Biochemical and Structural Characterization of the Subclass B1 Metallo-β-Lactamase VIM-4 ▿

The metallo-β-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn2+ at concentrations ranging from 0.4 to 100 μM showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 Å. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo- and apo-VIM-4 enzymes revealed that Zn2+ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure

Marché de services en vue de simuler l’impact, sur le régime hydrologique de l’Ourthe, de l’implantation de bassins écrêteurs dans les vallées de l’Ourthe et de l’Amblève (MOHICAN)

Le modèle MOHICAN (« Modèle hydrologique intégré pour le calcul des crues et l’amplitude des niveaux d’eau ») a été développé conjointement par l’Université de Liège (Laboratoire d’hydrodynamique appliquée, Laboratoire de Géologie de l’Ingénieur et d’Hydrogéologie, Centre d’Etude et de Modélisation de l’environnement) et la Faculté Universitaire des Sciences Agronomiques de Gembloux (Unité d’Hydraulique agricole) pour le compte et avec le support du Ministère de l’Equipement et des Transports, Service d’Etudes Hydrologiques (MET/SETHY) de la Région wallonne. En 2004, le SETHY a demandé aux développeurs du projet de simuler l’impact sur le régime hydrologique de l’Ourthe, de bassins écrêteurs dans les vallées de l’Ourthe et de l’Amblève. Plus spécifiquement, les objectifs de l’étude étaient d’estimer l’efficacité réelle de ces bassins écrêteurs (Les Combes, 16.3 Mm³, Ourthe ; Gran Han, 15.0 Mm³, Ourthe ; Stoumont, 5.7 Mm³, Amblève) pour la diminution des débits de pointe et des hauteurs d’eau, en particulier lors de très grandes crues. Dans le cas des grandes crues testée, les simulations montrent clairement la grande sensibilité des résultats aux différentes combinaisons possibles des bassins écrêteurs et surtout aux lois de gestion à utiliser pour ces bassins : il n’existe pas une loi générale qui donne un résultat maximal pour tous les types de grandes crues, et la gestion combinée des bassins est délicate.MOHICA

Combination of biocompatible hydrogel precursors to apatitic calcium phosphate cements (CPCs): Influence of the in situ hydrogel reticulation on the CPC properties

International audienceIn the field of bone regenerative medicine, injectable calcium phosphate cements (CPCs) are used for decades in clinics, as bone void fillers. Most often pre-formed polymers (e.g. hyaluronic acid, collagen, chitosan, cellulose ethers…) are introduced in the CPC formulation to make it injectable and improve its cohesion. Once the cement has hardened, the polymer is simply trapped in the CPC structure and no organic sub-network is present. By contrast, in this work a CPC was combined with organic monomers that reticulated in situ so that a continuous biocompatible 3D polymeric sub-network was formed in the CPC microstructure, resulting in 2 a higher permeability of the CPC which might allow to accelerate its in vivo degradation. Two options were investigated depending whether the polymer was formed before the apatitic inorganic network or concomitantly. In the former case, conditions were found to reach a suitable rheology for easy injection of the composite. In addition, the in situ formed polymer was shown to strongly affect the size, density and arrangement of the apatite crystals formed during the setting reaction, thereby offering an original route to modulate the microstructure and porosity of apatitic cements

Marché de service pour la réalisation d’extensions au modèle global de simulation hydrologique MOHICAN

Ce rapport final présente une synthèse des travaux réalisés durant une dernière phase de développement du projet Mohican. Le modèle MOHICAN (pour MOdèle Hydrologique Intégré pour le calcul des Crues et l’Amplitude des Niveaux d’eau) est un modèle hydrologique opérationnel global à structure déterministe, permettant la représentation des phénomènes de crues et d'inondations dans le bassin de la Meuse et de ses affluents, pour la partie située en Région wallonne Une première version du modèle avait été développée en 2000 (voir xxxx). Pour rappel, il est composé d'un sous-modèle "sols", d'un sous-modèle "eaux souterraines", d'un sous-modèle "eaux de surface" et d'une structure d'assemblage et de pilotage des sous-modèles Cette deuxième phase visait principalement à - consolider le modèle - appliquer le modèle sur l'ensemble de la zone modélisée (la Meuse en Région Wallonne) - permettre l'implantation du modèle sur une machine de l'administrationMOHICA

Genomic Instability Is Defined by Specific Tumor Microenvironment in Ovarian Cancer: A Subgroup Analysis of AGO OVAR 12 Trial

International audienceBackground: Following disappointing results with PD-1/PD-L1 inhibitors in ovarian cancer, it is essential to explore other immune targets. The aim of this study is to describe the tumor immune microenvironment (TME) according to genomic instability in high grade serous ovarian carcinoma (HGSOC) patients receiving primary debulking surgery followed by carboplatin-paclitaxel chemotherapy +/− nintedanib. Methods: 103 HGSOC patients’ tumor samples from phase III AGO-OVAR-12 were analyzed. A comprehensive analysis of the TME was performed by immunohistochemistry on tissue microarray. Comparative genomic hybridization was carried out to evaluate genomic instability signatures through homologous recombination deficiency (HRD) score, genomic index, and somatic copy number alterations. The relationship between genomic instability and TME was explored. Results: Patients with high intratumoral CD3+ T lymphocytes had longer progression-free survival (32 vs. 19.6 months, p = 0.009) and overall survival (OS) (median not reached). High HLA-E expression on tumor cells was associated with a longer OS (median OS not reached vs. 52.9 months, p = 0.002). HRD profile was associated with high HLA-E expression on tumor cells and an improved OS. In the multivariate analysis, residual tumor, intratumoral CD3, and HLA-E on tumor cells were more predictive than other parameters. Conclusions: Our results suggest HLA-E/CD94-NKG2A/2C is a potential immune target particularly in the HRD positive ovarian carcinoma subgroup

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed