Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins

In the pharmaceutical industry, improving the early detection of drug-induced hepatotoxicity is essential as it is one of the most important reasons for attrition of candidate drugs during the later stages of drug development. The first objective of this study was to better characterize different cellular models (i.e., HepG2, HepaRG cells, and fresh primary human hepatocytes) at the gene expression level and analyze their metabolic cytochrome P450 capabilities. The cellular models were exposed to three different CYP450 inducers; beta-naphthoflavone (BNF), phenobarbital (PB), and rifampicin (RIF). HepG2 cells responded very weakly to the different inducers at the gene expression level, and this translated generally into low CYP450 activities in the induced cells compared with the control cells. On the contrary, HepaRG cells and the three human donors were inducible after exposure to BNF, PB, and RIF according to gene expression responses and CYP450 activities. Consequently, HepaRG cells could be used in screening as a substitute and/or in complement to primary hepatocytes for CYP induction studies. The second objective was to investigate the predictivity of the different cellular models to detect hepatotoxins (16 hepatotoxic and 5 nonhepatotoxic compounds). Specificity was 100% with the different cellular models tested. Cryopreserved human hepatocytes gave the highest sensitivity, ranging from 31% to 44% (depending on the donor), followed by lower sensitivity (13%) for HepaRG and HepG2 cells (6.3%). Overall, none of the models under study gave desirable sensitivities (80–100%). Consequently, a high metabolic capacity and CYP inducibility in cell lines does not necessarily correlate with a high sensitivity for the detection of hepatotoxic drugs. Further investigations are necessary to compare different cellular models and determine those that are best suited for the detection of hepatotoxic compounds

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

The Supercam Instrument Suite on the NASA Mars 2020 Rover: Body Unit and Combined System Tests

The SuperCam instrument suite provides the Mars 2020 rover, Perseverance, with a number of versatile remote-sensing techniques that can be used at long distance as well as within the robotic-arm workspace. These include laser-induced breakdown spectroscopy (LIBS), remote time-resolved Raman and luminescence spectroscopies, and visible and infrared (VISIR; separately referred to as VIS and IR) reflectance spectroscopy. A remote micro-imager (RMI) provides high-resolution color context imaging, and a microphone can be used as a stand-alone tool for environmental studies or to determine physical properties of rocks and soils from shock waves of laser-produced plasmas. SuperCam is built in three parts: The mast unit (MU), consisting of the laser, telescope, RMI, IR spectrometer, and associated electronics, is described in a companion paper. The on-board calibration targets are described in another companion paper. Here we describe SuperCam’s body unit (BU) and testing of the integrated instrument. The BU, mounted inside the rover body, receives light from the MU via a 5.8 m optical fiber. The light is split into three wavelength bands by a demultiplexer, and is routed via fiber bundles to three optical spectrometers, two of which (UV and violet; 245–340 and 385–465 nm) are crossed Czerny-Turner reflection spectrometers, nearly identical to their counterparts on ChemCam. The third is a high-efficiency transmission spectrometer containing an optical intensifier capable of gating exposures to 100 ns or longer, with variable delay times relative to the laser pulse. This spectrometer covers 535–853 nm (105–7070 cm−1 Raman shift relative to the 532 nm green laser beam) with 12 cm−1 full-width at half-maximum peak resolution in the Raman fingerprint region. The BU electronics boards interface with the rover and control the instrument, returning data to the rover. Thermal systems maintain a warm temperature during cruise to Mars to avoid contamination on the optics, and cool the detectors during operations on Mars. Results obtained with the integrated instrument demonstrate its capabilities for LIBS, for which a library of 332 standards was developed. Examples of Raman and VISIR spectroscopy are shown, demonstrating clear mineral identification with both techniques. Luminescence spectra demonstrate the utility of having both spectral and temporal dimensions. Finally, RMI and microphone tests on the rover demonstrate the capabilities of these subsystems as well

The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

Contribution of Major Ions in Identifying of Groundwater Flow in Dense Vegetation Cover Area: Case of Sassandra Watershed (South-Western Côte d'Ivoire)

In West Africa, particularly in Côte d'Ivoire, the groundwater is contained in hard-rock aquifers and serves as main source of drinking water supplies to the population. To improve access, several studies were conducted in various parts of the country. Most of them use mapping of lineaments related to tectonic fractures to represent corridors of groundwater. In this article, chemistry of major ions was used to highlight quantitatively the axes of groundwater movement, and mixing between different aquifers in Sassandra watershed which is located in the Southwest of the Ivory Coast. The sampling campaigns were accomplished respectively during the dry and wet seasons in the department of Soubré (8 590 km2), located in Sassandra watershed, area where the effects of climate change are observed. The processing of satellite images (optical and active) has produced a map of major lineaments. Geographic positions and technical data of boreholes were integrated into a geographic information system (GIS) to identify point near major lineaments for groundwater sampling and chemical analysis. The waters were collected, and then analyzed by using atomic absorption spectrometer (AAS) and a Varian Vista ICP. The results indicate that groundwater samplings are primarily Ca-HCO3 type or NaK-HCO3 and NaK-SO4 types. Calcium and low pH were encountered in the highlands where infiltration of meteoric water occurs relatively quickly through preferential pathways. Chadha diagram has highlighted differences in the chemistry of groundwater between aquifers on one hand, and between systems of surface runoff and deep runoff on the other hand. Most groundwater seems to move relatively quickly. In addition, some groundwaters show a denitrification coupled with pyrite oxidation. These groundwaters have been longer circulating along opened fractures with gentle slopes. The observations and hydrochemical characterization, especially SO42-/Cl- ratio, permitted to identify axes of groundwater movements in the study area. However, the major lineaments which are similar to major fractures are not primarily responsible for the groundwater motions. Rather, there are small fractures and topography which control the flow of groundwater in the crystalline hard-rock. Also, the groundwater levels are not always guided by the major lineaments observed. Some small lineaments and topography control fairly the groundwater flow

Évaluation de la potabilité des eaux souterraines dans un bassin versant tropical : cas du Sud-Ouest de la Côte d'Ivoire

International audienc

Biominéralisation du fer par une bactérie neutrophile gainée de type Leptothrix

International audienceBacteriogenic iron oxides (BIOS) produced by neutrophilic and acidophilic bacteria are widespread in the environment. Although BIOS have been recognized to have great potential for remediation in acidic mining environments, the importance of such bioremediation processes under near-neutral pH conditions is less documented (1,2). In this context, previous research on iron biomineralization at circumneutral pH has focused on Gallionella ferruginea and different Leptothrix species (3,4). Moreover, these stalk and sheath-forming bacteria cause numerous industrial issues such as bulking, clogging, etc. (5) and therefore understanding the role of iron on the ecology and physiology of these species could help better predicting their occurrence and activity in various surface environments. In this work we will present the iron biomineralization by a Leptothrix-like microorganism and we will discuss possible interactions between this process and the morphological characters of this bacterium species. The aim of this work is hence to investigate its iron biomineralization and how this impacts and/or is impacted by the filamentation and sheathforming process. For that purpose, we developed a protocol to test factors affecting filamentation by combining different molecular biology, microscopy and mineralogy techniques. Our results indicate various Fe biomineralization patterns specially related to the sheath surface depending on the growth conditions. Eventually, this study will help in better understanding the processes of iron biomineralization by sheath-forming bacteria and it will shed light on the mechanisms of filamentation, provinding material for further investigations on the potential of BIOS in sorbing heavy metals and radionuclides in near-neutral pH environments

Suivi de la croissance sous forme filamenteuse et planctonique de Sphaerotilus natans par une méthode de biologie moléculaire

International audienceIntroduction: Activated sludge is the most widespread biological wastewater treatment technology used over the world. However, the main problem of this process is due to the invasive proliferation of filamentous bacteria. Sphaerotilus natans is a model bacterium involved in certain cases of bulking. This bacterium is able to grow as planktonic cells or as sheathed filaments. Conventional microbiological methods are problematic under filamentous growth and PCR techniques can only quantify the total cell amount. Objectives: The aim of this work is to develop a method to quantify bulking-involved bacteria under their two growing morphologies: filamentous and planktonic, with the purpose of evaluating the factors inducting filamentation, such as nutrient availability. Materials & methods: A set of qPCR primers specifics to S. natans has been designed, to be used in pure cultures as well as in complex matrices (i.e. activated sludge). These primers are targeted against the gene sthA. qPCR has been used to quantify cells from global culture samples as well as 3 µm-pore size polycarbonate filters and filtrates, in which filaments and planktonic cells are respectively the sole cell form. The different fractions were observed in scanning electron microscopy through the filtration process to validate its efficiency. Results: The set of designed qPCR primers reveals high specificity to S. natans. It amplifies the strains ATCC 15291, 13338 and 13929 but not Leptothrix strains, which are phylogenetically close, or strain 29330, which has recently been reassigned as S. hippei. The 3 µm filtration allows effective separation of both growth forms, and filament free suspensions of planktonic cells are obtained. This method has been validated by monitoring the effect of nutrient-limited media on S. natans cultures. Its filamentous induction effect is clearly reflected by the growth kinetics obtained. Conclusion: This powerful method allows quantifying the effect of factors inducing bacterial filamentation and therefore it may shed light on bulking and other environmental processes where filamentous growth is crucial