Délégation Ile-de-France Sud

A scheelite crystal with residual concentration of erbium is cooled down to 10 mK, yielding a record spin coherence time of 23 ms.

Interferons (IFNs) are a family of secreted proteins with antiviral, antiproliferative, and immunomodulatory activities. The different biologic actions of IFN are believed to be mediated by the products of specifically IFN-stimulated genes (ISG) in the target cells. The IFN response is the first line of defense against viral infections. Viruses, which require the cellular machinery for their replication, have evolved different ways to counteract the action of IFN by inhibiting IFN production or Jak-Stat signaling or by altering ISG products. This review focuses on the role of viral proteins from the RNA virus family, particularly rabies P protein. P protein mediates inhibition of the IFN system by different pathways: it inhibits IFN production by impairing IFN regulatory factor-3 (IRF-3) phosphorylation and IFN signaling by blocking nuclear transport of Stat1 and alters promyelocytic leukemia (PML) nuclear bodies by retaining PML in the cytoplasm.

Due to the relative transparency of its embryos and larvae, the zebrafish is an ideal model organism for bioimaging approaches in vertebrates. Novel microscope technologies allow the imaging of developmental processes in unprecedented detail, and they enable the use of complex image-based read-outs for high-throughput/high-content screening. Such applications can easily generate Terabytes of image data, the handling and analysis of which becomes a major bottleneck in extracting the targeted information. Here, we describe the current state of the art in computational image analysis in the zebrafish system. We discuss the challenges encountered when handling high-content image data, especially with regard to data quality, annotation, and storage. We survey methods for preprocessing image data for further analysis, and describe selected examples of automated image analysis, including the tracking of cells during embryogenesis, heartbeat detection, identification of dead embryos, recognition of tissues and anatomical landmarks, and quantification of behavioral patterns of adult fish. We review recent examples for applications using such methods, such as the comprehensive analysis of cell lineages during early development, the generation of a three-dimensional brain atlas of zebrafish larvae, and high-throughput drug screens based on movement patterns. Finally, we identify future challenges for the zebrafish image analysis community, notably those concerning the compatibility of algorithms and data formats for the assembly of modular analysis pipelines.

The SPP1 siphophage uses its long non-contractile tail and tail tip to recognize and infect the Gram-positive bacterium Bacillus subtilis. The tail-end cap and its attached tip are the critical components for host recognition and opening of the tail tube for genome exit. In the present work, we determined the cryo-electron microscopic (cryo-EM) structure of a complex formed by the cap protein gp19.1 (Dit) and the N terminus of the downstream protein of gp19.1 in the SPP1 genome, gp21(1-552) (Tal). This complex assembles two back-to-back stacked gp19.1 ring hexamers, interacting loosely, and two gp21(1-552) trimers interacting with gp19.1 at both ends of the stack. Remarkably, one gp21(1-552) trimer displays a "closed" conformation, whereas the second is "open" delineating a central channel. The two conformational states dock nicely into the EM map of the SPP1 cap domain, respectively, before and after DNA release. Moreover, the open/closed conformations of gp19.1-gp21(1-552) are consistent with the structures of the corresponding proteins in the siphophage p2 baseplate, where the Tal protein (ORF16) attached to the ring of Dit (ORF15) was also found to adopt these two conformations. Therefore, the present contribution allowed us to revisit the SPP1 tail distal-end architectural organization. Considering the sequence conservation among Dit and the N-terminal region of Tal-like proteins in Gram-positive-infecting Siphoviridae, it also reveals the Tal opening mechanism as a hallmark of siphophages probably involved in the generation of the firing signal initiating the cascade of events that lead to phage DNA release in vivo.

A Synechocytis 6714 mutant resistant to the phenol-type herbicide ioxynil was isolated and characterized. Sensitivity to DCMU and atrazine was tf measured in whole cells and isolated thylakoids. The mutant presents the same sensitivity to atrazine as the wild type and a slightly increased sensitivity to DCMU. A point mutation has been found at codon 266 in the psbAI coding locus (AAC to ACC) resulting in an amino acid change from asparagine to threonine in the D1 protein.

The beta-thymosin/WH2 actin-binding module shows an amazing adaptation to multifunctionality. The beta-thymosins are genuine G-actin sequesterers of moderate affinity for G-actin, allowing an efficient regulation of the G-actin/F-actin ratio in cells by amplifying changes in the critical concentration for filament assembly. In contrast, the first beta-thymosin domain of the protein Ciboulot makes with G-actin a complex that supports filament growth, such as profilin-actin. We illustrate how the use of engineered chimeric proteins, actin-binding and polymerization assays, crystallographic, NMR, and SAXS structural approaches complement each other to decipher the molecular basis for the functional versatility of these intrinsically disordered domains when they form various 1:1 complexes with G-actin. Multifunctionality is expanded in tandem repeats of WH2 domains present in WASP family proteins and proteins involved in axis patterning like Cordon-Bleu and Spire. The tandem repeats generate new functions such as filament nucleation and severing, as well as barbed end binding, which add up to the G-actin sequestering activity. Novel regulation pathways in actin assembly emerge from these additional activities.

In this paper, a wideband dual polarized self-complementary connected array antenna with low radar cross section (RCS) under normal and oblique incidence is presented. First, an analytical model of the multilayer structure is proposed in order to obtain a fast and reliable predimensioning tool providing an optimized design of the infinite array. The accuracy of this model is demonstrated thanks to comparative simulations with a full wave analysis software. RCS reduction compared to a perfectly conducting flat plate of at least 10 dB has been obtained over an ultrawide bandwidth of nearly 7:1 at normal incidence and 5:1 (3.8 to 19 GHz) at 60° in both polarizations. These performances are confirmed by finite element tearing and interconnecting computations of finite arrays of different sizes. Finally, the realization of a 28 × 28 cell prototype and measurement results are detailed.

Endothelin B receptor (ETBR) is a G protein-coupled receptor able to bind equally to the three identified human endothelin peptides. It is expressed primarily on vascular endothelial cells and involved in various physiological processes including vascular tone homeostasis, enteric nervous system development, melanogenesis and angiogenesis. Furthermore, overactivation or overexpression of ETBR have been associated with the development of various diseases such as cardiovascular disorders and cancers. Therefore, ETBR appears to be relevant target for the therapy or diagnosis of highly prevalent human diseases. In this study, we report the in vitro characterization of rendomab-B1, a monoclonal antibody (mAb) obtained by genetic immunization, which selectively recognizes the native form of human ETBR (hETBR). Rendomab-B1 is the first-reported mAb that behaves as a potent antagonist of hETBR. It recognizes an original extracellular conformational epitope on the receptor, distinct from the endothelin-1 (ET-1) binding site. Rendomab-B1 not only blocks ET-1-induced calcium signaling pathway and triggers rapid receptor internalization on recombinant hETBR-expressing cells, but also exerts pharmacological activities on human vascular endothelial cells, reducing both cell viability and ET-1-induced hETBR synthesis. In addition, binding experiments using rendomab-B1 on different melanoma cell lines reveal the structural and functional heterogeneity of hETBR expressed at the surface of these cancer cells, strongly suggesting the existence of tumor-specific receptors. Collectively, our results underscore the value of rendomab-B1 for research, therapeutic and diagnostic applications dealing with hETBR.

Abstract From fruits of Boehmeriaholosericea, six compounds 1‐6 were isolated by various chromatographic methods. Their structures were elucidated by extensive spectroscopic analysis, including ESI‐MS,1D NMR, 2D NMR spectra, they are identified as ruspolinone ( 1 ), benzyl β ‐D‐glucoside ( 2 ), 3,4‐dimethoxyacetophenone ( 3 ), adenine ( 4 ), adenosine ( 5 ) and uridine ( 6 ). All the compounds were obtained for the first time from Boehmeria genus.

This paper presents a prediction-based control law for linear difference equations subject to a distributed state delay and a pointwise input delay. We propose to use a prediction-based control to overcome the instability potentially related to the distributed delay. We obtain an explicit formulation of the controller, depending only on the state and input history and involving integral kernels, which are the solutions to recursive Volterra equations. In view of future delay-sensitivity analysis, we develop an alternative approach to prove closed-loop stability, recasting the input delay as a transport Partial Differential Equation. In an analog manner to the stability analysis methodology developed for linear Delay Differential Equations, we propose a backstepping transformation to map the closed-loop system to a distributed-delay free target system. Simulation results underline the efficiency of the proposed control design.

We discuss the expected dependence of the probability transitions for 2-photon and 3-photon absorption in Helium gas on the spatial and temporal structure of the exciting radiation pulses. Regarding spatial structure, we assumed a Gaussian radial intensity distribution; we find, as expected, that the 2-photon and 3-photon processes become negligible at distances D away from the focus, where D is of the order of the beam waist FWHM. Regarding temporal structure, we compared transition probabilities for square, Gaussian and cosine squared temporal profiles; we find that for the same FWHM, Gaussian and cosine squared pulses give essentially the same transition probabilities, but the square pulses are about twice as efficient. We finally studied the effect of sharp versus smooth rise and fall edges in the light pulse; we find negligible correlation with the shape of the pulse edges, and strong correlation with the pulse FWHM, i.e., with pulse total energy, as might be expected.

A new technique is presented to realize dual-linear polarization in four-arm sinuous antennas by simultaneously exciting all four arms of the antenna with a non-sequentially phased input. A hollow metallic cavity backing is used to obtain unidirectional radiation. The antenna exhibits a low input reflection coefficient in multiple bands across a frequency range from 1 to 4 GHz. A high level of cross-polarization rejection throughout the bandwidth of operation is demonstrated. Measurements show good agreement wtih electromagnetic simulation results.

The pharmacokinetic profile of a single dose (6 mg/kg) of alpha-dihydroergokryptine (alpha-DHEK) was established after oral administration in monkeys using a radio-immunoassay technique for non-metabolized drug. alpha-DHEK showed a plasma profile according to an open three-compartment pharmacokinetic model with a long half-life (mean = 5.787 h). The disposition of alpha-DHEK involves a fast absorption, a slow distribution phase and a slow elimination phase. alpha-DHEK showed an high total clearance and distribution volume; the drug is largely metabolized, as concluded from the very low urinary excretion.

Abstract In 2021, the Ocean Thematic Centre of the European Research Infrastructure “Integrated Carbon Observation System” conducted an international partial pressure of carbon dioxide ( p CO 2 ) instrument intercomparison. The goal was to understand how different types of instrumentation for the measurement of ocean p CO 2 compare to each other. During the two‐week long experiment, we installed various instruments in a tank facility using natural sea water (North Sea). These included direct air–water equilibration systems and membrane‐based flow‐through instruments along with submersible sensors and instruments that are normally installed on buoys and autonomous surface vehicles. In situ instruments were installed inside the tank and the flow‐through instruments were fed the same water using a pumping system. We changed the temperature (between 10°C and 28°C) and the seawater p CO 2 (between 250 and 800 μ atm) to observe instrument responses over a wide range. Since there is no reference for surface ocean p CO 2 measurements, we agreed on a set of instruments serving as intercomparison reference. All data from the different instruments were then compared against the intercomparison reference during periods of stable temperature and p CO 2 . The study provides important information to enhance future ocean carbon monitoring networks, but makes no direct recommendation for the use of any specific sensor. A major finding is that equilibration through direct air–water contact appears to be more consistent and independent of external factors than equilibration through a membrane or photometric detection. We found several instruments with no temperature measurements at the location of equilibration or with uncalibrated temperature sensors introducing significant uncertainty in the results.

We and others have previously shown that in the rat and the sheep gonadectomy increases the translational capacity of mRNAs encoding gonadotropin subunits alpha, LH beta and FSH beta. Injection of estradiol or of testosterone or dihydrotestosterone depresses the translational capacity of the mRNAs. After using estradiol to induce progesterone receptors in the pituitary of castrated animals, it was determined that progesterone does enhance the inhibitory effect of estradiol. We have also observed this inhibitory effect of gonadal steroids in vitro, suggesting that at least part of the steroid action is exerted at the pituitary level. Hybridization assay (Northern blot) using oligodeoxynucleotide probes complementary to a short portion in the cDNA strand of each subunit, showed gonadal steroids to act by decreasing the number of copies of mRNAs encoding LH and FSH subunits. Using anterior pituitary cells in culture, incubated in the presence of labeled methionine, we have confirmed our previous observation that GnRH stimulates the biosynthesis of the polypeptide chains of LH. This effect is not secondary due to LH release. It is not inhibited when incubation is performed in the presence of tunicamycin, an inhibitor of glycosylation. SDS-polyacrylamide gel electrophoresis of specific immunoprecipitates of polypeptides immunologically related to alpha allowed us to identify 3 forms of alpha-polypeptide differing in their apparent Mr:21K (partially glycosylated), 23K (authentic) and 25K (hyperglycosylated). Besides its stimulatory effect on the release and synthesis of LH, GnRH also stimulated the release of the 23K and 25K forms of alpha. In the presence of tunicamycin an additional 16K form of apoprotein-alpha was detected which accumulated within the cells. A cAMP analogue (8-Br-cAMP), intracellular cAMP generators (choleragen, forskolin), as well as an analogue of diacylglycerols (TPA) mimic the stimulatory action of GnRH. However, although no evidence has been obtained at present that either cAMP or diacylglycerols mediate the GnRH effect on the biosynthesis of the polypeptide chains of LH, our data suggest that phosphorylation of intracellular phosphoproteins plays a major role in this process.

Abstract Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domain that binds to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion.

Abstract Objectives Diffuse large B‐cell lymphoma (DLBCL) constitutes 30–40% of non‐Hodgkin lymphoma cases. Despite therapeutic advances, persistence of relapsed cases has been linked to the complex tumor microenvironment (TME) and its interactions with lymphoma cells. In particular, characterising T‐cell subsets, including rare cell types, and their interplay with the remaining TME is crucial for unravelling DLBCL pathogenesis and refining therapeutic strategies. Methods Using flow and spectral cytometry with unsupervised analysis, we investigated T‐cell subpopulations across DLBCL biopsies and control lymph nodes (LN). We also inferred communication pathways between T cells and other immune cells in the TME based on the correlation of ligand–receptor expression. Results Our analysis revealed a higher frequency of CD8 + follicular regulatory T (Tfr) cells in DLBCL biopsies compared to control LN. These cells exhibited an effector‐memory phenotype (CD45RA − CCR7 − ), expressed follicular markers (PD‐1 + CXCR5 + ) and had a regulatory profile (CD127 − CD25 + ) along with an activation/co‐stimulatory signature (HLA‐DR + , ICOS + , CD95 + ). Correlation analysis highlighted a co‐stimulatory interaction between lymphoma B cells and CD8 + Tfr cells through the ICOS/ICOSL pathway, which may contribute to a protumor effect. Validation in independent scRNAseq and flow cytometry datasets confirmed the notable prevalence of CD8 + Tfr cells in DLBCL biopsies. Conclusions Our study highlights the utility of high‐dimensional computational cytometry in elucidating T‐cell subpopulations, including an increased frequency of CD8 + follicular regulatory T cells and their communication patterns within the DLBCL TME. This unbiased approach sheds light on novel cellular mechanisms in DLBCL, uncovering potential targets and biomarkers for immunotherapy.

We want to study hyperbolic system in which ROE’s linearisation exists: it is the case of P — system. For no CFL condition and for scalar equation, it is obvious that only implicit schemes can be used. In the second part we show that for elementary waves, where the rarefaction waves are not too much important, the system is invertible and verify maximum rule about density for P — system.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

A relevant parameter characterizing a gasket is determined from the measurement of the coupling function between two wires. After applying the reciprocity theorem and making a few hypotheses, the parameter is found as a normalized surface impedance. Its viability is verified, by introducing it in a numerical code based on the electric field integral equation (EFIE). To improve the results, a numerical reciprocity technique is used. In order to carry out an efficient parametric study, a sub-domains decomposition technique is used.