# Université d'Évry-Val-d'Essonne

• Évry, France
Recent publications
Background Moyamoya angiopathy (MMA) is a rare cerebrovascular condition leading to stroke. Mutations in 15 genes have been identified in Mendelian forms of MMA, but they explain only a very small proportion of cases. Our aim was to investigate the genetic basis of MMA in consanguineous patients having unaffected parents in order to identify genes involved in autosomal recessive MMA. Methods Exome sequencing (ES) was performed in 6 consecutive consanguineous probands having MMA of unknown etiology. Functional consequences of variants were assessed using western blot and protein 3D structure analyses. Results Causative homozygous variants of NOS3, the gene encoding the endothelial nitric oxide synthase (eNOS), and GUCY1A3, the gene encoding the alpha1 subunit of the soluble guanylate cyclase (sGC) which is the major nitric oxide (NO) receptor in the vascular wall, were identified in 3 of the 6 probands. One NOS3 variant (c.1502 + 1G > C) involves a splice donor site causing a premature termination codon and leads to a total lack of eNOS in endothelial progenitor cells of the affected proband. The other NOS3 variant (c.1942 T > C) is a missense variant located into the flavodoxine reductase domain; it is predicted to be destabilizing and shown to be associated with a reduction of eNOS expression. The GUCY1A3 missense variant (c.1778G > A), located in the catalytic domain of the sGC, is predicted to disrupt the tridimensional structure of this domain and to lead to a loss of function of the enzyme. Both NOS3 mutated probands suffered from an infant-onset and severe MMA associated with posterior cerebral artery steno-occlusive lesions. The GUCY1A3 mutated proband presented an adult-onset MMA associated with an early-onset arterial hypertension and a stenosis of the superior mesenteric artery. None of the 3 probands had achalasia. Conclusions We show for the first time that biallelic loss of function variants in NOS3 is responsible for MMA and that mutations in NOS3 and GUCY1A3 are causing fifty per cent of MMA in consanguineous patients. These data pinpoint the essential role of the NO pathway in MMA pathophysiology.
In this paper we are interested in solving numerically quadratic SDEs with non-necessary continuous drift of the from Xt = x + ? t 0 b(s,Xs)ds + ? t 0 f (Xs)?2(Xs)ds + ? t 0 ?(Xs)dWs, where, x is the initial data b and ? are given coefficients that are assumed to be Lipschitz and bounded and f is a measurable bounded and integrable function on the whole space R. Numerical simulations for this class of SDE of quadratic growth and measurable drift, induced by the singular term f (x)?2(x), is implemented and illustrated by some examples. The main idea is to use a phase space transformation to transform our initial SDEs to a standard SDE without the discontinuous and quadratic term. The Euler-Maruyama scheme will be used to discretize the new equation, thus numerical approximation of the original equation is given by taking the inverse of the space transformation. The rate of convergence are shown to be of order 1/2.
This work addresses existence and stabilization problem for a hybrid neutral stochastic delay differential equations with Lévy noise (HNSDDELN). The coefficients of such systems do not satisfy the conventional linear growth conditions, but are subject to high nonlinearity. We first prove the existence and uniqueness of the solution. We then design a delay feedback controller to make an unstable HNSDDELN $H_{\infty }$ and asymptotically stable in ${\mathbb{L}}^{p}$. We end up with a numerical example that corroborates our theoretical findings.
Chlordecone (CLD), a Persistent Organic Pollutant, is still present in water and food chain of the French West Indies (FWI), leading to dramatical public health problems. One of the major issues is the lack of an easy, non-expensive, sensitive and robust method for the detection of chlordecone to ensure chlordecone-free water and foods for the residents of the FWI. Here we report on the development of a fluorescent molecular cage that allows a simple and convenient detection of chlordecone in water at environmental concentration. The specific structural features of chlordecone prompted us to choose hemicryptophanes as receptor. First, we optimized the size, shape of the cavity, as well as the recognition units, to identify the most efficient non fluorescent host for CLD complexation. Then, this selected compound was equipped with fluorophores at different positions in order to find the most efficient system for CLD detection by fluorescence. Among the two most promising fluorescent cages, the newly synthesized hemicryptophane with biphenyl moieties allowed us to develop a fast, easy, reproducible and cheap procedure to detect CLD in water. Its sensitivity and scalability, with modulation of hemicryptophane concentration enabled us to estimate CLD concentrations over five orders of magnitude (10-2 - 103 µg/L) including the environmental levels of contamination and the permissible limit for drinking water in the FWI.
In this paper, we investigate the existence and uniqueness of fractional differential equations (FDEs) by using the fixed-point theory (FPT). We discuss also the Ulam–Hyers–Rassias (UHR) stability of some generalized FDEs according to some classical mathematical techniques and the FPT. Finally, two illustrative examples are presented to show the validity of our results.
Our goal in this work is to demonstrate the existence and uniqueness of the solution to a class of Hadamard Fractional Itô–Doob Stochastic integral equations (HFIDSIE) of order φ∈(0,1) via the fixed point technique (FPT). Hyers–Ulam stability (HUS) is investigated for HFIDSIE according to the Gronwall inequality. Two theoretical examples are provided to illustrate our results.
The non-homogeneity of in-situ concrete is owing to the intrinsic variability of the material mixture, the workmanship, the construction technology, and the environmental conditions. There is the reason for varying compressive strength of existing reinforced concrete (RC) structures that lead to spatial variabilities of a measurement. In this study, an experimental program on a new existing 25-story RC building has been conducted in order to assess the spatial variability of compressive strength of the laboratory-tested specimens and the on-site cores, coincidentally to find the distribution of these results based on statistical analysis. The spatial variability of compressive strength is identified from 315 cast specimens on-site and 312 specimens collected from the existing structures by the core drilling method. More specifically, the concrete strength variability obtained in RC structural components on-site was investigated through small-scale variability within a single member, large-scale, and global-scale variability between different members made of the same concrete. The casting-in-place cube is the most convenient specimen to ensure that the used concrete complies with the requirements of the design project through the variation of compressive strength in a set of three specimens per batch. According to the analyses presented in this study, there has been a correlation between the spatial variability obtained from cubic specimens and the small-scale spatial variability as found in the core specimens. However, there is a considerable difference between the global and local spatial variability of on-site concrete compressive strength.
How cells respond to different external cues to develop along defined cell lineages to form complex tissues is a major question in systems biology. Here, we investigated the potential of retinoic acid receptor (RAR)–selective synthetic agonists to activate the gene regulatory programs driving cell specialization during nervous tissue formation from embryonic carcinoma (P19) and mouse embryonic (E14) stem cells. Specifically, we found that the synergistic activation of the RARβ and RARγ by selective ligands (BMS641 or BMS961) induces cell maturation to specialized neuronal subtypes, and to astrocytes and oligodendrocyte precursors. Using RAR isotype knockout lines exposed to RAR-specific agonists, interrogated by global transcriptome landscaping and in silico modeling of transcription regulatory signal propagation, revealed major RARα-driven gene programs essential for optimal neuronal cell specialization and hijacked by the synergistic activation of the RARβ and RARγ receptors. Overall, this study provides a systems biology view of the gene programs accounting for the previously observed redundancy between RARs, paving the way toward their potential use for directing cell specialization during nervous tissue formation.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disorder that is implicated in dysregulations in multiple biological pathways, orchestrated by interactions between genetic predisposition, metabolic syndromes and environmental factors. The limited knowledge of its pathogenesis is one of the bottlenecks in the development of prognostic and therapeutic options for MAFLD. Moreover, the extent to which metabolic pathways are altered due to ongoing hepatic steatosis, inflammation and fibrosis and subsequent liver damage remains unclear. To uncover potential MAFLD pathogenesis in humans, we employed an untargeted nuclear magnetic resonance (NMR) spectroscopy- and high-resolution mass spectrometry (HRMS)-based multiplatform approach combined with a computational multiblock omics framework to characterize the plasma metabolomes and lipidomes of obese patients without (n = 19) or with liver biopsy confirmed MAFLD (n = 63). Metabolite features associated with MAFLD were identified using a metabolome-wide association study pipeline that tested for the relationships between feature responses and MAFLD. A metabolic pathway enrichment analysis revealed 16 pathways associated with MAFLD and highlighted pathway changes, including amino acid metabolism, bile acid metabolism, carnitine shuttle, fatty acid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and steroid metabolism. These results suggested that there were alterations in energy metabolism, specifically amino acid and lipid metabolism, and pointed to the pathways being implicated in alerted liver function, mitochondrial dysfunctions and immune system disorders, which have previously been linked to MAFLD in human and animal studies. Together, this study revealed specific metabolic alterations associated with MAFLD and supported the idea that MAFLD is fundamentally a metabolism-related disorder, thereby providing new perspectives for diagnostic and therapeutic strategies.
Solid-state nanopores, fabricated by a controlled dielectric breakdown technique, were used to probe the dynamics of entrance and transport of dsDNA chains. Abstract Controlled dielectric breakdown (CDB) is gaining popularity for fabricating solid-state nanopores in situ with size control in a simple, low-cost, and scalable way. This technique could be used for a broad type of applications in the field of nucleic acid analysis and even for protein studies. In this work, we studied the entry and transport of double-stranded DNAs using a solid-state nanopore fabricated by CDB as a function of applied voltage for two different DNA lengths. We showed that the blockade rate increases exponentially with voltage up to 120 mV. The energy barrier depends on the chain length, and the dwell times decrease with applied voltage up to 120 mV. Moreover, no matter the chain length, it is possible to differentiate two families of blockade amplitudes, high and low ones, due to DNA folding.
Partial resistance in plants generally exerts a low selective pressure on pathogens, and thus ensuring their durability in agrosystems. However, little is known about the effect of partial resistance on the molecular mechanisms of pathogenicity, a knowledge that could advance plant breeding for sustainable plant health. Here we investigate the gene expression of Phytophthora capsici during infection of pepper (Capsicum annuum L.), where only partial genetic resistance is reported, using Illumina RNA-seq. Comparison of transcriptomes of P. capsici infecting susceptible and partially resistant peppers identified a small number of genes that redirected its own resources into lipid biosynthesis to subsist on partially resistant plants. The adapted and non-adapted isolates of P. capsici differed in expression of genes involved in nucleic acid synthesis and transporters. Transient ectopic expression of the RxLR effector genes CUST_2407 and CUST_16519 in pepper lines differing in resistance levels revealed specific host-isolate interactions that either triggered local necrotic lesions (hypersensitive response or HR) or elicited leave abscission (extreme resistance or ER), preventing the spread of the pathogen to healthy tissue. Although these effectors did not unequivocally explain the quantitative host resistance, our findings highlight the importance of plant genes limiting nutrient resources to select pepper cultivars with sustainable resistance to P. capsici.
Uncovering microscopic hydrophilicity and hydrophobicity at heterogeneous aqueous interfaces is essential as it dictates physical and chemical properties such as wetting, electrical double layer, reactivity. Here, we combine density functional theory-based MD simulations (DFT-MD) and both theoretical and experimental SFG spectroscopy to explore how the interfacial water responds in contact with self-assembled monolayers (SAM) of tunable hydrophilicity. We introduce a microscopic metric to track the transition from hydrophobic to hydrophilic interfaces, which combines a structural descriptor based on the preferential orientation within the water network in the topmost binding interfacial layer (BIL) and spectroscopic fingerprints of H-bonded and dangling OH groups of water pointing towards the surface carried by BIL-resolved SFG spectra. This metric builds a bridge between molecular descriptors of hydrophilicity/hydrophobicity and spectroscopically measured quantities, and provides a recipe to quantitatively or qualitatively interpret experimental SFG signals.
This paper studies a multi-period closed-loop inventory routing problem for perishable food that are carried by returnable transport items (RTIs) of different types. We formulate the problem as an integer linear programming (ILP) model considering RTIs with different food quality preserve ability, and the simultaneous delivery of food and pick-up of RTIs. The objective is to maximize the total profit of the holistic supply chain that equals to the selling revenue minus the summation of production, routing, inventory and RTI purchase costs. The proposed model is demonstrated to be correct and effective by conducting computational experiments on randomly generated instances.
Exploration of the chemical reaction space of chemical transformations in multicomponent mixtures is a challenge for modern computational protocols. In order to remove expert bias from mechanistic studies and to discover new chemistries, an automated graph-theoretical methodology is proposed to provide mechanistic analysis in catalytic systems. The primary advantage of the presented three-step approach over the existing automated pathways generation methods is the integrated ability to handle multicomponent catalytic systems of arbitrary complexity (mixtures of reactants, catalyst precursors, ligands, additives, and solvent). It is not limited to pre-defined chemical rules, does not require pre-alignment of reaction mixture components consistent with a reaction coordinate and is not agnostic to the chemical nature of transformations. Conformer exploration, Reactive event identification and Reaction network analysis are the main steps taken for understanding the underlying mechanistic pathways in catalytic mixtures given the reaction mixture as the input. Such a methodology allows to comprehensively explore the catalytic systems in realistic conditions for either previously observed or completely unknown reactive events. The expert bias is sought to be removed in either of the steps and chemical intuition is limited to the choice of the thermodynamic constraint imposed by the applicable experimental conditions in terms of threshold energy values for allowed transformations. The capabilities of the proposed methodology have been tested by exploring reactivity of Mn complexes relevant for catalytic hydrogenation chemistry to verify previously postulated activation mechanisms and unravel unexpected reaction channels relevant to rare deactivation events.
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• Département de Biologie
• LGRK CEA Evry
• UFR Sciences et Technologies
• Laboratoire IBISC - Informatique Biologie Intégrative et Systèmes Complexes
• Département de Biologie
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