Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome

International audienceNatural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg⋅L −1 for male rats and 40 mg⋅L −1 for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg⋅L −1 NU. In male rats, spatial working memory and anxiety-and depressive-like behaviour were only altered by exposure to 40 mg⋅L −1 NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function

Role of oxygen exposure on the differentiation of human induced pluripotent stem cells in 2D and 3D cardiac organoids

Introduction Human induced pluripotent stem cells (hiPSC) have the ability to differentiate theoritically into any cell type. The development of organoid systems exhibiting the essential features of human organ such as liver and heart is of high interest. Optimizing the culture conditions to obtain the highest cardiac organoids efficacy is crucial. In fact, cardiac differentiation protocols have been established by essentially focusing on specific growth factors on hiPSC differentiation efficiency. However, the optimal environmental factors such as the optimal oxygen exposure to obtain cardiac myocytes in network are still unclear. The mesoderm germ layer differentiation is known to be enhanced by low oxygen exposure. Yet, the effect of low oxygen exposure on the molecular and functional maturity of the hiPSC-derived cardiomyocytes remains unexplored. Aims We aimed here at comparing the molecular and functional consequences of low (5% O2 or LOE) and high oxygen exposure (21% O2 or HOE) on cardiac differentiation of hiPSCs in 2D monolayer and 3D organoids protocols. Methods hiPSC-CMs were differentiated through both the 2D (monolayer) and 3D (embryoid body) protocols using several lines. Cardiac marker expression and cell morphology were assessed using qRT-PCR and immunofluorescence. The mitochondrial localization and metabolic properties were evaluated by high-resolution respirometry and mitochondrial staining. The intracellular Ca2+ handling and contractile properties were also monitored using confocal fluorescent microscopy and atomic force microscopy. Results Our results indicated that the 2D cardiac monolayer can only be differentiated in HOE. The 3D cardiac organoids containing hiPSC-CMs in LOE exhibited higher cardiac markers expression such as troponin T (TnTc), RyR2, Serca2a, alpha and beta heavy myosin chains. Moreover, we found enhanced contractile force, hypertrophy and steadier SR Ca2+ release reflected by a more regular spontaneous Ca2+ transients associated with a higher maximal amplitude and lower spontaneous Ca2+ events revealing a better SR Ca2+ handling in LOE. Similar beat rate, preserved distribution of mitochondria and similar oxygen consumption by the mitochondrial respiratory chain complexes were also observed. Conclusions Our results brought evidences that LOE is moderately beneficial for the 3D cardiac organoids with hPSC-CMs exhibiting further maturity. In contrast, the 2D cardiac monolayers strictly require HOE.Introduction Human induced pluripotent stem cells (hiPSC) have the ability to differentiate theoritically into any cell type. The development of organoid systems exhibiting the essential features of human organ such as liver and heart is of high interest. Optimizing the culture conditions to obtain the highest cardiac organoids efficacy is crucial. In fact, cardiac differentiation protocols have been established by essentially focusing on specific growth factors on hiPSC differentiation efficiency. However, the optimal environmental factors such as the optimal oxygen exposure to obtain cardiac myocytes in network are still unclear. The mesoderm germ layer differentiation is known to be enhanced by low oxygen exposure. Yet, the effect of low oxygen exposure on the molecular and functional maturity of the hiPSC-derived cardiomyocytes remains unexplored. Aims We aimed here at comparing the molecular and functional consequences of low (5% O2 or LOE) and high oxygen exposure (21% O2 or HOE) on cardiac differentiation of hiPSCs in 2D monolayer and 3D organoids protocols. Methods hiPSC-CMs were differentiated through both the 2D (monolayer) and 3D (embryoid body) protocols using several lines. Cardiac marker expression and cell morphology were assessed using qRT-PCR and immunofluorescence. The mitochondrial localization and metabolic properties were evaluated by high-resolution respirometry and mitochondrial staining. The intracellular Ca2+ handling and contractile properties were also monitored using confocal fluorescent microscopy and atomic force microscopy. Results Our results indicated that the 2D cardiac monolayer can only be differentiated in HOE. The 3D cardiac organoids containing hiPSC-CMs in LOE exhibited higher cardiac markers expression such as troponin T (TnTc), RyR2, Serca2a, alpha and beta heavy myosin chains. Moreover, we found enhanced contractile force, hypertrophy and steadier SR Ca2+ release reflected by a more regular spontaneous Ca2+ transients associated with a higher maximal amplitude and lower spontaneous Ca2+ events revealing a better SR Ca2+ handling in LOE. Similar beat rate, preserved distribution of mitochondria and similar oxygen consumption by the mitochondrial respiratory chain complexes were also observed. Conclusions Our results brought evidences that LOE is moderately beneficial for the 3D cardiac organoids with hPSC-CMs exhibiting further maturity. In contrast, the 2D cardiac monolayers strictly require HOE

Bio-indicateurs potentiels d'atteinte multi-organe : application au cas des victimes d'irradiation accidentelles

Accidental irradiations induce a complex pathological situation, difficult to assess and to treat. However, recent results describing new biological indicators of radiation-induced damages such as Flt3-ligand, citrulline and oxysterol concentration in the plasma, together with results obtained in large animal models of high dose irradiation, allowed a better understanding of pathophysiological mechanisms induced by uncontrolled irradiations. This conducted to leave the classical paradigm of the acute radiation syndrome, described as the association of three individual syndromes, the hematopoietic syndrome, the gastro-intestinal syndrome and the cerebrovascular syndrome, in favour of a multiple organ dysfunction syndrome, with the implication of other organs and systems. Follow-up of victims from two recent radiation accidents brings a confirmation of the usefulness of the newly described biological indicators, and also a partial confirmation of this new concept of a multiple organ dysfunction syndrome. © 2009 Elsevier Masson SAS. All rights reserved.Les irradiations accidentelles conduisent à des situations pathologiques complexes, difficiles à évaluer et à traiter. Cependant, des résultats récents ont permis de définir de nouveaux bio-indicateurs de dommages radio-induits comme le Flt3-ligand, la citrulline ou les oxystérols plasmatiques. Par ailleurs, des études sur des modèles animaux ont permis une évolution de la compréhension des mécanismes physiopathologiques des irradiations complexes à forte dose. Cette évolution conduit à abandonner le concept de syndrome aigu d’irradiation comme étant une association de trois syndromes bien individualisés, le syndrome hématopoïétique, le syndrome gastro-intestinal et le syndrome cérébrovasculaire au profit d’un concept de syndrome de dysfonctionnement multi-organes, avec l’implication d’autres systèmes physiologiques. Le suivi des victimes de deux accidents d’irradiation récents a permis de confirmer la validité des nouveaux bio-indicateurs utilisés, mais a apporté aussi un début de confirmation de ce concept de syndrome de dysfonctionnement multi-organes induit par une irradiation accidentelle

An Adaptive QoE‐Based Network Interface Selection for Multi‐homed eHealth Devices

International audienceConventional network control mechanisms are no longer suitable for Internet of Things (IoT) because they don’t allow scalability with a guarantee of Quality of Experience (QoE) especially when it comes to the health sector characterized by its real time and critical life aspects. That’s why we need to think differently about control. One aspect consists of improving the network accessibility by considering Multi-homed terminals using multiple network access points simultaneously. In this paper we present a new Q-Learning-based adaptive network interface selection approach. Experimental results show that the proposed approach involve QoE compared to a simple linear programming approach. abstract environment

Uranium appauvri: Perturbateur métabolique?

The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolising vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions.Année de parution : 2011 La présence d’uranium dans l’environnement peut conduire à long terme à une contamination de la chaîne alimentaire et/ou des eaux destinées à la consommation humaine, soulevant alors de nombreuses interrogations scientifiques et sociétales quant aux conséquences de cette exposition sur la santé des populations. Les effets biologiques d’une exposition chronique à de faibles niveaux sont peu connus. Cependant, les résultats de différentes études récentes montrent que ce type de contamination à l’uranium appauvri induirait des effets biologiques de types moléculaires subtils, mais significatifs, dans des organes tels que le cerveau, le foie, les reins et les testicules. La grande nouveauté dans les effets induits après contamination interne par l’uranium est la mise en évidence d’effets sur un certain nombre de métabolismes majeurs de l’organisme comme le métabolisme de la vitamine D, du cholestérol, des hormones stéroïdiennes, de l’acétylcholine et des xénobiotiques. Ces données scientifiques suggèrent fortement que l’uranium est susceptible d’interférer avec de nombreuses voies métaboliques. Ainsi, il pourrait contribuer, avec d’autres substances artificielles présentes dans l’environnement, à l’augmentation des risques sanitaires dans certaines régions du globe