TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD

Modification de fibres naturelles par radiogreffage

National audienceLes fibres naturelles d’origine végétale suscitent un vif intérêt dans de nombreux domaines (textile, construction, automobile, maritime). Certaines de leurs caractéristiques comme leur inflammabilité ainsi que leur hydrophilie représentent cependant des inconvénients majeurs pour de nombreuses applications. Des recherches sont aujourd’hui menées dans les milieux académique et industriel pour développer des méthodes efficaces de fonctionnalisation ou de modification de surface de ces fibres pour améliorer leurs performances. A cet égard, le radio greffage, reposant sur l’usage de rayonnements ionisants (gamma ou e-beam) représente une méthode pertinente par rapport aux méthodes chimiques ou enzymatiques classiques. Elle permet de générer sur les fibres des radicaux ou des groupes fonctionnels permettant le greffage de molécules d’intérêt offrant alors un large spectre de possibilités pour la modification des fibres [1][2]. Néanmoins, les modifications induites par ce traitement sont dépendantes d’un grand nombre de facteurs, dont notamment la structure du substrat qui influence la nature et la quantité des espèces actives formées. Pour évaluer son importance et mieux comprendre l’impact de ce paramètre, la Résonnance Paramagnétique Electronique (RPE) semble être un outil de choix. Cette présentation vise alors à exposer les conclusions tirées de l’application de cette technique à l’étude de fibres naturelles irradiées

Radio-grafting of phosphorus flame retardant on flax fabrics: Pre-irradiation method

International audienceThis work is focused on the functionalization of flax fibers aiming to improve their flame retardancy by grafting a phosphorus-based flame retardant (FR), dimethyl(methacryloxy) methyl phosphonate (MAPC1). The pre-irradiation method [1], [2] was used, and the grafting process follows three main steps namely: the irradiation of flax fibers, the impregnation of irradiated fibers in FR solution and finally a washing step to remove unreacted monomer units and free oligomers and polymers chains not covalently bonded to the flax structure. The presence of radicals on the flax fibers after irradiation was confirmed by Electron Paramagnetic Resonance. Grafting efficiency was assessed by infrared spectroscopy and quantified using Inductively Coupled Plasma. The location of the grafted phosphorus polymer chains was assessed by Scanning Electron Microscope coupled with Energy Dispersive X-ray spectrometer using phosphorus mapping of modified fibers. The effect of phosphorus grafting on thermal properties and fire behavior of flax fibers was studied using thermogravimetric analysis, pyrolysis combustion flow calorimetry and cone calorimetry. Different parameters were studied such as the radiation dose, the temperature and the duration of the grafting reaction and the monomer concentration. In particular, it was observed that MAPC1 was grafted in a homogeneous way into the bulk of the elementary flax fibers leading to high phosphorus rate of around 2 wt% for a dose 10 kGy and up to 7 wt% for a dose 100 kGy leading to high charring and low flammable fibers

A methodology to go from stakeholder’s expectations to research questions: implementation on organic food processing

To develop research projects on organic food processing, the French Research Institute of Organic Farming and the French National Institute for Agricultural Research co-organised a participatory meeting to define shared research questions and involve stakeholders (researchers, private companies, representatives of funding agencies and consumers). Based on the Town Hall Meeting method, it enabled attendees to express and discuss their points of view on proposals they made together. This led to twenty-two research questions about bio-compatibility, conservation, sustainability, adaptation to the food system and flexibility, socio-economic or health. It also led to mid-term strategic agenda. Some of these questions are currently used to build multidisciplinary projects in the framework of a French organic processing network

Exploring the Use of Ramsey-CPT Spectroscopy for a Microcell-Based Atomic Clock

International audienceWe investigate the application of Ramsey spectroscopy for the development of a microcell atomic clock based on coherent population trapping (CPT). The dependence of the central Ramsey-CPT fringe properties on key experimental parameters is first studied for optimization of the clock's short-term frequency stability. The sensitivity of the clock frequency to light-shift effects is then studied. In comparison with the continuous-wave (CW) regime case, the sensitivity of the clock frequency to laser power variations is reduced by a factor up to 14 and 40.3 for dark times of 150 and 450 µs, respectively, at the expense of intensity 3.75 times higher for short-term stability optimization. The dependence of the clock frequency on the microwave power is also reduced in the Ramsey case. We demonstrate that the Ramsey-CPT interrogation improves the clock Allan deviation for averaging times higher than 100 s. With a dark time of 450 µs, a clock fractional frequency stability of 3.8 × 10 −12 at 10 4 s is obtained, in comparison with the level of 8 × 10 −11 obtained in the standard CW case, in similar environmental conditions. These results demonstrate that Ramsey-based interrogation protocols might be an attractive approach for the development of chip-scale atomic clocks (CSACs) with enhanced mid-and long-term stability

Platinum group elements and sulfur in hydrothermal fluids: a love story told by in situ spectroscopy, molecular dynamics, and thermodynamics

International audienceKnowledge of Platinum Group Elements (PGE) speciation in hydrothermal fluids is essential to better understanding the transport of these metals in the Earth's crust and to identifying potential hydrothermal deposits where PGE may be present in economic grades. Existing data on aqueous chloride, sulfate, and hydroxide complexes of PGEs indicate extremely low metal contents (< ppt to ppb) in fluids from most geological settings [1-3] that cannot explain multiple instances of PGE concentration and mobilization in hydrothermal systems, thus appealing to an important role of sulfide (HS–) and, potentially, trisulfur (S3–) ligands [4] in PGE transport. To quantify the effect of sulfur on the solubility of platinum and palladium in hydrothermal fluids, we combined in situ solubility (Fig. 1A) and X-ray absorption spectroscopy (XAS; Fig. 1B) measurements with molecular dynamics (MD; Fig. 1C) and thermodynamic (TD) simulations [5]. Our results show that two main complexes transport these metals in hydrothermal fluids across a wide pH range (4–8), temperature and pressure (up to at least 350 °C and 1000 bar): Pt(HS)42– and Pd(HS)42– in H2S/HS– solutions, Pt(HS)2(S3)22– and Pd(HS)2(S3)22– in H2S/SO42–/S3– solutions. The role of the trisulfur ion in PGE hydrothermal transport thus appears to be particularly crucial [5,6], with solubilities (10s ppm Pt, Pd) up to 10,000 times higher than those of the ‘traditional’ complexes with H2S/HS–. Our results offer perspectives for the exploration of new PGE resources, their extraction and recycling, and hydrothermal synthesis of PGE-based nanomaterials. Future research on other metals in fluid-mineral systems will benefit from the combined approach implemented in this study, as well as an open-access database of XAS spectra of Pt reference compounds acquired in our work [7].[1] Bazarkina et al. (2014), GCA 146, 107–131; [2] Kokh et al. (2017), GCA 197, 433–466; [3] Tagirov et al. (2019), GCA 254, 86–101; [4] Pokrovski and Dubessy (2015), EPSL 411, 298–309; [5] Laskar et al. (2022), GCA 336, 407–422; [6] Pokrovski et al. (2021), PNAS 118, e2109768118; [7] Laskar et al. (2022), Minerals 12, 1602

Boron-10 conversion layer for ultra-cold neutron detection

International audienceWe report on the development of a 10B conversion layer optimized for ultra-cold neutron detection with silicon detectors. The efficiency of this layer is high and roughly uniform over a large ultra-cold neutron velocity range. The designed titanium-boron-nickel multilayer film was deposited on silicon using a microwave plasma-assisted co-sputtering method (first, for test purpose, on silicon wafers, then directly on the surface of a CCD sensor). The obtained sensor was then tested using both cold and ultra-cold neutrons

Prognostic value of FDG-PET indices for the assessment of histological response to neoadjuvant chemotherapy and outcome in pediatric patients with Ewing sarcoma and osteosarcoma.

The objective of this retrospective work was to evaluate the prognostic value on histological response and survival of quantitative indices derived from FDG-PET performed before and after chemotherapy (CHT), in a homogeneous pediatric Ewing sarcoma (EWS) and Osteosarcoma (OST) population.Thirty-one patients with EWS and 31 with OST were included. All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had FDG-PET at diagnosis and after CHT, prior to surgery. Several parameters were evaluated: SUVmax, SUVpeak, SUVmean, metabolic tumor volume, total lesion glycolysis, 7 textural features and 3 shape features (SF). The segmentation was performed using an adaptive approach. Results were compared to histopathological regression of the resected tumor and to clinical follow-up for survival evaluation.For EWS, univariate analysis did not highlight any prognostic value on histological response, or survival regardless of all the considered metrics. For OST, only one of the SF, namely elongation, was significantly associated with PFS and OS on both univariate and multivariate analysis (PFS: p = 0.019, HR = 5.583; OS: p = 0.0062, HR = 7.113).Only elongation determined on initial FDG-PET has a potential interest as a prognostic factor of PFS and OS in pediatric OST patients. Unlike recent studies of the literature realized in adult population, all the metrics reveal limited additional prognostic value in pediatric EWS patients. This seems to reinforce the question of whether children experience different subtypes of the same pathologies than older patients, with different outcomes

Prognostic values (<i>p value</i> and <i>Hazard Ratios</i> when p-value < 0.05) of classical prognostic factors derived from initial staging and of metrics derived from initial FDG-PET, on univariate analysis.

<p>Prognostic values (<i>p value</i> and <i>Hazard Ratios</i> when p-value < 0.05) of classical prognostic factors derived from initial staging and of metrics derived from initial FDG-PET, on univariate analysis.</p