Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers

: Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers

Publisher Copyright: © 2023, The Author(s).Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants.Peer reviewe

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effet de l'exercice sur les concentrations d'androgènes chez la jeune femme<br />Analyse de traces dans les urines<br />Mise au point d'une phase d'extraction à base d'empreinte moléculaire

The illegal consumption of nandrolone is determined by the detection of its metabolites, norandosterone and noretiocholanolone, in urine samples. A three-extraction-step method followed by GC-MS analysis was developed in order to assess the influence of physical exercise on their endogen concentrations, as well as on the steroids dehydroepiandrosterone and androsterone, in female urine samples. Data collected from 400 urines were corrected with the creatinine level of the samples, representative of urine dilution, and statistically evaluated. Only a moderate influence of long term exercise on androsterone levels was shown, and no effect on nandrolone metabolites was demonstrated. Hormonal status was also investigated by the evaluation of oral contraceptive intake and menstrual cycle phase effects on the analyte concentrations.A new stationary phase, based on molecularly imprinted polymers (MIP), was synthesised to improve the selectivity of nandrolone metabolite extractions. Non covalent interactions were established between the MIP and androsterone, the template molecule. Theses interactions were used to adsorb nandrolone metabolites and extract them from the sample during percolation on solid phase extraction cartridge. Specific adsorption was observed with the use of an appropriate solvent and the results show the potential for the trace analysis of these metabolites in anti-doping testing.La consommation frauduleuse de nandrolone est détectée dans les urines par la présence de ses métabolites isomères norandrostérone et norétiocholanolone. Afin de contrôler si, chez la femme, une activité sportive peut être responsable de l'augmentation de leurs productions endogènes, ainsi que de celles de la déhydroépiandrostérone et de l'androstérone, une méthode d'analyse urinaire faisant intervenir trois extractions sur phase solide suivies d'une analyse par GC-MS a été mise au point. Une correction des concentrations brutes en analytes a été appliquée par rapport au taux de créatinine, marqueur de la dilution des urines. Le traitement statistique des résultats obtenu à partir de 400 urines n'a montré aucun effet de l'exercice sur les concentrations en métabolites de la nandrolone, mais un effet modéré de l'exercice aérobie sur les concentrations en androstérone. Le statut hormonal des individus (phase du cycle menstruel et prise de contraceptif) a également été évalué. Une amélioration de l'extraction a été ensuite proposée par la synthèse d'une phase stationnaire polymérique à impression moléculaire (MIP). Le MIP a été synthétisé dans des conditions favorisant la mise en place d'interactions non covalentes avec l'androstérone, ces mêmes interactions étant ensuite mises à contribution dans la rétention de la norandrostérone et de ses isomères lors de la percolation d'un échantillon sur la phase d'extraction. Conduisant à des résultats prometteurs, la technique semble intéressante en vue de l'analyse de traces de métabolites de la nandrolone grâce à une amélioration de la sélectivité de la méthode globale d'analys

Effet de l'exercice sur les concentrations d'androgènes chez la jeune femme (analyse de traces dans les urines)

La consommation frauduleuse de nandrolone est détectée dans les urines par la présence de ses métabolites isomères norandrostérone et norétiocholanolone. Afin de contrôler si, chez la femme, une activité sportive peut être responsable de l'augmentation de leurs productions endogènes, ainsi que de celles de la déhydroépiandrostérone et de l'androstérone, une méthode d'analyse urinaire faisant intervenir trois extractions sur phase solide suivies d'une analyse par GC-MS a été mise au point. Une correction des concentrations brutes en analytes a été appliquée par rapport au taux de créatinine, marqueur de la dilution des urines. Le traitement statistique des résultats obtenu à partir de 400 urines n'a montré aucun effet de l'exercice sur les concentrations en métabolites de la nandrolone, mais un effet modéré de l'exercice aérobie sur les concentrations en androstérone. Le statut hormonal des individus (phase du cycle menstruel et prise de contraceptif) a également été évalué. Une amélioration de l'extraction a été ensuite proposée par la synthèse d'une phase stationnaire polymérique à impression moléculaire (MIP). Le MIP a été synthétisé dans des conditions favorisant la mise en place d'interactions non covalentes avec l'androstérone, ces mêmes interactions étant ensuite mises à contribution dans la rétention de la norandrostérone et de ses isomères lors de la percolation d'un échantillon sur la phase d'extraction. Conduisant à des résultats prometteurs, la technique semble intéressante en vue de l'analyse de traces de métabolites de la nandrolone grâce à une amélioration de la sélectivité de la méthode globale d'analyseThe illegal consumption of nandrolone is determined by the detection of its metabolites, norandosterone and noretiocholanolone, in urine samples. A three-extraction-step method followed by GC-MS analysis was developed in order to assess the influence of physical exercise on their endogen concentrations, as well as on the steroids dehydroepiandrosterone and androsterone, in female urine samples. Data collected from 400 urines were corrected with the creatinine level of the samples, representative of urine dilution, and statistically evaluated. Only a moderate influence of long term exercise on androsterone levels was shown, and no effect on nandrolone metabolites was demonstrated. Hormonal status was also investigated by the evaluation of oral contraceptive intake and menstrual cycle phase effects on the analyte concentrations. A new stationary phase, based on molecularly imprinted polymers (MIP), was synthesised to improve the selectivity of nandrolone metabolite extractions. Non covalent interactions were established between the MIP and androsterone, the template molecule. Theses interactions were used to adsorb nandrolone metabolites and extract them from the sample during percolation on solid phase extraction cartridge. Specific adsorption was observed with the use of an appropriate solvent and the results show the potential for the trace analysis of these metabolites in anti-doping testingLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Efficiency of wipe sampling on hard surfaces for pesticides and PCB residues in dust

International audiencePesticides and polychlorinated biphenyls (PCBs) are commonly found in house dust and have been described as a valuable matrix to assess indoor pesticide and PCB contamination. The aim of this study was to assess the efficiency and precision of cellulose wipe for collecting 48 pesticides, eight PCBs, and one synergist at environmental concentrations. First, the efficiency and repeatability of wipe collection were determined for pesticide and PCB residues that were directly spiked onto three types of household floors (tile, laminate, and hardwood). Second, synthetic dust was used to assess the capacity of the wipe to collect dust. Third, we assessed the efficiency and repeatability of wipe collection of pesticides and PCB residues that was spiked onto synthetic dust and then applied to tile. In the first experiment, the overall collection efficiency was highest on tile (38%) and laminate (40%) compared to hardwood (34%), p<0.001. The second experiment confirmed that cellulose wipes can efficiently collect dust (82% collection efficiency). The third experiment showed that the overall collection efficiency was higher in the presence of dust (72% vs. 38% without dust, p<0.001). Furthermore, the mean repeatability also improved when compounds were spiked onto dust (<30% for the majority of compounds). To our knowledge, this is the first study to assess the efficiency of wipes as a sampling method using a large number of compounds at environmental concentrations and synthetic dust. Cellulose wipes appear to be efficient to sample the pesticides and PCBs that adsorb onto dust on smooth and hard surfaces

Semi-targeted metabolomic approaches to validate potential markers of health for micronutrients: analytical perspectives

International audienceRecommended dietary allowances for micronutrients fluctuate noticeably within European Union countries. The Network of Excellence EURRECA (EURopean micronutrient RECommendations Aligned) aims at harmonising micronutrient intake recommendations through population groups. The lack of proper markers of status for some micronutrients limits progress in this area: metabolomics could help identifying such new markers. We developed an original metabolomic strategy in order to monitor the largest fraction of a list of > 270 metabolites known to be influenced by the micronutrients of interest. To improve the coverage of these metabolites in plasma, a multi platform approach was performed using both liquid and gas chromatography coupled to mass spectrometry. A sample preparation protocol based on a three-step plasma fractionation has been set up, using both liquid and solid phase extractions. Four fractions were obtained containing respectively polar metabolites, neutral lipids, free fatty acids and polar lipids. Recoveries were determined using spiked plasma samples, and the advantages and drawbacks of the fractionation method compared to a commonly used single preparation step method were investigated in terms of metabolites detection and robustness. Fractionation improved coverage of the endogenous metabolome more than twice in terms of extracted features, allowing to identify 90 metabolites

P-gp expression levels in the erythrocytes of brown trout: a new tool for aquatic sentinel biomarker development

International audienceP-glycoprotein (P-gp) is a ubiquitous membrane detoxification pump involved in cellular defence against xenobiotics. Blood is a hub for the trade and transport of physiological molecules and xenobiotics. Our recent studies have highlighted the expression of a 140-kDa P-gp in brown trout erythrocytes in primary cell culture and its dose-dependent response to Benzo[a]pyrene pollutant

Agricultural and domestic pesticides in house dust from different agricultural areas in France

International audienc

Impaired liver function in Xenopus tropicalis exposed to benzo[a]pyrene: transcriptomic and metabolic evidence

BACKGROUND: Despite numerous studies suggesting that amphibians are highly sensitive to cumulative anthropogenic stresses, the role pollutants play in the decline of amphibian populations remains unclear. Amongst the most common aquatic contaminants, polycyclic aromatic hydrocarbons (PAHs) have been shown to induce several adverse effects on amphibian species in the larval stages. Conversely, adults exposed to high concentrations of the ubiquitous PAH, benzo[a]pyrene (BaP), tolerate the compound thanks to their highly efficient hepatic detoxification mechanisms. Due to this apparent lack of toxic effect on adults, no studies have examined in depth the potential toxicological impact of PAH on the physiology of adult amphibian livers. This study sheds light on the hepatic responses of Xenopus tropicalis when exposed to high environmentally relevant concentrations of BaP, by combining a high throughput transcriptomic approach (mRNA deep sequencing) and a characterization of cellular and physiological modifications to the amphibian liver. RESULTS: Transcriptomic changes observed in BaP-exposed Xenopus were further characterized using a time-dependent enrichment analysis, which revealed the pollutant-dependent gene regulation of important biochemical pathways, such as cholesterol biosynthesis, insulin signaling, adipocytokines signaling, glycolysis/gluconeogenesis and MAPK signaling. These results were substantiated at the physiological level with the detection of a pronounced metabolic disorder resulting in a possible insulin resistance-like syndrome phenotype. Hepatotoxicity induced by lipid and cholesterol metabolism impairments was clearly identified in BaP-exposed individuals. CONCLUSIONS: Our data suggested that BaP may disrupt overall liver physiology, and carbohydrate and cholesterol metabolism in particular, even after short-term exposure. These results are further discussed in terms of how this deregulation of liver physiology can lead to general metabolic impairment in amphibians chronically exposed to contaminants, thereby illustrating the role xenobiotics might play in the global decline in amphibian populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-666) contains supplementary material, which is available to authorized users