease-cleaved CD95L is accumulated and analyze whether this soluble ligand may play a significant role in the pathology progression. Based on the TNFα-targeting therapeutics, we envision that targeting the soluble form of CD95L may represent a very attractive therapeutic option in the pathologies depicted herein.

In intrapulmonary arteries (IPAs), mechanical forces due to blood flow control vessel tone, and these forces change during pulmonary hypertension (PH). Piezo1, a stretch-activated calcium channel, is a sensor of mechanical stress present in both endothelial cells (ECs) and smooth muscle cells (SMCs). The present study investigated the role of Piezo1 on IPA in the chronic hypoxia model of PH. Rats were raised in chronically hypoxic conditions for 1 (1W-CH, early stage) or 3 weeks (3W-CH, late-stage) of PH or in normoxic conditions (Nx). Immunofluorescence labeling and patch-clamping revealed the presence of Piezo1 in both ECs and SMCs. The Piezo1 agonist, Yoda1, induced an IPA contraction in Nx and 3W-CH. Conversely, Yoda1 induced an endothelial nitric oxide (eNOS) dependent relaxation in 1W-CH. In ECs, the Yoda1-mediated intracellular calcium concentration ([Ca2+]i) increase was greater in 1W-CH as compared to Nx. Yoda1 induced an EC hyperpolarization in 1W-CH. The eNOS levels were increased in 1W-CH IPA compared to Nx or 3W-CH PH and Yoda1 activated phosphorylation of Akt (Ser473) and eNOS (Ser1177). Thus, we demonstrated that endothelial Piezo1 contributes to intrapulmonary vascular relaxation by controlling endothelial [Ca2+]i, endothelial-dependent hyperpolarization, and Akt-eNOS pathway activation in the early stage of PH.

Transient receptor potential vanilloid 4 (TRPV4) is a polymodal Ca2+-permeable channel involved in various hypoxia-sensitive pathophysiological phenomena. Different tools are available to study channel activity, requiring cells to be cultured at specific optimal densities. In the present study, we examined if cell density may influence the effect of hypoxia on TRPV4 activity. Transiently TRPV4-transfected HEK293T cells were seeded at low or high densities corresponding to non-confluent or confluent cells, respectively, on the day of experiments, and cultured under in vitro normoxia or hypoxia. TRPV4-mediated cytosolic Ca2+ responses, single-channel currents, and Ca2+ influx through the channel were measured using Ca2+ imaging/microspectrofluorimetric assay, patch-clamp, and Bioluminescence Resonance Energy Transfer (BRET), respectively. TRPV4 plasma membrane translocation was studied using confocal microscopy, biotinylation of cell surface proteins, and BRET. Our results show that hypoxia exposure has a differential effect on TRPV4 activation depending on cell confluence. At low confluence levels, TRPV4 response is increased in hypoxia, whereas at high confluence levels, TRPV4 response is strongly inhibited, due to channel internalization. Thus, cell density appears to be a crucial parameter for TRPV4 channel activity.

International audience; Since the Nobel Prize award more than twenty years ago for discovering the core apoptotic pathway in C. elegans, apoptosis and various other forms of regulated cell death have been thoroughly characterized by researchers around the world. Although many aspects of regulated cell death still remain to be elucidated in specific cell subtypes and disease conditions, many predicted that research into cell death was inexorably reaching a plateau. However, this was not the case since the last decade saw a multitude of cell death modalities being described, while harnessing their therapeutic potential reached clinical use in certain cases. In line with keeping research into cell death alive, francophone researchers from several institutions in France and Belgium established the French Cell Death Research Network (FCDRN). The research conducted by FCDRN is at the leading edge of emerging topics such as non-apoptotic functions of apoptotic effectors, paracrine effects of cell death, novel canonical and non-canonical mechanisms to induce apoptosis in cell death-resistant cancer cells or regulated forms of necrosis and the associated immunogenic response. Collectively, these various lines of research all emerged from the study of apoptosis and in the next few years will increase the mechanistic knowledge into regulated cell death and how to harness it for therapy.

The complete mitogenome of the lizard Iphisa elegans Gray, 1851 was sequenced using a shotgun approach on an Illumina HiSeq 3000 platform, providing the first mitogenome for Gymnophthalmidae. The genome was 18,622 bp long, with 13 protein-coding genes, two rRNA (12S and 16S), and 22 tRNA, as well as the control region. A maximum likelihood phylogenetic analysis including I. elegans and all other available mitogenomes of Squamata provided a tree in accordance with previous phylogenetic relationships inferred for Squamata.

International audience; The development and use of nanomaterials, especially of nickel oxide nanoparticles (NiONPs), is expected to provide many benefits but also has raised concerns about the potential human health risks. Inhaled NPs are known to exert deleterious cardiovascular side effects, including pulmonary hypertension. Consequently, patients with pulmonary hypertension (PH) could be at increased risk for morbidity. The objective of this study was to compare the toxic effects of NiONPs on human pulmonary artery endothelial cells (HPAEC) under physiological and pathological conditions. The study was conducted with an in vitro model mimicking the endothelial dysfunction observed in PH. HPAEC were cultured under physiological (static and normoxic) or pathological (20% cycle stretch and hypoxia) conditions and exposed to NiONPs (0.5–5 μg/cm2) for 4 or 24 h. The following endpoints were studied: (i) ROS production using CM-H2DCF-DA and MitoSOX probes, (ii) nitrite production by the Griess reaction, (iii) IL-6 secretion by ELISA, (iv) calcium signaling with a Fluo-4 AM probe, and (v) mitochondrial dysfunction with TMRM and MitoTracker probes. Our results evidenced that under pathological conditions, ROS and nitrite production, IL-6 secretions, calcium signaling, and mitochondria alterations increased compared to physiological conditions. Human exposure to NiONPs may be associated with adverse effects in vulnerable populations with cardiovascular risks

Study of the initial steps of the CD95-mediated signaling pathways is a field of intense research and a long list of actors has been described in the literature. Nonetheless, the dynamism of protein-protein interactions (PPIs) occurring in the presence or absence of its natural ligand, CD95L, and the cellular distribution where these PPIs take place render it difficult to predict what will be the cellular outcome associated with the receptor engagement. Accordingly, CD95 stimulation can trigger apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphatidylinositol-3-kinase (PI3K). Recent data suggest that CD95 can also activate pattern recognition receptors (PRRs) known to sense damage-associated molecular patterns (DAMPs) such as DNA debris and dead cells. This activation might contribute to the pro-inflammatory role of CD95 and favor cancer development or severity of chronic inflammatory and auto-immune disorders. Herein, we discuss some of the molecular links that might connect the CD95 signaling to DAMP sensors.

The complete mitogenome of the lizard Iphisa elegans Gray, 1851 was sequenced using a shotgun approach on an Illumina HiSeq 3000 platform, providing the first mitogenome for Gymnophthalmidae. The genome was 18,622 bp long, with 13 protein-coding genes, two rRNA (12S and 16S), and 22 tRNA, as well as the control region. A maximum likelihood phylogenetic analysis including I. elegans and all other available mitogenomes of Squamata provided a tree in accordance with previous phylogenetic relationships inferred for Squamata.

Information on temperature and composition of planetary mantles can be obtained from electrical conductivity profiles derived from induced magnetic field analysis. This requires a modeling of the conductivity for each mineral phase at conditions relevant to planetary interiors. Interpretation of iron-rich Martian mantle conductivity profile therefore requires a careful modeling of the conductivity of iron-bearing minerals. In this paper, we show that conduction mechanism called small polaron is the dominant conduction mechanism at temperature, water and iron content conditions relevant to Mars mantle. We then review the different measurements performed on mineral phases with various iron content. We show that, for all measurements of mineral conductivity reported so far, the effect of iron content on the activation energy governing the exponential decrease in the Arrhenius law can be modeled as the cubic square root of the iron content. We recast all laboratory results on a common generalized Arrhenius law for iron-bearing minerals, anchored on Earth's mantle values. We then use this modeling to compute a new synthetic profile of Martian mantle electrical conductivity. This new profile matches perfectly, in the depth range [100,1000] km, the electrical conductivity profile recently derived from the study of Mars Global Surveyor magnetic field measurements.

The death receptor CD95 (also known as Fas) induces apoptosis through protein/protein association and the formation of the death-inducing signaling complex. On the other hand, in certain biological conditions, this receptor recruits different proteins and triggers the formation of another complex designated motility-inducing signaling complex, which promotes cell migration and inflammation. This pathway relies on a short sequence of CD95, called calcium-inducing domain (CID), which interacts with the phospholipase PLCγ1. To better understand how CID/PLCγ1 interaction occurs, we synthesized different α-AA peptides mimicking CID. Some of these peptidomimetics are as potent as the natural peptide to disrupt the CID/PLCγ1 interaction and cell migration, and showed improved pharmacokinetic properties. We also generated biotinyl- and palmitoyl-labelled peptidomimetics, useful chemico-biological tools to further explore the pro-inflammatory signal of CD95, which plays an important role in the pathogenesis of lupus and other autoimmune diseases.

International audience; The Lesser Antilles are a densely populated region where local populations and industrial facilities are concentrated at the coastlines, and are therefore exposed to many rapid-onset hazards such as hurricanes and tsunamis. However, the historical catalog of these events is too short to allow risk assessment and return period estimations, and it needs to be completed with long-term records of washover deposits in coastal sedimentary environments such as lagoons. In this study, two sediment cores were taken in March 2018 in a small coastal lagoon on Scrub Island (northeastern Caribbean). Sedimentological, geochemical, microfaunal and chronological analyses enabled us to identify 25 sandy layers resulting from high-energy-marine floods. Two of these layers were interpreted as tsunami deposits based on sedimentological (rip-up clast of the underlying cohesive substrate and internal mud laminae), and geochemical evidence. The most recent deposit is associated with the transatlantic tsunami triggered by the 1755 CE Lisbon earthquake. The older one is the thickest sandy layer recorded in the lagoon, with an age range of 1364-1469 cal. CE, as determined using 14 C dating. This event was recorded in sedimentary archives of both the northern and the southern part of the Caribbean, with its large spatial extent, supporting a distant tsunamigenic origin. The 23 remaining sandy layers were interpreted as storm deposits, based on sedimentological and chronological data, with the three most recent layers being correlated with historical hurricanes. This new 1600 year-long record displays similarities with that of the Bahamas, with the periods of intense hurricane activity being in antiphase with those of the northeastern US coast. This regional comparison may provide evidence for a latitudinal forcing of hurricane tracks through time in relation to climate fluctuations.

Objective Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNα secretion. These receptors use the γ-chain of high-affinity Fc receptor (FcR) for IgE, FcɛRI. We undertook this study to test our hypothesis that IgE engagement of FcɛRI on PDCs may impact IFNα production in SLE patients. Methods Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcɛRI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNα production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR. Results We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcɛRI expression in an IgE dose–dependent manner. IgE-treated PDCs significantly decreased IFNα secretion and down-regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7. Conclusion Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs.

CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca

This paper presents, for the first time, the evolution of local strain fields around intragranular cracking in polycrystalline ice, at the onset of tertiary creep. Owing to the high homologous temperature conditions and relatively low compressive stress applied, stress concentration at crack tips is relaxed by plastic mechanisms associated with dynamic recrystallization. Strain field evolution followed by Digital Image Correlation indirectly shows the redistribution of stresses during crack opening, but also driven by crack tip plasticity mechanisms and recrystallization. Such redistribution induces modifications in the local strain deformation bands, and crack closure during deformation. A strong interaction between cracking and dynamic recrystallization is therefore evidenced at the ductile to brittle transition in ice deformed at high homologous temperature.

Lack of resolution on species boundaries and distribution can hamper inferences in many fields of biology, notably biogeography and conservation biology. This is particularly true in megadiverse and under surveyed regions such as Amazonia, where species richness remains vastly underestimated. Integrative approaches using a combination of phenotypic and molecular evidence have proved extremely successful in reducing knowledge gaps in species boundaries, especially in animal groups displaying high levels of cryptic diversity like amphibians. Here we combine molecular data (mitochondrial 16S rRNA and nuclear TYR, POMC, and RAG1) from 522 specimens of Anomaloglossus, a frog genus endemic to the Guiana Shield, including 16 of the 26 nominal species, with morphometrics, bioacoustics, tadpole development mode, and habitat use to evaluate species delineation in two lowlands species groups. Molecular data reveal the existence of 18 major mtDNA lineages among which only six correspond to described species. Combined with other lines of evidence, we confirm the existence of at least 12 Anomaloglossus species in the Guiana Shield lowlands. Anomaloglossus appears to be the only amphibian genus to have largely diversified within the eastern part of the Guiana Shield. Our results also reveal strikingly different phenotypic evolution among lineages. Within the A. degranvillei group, one subclade displays acoustic and morphological conservatism, while the second subclade displays less molecular divergence but clear phenotypic divergence. In the A. stepheni species group, a complex evolutionary diversification in tadpole development is observed, notably with two closely related lineages each displaying exotrophic and endotrophic tadpoles. (C) 2017 Elsevier Inc. All rights reserved.

Intracellular calcium signals regulate cell function and cell survival by controlling many processes. CD95 engagement results in distinct intracellular calcium signals that control the cell fate, apoptosis, or survival, depending on the ligand (membrane or soluble). Intracellular calcium determination is an exquisite readout to explore the molecular mechanisms elicited by CD95 engagement. The most widely applied methods for studying calcium signaling pathways use fluorescent indicators and imaging methods with fluorescence microscopy. This technical approach, however, requires many precautions that we discuss in this chapter.

GA101/obinutuzumab is a novel type II anti-CD20 monoclonal antibody (mAb), which is more effective than rituximab (RTX) in preclinical and clinical studies when used in combination with chemotherapy. Ca2+ signaling was shown to play a role in RTX-induced cell death. This report concerns the effect of GA101 on Ca2+ signaling and its involvement in the direct cell death induced by GA101. We reveal that GA101 triggered an intracellular Ca2+ increase by mobilizing intracellular Ca2+ stores and activating Orai1-dependent Ca2+ influx in non-Hodgkin lymphoma cell lines and primary B-Cell Chronic Lymphocytic Leukemia (B-CLL) cells. According to the cell type, Ca2+ was mobilized from two distinct intracellular compartments. In Raji, BL2, and B-CLL cells, GA101 induced a Ca2+ release from lysosomes, leading to the subsequent lysosomal membrane permeabilization and cell death. Inhibition of this calcium signaling reduced GA101-induced cell death in these cells. In SU-DHL-4 cells, GA101 mobilized Ca2+ from the endoplasmic reticulum (ER). Inhibition of ER replenishment, by blocking Orai1-dependent Ca2+ influx, led to an ER stress and unfolded protein response (UPR) which sensitized these cells to GA101-induced cell death. These results revealed the central role of Ca2+ signaling in GA101&rsquo, s action mechanism, which may contribute to designing new rational drug combinations improving its clinical efficacy.

International audience; Lightening structure is one of the goals of many fields of research. As a result, magnesium alloys are studied due to their low density. However, one drawback of these alloys is their low formability at room temperature due to their hex-agonal closed-packed structure. In the present work, the forming capacity of an AZ31 Mg alloys has been studied using a mini deep-drawing device, image correlation techniques and tests (tension and expansion) at temperatures contained between 20°C and 200°C. To investigate formability limits of Mg alloys in expansion, major and minor strains data were generated using hemispherical punch tests and analyzed with 3D digital images correlation techniques. Thanks to images correlation, strains on the surface of the samples were observed by means of a double digitization of the sample in three dimensions before and after deformation by using stereoscopic vision and triangulation. Image correlations have also been used in 2D to measure strains on the surface of the tensile test samples. These tests gave interesting in-formation on the evolution of various parameters such as hardening coefficient, strain rate sensitivity parameter, and Lankford coefficient, which may affect the behavior of the alloys. Finally, the forming limits in both configurations (tension and expansion) were compared and discussed.

This paper presents an identification algorithm dedicated to the Modal Analysis of physical objects. This algorithm was specifically designed to process cases where short duration tests with multiple-input excitations are used to identify the system. To conform to these particular conditions, an iterative identification method was developed. It makes use of an appropriate parametrization of multivariable transfer functions based on structured matrix fractions. The identification problem is solved in the frequency domain using an output-error formulation. This paper details this algorithm which is evaluated on an example illustrative of the in-flight modal analysis of an aircraft.

Many Amazonian frog species that are considered widely distributed may actually represent polyspecific complexes.. A minute tree frog from the Guiana Shield originally assigned to the allegedly widely distributed Dendropsophus brevifrons proved to be a yet undescribed species within the D. parviceps group. We herein describe this new species and present a phylogeny for the D. parviceps group. The new species is diagnosed from other Dendropsophus of the parviceps group by its small body size (19.6-21.7 mm in males, 22.1-24.5 mm in females), thighs dorsally dark grey with cream blotches without bright yellow patch, absence of dorsolateral and canthal stripe, and an advertisement call comprising trills (length 0.30-0.35 s) composed of notes emitted at a rate of 131-144 notes/s, generally followed by click series of 2-3 notes. Its tadpole is also singular by having fused lateral marginal papillae and absence of both labial teeth and submarginal papillae. Genetic distances (p-distance) aregt;5.3% on the 12S andgt;9.3% on the 16S from D. brevifrons, its closest relative. This species occurs from the Brazilian state of Amapá, across French Guiana and Suriname to central Guyana and is likely to also occur in adjacent Brazilian states and eastern Venezuela. This species is not rare but is difficult to collect because of its arboreal habits and seasonal activity peaks.

Among the terrestrial planets, Mercury's composition is characterized by two specific features: a high density and a low surface FeO content. Based on these two constraints, different geochemical models have been proposed, according to different formation scenarios. Here thermodynamical modeling is used to derive the mantle and crust mineralogy associated with these geochemical models. For each mineralogy, the electrical conductivity profile and associated electromagnetic data are computed. Due to the very different oxide/silicate ratios, most geochemical models proposed for Mercury's formation show very different electromagnetic signatures. As a result, future measurements with MESSENGER and BepiColombo missions will help differentiating between different interior models and different formation scenarios.

This paper addresses the problem of the identification of multivariable linear systems from measured or estimated samples of the impulse response. Most techniques are based on a low rank approximation of a block-Hankel matrix computed by a truncated singular value decomposition. The main drawback of such approaches is that the block-Hankel structure is not preserved in the approximation. Therefore these methods do not actually perform a term-wise fitting on the samples of the impulse response. Since the beginning of the 1990s, several algorithms were proposed for computing low rank approximations that maintain the matrix structure. But the methods available up until now still include limitations. In this article, three general and equivalent solutions to this identification problem are proposed in the general case of multiple-input multiple-output (MIMO) systems. They derive from a specific parametrization and perform a term-wise minimization of a least squares criterion on the samples of the impulse response.

International audience; Optical full-field measurement methods such as Digital Image Correlation (DIC) are increasingly used in the field of experimental mechanics, but they still suffer from a lack of information about their metrological performances. To assess the performance of DIC techniques and give some practical rules for users, a collaborative work has been carried out by the Workgroup "Metrology" of the French CNRS research network 2519 "MCIMS (Mesures de Champs et Identification en Mécanique des Solides / Full-field measurement and identification in solid mechanics, http://www.ifma.fr/lami/gdr2519)". A methodology is proposed to assess the metrological performances of the image processing algorithms that constitute their main component, the knowledge of which being required for a global assessment of the whole measurement system. The study is based on displacement error assessment from synthetic speckle images. Series of synthetic reference and deformed images with random patterns have been generated, assuming a sinusoidal displacement field with various frequencies and amplitudes. Displacements are evaluated by several DIC packages based on various formulations and used in the French community. Evaluated displacements are compared with the exact imposed values and errors are statistically analyzed. Results show general trends rather independent of the implementations but strongly correlated with the assumptions of the underlying algorithms. Various error regimes are identified, for which the dependence of the uncertainty with the parameters of the algorithms, such as subset size, gray level interpolation or shape functions, is discussed.

International audience; In this paper, the mechanical behaviour of an unfilled silicone rubber is analysed. Firstly, silicone samples were subjected to five homogeneous tests: tensile, pure shear, compression, plane strain compression and bulge tests. During the tests, full-field measurements of the strain on the surface of deformed samples were obtained using a Digital Image Correlation technique. Results show that the Mullins effects and hysteresis, as well as strain rate sensitivity, can be considered as negligible. Results also emphasise the influence of the loading path. Then, five well-known hyperelastic models (neo-hookean, Mooney, Gent, Haines and Wilson and Ogden models) were fitted to the experimental data. Finally, a heterogeneous test was realised by stretching a silicone plate sample containing holes. Finite element simulations of this experiment have been performed with the hyperelastic models. The comparison of experimental and numerical results emphasises the importance of the choice of the hyperelastic modelling in the simulation of strain fields.

This paper presents experimental tensile test results obtained on flat aluminum magnesium alloy samples on a hard machine. The mechanical response, kinematic fields and acoustic emissions were simultaneously obtained in an experimental setup. Propagation instabilities associated with the Portevin-Le-Châtelier effect were observed as localized intense strain increment bands. Depending on the strain rate, A, B or C types were studied on the basis of stress drops, acoustic emission and strain fields. Then the band characteristics (position, orientation, width, thickness reduction, intensity, acoustic emission, principal strain direction) were presented in various strain rate conditions.

The aim of this work is to propose a non-standard tensile test suitable for the identification of material parameters using full-field strain measurements and finite element analysis. The shape of the sample to be used in this new test must verify three criteria: (i) large heterogeneity of the strain in the gauge area, (ii) large strain-paths diversity and (iii) a good sensitivity of the strain field to the material parameters. After identifying the mechanical parameters of a dual-phase steel sheet using σ – e and r – α curves, samples of different shapes were studied in order to choose the one that presents the best compromise between the three criteria. The comparison between simulated and measured fields shows a qualitative accordance. Taking into account the difference between these fields in the expression of the cost-function to minimize is expected to improve the quality of the identified material parameters.

Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNα secretion. These receptors use the γ-chain of high-affinity Fc receptor (FcR) for IgE, FcɛRI. We undertook this study to test our hypothesis that IgE engagement of FcɛRI on PDCs may impact IFNα production in SLE patients.Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcɛRI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNα production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR.We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcɛRI expression in an IgE dose-dependent manner. IgE-treated PDCs significantly decreased IFNα secretion and down-regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7.Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs.

The Portevin–Le Chatelier (PLC) phenomenon is investigated by means of a two-dimensional measurement of displacement fields using the digital image correlation method. The strain fields obtained highlight in a quantitative way the nucleation and the displacement of PLC bands. The local strain, the width and the velocity of the PLC bands are measured. Effects of strain and strain rate are studied. The results show the close relationship between the organization of stress drops, the dynamics of the associated deformation bands and their parameters.

The main result of this work is to show that macroseismic intensity decay with distance strongly depends on the epicentral intensity. An attenuation law that takes this parameter into account is proposed for Metropolitan France, from the analysis of SISFRANCE macroseismic database. Such a model significantly reduces the difference between observed and theoretical intensities. A map of the attenuation variations is also set up for Metropolitan France. No major site effects are observed, but at a broad scale, young Alpine regions display a stronger attenuation than old Hercynian regions. To cite this article: P. Arroucau et al., C. R. Geoscience 338 (2006).

The spider venom alpha-latrotoxin (alpha-LTX) induces massive exocytosis after binding to surface receptors, and its mechanism is not fully understood. We have investigated its action using toxin-sensitive MIN6 beta-cells, which express endogenously the alpha-LTX receptor latrophilin (LPH), and toxin-insensitive HIT-T15 beta-cells, which lack endogenous LPH. alpha-LTX evoked insulin exocytosis in HIT-T15 cells only upon expression of full-length LPH but not of LPH truncated after the first transmembrane domain (LPH-TD1). In HIT-T15 cells expressing full-length LPH and in native MIN6 cells, alpha-LTX first induced membrane depolarization by inhibition of repolarizing K(+) channels followed by the appearance of Ca(2+) transients. In a second phase, the toxin induced a large inward current and a prominent increase in intracellular calcium ([Ca(2+)](i)) reflecting pore formation. Upon expression of LPH-TD1 in HIT-T15 cells just this second phase was observed. Moreover, the mutated toxin LTX(N4C), which is devoid of pore formation, only evoked oscillations of membrane potential by reversible inhibition of iberiotoxin-sensitive K(+) channels via phospholipase C, activated L-type Ca(2+) channels independently from its effect on membrane potential, and induced an inositol 1,4,5-trisphosphate receptor-dependent release of intracellular calcium in MIN6 cells. The combined effects evoked transient increases in [Ca(2+)](i) in these cells, which were sensitive to inhibitors of phospholipase C, protein kinase C, or L-type Ca(2+) channels. The latter agents also reduced toxin-induced insulin exocytosis. In conclusion, alpha-LTX induces signaling distinct from pore formation via full-length LPH and phospholipase C to regulate physiologically important K(+) and Ca(2+) channels as novel targets of its secretory activity.

Due to the high flexibility of modern transportation aircraft, a precise knowledge of their aeroelastic behaviour is required to design the flight control system. For this purpose, an identification toolbox named Harrisa ® was developed at ONERA. It was extensively used by Airbus for the development of the A340-600. The requirements for the recent Airbus A380 increased tremendously concerning the size of the models to be identified. Efficient identification techniques had then to be worked out. This paper introduces EFERA an extremely rapid realization algorithm that is compatible with an interactive use on such large-scale systems.

The effect of the microstructure heterogeneity on the global and local tensile properties of friction stir welded joints in 5251 (O temper) and AA2024 (T351 and T6 tempers) aluminium alloys has been investigated. Micro-tensile tests parallel to the welding direction have been carried out in the regions representative of the main microstructural zones. The digital image correlation technique (DIC) has been used during transverse tensile tests for mapping the strain distribution and to determine the local stress–strain curves. A 3-D finite elements model has been developed to predict the weld behaviour from the tensile curves of the individual regions of the weld. The tensile properties of the 5251 O weld are relatively homogeneous leading to high ductility and fracture in the base material. In contrast, the tensile properties of the various regions of the 2024 T351 and 2024 T6 welds are very heterogeneous and essentially controlled by the state of precipitation. The thermo-mechanically affected zone is the weakest region where the strain localises during a transverse tensile test. The 2024 T6 base material is stronger than the 2024 T351 alloy, leading to a more pronounced strain localisation during transverse tensile tests and a lower overall ductility. Local tensile data obtained by strain mapping are in good agreement with the curves obtained by micro-tensile tests, and these results can be safely used in a finite elements model to predict the behaviour of the overall weld assembly.

Flutter flight tests is a crucial and feared phase of the flight test program of a new aircraft. The specific operational context of flutter surveillance implies the development of automatic and reliable tools operating in real-time. At ONERA, we recently developed a toolbox dedicated to data processing for flutter tests. It was used for the latest Airbus aircraft from the A340-600 up to the A380. In this article, we present the main procedure of the toolbox : the identification routine together with the graphical interfaces that were designed to help the operator to get a rapid knowledge of the identification results.

The anti-CD20 mAb, rituximab, is routinely used to treat B cell malignancies. However, a majority of patients relapse. An improvement in the complete response was obtained by combining rituximab with chemotherapy, at the cost of increased toxicity. We reported that rituximab induced the colocalization of both the Orai1 Ca2+ release-activated Ca2+ channel (CRAC) and the endoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 with CD20 and CD95 into a cluster, eliciting a polarized store-operated Ca2+ entry (SOCE). We observed that blocking this Ca2+ entry with downregulation of Orai1, pharmacological inhibitors, or reducing calcemia with hypocalcemic drugs sensitized human B lymphoma cell lines and primary human lymphoma cells to rituximab-induced apoptosis in vitro, and improved the antitumoral effect of rituximab in xenografted mice. This revealed that Ca2+ entry exerted a negative feedback loop on rituximab-induced apoptosis, suggesting that associating CRAC channel inhibitors or hypocalcemic agents with rituximab may improve the treatment of patients with B cell malignancies. The calcium-dependent proteins involved in this process appear to vary according to the B lymphoma cell type, suggesting that CRAC-channel targeting is likely to be more efficient than calcium-dependent protein targeting.

Prolactin (PRL) is involved in numerous biological processes in peripheral tissues and the brain. Although numerous studies have been conducted to elucidate the signal transduction pathways associated with the PRL receptor, very few have examined the role of ion conductances in PRL actions. We used the patch-clamp technique in “whole cell” configuration and microspectrofluorimetry to investigate the effects of PRL on membrane ion conductances in the U87-MG human malignant astrocytoma cell line, which naturally expresses the PRL receptor. We found that a physiological concentration (4 nM) of PRL exerted a biphasic action on membrane conductances. First, PRL activated a Ca2+-dependent K+current that was sensitive to CTX and TEA. This current depended on PRL-induced Ca2+mobilization, through a JAK2-dependent pathway from a thapsigargin- and 2-APB-sensitive Ca2+pool. Second, PRL also activated an inwardly directed current, mainly due to the stimulation of calcium influx via nickel- and 2-APB-sensitive calcium channels. Both phases resulted in membrane hyperpolarizations, mainly through the activation of Ca2+-dependent K+channels. As shown by combined experiments (electrophysiology and microspectrofluorimetry), the PRL-induced Ca2+influx increased with cell membrane hyperpolarization and conversely decreased with cell membrane depolarization. Thus PRL-induced membrane hyperpolarizations facilitated Ca2+influx through voltage-independent Ca2+channels. Finally, PRL also activated a DIDS-sensitive Cl-current, which may participate in the PRL-induced hyperpolarization. These PRL-induced conductance activations are probably related to the PRL proliferative effect we have already described in U87-MG cells.

The mechanical behaviour of dry woven fabrics as composite reinforcements is investigated using optical strain measurements during pure shear tests performed on a picture frame device. This optical measurement technique has many advantages, including the absence of contact with the sample. A change in lens allows measurements at different scales, from a whole sample (macroscopic measurement), to a few unit patterns only (mesoscopic measurement). On top of that, the out of plane displacement may be obtained by a stereoscopic method, using two symmetric points of view. Thus, detailed description of a pure shear test may be conducted, leading us to explain the forming of wrinkles within the woven sample, concluding the test.

Prolactin (PRL) has several physiological effects on peripheral tissues and the brain. This hormone acts via its membrane receptor (PRL-R) to induce cell differentiation or proliferation. Using reverse transcription-polymerase chain reaction (RT-PCR) combined with Southern blot analysis, we detected PRL-R transcripts in a human glioma cell line (U87-MG) and in primary cultured human glioblastoma cells. These transcripts were deleted or not in their extracellular domains. We examined the effects of PRL on intracellular free Ca2+ concentration ([Ca2+](i)) in these cells in order to improve our understanding of the PRL transduction mechanism, which is still poorly documented. [Ca2+](i) was measured by microspectrofluorimetry using indo-1 as the Ca2+ fluorescent probe. Spatiotemporal aspects of PRL-induced Ca2+ signals were investigated using high-speed fluo-3 confocal imaging. We found that physiological concentrations (0.4-4 nM) of PRL-stimulated Ca2+ entry and intracellular Ca2+ mobilization via a tyrosine kinase-dependent mechanism. The two types of Ca2+ responses observed were distinguishable by their kinetics: one showing a slow (type I) and the other a fast (type II) increase in [Ca2+](i). The amplitude of PRL-induced Ca2+ increases may be sufficient to provoke several physiological responses, such as stimulating proliferation. Furthermore, PRL induced a dose-dependent increase in [3H]thymidine incorporation levels and in cellular growth and survival, detected by the MTT method. These data indicate that PRL induced mitogenesis of human glioma cells.

We have examined the spatiotemporal aspects of PRL-induced Ca2+ signals using high-speed fluo-3 confocal imaging. We found that PRL stimulated Ca2+ entry and intracellular Ca2+ mobilization. Ca2+ influx was seen as a peripheral increase in [Ca2+]i without amplification in the nucleus region. Intracellular Ca2+ mobilization was seen as a propagating intracellular calcium wave with a strong amplification in the nuclear region. The amplitude of PRL-induced Ca2+ increases would be sufficient to stimulate cell proliferation. Furthermore, PRL induced an increase in [3H]thymidine incorporation. These data suggest that PRL would be able to induce mitogenesis through a Ca2+-dependent pathway.