Strain-Transcendent Immune Response to Recombinant Var2CSA DBL5-ε Domain Block P. falciparum Adhesion to Placenta-Derived BeWo Cells under Flow Conditions

BACKGROUND: Pregnancy-associated malaria (PAM) is a serious consequence of the adhesion to the placental receptor chondroitin sulfate A (CSA) of Plasmodium falciparum-infected erythrocytes (PE) expressing the large cysteine-rich multi-domain protein var2CSA. Women become resistant to PAM, and develop strain-transcending immunity against CSA-binding parasites. The identification of var2CSA regions that could elicit broadly neutralizing and adhesion-blocking antibodies is a key step for the design of prophylactic vaccine strategies. METHODOLOGY: Escherichia coli expressed var2CSA DBL domains were refolded and purified prior to immunization of mice and a goat. Protein-G-purified antibodies were tested for their ability to block FCR3(CSA)-infected erythrocytes binding to placental (BeWo) and monkey brain endothelial (ScC2) cell lines using a flow cytoadhesion inhibition assay mimicking closely the physiological conditions present in the placenta at shear stress of 0.05 Pa. DBL5-ε, DBL6-ε and DBL5-6-ε induced cross-reactive antibodies using Alum and Freund as adjuvants, which blocked cytoadhesion at values ranging between 40 to 96% at 0.5 mg IgG per ml. Importantly, antibodies raised against recombinant DBL5-ε from 3 distinct parasites genotypes (HB3, Dd2 and 7G8) showed strain-transcending inhibition ranging from 38 to 64% for the heterologuous FCR3(CSA). CONCLUSIONS: Using single and double DBL domains from var2CSA and Alum as adjuvant, we identified recombinant subunits inducing an immune response in experimental animals which is able to block efficiently parasite adhesion in a flow cytoadhesion assay that mimics closely the erythrocyte flow in the placenta. These subunits show promising features for inclusion into a vaccine aiming to protect against PAM

Review of patient-specific simulations of transcatheter aortic valve implantation

International audienceTranscatheter Aortic Valve Implantation (TAVI) accounts for one of the most promising new cardiovascular procedures. This minimally invasive technique is still at its early stage and is constantly developing thanks to imaging techniques, computer science, biomechanics and technologies of prosthesis and delivery tools. As a result, patient-specific simulation can find an exciting playground in TAVI. It canexpress its potential by providing the clinicians with powerful decision support, offering great assistance in their workflow. Through a review of the current scientific field, we try to identify the challenges and future evolutions of patient-specific simulation for TAVI. This review article is an attempt to summarize and coordinate data scattered across the literature about patient-specific biomechanical simulation for TAVI

Observational constraints on the origin of the elements. V. Non-LTE abundance ratios of [Ni/Fe] in Galactic stars and enrichment by sub-Chandrasekhar mass SNe

We constrain the role of different SN Ia channels in the chemical enrichment of the Galaxy by studying the abundances of nickel in Galactic stars. We investigate four different SN Ia sub-classes, including the classical single-degenerate near-Chandrasekhar mass SN Ia, the fainter SN Iax systems associated with He accretion from the companion, as well as two sub-Ch mass SN Ia channels. The latter include the double-detonation of a white dwarf accreting helium-rich matter and violent white dwarf mergers. NLTE models of Fe and Ni are used in the abundance analysis. In the GCE models, we include new delay time distributions arising from the different SN Ia channels, as well as recent yields for core-collapse supernovae and AGB stars. The data-model comparison is performed using a Markov chain Monte Carlo framework that allows us to explore the entire parameter space allowed by the diversity of explosion mechanisms and the Galactic SN Ia rate, taking into account the uncertainties of the observed data. We show that NLTE effects have a non-negligible impact on the observed [Ni/Fe] ratios in the Galactic stars. The NLTE corrections to Ni abundances are not large, but strictly positive, lifting the [Ni/Fe] ratios by ~+0.15 dex at [Fe/H] =-2. We find that that the distributions of [Ni/Fe] in LTE and in NLTE are very tight, with a scatter of < 0.1 dex at all metallicities, supporting earlier work. In LTE, most stars have scaled-solar Ni abundances, [Ni/Fe] = 0, with a slight tendency for sub-solar [Ni/Fe] ratios at lower [Fe/H]. In NLTE, however, we find a mild anti-correlation between [Ni/Fe] and metallicity, and a slightly elevated [Ni/Fe] ratios at [Fe/H] < -1.0. The NLTE data can be explained by the GCE models calculated with a substantial, ~ 75%, fraction of sub-Ch SN Ia.Comment: accepted for publication in Astronomy & Astrophysics, abridged version of the abstrac

Near-infrared monitoring of roller compacted ribbon density: investigating sources of variation contributing to noisy spectral data

The aim of this study was to highlight how variability in roller compacted ribbon quality can impact on NIR spectral measurement and to propose a simple method of data selection to remove erroneous spectra. The use of NIR spectroscopy for monitoring ribbon envelope density has been previously demonstrated, however to date there has been limited discussion as to how spectral data sets can contain erroneous outliers due to poor sample presentation to the NIR probes. In this study compacted ribbon of variable quality was produced from three separate blends of microcrystalline cellulose (MCC)/lactose/magnesium stearate at 8 Roll Force settings (2–16 kN/cm). The three blends differed only in the storage conditions of MCC prior to blending and compaction. MCC sublots were stored at ambient (41% RH/20 °C), low humidity (11% RH/20 °C) and high humidity (75% RH/40 °C) conditions prior to blending. Ribbon envelope density was measured and ribbon NIR spectral data was acquired at line using a multi-probe spectrometer (MultiEye™ NIR). Initial inspection of the at-line NIR spectral data set showed a large degree of variability which indicated that some form of data cleaning was required. The source of variability in spectral measurements was investigated by subjective visual examination and by statistical analysis. Spectral variability was noted due to the storage conditions of MCC prior to compaction, Roll Force settings and between individual ribbon samples sampled at a set Roll Force/Blend combination. Variability was also caused by ribbon presentation to probes, such as differences in the presentation of broken, curved and flat intact ribbons. Based on the subjective visual examination of data, a Visual Discard method was applied and was found to be particularly successful for blends containing MCC stored at ambient and low humidity. However the Visual Discard method of spectra cleaning is subjective and therefore a non-subjective method capable of screening for erroneous probe readings was developed. For this data set a Trimmed Mean method was applied to set a limit on how data is cleaned from the data set allowing for the removal of a faulty probe reading (25% of data) or a poor sample (33% of data). The 33% Trimmed Mean reduced the impact of spectral variation or misreads between samples or probes and was found to be as successful as the Visual Discard method at cleaning the data set prior to development of the calibration equation

Analyse protéomique des glioblastones: Quel est le meilleur contrôle?

National audienc

Species recognition limits mating between hybridizing ant species

Identifying mechanisms limiting hybridization is a central goal of speciation research. Here, we studied pre-mating and post-mating barriers to hybridization between two ant species, Formica selysi and Formica cinerea. These species hybridize in the Rhône valley in Switzerland, where they form a mosaic hybrid zone, with limited introgression from F. selysi into F. cinerea. There was no sign of temporal isolation between the two species in the production of queens and males. With choice experiments, we showed that queens and males strongly prefer to mate with conspecifics. Yet, we did not detect post-mating barriers caused by genetic incompatibilities. Specifically, hybrids of all sexes and castes were found in the field and F1 hybrid workers did not show reduced viability compared to non-hybrid workers. To gain insights into the cues involved in species recognition, we analyzed the cuticular hydrocarbons of queens, males and workers and staged dyadic encounters between workers. Cuticular hydrocarbon profiles differed markedly between species, but were similar in F. cinerea and hybrids. Accordingly, workers also discriminated species, but they did not discriminate F. cinerea and hybrids. We discuss how the CHC-based recognition system of ants may facilitate the establishment of pre-mating barriers to hybridization, independent of hybridization costs. This article is protected by copyright. All rights reserved

Cell nucleus elastography with the adjoint-based inverse solver

Background and Objectives: The mechanics of the nucleus depends on cellular structures and architecture, and impact a number of diseases. Nuclear mechanics is yet rather complex due to heterogeneous distribution of dense heterochromatin and loose euchromatin domains, giving rise to spatially variable stiffness properties. Methods: In this study, we propose to use the adjoint-based inverse solver to identify for the first time the nonhomogeneous elastic property distribution of the nucleus. Inputs of the inverse solver are deformation fields measured with microscopic imaging in contracting cardiomyocytes. Results: The feasibility of the proposed method is first demonstrated using simulated data. Results indicate accurate identification of the assumed heterochromatin region, with a maximum relative error of less than 5%. We also investigate the influence of unknown Poisson's ratio on the reconstruction and find that variations of the Poisson's ratio in the range [0.3-0.5] result in uncertainties of less than 15% in the identified stiffness. Finally, we apply the inverse solver on actual deformation fields acquired within the nuclei of two cardiomyocytes. The obtained results are in good agreement with the density maps obtained from microscopy images. Conclusions: Overall, the proposed approach shows great potential for nuclear elastography, with promising value for emerging fields of mechanobiology and mechanogenetics