Modification des propriétés physico-chimiques des carraghénanes par la purification et caractérisation de carraghénane-sulfatases

Les carraghénanes sont des galactanes sulfatés extraits de la paroi de certaines algues rouges. Ces polysaccharides d origine marine présentent des propriétés rhéologiques uniques et sont très largement exploités dans l industrie agro-alimentaire, cosmétique, et pharmaceutique comme agents de texture (gélifiants et épaississants). Ils sont composés d unités galactoses liées alternativement par des liaisons (1->3) et (1->4), et diffèrent par la présence ou non d un pont 3,6 anhydro et par leur degré de sulfatation. Cependant, les carraghénanes sont des hétéropolymères et présentent dans la nature des structures hybrides. La grande diversité structurale de ces polysaccharides dont la composition varie en fonction de nombreux facteurs (espèce de l algue, site et saison de récolte, procédés d extraction) offre un large panel de propriétés physico-chimiques exploitable dans diverses applications. Afin de contrôler les propriétés physico-chimiques des carraghénanes, il est donc nécessaire de maîtriser leurs structures chimiques. Dans ce but, la purification d enzymes de désulfatation - appelées sulfatases - a été entreprise, permettant ainsi de jouer directement sur la gélification des carraghénanes. Ces enzymes catalysent l hydrolyse des esters sulfatés de nombreux composés biologiques et sont impliquées dans divers processus métaboliquesCarrageenans are sulfated galactans extracted from cell wall of numerous species of red seaweeds. These polysaccharides of marine origin present unique rheological properties, and are widely used as texturing agents in the food, cosmetic, and pharmaceutical industries. They are composed of galactose units linked alternatively by (1->3) and (1->4) links, and differ by the occurence of 3,6-anhydro bridge and their degree of sulfatation. However, carrageenans are heteropolymers and present complex hybrid stuctures in nature. The variability of carrageenan composition, which depends on algal species, life stage and extraction processes, offers a wide range of physico-chemical properties for various applications. In order to master the rheological properties of carrageenans, it s necessary to control their chemical structures. To this end, the purification of enzymes of desulfatation -called sulfatases- was undertaken allowing monitoring directly on the gelling properties of these polysaccharides. These enzymes catalyse the hydrolysis of sulfate esters bonds of many biological compounds, and are involved in many metabolic processesPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

FabSpaces at ImageCLEF 2017 - Population Estimation (Remote) Task

International audienceThe paper summarizes the participation of the 6 FabSpaces to the population estimation (remote) pilot task at ImageCLEF 2017 Lab. FabSpace 2.0 is an open-innovation network for geodata-driven innovation that aims at improving universities contribution to the socioeconomic and environmental performance of societies. In the framework of the ImageCLEF Lab, the 6 FabSpaces participated although only four of them succeeded in submitting a run. This paper summarizes their participations. For each FabSpace, we present the local organization to participate to the CLEF Lab, the participants and their work. We conclude this paper with some lessons we learned from this participation

Characterization and Pharmacological Validation of a Preclinical Model of NASH in Göttingen Minipigs

International audienceBackground: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, which is associated with features of metabolic syndrome. NAFLD may progress in a subset of patients into nonalcoholic steatohepatitis (NASH) with liver injury resulting ultimately in cirrhosis and potentially hepatocellular carcinoma. Today, there is no approved treatment for NASH due to, at least in part, the lack of preclinical models recapitulating features of human disease. Here, we report the development of a dietary model of NASH in the Göttingen minipig.Methods: First, we performed a longitudinal characterization of diet-induced NASH and fibrosis using biochemical, histological, and transcriptional analyses. We then evaluated the pharmacological response to Obeticholic acid (OCA) treatment for 8 weeks at 2.5mg/kg/d, a dose matching its active clinical exposure.Results: Serial histological examinations revealed a rapid installation of NASH driven by massive steatosis and inflammation, including evidence of ballooning. Furthermore, we found the progressive development of both perisinusoidal and portal fibrosis reaching fibrotic septa after 6 months of diet. Histological changes were mechanistically supported by well-defined gene signatures identified by RNA Seq analysis. While treatment with OCA was well tolerated throughout the study, it did not improve liver dysfunction nor NASH progression. By contrast, OCA treatment resulted in a significant reduction in diet-induced fibrosis in this model.Conclusions: These results, taken together, indicate that the diet-induced NASH in the Göttingen minipig recapitulates most of the features of human NASH and may be a model with improved translational value to prioritize drug candidates toward clinical development

Sample return of primitive matter from the outer Solar System

The last thirty years of cosmochemistry and planetary science have shown that one major Solar System reservoir is vastly undersampled in the available suite of extra-terrestrial materials, namely small bodies that formed in the outer Solar System (>10 AU). Because various dynamical evolutionary processes have modified their initial orbits (e.g., giant planet migration, resonances), these objects can be found today across the entire Solar System as P/D near-Earth and main-belt asteroids, Jupiter and Neptune Trojans, comets, Centaurs, and small (diameter < 200 km) trans-Neptunian objects. This reservoir is of tremendous interest, as it is recognized as the least processed since the dawn of the Solar System and thus the closest to the starting materials from which the Solar System formed. Some of the next major breakthroughs in planetary science will come from studying outer Solar System samples (volatiles and refractory constituents) in the laboratory. Yet, this can only be achieved by an L-class mission that directly collects and returns to Earth materials from this reservoir. It is thus not surprising that two White Papers advocating a sample return mission of a primitive Solar System small body (ideally a comet) were submitted to ESA in response to its Voyage 2050 call for ideas for future L-class missions in the 2035-2050 time frame. One of these two White Papers is presented in this article.ISSN:0922-6435ISSN:1572-950

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society