NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis.: Brain precursor cells and gliomas

International audienceGliomas are the most common primary brain tumor affecting human adults and remain a therapeutic challenge because cells of origin are still unknown. Here, we investigated the cellular origin of low-grade gliomas in a rat model based on transplacental exposure to N-ethyl-N-nitrosourea (ENU). Longitudinal magnetic resonance imaging coupled to immunohistological and immunocytochemical analyses were used to further characterize low-grade rat gliomas at different stages of evolution. We showed that early low-grade gliomas have characteristics of oligodendroglioma-like tumors and exclusively contain NG2-expressing slow dividing precursor cells, which express early markers of oligodendroglial lineage. These tumor-derived precursors failed to fully differentiate into oligodendrocytes and exhibited multipotential abilities in vitro. Moreover, a few glioma NG2+ cells are resistant to radiotherapy and may be responsible for tumor recurrence, frequently observed in humans. Overall, these findings suggest that transformed multipotent NG2 glial precursor cell may be a potential cell of origin in the genesis of rat ENU-induced oligodendroglioma-like tumors. This work may open up new perspectives for understanding biology of human gliomas

Complex genetic patterns in human arise from a simple range-expansion model over continental landmasses

© 2018 Kanitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Although it is generally accepted that geography is a major factor shaping human genetic differentiation, it is still disputed how much of this differentiation is a result of a simple process of isolation-by-distance, and if there are factors generating distinct clusters of genetic similarity. We address this question using a geographically explicit simulation framework coupled with an Approximate Bayesian Computation approach. Based on six simple summary statistics only, we estimated the most probable demographic parameters that shaped modern human evolution under an isolation by distance scenario, and found these were the following: an initial population in East Africa spread and grew from 4000 individuals to 5.7 million in about 132 000 years. Subsequent simulations with these estimates followed by cluster analyses produced results nearly identical to those obtained in real data. Thus, a simple diffusion model from East Africa explains a large portion of the genetic diversity patterns observed in modern humans. We argue that a model of isolation by distance along the continental landmasses might be the relevant null model to use when investigating selective effects in humans and probably many other species

Radiofrequency and mechanical tests of silver coated CuCrZr contacts for the ITER ion cyclotron antenna

The ITER Ion Cyclotron Resonance Heating (ICRH) system is designed to couple to the plasma 20 MW of RF power from two antennas in the 40–55 MHz frequency range during long pulses of up to 3600 s and under various plasma conditions with Edge Localized Modes. Radio-Frequency (RF) contacts are integrated within the ITER ICRH launcher in order to ensure the RF current continuity and ease the mechanical assembly by allowing the free thermal expansion of the Removable Vacuum Transmission Line coaxial conductors during RF operations or during 250 °C baking phases. A material study has been carried out to determine which materials and associated coatings are relevant for RF contacts application in ITER. In parallel, RF tests have been performed with a new prototype of Multi-Contact® LA-CUT/0,25/0 contacts made of silver-coated CuCrZr louvers. During these tests on a RF vacuum resonator, currents between 1.2 kA and 1.3 kA peak have been reached a few tens of times in steady-state conditions without any visible damage on the louvers. A final 62 MHz pulse ending in a 300 s flat top at 1.9 kA resulted in severe damage to the contact. In addition, a test bed which performs sliding test cycles has been built in order to reproduce the wear of the contact prototype after 30 000 sliding cycles on a 3 mm stroke at 175 °C under vacuum. The silver coating of the louvers is removed after approximately a hundred cycles whilst, to the contrary, damage to the CuCrZr louvers is relatively low

A Rouse-based method to integrate the chemical composition of river sediments : application to the Ganga basin

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): F04012, doi:10.1029/2010JF001947.The Ganga River is one of the main conveyors of sediments produced by Himalayan erosion. Determining the flux of elements transported through the system is essential to understand the dynamics of the basin. This is hampered by the chemical heterogeneity of sediments observed both in the water column and under variable hydrodynamic conditions. Using Acoustic Doppler Current Profiler (ADCP) acquisitions with sediment depth profile sampling of the Ganga in Bangladesh we build a simple model to derive the annual flux and grain size distributions of the sediments. The model shows that ca. 390 (±30) Mt of sediments are transported on average each year through the Ganga at Haring Bridge (Bangladesh). Modeled average sediment grain size parameters D50 and D84 are 27 (±4) and 123 (±9) μm, respectively. Grain size parameters are used to infer average chemical compositions of the sediments owing to a strong grain size chemical composition relation. The integrated sediment flux is characterized by low Al/Si and Fe/Si ratios that are close to those inferred for the Himalayan crust. This implies that only limited sequestration occurs in the Gangetic floodplain. The stored sediment flux is estimated to c.a. 10% of the initial Himalayan sediment flux by geochemical mass balance. The associated, globally averaged sedimentation rates in the floodplain are found to be ca. 0.08 mm/yr and yield average Himalayan erosion rate of ca. 0.9 mm/yr. This study stresses the need to carefully address the average composition of river sediments before solving large-scale geochemical budgets.This work was supported by INSU program “Relief de la Terre” and ANR Calimero. Valier Galy was supported by the U.S. National Science Foundation (grant OCE‐0851015)

Commercially Available Outbred Mice for Genome-Wide Association Studies

Genome-wide association studies using commercially available outbred mice can detect genes involved in phenotypes of biomedical interest. Useful populations need high-frequency alleles to ensure high power to detect quantitative trait loci (QTLs), low linkage disequilibrium between markers to obtain accurate mapping resolution, and an absence of population structure to prevent false positive associations. We surveyed 66 colonies for inbreeding, genetic diversity, and linkage disequilibrium, and we demonstrate that some have haplotype blocks of less than 100 Kb, enabling gene-level mapping resolution. The same alleles contribute to variation in different colonies, so that when mapping progress stalls in one, another can be used in its stead. Colonies are genetically diverse: 45% of the total genetic variation is attributable to differences between colonies. However, quantitative differences in allele frequencies, rather than the existence of private alleles, are responsible for these population differences. The colonies derive from a limited pool of ancestral haplotypes resembling those found in inbred strains: over 95% of sequence variants segregating in outbred populations are found in inbred strains. Consequently it is possible to impute the sequence of any mouse from a dense SNP map combined with inbred strain sequence data, which opens up the possibility of cataloguing and testing all variants for association, a situation that has so far eluded studies in completely outbred populations. We demonstrate the colonies' potential by identifying a deletion in the promoter of H2-Ea as the molecular change that strongly contributes to setting the ratio of CD4+ and CD8+ lymphocytes

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Application of QuEChERS based methodology for the analysis of pesticides in sediments

The analysis of micropollutants present in sediments generally requires to carry out a complex protocol including several successive steps for sample extraction and purification. The most popular method, the extraction by pressurised fluid, is very efficient for extracting the target analytes but also for all the other potentially interfering components that might be present within the matrix. Moreover, this technique is relatively expensive since dedicated equipment is needed. The QuEChERS approach, developed initially for the analysis of pesticides in fruits and vegetables, can be regarded as an alternative technique to simplify this step. It is easy to handle, relatively cheap and with low solvent consumption. Therefore, this technique has been evaluated in this study for the analysis of pesticides in sediments. The priority pesticides and the substances candidate to integrate the Water Framework Directive (2000/60/EC) list of pollutants were considered. Since the purification step of the QuEChERS technique is not intended to remove all interferents from the sample matrix, the analysis was performed by gas chromatography followed by a selective detection using tandem mass spectrometry. A QuEChERS type method and purification protocol based on the approach generally carried out for fruits and vegetables was applied. Therefore, an extraction with vortex agitation using acetonitrile was performed followed by a purification step by dispersive solid phase extraction with sodium sulfate, C18 or PSA. Initial tests were carried out on dry sediments but addition of 10 to 20% of water (v/w) increased the recovery of most of the pesticides tested. With this approach, recoveries ranging from 80 to 120 % were obtained for most of tested compounds. Limit of quantification were determined around 10 ng/g with linearity range up to 500 ng/g. This protocol was tested on certified reference material which provided satisfying results in most cases. Overall, the QuEChERS based approach appeared suitable for the analysis of pesticides in sediments

A simple QuEChERS-like extraction approach for molecular chemical characterization of organic aerosols: application to nitrated and oxygenated PAH derivatives (NPAH and OPAH) quantified by GC–NICIMS

International audienceAn extraction procedure based on the Quick Easy Cheap Effective Rugged and Safe (QuEChERS) approach has been developed and used for analysis of particle-bound nitrated and oxygenated PAH derivatives (NPAH and OPAH, respectively). Several analytical conditions, for example GC injection temperature and MS detection settings, were optimized. This analytical procedure enabled simultaneous GC–NICIMS quantification of 32 NPAH and 32 OPAH (or other oxygenated compounds), including typical components of secondary organic aerosol (SOA) formed by photooxidation of PAH (e.g. 2-formyl-trans-cinnamaldehyde and 6H-dibenzo[b,d]pyran-6-one). The QuEChERS-like approach was optimized, including the nature of the extraction solvent, the sorbent used for clean-up, and extraction time. The final extraction procedure was based on brief mechanical agitation (vortex mixing for 1.5 min), with 7 mL acetonitrile as solvent. Because dispersive solid-phase extraction (d-SPE) did not provide satisfactory results, SPE using SiO2 was selected for sample purification. Identical results were obtained when the QuEChERS-like and traditional pressurised solvent extraction (PLE) procedures were compared for analysis of fortified ambient air particle samples. The procedure was validated by analysis of two aerosol standard reference materials (NIST SRM 1649b (urban dust) and SRM 2787 (fine particulate matter, <10 µm)). For numerous NPAH and OPAH, this is the first report of their quantification in both SRMs. Compared with other extraction methods, including PLE, the QuEChERS-like procedure resulted in increased productivity and reduced extraction cost. This paper shows that QuEChERS-like extraction procedures can be suitably adapted for molecular chemical characterization of aerosol samples and could be extended to other categories of compound