Impacts of new agricultural practices on soil erosion during the Bronze Age in the French Prealps

International audienceIn order to better understand the evolution of past climate-human-environment interactions in the North-western Alps during the Holocene, we have analysed the lipid content of two cores taken from the sediments of Lake le Bourget (French Alps). By using a specific molecular biomarker of Panicum miliaceum (broomcorn millet) previously defined and a new molecular marker of soil erosion, we demonstrate that the onset of millet cultivation coincides with the onset of major soils erosion in the catchment during the Middle Bronze Age. Although archaeological and archaeobotanical investigations indicate a discrete human occupation of the lakeshores at this period, they also point to a regional change in agricultural practices that deeply affected soils. The evolution of millet cultivation appears in strong connection with climatic variations, estimated in the same cores from the variations in titanium, a proxy of hydrological changes in the region. Social and cultural triggers cannot be discarded at this stage. Such an approach applied to more sedimentary archives shows high potential to unravel the temporal and spatial dynamics of human land-use

Le lac du Bourget (Savoie, France) à l'Âge du Bronze : végétation, impacts anthropiques et climat

Lake Bourget (Savoie, France) during the Bronze Age: vegetation, anthropogenic impacts and climate Pollen analyses performed on three archaeological sites located on the east shore of Lake Bourget (Savoie, France) provide a detailed record of human impacts and vegetation history during the Bronze Age. The end of the Neolithic period and the entire early Bronze Age are characterized in pollen diagrams by a discreet settlement around Lake Bourget and low human impact on the forested landscape, in spite of climatic improvement. The middle Bronze Age, contemporaneous of a climatic reversal, is related to the rarefaction of anthropogenic indicators. A new human impact occurs at the beginning of the late Bronze Age. A brief high lake level, correlated to the abandonment of agropastoral activities, appears during the more intensive occupation at the end of the late Bronze Age. The beginning of the Iron Age is related to a new abandonment of the shore. In the last part of this paper, pollen analyses are correlated to the results of lake levels recorded and molecular markers preserved in a deep lacustrine core.L'étude de trois analyses polliniques effectuées sur les sites archéologiques de Chindrieux (Châtillon) et de Tresserve (Le Saut de la Pucelle), sur la rive est du lac du Bourget (Savoie, France) permet de reconstituer l'histoire de la végétation et des impacts anthropiques au cours de la période de l'Âge du Bronze. La fin du Néolithique et le Bronze ancien sont caractérisés par une occupation discrète des alentours du Bourget et donc par un faible impact anthropique sur l'environnement très forestier, en dépit d'un climat plutôt favorable. La période du Bronze moyen, contemporaine d'une péjoration climatique, correspond à la quasi-disparition de tout impact anthropique. Le début du Bronze final voit le retour toujours discret des activités humaines, activités qui s'amplifient soudainement au cours de la fin du Bronze final. On observe alors une tripartition des événements : une courte phase de transgression lacustre et de déprise agricole scinde la fin du Bronze final. Le début de l'Âge du Fer correspond à une nouvelle déprise agricole. Dans une dernière partie, les résultats des analyses paléoclimatiques et chimiques obtenues sur un forage profond au milieu du lac sont intégrés aux résultats polliniques

Quantitative reconstruction of climatic variations during the Bronze and early Iron ages based on pollen and lake-level data in the NW Alps, France

International audienceVegetation and lake-level data from the archaeological site of Tresserve, on the eastern shore of Lake Le Bourget (Savoie, France), are used to provide quantitative estimates of climatic variables over the period 4000-2300 cal BP in the northern French Pre-Alps, and to examine the possible impact of climatic changes on societies of the Bronze and early Iron Ages. The results obtained indicate that phases of higher lake level at 3500-3100 and 2750-2350 cal BP coincided with major climate reversals in the North Atlantic area. In west-central Europe, they were marked by cooler and wetter conditions. These two successive events may have affected ancient agricultural communities in west-central Europe by provoking harvest failures, more particularly due to increasing precipitation during the growing season. However, archaeological data in the region of Franche-Comté (Jura Mountains, eastern France) show a general expansion of population density from the middle Bronze Age to the early Iron Age. This suggests a relative emancipation of proto-historic societies from climatic conditions, probably in relation to the spread of new modes of social and economic organisation

Development of new multimodal fluorinated and iodinated radiotracers for both PET imaging and targeted radionuclide therapy of melanoma

Le mélanome cutané est un cancer très invasif, dont l'évolution est rapidement fatale au stade métastatique du fait d'une absence de thérapies réellement efficaces. Face à ce constat, une stratégie de multimodalité a été évaluée au moyen d'un vecteur spécifique des cellules de mélanome et présentant la double potentialité diagnostique (imagerie TEP) et thérapeutique (radiothérapie interne vectorisée (RIV)) en fonction du radioélément introduit. Dans ce but, des analogues iodés et fluorés d'ICF01012, un vecteur ciblant la mélanine surexprimée dans un grand nombre de mélanomes, ont été synthétisés puis radiomarqués (iode-125 d'une part et fluor-18 d'autre part). Les profils pharmacocinétiques des radiotraceurs ont par la suite été étudiés in vivo sur modèle murin de mélanome, par imagerie scintigraphique γ (125I) et par imagerie TEP (18F). A l'issue de ces études, le traceur 4 a été sélectionné comme molécule leader de cette série, en raison d'un tropisme tumoral spécifique, élevé et durable, associé à élimination rapide des tissus non-cibles. Ce composé a ensuite été radiomarqué à l'iode-131 pour une évaluation en RIV sur le même modèle murin. Le traitement avec [131I]4 a induit une inhibition significative de la croissance tumorale et une augmentation significative de la médiane de survie. Au vu des résultats prometteurs obtenus avec le traceur 4, des études de métabolisme sur le même modèle murin ont été effectuées. En conclusion, en termes de chimie, radiochimie, stabilités in vitro et in vivo, TEP et RIV, le traceur 4 a validé notre concept de multimodalité. A terme, ce composé pourrait être transféré pour des études cliniques afin : de sélectionner les patients présentant des lésions de mélanome pigmentées (18F/TEP) et donc susceptibles de répondre au protocole de RIV ; de traiter ces patients (131I/RIV) ; de suivre la réponse au traitement (18F/TEP). En parallèle a été développé le premier groupement prosthétique iodé et fluoré multimodal, le 4-fluoro-3-iodobenzoate de tétrafluorophényle 108, pour le marquage de vecteurs d'intérêt (peptides, protéines, nanoparticules…). Le composé 108 et les précurseurs de radiomarquages correspondants ont été synthétisés en peu d'étapes, avec de bons rendements. Les radiomarquages ont ensuite été mis au point, et ont permis d'obtenir [125I]108 et [18F]108 en des temps relativement courts, avec d'excellents rendements et puretés radiochimiques. Le groupement prosthétique a ensuite été couplé avec succès à un ligand organique et deux peptides. En conclusion, nous avons démontré que le composé multimodal 108 peut être utilisé pour la radiofluoration et la radioiodation de vecteurs d'intérêt, autorisant des applications à la fois diagnostiques (TEP/18F) et thérapeutiques (RIV/131I) pour la prise en charge de nombreux cancers.Melanoma is the most serious form of skin cancer with a poor prognosis for patients with metastatic disease. Our project deals with a multimodal approach, using a single fluorinated and iodinated melanintargeting compound, and offering both imaging (PET/18F) and therapeutic (targeted radionuclide therapy (TRT)/131I) applications, depending on the radioisotope introduced. Furthermore, using PET imaging, our strategy allows a selection of TRT-responded patients (i.e. bearing pigmented metastases) as well as a monitoring of treatment response. In previous works, the iodinated quinoxaline-carboxamide compound ICF01012 was evaluated in a TRT protocol, using melanoma-bearing mice models. It demonstrated efficacy, with significant inhibition of tumoural growth and improvement of the median survival. Based on these results, iodinated and fluorinated analogs of ICF01012 were synthesized, for multimodality purposes. All new compounds were then radiolabelled with iodine-125 and fluorine-18 (fully automated radiosyntheses), with good radiochemical yields and excellent radiochemical purities. For pharmacokinetic profile studies on melanoma-bearing mice, [125I]radiotracers were evaluated by γ-scintigraphy and [18F]radiotracers by PET. Compound 4 emerged as the lead tracer, with a specific and long-lasting tumoural uptake and a fast clearance from non-specific tissues, leading to highly contrasted images. The tracer 4 was then radiolabelled with iodine-131, with excellent radiochemical yield and purity, to perform a TRT assay on the same melanoma model. Treatment with [131I]4 significantly inhibited tumoural growth and lung metastasis occurrence. Moreover, it significantly improved the median survival. As tracer 4 demonstrated promising results in PET imaging and TRT of melanoma, its metabolism was investigated with [125I]4 and [18F]4: radiotracers were found unchanged in melanin-containing tissues (tumour and eyes), while a fast breakdown was observed in excretion organs and fluids (four metabolites were identified). In conclusion, in terms of chemistry, radiochemistry, in vitro and in vivo stability, PET imaging and TRT, compound 4 validated our multimodality concept. We also developed the first bimodal fluorinated and iodinated prosthetic group, the 2,3,5,6-tetrafluorophenyl 4-fluoro-3-iodobenzoate (108), as a suitable acylating agent for the labelling of a large variety of compounds. In this approach, this new compound allows applications in diagnosis (PET imaging/18F) and therapy (TRT/131I). Compound 108 and its corresponding precursors for radiolabelling were synthesized in very few steps, with good yields. [125I]108 was then prepared in one-step starting from a perfluorostannane precursor, and purified by F-SPE cartridge to avoid time-consuming HPLC. As for [18F]108, it was produced by a fully automated three steps, two-pots radiosynthesis process. [125I]108 and [18F]108 were both obtained in a short time, with excellent radiochemical yields and purities. These prosthetic groups were then successfully used to radiolabel small organic ligand N,N-diethylethylenediamine and peptides NDP-MSH and PEG3[c(RGDyK)]2, in mild conditions, with good yields. In conclusion, we demonstrated that compound 108 could be a promising acylating bimodal prosthetic group for radiofluorination and radioiodination of small organic molecules, peptides, proteins, antibodies as well as nanoparticles

Unilever’s Response to the Future of Work

On a sunny February morning in 2020, Nick Dalton, executive vice president HR business transformation at Unilever—a British-Dutch corporation with 2019 revenues of €52 billion—hurried through the streets of London to his office. As he stopped for a coffee in the atrium of the art deco building, he couldn’t help but think about his upcoming meeting with company CEO, Alan Jope, and chief HR officer, Leena Nair. Founded in 1929, Unilever was one of the world’s largest consumer goods companies, employing 155,000 people across more than 100 countries. “But the world is changing, and it is changing fast,” Dalton thought. Artificial intelligence, machine learning, and automation would dramatically change the future of work in the next five years. Unilever needed to act swiftly. In 2016, Dalton had launched Unilever’s Future of Work initiative—an overarching plan to prepare the workforce for a digitalized and highly automated era. The plan focused on accelerating the speed of change within Unilever, reskilling staff through a culture of lifelong learning, and adopting flexible work practices. Despite success over the last three years, the program still faced significant challenges. Dalton reflected, “What we are trying to do in terms of the future of work is an integrated, almost systemic intervention. It’s not a one-off initiative. The ideas in some way are quite easy. The issue is how you link them and implement them, particularly on a global scale.” Since Unilever placed sustainability and positive social impact at the core of its strategy, the company was also determined to cushion the effects of new technologies on labor. Taking a gulp of coffee, Dalton reflected on the program and its future. Had they done enough, or should they add more? Would this make Unilever better and its workforce better

Heat inactivation of polyphenol oxidase and peroxidase as a function of water activity : a case study of mango drying

An innovative method was developed to study the specific uncoupled effect of temperature and water activity (Aw) during mango drying. Thermal treatment of reconstituted lyophilized mango powder at targeted Aw enabled evaluation of the inactivation of polyphenol oxidase and peroxidase activity in a range 0.98-0.6 Aw and a time-temperature range of 1-4h and 50-60 degrees C. We established that thermal treatment of the enzymatic extract was not the same as the inactivation phenomena that occurred in the mango matrix, mainly due to differences in the pH of the buffer extract (6.4) and reconstituted food matrix (3.8). Even if the inactivation of these two enzymes was directly correlated with the temperature of the treatment, this behavior was also strongly linked to the Aw. A two-step change in the fruit was observed at high Aw (i.e., at 0.98 in fresh fruit), polyphenol oxidase (PPO) was shown to be more thermostable than peroxidase (POD), whereas when evaporation reduced the Aw to around 0.6, the opposite behavior was observed. As a consequence, enzymatic inactivation during drying should be considered as the result of the coupled effects of time-temperature and water activity

L’énergie nucléaire en Europe centrale et orientale

En rejoignant l’Union Européenne en 2004 et 2007, les pays d’Europe centrale et orientale que sont la Bulgarie, la Hongrie, la République Tchèque, la Roumanie, la Slovaquie et la Slovénie ont contribué à rééquilibrer la proportion des pays partisans de l’énergie nucléaire en Europe. Ces pays, tous équipés de réacteurs nucléaires, ont dû engager des programmes de modernisation qu’ils poursuivent aujourd’hui en parallèle avec les programmes d’extension de durée de vie et la construction ou la préparation de nouvelles unités. L’entrée dans l’Union Européenne s’est aussi accompagnée de responsabilités nouvelles telles qu’une gestion des déchets et des combustibles usés compatible avec les normes en vigueur dans l’UE. Dans cet article, un panorama de la situation actuelle du nucléaire et de son évolution prévue à court et moyen terme est présenté pour chacun de ces pays ainsi que pour la roatie, qui va rejoindre prochainement l’Union

New Chelators for Low Temperature Al18F-Labeling of Biomolecules

The AlF labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {AlF} core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 °C. Therefore, we have developed new polydentate ligands for the complexation of {AlF} with good radiochemical yields at a temperature of 40°C. The stability of the new AlF-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the AlF-L3 complex was found to be comparable to that of the previously reported AlF-NODA complex up to 60 min in rat serum. Moreover, the biodistribution of AlF-L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator HL3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand HL3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the AlF-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules