Pathophysiology of the Belgrade rat

The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis

Caractérisation des produits phytosanitaires périmés (le méthyle parathion et le fénitrothion) étude de la dégradation du fénitrothion par hydrolyse

78 p. ; ill. ; 30 cmLes organophosphorés sont très largement utilisés comme pesticides à efficacité élevée. Cependant ces produits ont souvent des effets secondaires sur l’environnement et sur la santé de l’être humain. L’objectif de notre travail a consisté en la caractérisation de deux insecticides périmés le fénitrothion technique et le méthyle parathion 1.25 % dans le but de les dégrader chimiquement ou de les recycler. Durant la première partie, Les résultats analytiques effectués par GC-FID et GC/MS ont montré que la matière active est partiellement altérée et certains métabolites formés au cours de l’entreposage peuvent se révéler plus toxiques que le produit de départ. Dans la deuxième partie, nous avons étudié la possibilité d’une dégradation chimique du fénitrothion par réaction d’hydrolyse basique et l’effet du peroxyde d’hydrogène H2O2 sur la vitesse de la réaction puis l’influence de la température et du pH sur la vitesse de l’hydrolys

Mapping characterisation of vertical and lateral differentiation of the deformation : application to the Ardenne platform sedimentary cover

La terminaison occidentale du Massif Ardennais expose largement, dans le Nord de la France la déformation varisque. Elle montre des structures plissées-faillées affectant des roches sédimentaires non métamorphiques à épi métamorphiques datées Dévonien à Carbonifère. Une image plus précise de la géométrie profonde du Front Nord Varisque est fournie par la ré-interprétation du profil sismique M146. Le trait majeur est l'existence d'un chevauchement basal d'échelle crustale, faiblement penté vers le Sud, dont l'émergence correspond à la zone faillée du Midi. Cette dernière limite au Nord l'Allochtone Ardennais chevauchant le Bassin Houiller namuro-westphalien et son substratum brabançon. Le chevauchement basal Ardennais accommode un déplacement vers le NNW dont une part importante s'est faite au cours d'un événement en hors-séquence. Au Sud de la zone faillée du Midi, l'Avesnois exhibe des structures plissées-faillées de second ordre globalement à vergence nord orientées ENE-WSW. Ces structures affectent une série lithologiquement très hétérogène. Les contrastes rhéologiques induits contrôlent fortement le style de déformation. Une nouvelle étude cartographique a permis de préciser la géométrie et la cinématique de déformation. Elle précise (1) que le niveau épais incompétent du Famennien a joué le rôle d'un décollement diffus découplant le Dévonien moyen et le Dinantien, (2) que le modèle géométrique de plissement démontré à l'aplomb de discontinuités synsédimentaires précoces, correspond au type « pli disharmonique ». Le plissement dans les unités post-Famennien Inférieur se fait par rotation des flancs autour de charnières fixes. Pour le Famennien Inférieur, le raccourcissement est accommodé par la présence de plusieurs charnières de plis d'ordre élevé dans les zones charnières de plis d'ordre inférieur et par fluage, (3) que les structures ont été re-déformées tardivement par une onde de déformation à vergence sud, soulignant le blocage global de l'allochtonie sur l'avant pays brabançon.The Western Ardennes Paleozoic massif forms the primordial exposure of the Variscan deformation front in Northern France. It includes folded and thrusted units composed of non metamorphic to epi-metamorphic rocks of mostly Devonian-Carboniferous age. Along a Western Ardennes transect imaged by the M146 seismic profile, the thrust front is characterized by a major crustal scale south-dipping thrust zone whose emergence corresponds to the c1assical "Midi" thrust zone. The latter induces the thrusting of the Ardennes-Avesnois fold-and-thrust belt onto the dismembered molassic Namurian-Westphalian coal-bearing foreland basin and its Brabant-type substratum. The main Ardennes basal thrust accommodates a significant part of the motion occuring during a late out-ofsequence event. South of this main thrust, Avesnois area display second order thrust-related folds with a general ENE-WSW trend and a NNW vergence. These structures involve a strongly heterogeneous Iithological sequence. The induced rheological contrasts strongly control the deformation style. New cartographic and structural studies, mainly carried out in the Famennian sequences, allowed us to precise the geometry and kinematics of the fold-thrust structures. As a whole, these data indicate (1) that the thick Incompetent Famennian layers acted as a distributed complex décollement-zone decoupling shortening between the Mid-Devonian and Dinantian layers, (2) that the geometrical folding model demonstrated above early synsedimentary discontinuities corresponds to disharmonic fold types. the folding in the post-Lower Famennian levels occurred by flank rotation around fixed hinge zones. For the lower-Famennian incompetent levels, shortening is accommodated by the presence of several fold hinges in folds hinge zone and by buckling. (3) that the foreland-directed thrust related folds were lately deformed by backwards thrusting, highlighting the overall difficulty of the forward propagation of the thrust front onto the Brabant foreland

Etude de la protéine mitochondriale ATD3A, topologie, adressage à la mitochondrie et interaction avec la calciprotéine S100B

PARIS-BIUP (751062107) / SudocSudocFranceF

Ontology-based hybrid commonsense reasoning framework for handling context abnormalities in uncertain and partially observable environments

International audienceAmbient intelligence (AmI) systems aim to provide users with context-aware assistance services intended to improve the quality of their lives in terms of autonomy, safety, and well-being. Taking the uncertainty and partial observability of these environments into account is of major importance for context recognition and, more specifically, to detect and solve context abnormalities such as those related to the user's behavior or those related to context attribute prediction. In this paper, an ontology-based framework integrating machine learning and probabilistic planning within commonsense reasoning is proposed to recognize the user's context and abnormalities associated with it. The reasoning is performed using event calculus in answer set programming (ECASP); ECASP allows for abductive and temporal reasoning, which results in an eXplainable AI (XAI) approach. A context ontology is proposed to axiomatize the reasoning and introduce the notion of probabilistic fluents into the EC formalism in order to perform probabilistic reasoning. The reasoning incorporates probabilistic planning based on a partially observable Markov decision process (POMDP) to solve knowledge incompleteness. To evaluate the proposed framework, real-life scenarios, based on the Orange4Home and SIMADL public datasets are implemented and discussed

Hybrid approach for anticipating human activities in Ambient Intelligence environments

International audienceRecognising the human context in terms of ongoing human activities is of major importance to ensure an efficient context-aware assistance. In this paper, a hybrid approach combining deep learning and probabilistic commonsense reasoning is proposed for anticipating human activities in AmI environments. Deep learning models are exploited for recognising environment objects, human hands and user’s indoor locations. To implement probabilistic commonsense reasoning, probabilistic fluents are introduced in the formalism of event calculus formulated in answer set programming (ECASP). The reasoning axiomatization is based on an ontology describing the user’s context when performing an activity. Using reasoning based on temporal projection and abduction enables an eXplainable AI (XAI) approach for activity anticipation. Experimental results show the high accuracy of inferences in terms of activity anticipation and a very low computation time in knowledge-intensive scenarios, rendering the system compatible with real-time applications

Caractérisation cartographique d'une différenciation verticale et horizontale de la déformation (application à la couverture sédimentaire de la plate-forme ardennaise)

La terminaison occidentale du Massif Ardennais expose largement, dans le Nord de la France la déformation varisque. Elle montre des structures plissées-faillées affectant des roches sédimentaires non métamorphiques à épi métamorphiques datées Dévonien à Carbonifère. Une image plus précise de la géométrie profonde du Front Nord Varisque est fournie par la ré-interprétation du profil sismique M146. Le trait majeur est l'existence d'un chevauchement basal d'échelle crustale, faiblement penté vers le Sud, dont l'émergence correspond à la zone faillée du Midi. Cette dernière limite au Nord l'Allochtone Ardennais chevauchant le Bassin Houiller namuro-westphalien et son substratum brabançon. Le chevauchement basal Ardennais accommode un déplacement vers le NNW dont une part importante s'est faite au cours d'un événement en hors-séquence. Au Sud de la zone faillée du Midi, l'Avesnois exhibe des structures plissées-faillées de second ordre globalement à vergence nord orientées ENE-WSW. Ces structures affectent une série lithologiquement très hétérogène. Les contrastes rhéologiques induits contrôlent fortement le style de déformation. Une nouvelle étude cartographique a permis de préciser la géométrie et la cinématique de déformation. Elle précise (1) que le niveau épais incompétent du Famennien a joué le rôle d'un décollement diffus découplant le Dévonien moyen et le Dinantien, (2) que le modèle géométrique de plissement démontré à l'aplomb de discontinuités synsédimentaires précoces, correspond au type pli disharmonique . Le plissement dans les unités post-Famennien Inférieur se fait par rotation des flancs autour de charnières fixes. Pour le Famennien Inférieur, le raccourcissement est accommodé par la présence de plusieurs charnières de plis d'ordre élevé dans les zones charnières de plis d'ordre inférieur et par fluage, (3) que les structures ont été re-déformées tardivement par une onde de déformation à vergence sud, soulignant le blocage global de l'allochtonie sur l'avant pays brabançon.The Western Ardennes Paleozoic massif forms the primordial exposure of the Variscan deformation front in Northern France. It includes folded and thrusted units composed of non metamorphic to epi-metamorphic rocks of mostly Devonian-Carboniferous age. Along a Western Ardennes transect imaged by the M146 seismic profile, the thrust front is characterized by a major crustal scale south-dipping thrust zone whose emergence corresponds to the c1assical "Midi" thrust zone. The latter induces the thrusting of the Ardennes-Avesnois fold-and-thrust belt onto the dismembered molassic Namurian-Westphalian coal-bearing foreland basin and its Brabant-type substratum. The main Ardennes basal thrust accommodates a significant part of the motion occuring during a late out-ofsequence event. South of this main thrust, Avesnois area display second order thrust-related folds with a general ENE-WSW trend and a NNW vergence. These structures involve a strongly heterogeneous Iithological sequence. The induced rheological contrasts strongly control the deformation style. New cartographic and structural studies, mainly carried out in the Famennian sequences, allowed us to precise the geometry and kinematics of the fold-thrust structures. As a whole, these data indicate (1) that the thick Incompetent Famennian layers acted as a distributed complex décollement-zone decoupling shortening between the Mid-Devonian and Dinantian layers, (2) that the geometrical folding model demonstrated above early synsedimentary discontinuities corresponds to disharmonic fold types. the folding in the post-Lower Famennian levels occurred by flank rotation around fixed hinge zones. For the lower-Famennian incompetent levels, shortening is accommodated by the presence of several fold hinges in folds hinge zone and by buckling. (3) that the foreland-directed thrust related folds were lately deformed by backwards thrusting, highlighting the overall difficulty of the forward propagation of the thrust front onto the Brabant foreland.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

Iron, Heme Synthesis and Erythropoietic Porphyrias: A Complex Interplay

Erythropoietic porphyrias are caused by enzymatic dysfunctions in the heme biosynthetic pathway, resulting in porphyrins accumulation in red blood cells. The porphyrins deposition in tissues, including the skin, leads to photosensitivity that is present in all erythropoietic porphyrias. In the bone marrow, heme synthesis is mainly controlled by intracellular labile iron by post-transcriptional regulation: translation of ALAS2 mRNA, the first and rate-limiting enzyme of the pathway, is inhibited when iron availability is low. Moreover, it has been shown that the expression of ferrochelatase (FECH, an iron-sulfur cluster enzyme that inserts iron into protoporphyrin IX to form heme), is regulated by intracellular iron level. Accordingly, there is accumulating evidence that iron status can mitigate disease expression in patients with erythropoietic porphyrias. This article will review the available clinical data on how iron status can modify the symptoms of erythropoietic porphyrias. We will then review the modulation of heme biosynthesis pathway by iron availability in the erythron and its role in erythropoietic porphyrias physiopathology. Finally, we will summarize what is known of FECH interactions with other proteins involved in iron metabolism in the mitochondria

Mediterranean Sea and anthropogenic influences on ambient vibration amplitudes in the low-frequency and high-frequency domains in the Algiers region

Ambient vibrations have been continuously recorded at Dar El Beida, about 20 km from Algiers (Algeria). This data set allows determining that, in the low-frequency domain (<1 Hz), ambient vibration sources are mainly linked to Mediterranean Sea effects, while in the high-frequency domain, they are closely related to anthropogenic activity. Climatic conditions have an influence on the ambient vibration spectral amplitudes in the low-frequency domain, which is not the case in the high-frequency domain. The limit between the low-frequency and high-frequency domain, based on natural versus anthropogenic activity, is not clear cut and lies between 1.25 and 1.50 Hz. Variations of H/V peak amplitudes in the low-frequency domain are clearly linked to the climatic conditions. In the high-frequency domain, H/V peaks are not related to climatic conditions and cannot be clearly related to anthropogenic source changes

GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia

International audienceNon-syndromic microcytic congenital sideroblastic anemia (cSA) is predominantly caused by defective genes encoding for either ALAS2, the first enzyme of heme biosynthesis pathway or SLC25A38, the mitochondrial importer of glycine, an ALAS2 substrate. Herein we explored a new case of cSA with two mutations in GLRX5, a gene for which only two patients have been reported so far. The patient was a young female with biallelic compound heterozygous mutations in GLRX5 (p.Cys67Tyr and p.Met128Lys). Three-D structure analysis confirmed the involvement of Cys67 in the coordination of the [2Fe2S] cluster and suggested a potential role of Met128 in partner interactions. The protein-level of ferrochelatase, the terminal-enzyme of heme process, was increased both in patient-derived lymphoblastoid and CD34+ cells, however, its activity was drastically decreased. The activity of ALAS2 was found altered and possibly related to a defect in the biogenesis of its co-substrate, the succinyl-CoA. Thus, the patient exhibits both a very low ferrochelatase activity without any accumulation of porphyrins precursors in contrast to what is reported in erythropoietic protoporphyria with solely impaired ferrochelatase activity. A significant oxidative stress was evidenced by decreased reduced glutathione and aconitase activity, and increased MnSOD protein expression. This oxidative stress depleted and damaged mtDNA, decreased complex I and IV activities and depleted ATP content. Collectively, our study demonstrates the key role of GLRX5 in modulating ALAS2 and ferrochelatase activities and in maintaining mitochondrial function