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Unbiased drug target engagement deconvolution and mechanism of action elucidation are major challenges in drug development. Modification-free target engagement methods, such as thermal proteome profiling, have gained increasing popularity in the last several years. However, these methods have limitations, and, in any case, new orthogonal approaches are needed. Here, we present a novel isothermal method for comprehensive characterization of protein solubility alterations using the effect on protein solubility of cations and anions in the Hofmeister series. We combine the ion-based protein precipitation approach with Proteome-Integrated Solubility Alteration (PISA) analysis and use this I-PISA assay to delineate the targets of several anticancer drugs both in cell lysates and intact cells. Finally, we demonstrate that I-PISA can detect solubility changes in minute amounts of sample, opening chemical proteomics applications to small and rare biological material.

Land is the principal support for human livelihoods as it supplies food, freshwater and multiple other ecosystem services. In the current context of global anthropization and climate change, soil erosion is becoming a threat for human societies and one of the question that most deserve the attention of the entire world & scientific community. Given the large uncertainties underlying the drivers of land erosion, it is crucial to assess the impact of human activities and climate fluctuations over erosion, especially in mountain areas, where erosion is the highest. Only studies combining large spatial and temporal approaches allow to assess the effect of the different forcing factors on soil erosion rates. Here, we apply a retrospective approach based on lake sediments to reconstruct the long-term evolution of erosion in alpine landscapes. Lake Bourget, located in the northern French, acts as a natural sink for a fraction of the erosion products from its large catchment. We combined a multiproxy study of lacustrine sediment sections covering the Holocene with a source-to-sink method, using isotopic geochemistry (εNd). The applied methodology allows us to disentangle the role of climate and land use as erosion forcing factors through their differential impact on the various rock types present in the catchment. Indeed, high-altitude areas of the study site, where the erosion is dominated by precipitation and glacier advances, present isotopic signature different from those of the sedimentary rocks located in the rest of the catchment, where both human activities and precipitations impact erosion through time. To understand the effect of human activities, erosion signals from high-altitude and the rest of the catchment were compared to local and regional indexes of human activities, obtained from pollen and environmental DNA studies conducted on lake sediment sequences. For the last 3.8 kyr, climate fluctuations alone cannot explain measured erosion trends. Between the Late Bronze Age and the modern times, human activities are at the origin of a two-fold increase of the erosion rates in the Alps. Human activities, by modifying the soil erodibility through land-use (agriculture, grazing, ore extraction and deforestation) is the dominant forcing factor of the physical erosion in mountainous environment of the European Alps at least for the last 3800 years.

Sedimentary sequences have received a growing interest as a support for conducting climatic and environmental reconstructions covering the 20th century period, which has been highly impacted by socio-environmental changes. South-America is one of the regions of the world the most impacted by these changes (e.g. agricultural expansion, extreme climatic events) which induce many deleterious consequences (e.g. increase of soil erosion, transfer of contaminants). However, quantitative information regarding soil erosion and sediment accumulation processes at the catchment scale is currently lacking to determine the magnitude of these phenomena and promote effective policies to mitigate their environmental and economic impacts.Fallout of anthropogenic radionuclides (137Cs, 239Pu and 240Pu) emitted by atmospheric nuclear weapon tests conducted between 1945 and 1980 provides an opportunity to overcome this lack of information. Indeed, artificial radionuclides bound to fine-grained sediment have been increasingly recognized as powerful tools to conduct environmental, climatic and soil redistribution rate reconstructions during the Anthropocene. Although spatial and temporal reconstructions of this fallout have been conducted worldwide, this information remains scarce in South America. In addition, scientific controversies emerged regarding the contribution of French atmospheric nuclear tests to the deposition of artificial radionuclides in this region of the world, requiring further investigation.Based on a compilation of 137Cs inventories in undisturbed soil profiles (n=96) and a digital soil mapping approach, an open-access baseline map of 137Cs fallout at the subcontinental scale of South America was created. The results showed that the 137Cs inventory technique should be appropriate to reconstruct soil erosion in intensive agricultural landscapes of Chile, Argentina, Uruguay and southern Brazil and theoretically applicable in Paraguay, Bolivia and Peru. Compared to previous estimations, higher levels of 137Cs fallout were observed between 20 and 60° South latitude. Additional measurements were therefore conducted in undisturbed soils and lake sediment cores collected at these latitudes by analyzing the 240Pu/239Pu atomic ratios, which is a powerful tool to determine the sources and their respective contributions to the deposition of anthropogenic radionuclides. Significantly lower plutonium atom ratios were found and attributed to the higher contribution (up to 60% in Uruguay) of the fallout following French atmospheric nuclear tests between 1966 and 1974.This refined chronology and spatial distribution of bomb-derived fallout will undoubtedly be useful to avoid misinterpretations of sediment core dating and reconstruct soil redistribution rates during the Anthropocene in South America.

On April 7th 2022 we learnt the devastating news: our friend and colleague, Bruno Wilhelm, had passed in the mountain while ascending a steep slope in the aim of skiing it. One year after, our group, within which he came and grow to science up to the defence of his PhD thesis in 2012, is still graving. In that context, we are grateful to the organisers of this session for offering us the opportunity of reminding our scientific community the multiple advancements it owes to Bruno.Bruno Wilhelm indeed did a hard and innovative work in the aim of reading the geological record of lakes. He focused himself on the recording of extreme events in lake sediments. In this keynote, we will emphasize how Bruno proposed original ways of characterising what we call “instant deposits”, mostly in the early stages of his too short career. He then particularly worked the question of distinguishing among triggering factors of those “alien” layers that often interbed within lake sediment calm sedimentation. Bruno also proposed a detailed reflexion aiming at quantifying or, at least, ranking the intensity of those triggering events. He hence proposed several ways of assessing past floods intensity. In the same spirit, he explicitly proposed a procedure to assess the “recordability” of past earthquake events within a given lake system, based on historical chronicles. He also led a common reflexion about the ability of lake sediment to record a regional flood signal. After his PhD he committed himself in the scientific animation of the PAGES’ “Floods” working group which led him to coordinate the establishment of a comprehensive database and to participate in the redefinition of a collaborative work to better understand past flood patterns in the iam of anticipating future changes due to global warming.It is undeniable that Bruno Wilhelm had a brilliant and far too short career. However, with this speech we hope that the community will be even more aware about the important legacy he left us.

The North Anatolian Fault (NAF), located in Turkey, is one of the world's most active faults and accommodates Anatolia's westward motion relative to Eurasia. Over the last century, several earthquakes (M>6.8) have migrated from east to west. It is in the Marmara region, south of Istanbul, that the subsequent rupture is expected. However, this is where the geometry of the fault becomes more complex. It divides into three branches, one of which borders Lake Iznik and the southern Marmara Sea. As there is now very little seismic activity along this portion of the NAF (MNAF), and GPS only detects small displacements (Reilinger et al., 2006), it is thought to be inactive. However, the city of Iznik, the cradle of Christianity, has preserved valuable historical evidence in contrast to its observations. Therefore, to better understand the seismic hazard in this area, it is necessary to catalogue the seismic activity and locate past ruptures.Two active faults were discovered in Lake Iznik thanks to our geophysical and coring campaigns (Gastineau et al., 2021). The study of short (

Between 1972 and 1993, in the French West Indies (Martinique and Guadeloupe), farmers applied a toxic organochlorine insecticide, chlordecone, to control the banana weevil. In the late 1990s, the intensification of agricultural practices in the West Indies led to accelerated soil erosion and sediment transfers to river systems and the sea (Sabatier et al., 2021). This increase in soil erosion leading in turn to a release of chlordecone stored in polluted agricultural soils. These accelerated lateral transfers of sediments are strongly controlled by land use and agricultural practices. The identification of soil erosion sources is therefore essential to effectively fight against the consequences of erosion on the resurgence of chlordecone. Using sediment tracing tools applied to coastal marine sediment archives, the objective of the current research was to model the potential changes in sediment sources throughout time in the West Indian catchments. Banana and sugarcane crops, forests, channel banks and landslides were targeted here as potential sources of sediment.To this end, soil samples were collected across the Galion catchment at locations presenting contrasted soil types and land use contexts. In addition, a marine sediment core was collected in the Galion Bay in April 2017. In order to quantify source contributions, a suite of physico-chemical properties was measured in both soil and sediment samples.Subsoils provided instead the main source of sediment in the Galion catchment (between 40 and 50% of sediment). In contrast, the contribution of cultivated soils increased during the 1960s (15 to 30% of sediment) and showed a second increase phase in the late 1990s (30 to 40% of sediment). These phases of increases were interrupted by decreases and major sediment contributions from subsoils. These increases of cultivated soils contributions can be explained by changes in agricultural practices (mechanization, irrigation) since the 1960s and the glyphosate introduction in the late 1990s, which increased soil erosion under cropland. Subsoils contribution increases correlate well with period of extreme events like Matthew cyclone in 2016.Overall, the comparison between the calculated sediment contributions and the reconstructed chlordecone fluxes shows that the decreases in subsoil contributions correlate well with those of chlordecone concentrations in marine sediments. In contrast, the increases of cultivated soil contributions to sediment correspond well to increases of chlordecone concentrations in sediment.Accordingly, these results showed the chlordecone contamination dilution due to increase of subsoil erosion. In the future, river sediment samples, collected with sediment traps, will also be analyzed using the same procedure to provide more detailed spatially-distributed information regarding erosion source contributions across the catchment.

International audience; Understanding the uranium (U) cycle – reservoirs and processes – at the watershed scale is key to manage contaminated areas, to elucidate ore formation processes as well as to implement paleoenvironmental research. Here, we investigated the different steps of the U cycle, from sources to sinks, and the relative roles of redox processes and organic matter in the control of U mobility in the naturally U-rich small mountainous watershed of Lake Nègre (France). We interpret the U repartition in U reservoirs through chemical, isotopic (δ238U and (234U/238U)) and speciation analyses, in the light of anterior studies of the site. We show that U(VI) originates from the leaching of U-rich rock fractures and is transported in dissolved forms. Wetlands and meadow soils then act as intermediary sinks where U(VI) is complexed by organic matter (up to > 5000 µg/g) and subsequently partly reduced to U(IV). Dissolved U is also supplied to the lake, in addition to particulate and colloidal U resulting from soil physical erosion. After entering the lake, most U(VI)-bearing organic particles settle in the sediments and U(VI) is reduced to U(IV), resulting in high sedimentary U concentrations (up to > 1000 µg/g), while a fraction of U is potentially desorbed from particles. Remaining dissolved U is exported from the watershed through the lake outlet stream. In this high-mountain lake catchment, the U cycle is mainly controlled by organic matter complexation and particulate transport, though U reduction in the lake sediments may help to its long-term immobilization.

Technical improvements at the end of the Bronze Age led to the rise of a 1rst generation of major sea powers around the Mediterranean Sea, such as Etruria in modern Italy. The Etruscan coast was the fringed by a series of large lagoons. Only one survives today: the lagoon of Orbetello. The lagoon is preserved by two subparallel sand spits that connect former Argentario island to mainland Italy, as situation that today protects it from rapid infilling. A third sand spit, in the middle of the lagoon, hosts the Etruscan city of Orbetello. Today, three canals connect the lagoon to the sea. A massive phase of eutrophication driven by the ingress of fertilizers has plagued the lagoon in late 20th Century. Eutrophication at times has spurred fish and bird kills, and the release of mercury in the water column. Major contingency plans have been implemented to fight off eutrophication, with various success. However little is known of the lagoon management and the evolution of Orbetello before the 17th century CE. Nonetheless, the wealth of the city and the health of its lagoon have been tightly related during the past three millennia. To track this coevolution, a large team of researcher has been assembled to conduct an analysis of the lagoon sediments using XRF scanning of cored sediments, SMIR, Rock Eval, hyperspectral imaging of chromatic pigments, analysis of mercury and phosphorus content, ostracods and pollen assemblages, to document the links between sediment facies, eutrophication and salinity crises, as a result of successive phases of rise and demise of lagoon management over the past three millennia. Here, we focus on the sub-bottom imaging conducted in the very shallow (< 1.5m) waters of this extensive (30 km2) lagoon. The Exail Echoes 10 000 sub-bottom profiler reveals individual layers that can be traced across the lagoon, allowing stratigraphic correlations between cores, and highlighting the environmental significance of the sedimentary facies. Acoustic imaging using a 3.5 kHz Chirp systems from Exail (Haliotis R/V) was conducted offshore to document the architecture of the sand spits protecting the lagoon. The architecture of the deposits, 14C, OSL, and U-Th dating reveal that the lagoon results from the drowning of strandplains that started forming on both side of the older, central sand spit, at the end of the postglacial transgression. Drowning accompanied the final rise in sea level over the past 6.5 ka, forming two lagoons on both sides of the central spit. These initial lagoons eventually coalesced after drowning the central sand spit. Continuation of the lagoon level rise since Antiquity led to the flooding of Bronze Age, Etruscan and Roman settlements. Sub-bottom imaging in the lagoon reveals buried structures possibly used for navigation and salinity control. Sedimentation is marked by an alternation of black, shelly organic silty clays and decimeter-thick layers of broken shells. Radiocarbon dating indicates that the cores capture up to five millennia of sedimentation, with a sharp decrease in sedimentation rates four millennia ago.

Low-lying coasts and small islands, such as in the Lesser Antilles, are particularly vulnerable to hurricane-induced marine floods. In September 2017, Category 5 Hurricane Irma, with winds up to 360 km/h, hit the northern Caribbean islands and caused the destruction of 95 % of the structures on Barbuda Island. We investigated the geomorphological impacts and the sedimentological record of this hurricane in Barbuda’s Codrington Lagoon. Following Hurricane Irma, two wide inlets developed across the Codrington sandy barrier. One of these inlets enlarged and was still opened four years later. From available data, it seems that this barrier remained continuous for the last 250 years before Hurricane Irma. At a longer time scale, very high-resolution seismic exploration combined with sediment cores sampled in Codrington Lagoon were used to investigate Irma deposit and environmental changes for the last 3700 years. The evolution from a low-energy small and shallow lagoon to the modern wide and high-energy lagoon recorded by the lagoon sediment-fill was related to both long-term sea-level rise and subsidence. The top of the lagoon fill consists of a thick and extensive sand sheet recording an abrupt increase in energy. Given its location at the top of the cores, its very recent age supported by short-lived radionuclides data, together with large inlets opening and barrier erosion after Irma implying a large sand supply to the lagoon, this sand sheet was attributed to Hurricane Irma. From our cores, it appears that this deposit is unique over more than 3700 years. Both the opening of a new inlet and the thick upper sand sheet support the exceptional character of Irma at the scale of centuries to millennia. Our study reinforces the idea that Hurricane Irma was exceptional in terms of intensity and may be associated with global warming.

Holocene climate in the high tropical Andes was characterized by both gradual and abrupt changes, which disrupted the hydrological cycle and impacted landscapes and societies. High-resolution paleoenvironmental records are essential to contextualize archaeological data and to evaluate the sociopolitical response of ancient societies to environmental variability. Middle-to-Late Holocene water levels in Lake Titicaca were reevaluated through a transfer function model based on measurements of organic carbon stable isotopes, combined with high-resolution profiles of other geochemical variables and paleoshoreline indicators. Our reconstruction indicates that following a prolonged low stand during the Middle Holocene (4000 to 2400 BCE), lake level rose rapidly ~15 m by 1800 BCE, and then increased another 3 to 6 m in a series of steps, attaining the highest values after ~1600 CE. The largest lake-level increases coincided with major sociopolitical changes reported by archaeologists. In particular, at the end of the Formative Period (500 CE), a major lake-level rise inundated large shoreline areas and forced populations to migrate to higher elevation, likely contributing to the emergence of the Tiwanaku culture., Proceedings of the National Academy of Sciences of the United States of America, 120 (2), ISSN:0027-8424, ISSN:1091-6490

International audience; We present the first high-resolution Holocene pollen, plant-macrofossil, and charcoal records from the upper-montane zone in the central Dinaric Alps. Drawing on these new records from well-dated lacustrine sediments of Zminje Jezero (ca. 1500 m a.s.l.; Montenegro) and on independent chironomid-inferred summer temperatures, we explore long-term ecosystem responses to variations in climate, fire disturbances and land use, as well as legacy effects of past environmental changes. A mixed spruce-fir forest established in the upper-montane zone around 9500 cal BP, and Fagus sylvatica became co-dominant with the two conifers after 5000 cal BP. Prehistoric land-use pressure was overall remarkably low, but increased since 2000 cal BP and was highest after the Middle Ages. We found a significant positive relationship between biomass burning and summer temperature, indicating that fires were mostly climate driven. Picea abies was insensitive to summer temperature, biomass burning and human impact, which supports the view that spruce forests may not be significantly impacted by fire. In contrast, Abies alba and other disturbance-sensitive trees ( Tilia, Ulmus, Fraxinus excelsior-type) show significant negative responses to land-use pressure and positive responses to summer temperature. This supports the notion that these species may be well-adapted to warmer-than present summer temperatures and that their populations declined in recent millennia due to land-use activities. Conversely, F. sylvatica was sensitive to summer temperatures but was promoted by low biomass burning, indicating that its expansion in the spruce-fir dominated forest was enhanced by the onset of cooler and possibly also moister climatic conditions as well as by fire disturbances.

Dating recent sediment archives (

Introduction: The emergence of real-life health databases has opened the door to studies for signal detection in pharmacovigilance without the formulation of an a priori hypothesis, i.e., without defining a drug/adverse drug event (ADR) pair. Our objective was to perform a systematic review of this type of study and the statistical methods used in this context. Methods: Studies about drug signal detection without a priori hypotheses published in the MEDLINE database between 2012 and 2021 were included. Database name and type, statistical methods, ATC class for the studied drug(s) and SOC MedDRA classification for the studied ADR were extracted. Results: Ninety-two studies were included. Pharmacovigilance databases were the most used type of database. Most studies performed a disproportionality analysis using frequentist or Bayesian methods. The most studied drug classes were anti-infectives, nervous system drugs, and antineoplastics and immunomodulators. No common procedure was implemented to correct for multiple testing. Conclusions: There are very few statistical methods used for drug signal detection without a priori hypotheses, with no consensus-based method and no interest in multiple testing correction. This review argues for the establishment of guidelines to perform such studies.

Most drugs are used in the clinic and drug candidate target multiple proteins, and thus detailed characterization of their efficacy targets is required. While current methods rely on quantitative measurements at thermodynamic equilibrium, kinetic parameters such as the residence time of a drug on its target provide a better proxy for efficacy in vivo. Here, we present a residence time proteome integral solubility alteration (ResT-PISA) assay, which facilitates monitoring temporal protein solubility profiles after drug removal ("off-curve") in cell lysates or intact cells, quantifying the lifetime of drug-target interaction. A compressed version of the assay measures the integral under the off-curve enabling the multiplexing of binding affinity and residence time assessments into a single proteomic analysis. We introduce a combined scoring system for three parametric dimensions to improve prioritization of targets. By providing complementary information to other characteristics of drug-target interaction, the ResT-PISA approach will be useful in drug development and precision medicine.

International audience; Atmospheric nuclear tests (1945-1980) have led to radioactive fallout across the globe. French tests in Polynesia (1966-1974) may influence the signature of fallout in South America in addition to those conducted by USA and former USSR until 1963 in the Northern hemisphere. Here, we compiled the $^{240}$Pu/$^{239}$Pu atom ratios reported for soils of South America and conducted additional measurements to examine their latitudinal distributions across this continent. Significantly lower ratio values were found in the 20-45° latitudinal band (0.04 to 0.13) compared to the rest of the continent (up to 0.20) and attributed to the contribution of the French atmospheric tests to the ultra-trace plutonium levels found in these soils. Based on sediment cores collected in lakes of Chile and Uruguay, we show the added value of measuring $^{240}$Pu/$^{239}$Pu atom ratios to refine the age models of environmental archives in this region of the world.

International audience; The widespread use of pesticides in agriculture during the last several decades has contaminated soils and different Critical Zone (CZ) compartments, defined as the area extended from the top of the vegetation canopy to the groundwater table, and it integrates interactions of the atmosphere, lithosphere, biosphere, and hydrosphere. However, the long-term fate, storage, and transfer dynamics of persistent pesticides in CZ in a changing world remain poorly understood. In the French West Indies, chlordecone (CLD), a toxic organochlorine insecticide, was extensively applied to banana fields to control banana weevil from 1972 to 1993 after which it was banned. Here, to understand CZ trajectories we apply a retrospective observation based on marine sediment core analyses to monitor long-term CLD transfer, fate, and consequences in Guadeloupe and Martinique islands. Both CLD profiles show synchronous chronologies. We hypothesized that the use of glyphosate, a postemergence herbicide, from the late 1990s onward induced CZ modification with an increase in soil erosion and led to the release of the stable CLD stored in the soils of polluted fields. CLD fluxes drastically increased when glyphosate use began, leading to widespread ecosystem contamination. As glyphosate is used globally, ecotoxicological risk management strategies should consider how its application affects persistent pesticide storage in soils, transfer dynamics, and widespread contamination.

It has proven difficult to identify the underlying genes in complex autoimmune diseases. Here, we use forward genetics to identify polymorphisms in the vitamin D receptor gene (Vdr) promoter, controlling Vdr expression and T cell activation. We isolated these polymorphisms in a congenic mouse line, allowing us to study the immunomodulatory properties of VDR in a physiological context. Congenic mice overexpressed VDR selectively in T cells, and thus did not suffer from calcemic effects. VDR overexpression resulted in an enhanced antigen-specific T cell response and more severe autoimmune phenotypes. In contrast, vitamin D3-deficiency inhibited T cell responses and protected mice from developing autoimmune arthritis. Our observations are likely translatable to humans, as Vdr is overexpressed in rheumatic joints. Genetic control of VDR availability codetermines the proinflammatory behavior of T cells, suggesting that increased presence of VDR at the site of inflammation might limit the antiinflammatory properties of its ligand.

Most drugs used in the clinic and drug candidates target multiple proteins, and thus detailed characterization of their efficacy targets is required. While current methods rely on quantitative measurements at thermodynamic equilibrium, kinetic parameters such as the residence time of a drug on its target provide a better proxy for efficacy in vivo. Here, we present Residence Time Proteome Integral Solubility Alteration (ResT-PISA) assay which provides monitoring temporal protein solubility profiles after drug removal (“off-curve”) in cell lysate or intact cells, quantifying the lifetime of drug-target interaction. A compressed version of the assay measures the integral under the off-curve enabling the multiplexing of binding affinity and residence time assessments into a single proteomic analysis. We introduce a combined scoring system for three parametric dimensions to improve prioritization of targets. By providing complementary information to other characteristics of drug-target interaction, ResT-PISA approach will be useful in drug development and precision medicine.

At the end of the Bronze Age, technical improvements have made possible the rise of the first generation of major sea powers around the Mediterranean realm, such as Etruria in Italy. The Etruscan coast was fringed by large lagoons, of which only one survives today: the lagoon of Orbetello. This peculiar lagoon is held between two sand spits that connect the former island of Argentario to the mainland. A third sand spit lies in the middle of the lagoon, and supports the Etruscan city of Orbetello. Archeological investigations suggest that the lagoon was connected to the sea through a natural outlet until the 9th century BCE, when an integrated management plan of the lagoon was implemented to optimize fishing. Subsequent closure of the natural outlet implies that lagoon management heavily subsequently relied on man-made openings to maintain the lagoon connected to the sea and nearby rivers. Today, three canals connect the lagoon to the sea. Management plans were implemented in the late 20th Century to fight a massive phase of eutrophication driven by excess release of fertilizers. Eutrophication as responsible for extensive fish kills, and to the release of mercury in the water column. Little is known about lagoon management and the evolution of the city before the 17th century CE, but it is clear that the wealth of the city of Orbetello and the health of its lagoon have been strongly correlated over the past three millennia. To track this coevolution, we conducted a coring campaign coupled to sub-bottom imaging in the very shallow (2) lagoon. iXblue Echoes 10 000 sub-bottom profiler reveals individual layers that can be traced across the lagoon, allowing stratigraphic correlations between cores, and highlighting the environmental significance of the sedimentary facies. Architecture of the deposits reveals a pronounced transgression of the lagoon over its shallowly inward-dipping margins since Antiquity. This led to the flooding of an array of regularly-spaced Roman farms along its southern shorelines, and to a more important flooding of Etruscan structures. Lagoon level rise was driven by a combination of regional sea level rise and fluctuations in the hydraulic balance of the lagoon, controlled by the opening and closure of canals. Sub-bottom imaging reveals buried structures tentatively interpreted as docks and canals used for navigation and salinity control. Sediment analyses under XRF scanning, Rock Eval, and hyperspectral imaging reveals that sedimentation is marked by an alternation of black, shelly organic silty clays and decimeter-thick layers of broken shells. Radiocarbon dating indicates that the cores capture up to five millennia of sedimentation. Ongoing analysis of mercury and phosphorus content, ostracods and pollen assemblages, and chromatic pigments in the organic fractions are expected to document the links between sediment facies, eutrophication and salinity crises, and the rise and demise of land and lagoon management through the past three millennia. A sub-bottom profiling campaign in June 2022 is aimed at mapping the observed structure. Further coring is planned near putative man-made structures next Fall.

International audience; The trajectories of mountain socio-ecosystems are complex and influenced by numerous factors (climate, human practices, slope, etc.). This study combined methods used in palynology, ecology and history to produce complementary data to improve understanding of the trajectories of an alpine socio-ecosystem over the last 500 years. Past changes in vegetation cover and land use were reconstructed along with their impacts on erosion dynamics in Montainmont, a commune in the French Alps. A paleoenvironmental analysis (pollen, coprophilous fungi, sedimentology, geochemistry) was conducted on lake sediment, providing a 500-year record of vegetation and erosion dynamics, and mixed farming history. The historical analysis focused on the reconstruction of the customs and habits of the community of Montaimont through the examination of the historical archives of their administrative district. The historical records provided quantitative data on changes in the forest at the plot scale and qualitative information on landscape management. The ecological approach focused on land use analyses using photo-interpretation of aerial ortho-photographs since the 1950s. This data set was used to conduct a spatially explicit analysis of social-environmental interactions in the past. By combining the three approaches, we were able to document changes in vegetation cover over time as well as changes in forestry and agricultural activities. Our analyses reveal a key tipping point during the past century. The community of Montaimont originally used its landscape for mixed farming activities coupled with intensive exploitation of the forest. During the twentieth century, a major socio-ecological change occurred when crop farming ceased, and forest use decreased. This land abandonment led to spontaneous reforestation. This study demonstrates that an interdisciplinary approach bridges the blind spots inherent to each disciplinary approach, facilitating a better understanding of socio-ecological trajectories.

Adverse drug reaction is a major public health issue. The increasing availability of medico-administrative databases offers major opportunities to detect real-life pharmacovigilance signals. We have recently adapted a pharmacoepidemiological method to the large dimension, the WCE (Weigthed Cumulative Exposure) statistical model, which makes it possible to model the temporal relationship between the prescription of a drug and the appearance of a side effect without any a priori hypothesis. Unfortunately, this method faces a computational time problem. The objective of this paper is to describe the implementation of the WCE statistical model using Graphics Processing Unit (GPU) programming as a tool to obtain the spectrum of adverse drug reactions from medico-administrative databases. The process is divided into three steps: pre-processing of care pathways using the Python library Panda, calculation of temporal co-variables using the Python library "KeOps", estimation of the model parameters using the Python library "PyTorch" - standard in deep learning. Programming the WCE method by distributing the heaviest portions (notably spline calculation) on the GPU makes it possible to accelerate the time required for this method by 1000 times using a computer graphics card and up to 10,000 times with a GPU server. This implementation makes it possible to use WCE on all the drugs on the market to study their spectrum of adverse effects, to highlight new vigilance signals and thus to have a global vigilance tool on medico-administrative database. This is a proof of concept for the use of this technology in epidemiology.

Understanding past water-level changes are essential to human development. Changes in lake levels can result in the displacement of populations due to rising water levels, or be a limiting factor in the case of irrigation for agriculture or in terms of water resources. Lake-level fluctuations can be the consequence of outlet modification, human activity, or on a longer time scale, of climatic change or tectonic activity.In Turkey, several studies showed that the water level of numerous lakes significantly changed since the Last Glacial Maximum (LGM). Here, we present the history of Lake Iznik (83 m above sea level) which is the fifth-largest lake in Turkey. Based on high-resolution seismic profiles, sediment cores and bathymetry, we document new insights into its lake-level variations since the late Pleistocene. An important transgressional phase with a highstand (> 50 m above the modern lake level) of uncertain age is documented during the late Pleistocene, preceding the LGM (> 40 ka BP). Before this highstand, the lake level was substantially lower by at least ~ 60 m. The stepwise transgression that led to this highstand is associated with the formation of a series of up to 13 buried paleoshorelines. This phase of high lake level is followed by a sedimentation pattern marked by strong lateral differences in sediment accumulation in the northern part of the lake. These pronounced lateral differences are partly caused by lacustrine contourite drifts due to strong currents, or by prograding delta clinoforms. The younger phases (< 18 ka BP) are characterized by different regressional/transgressional cycles with a major lowstand at ~ 50 m below the present-day lake level during the early Holocene, probably related to a dryer climate. Today, the lake level continues to fluctuate as shown by one of the most important archaeological discoveries of this decade. During a 2014 aerial photo survey, the fourth to fifth century CE St. Neophytos Basilica was discovered underwater in Lake Iznik, 20 m from the shore at an average depth of 2 m (e.g. Şahin & R. Fairchild, 2018). However, it is more difficult to distinguish anthropogenic from climatic influences in recent times.Reference: Şahin, M., & Fairchild, M. R. (2018). Nicea's underwater basilica. Biblical Archaeology Review, 44(6), 30–37.

(IF 10.75; Q1); International audience; Hyperspectral imaging (HSI) is a non-destructive, high-resolution imaging technique that is currently under significant development for analyzing geological areas with remote devices or natural samples in a laboratory. In both cases, the hyperspectral image provides several sedimentary structures that must be separated to temporally and spatially describe the sample. Sediment sequences are composed of successive deposits (strata, homogenite, flood) that are visible depending on sample properties. The classical methods to identify them are time-consuming, have a low spatial resolution (millimeters) and are generally based on naked-eye counting. In this study, we compare several supervised classification algorithms to discriminate sedimentological structures in lake sediments. Instantaneous events in lake sediments are generally linked to extreme geodynamical events (e.g., floods, earthquakes), so their identification and counting are essential to understand long-term fluctuations and improve hazard assessments. Identification and counting are done by reconstructing a chronicle of event layer occurrence, including estimation of deposit thicknesses. Here, we applied two hyperspectral imaging sensors (Visible Near-Infrared, VNIR, 60 μm, 400–1000 nm; Short Wave Infrared, SWIR, 200 μm, 1000–2500 nm) on three sediment cores from different lake systems. We highlight that the SWIR sensor is the optimal one for creating robust classification models with discriminant analyses (prediction accuracies of 0.87–0.98). Indeed, the VNIR sensor is impacted by the surface reliefs and structures that are not in the learning set, which causes mis-classification. These observations are also valid for the combined sensor (VNIR-SWIR) and the RGB images. Several spatial and spectral pre-processing were also compared and enabled one to highlight discriminant information specific to a sample and a sensor. These works show that the combined use of hyperspectral imaging and machine learning improves the characterization of sedimentary structures compared to conventional methods.

International audience; The actual health risk and associated diseases induced by the presence of pesticides and other organic pollutants in most environmental media worldwide are largely underestimatedbecause current analytical methods measure only the extractable fraction of the pollutant, whereas there is now ample evidence that a large part of pollutants are trapped as bound residues in complex organo-mineral matrixes, and are thus unanalyzable by current tools. Once trapped, pollutants can be stored for long periods, then released in the biosphere upon suitable conditions such as soil erosion and climate change. This ‘resurrection’ and underlying mechanisms of trapping, storage and release are poorly known. Here we discuss the limit of knowledge on bound pollutants and their later release, with examples of organochlorines in glaciers, vineyards and banana plantations. Unexpectedly, soil application of a modern pesticide such as glyphosate, can lead to the resurrection of ancient, actually banned pesticides such as chlordecone and dichlorodiphenyltrichloroethane (DDT) (Fig. 1).

Geochimica et cosmochimica acta 338, 322 - 346 (2022). doi:10.1016/j.gca.2022.10.018, Understanding the controls on uranium (U) mobility in the environment is key to improve the management of sites contaminated by U mining activities. Previous research has shown that natural or engineered wetlands are particularly able to scavenge high amounts of U(VI) and U(IV) under noncrystalline forms. However, questions remain on the respective roles of sorption and reduction processes in the removal of U from running waters in wetlands, as well as on the long-term stability of U storage. Here, we performed a series of geochemical, isotopic (δ238U, (234U/238U)), microscopic (SEM-EDXS, EPMA) and spectroscopic (µ-XRF, µ-XAS, XANES and EXAFS at the U L3 and M4-edges and Fe K-edge) investigations to determine the modes of U accumulation and assess U mobility in a natural exceptionally U-enriched (up to 5000 µg/g) wetland on the shore of Lake Nègre (Mediterranean Alps, France). Uranium (VI) was largely dominant in the two studied soil cores, except a few samples containing as much as ∼50 % U(IV). At the particle scale, U is associated to a variety of organic constituents of the soil matrix with a homogenous oxidation state. Bulk EXAFS spectroscopy at the U L3-edge shows that U is mostly mononuclear, with dominant monodentate binding to organic moieties (C neighbors at ∼3.45 Å). An additional minor fraction of U under polymeric forms is inferred from wavelet (CCWT) analysis of the EXAFS data. These observations are reinforced by 1 M bicarbonate extractions that result in the dissolution of 82–96 % of total U, including putative polymeric species. At the wetland scale, similar or slightly fractionated isotopic ratios (δ238U) between the wetland-feeding creek waters and the wetland soils are observed, supporting the idea that U(VI) sorption on organic matter is the primary U scavenging mechanism. Furthermore, it indicates that partial U(VI) reduction to U(IV) occurs as a second step, after sorption. Analysis of U decay chain disequilibria in the cores as a function of depth suggests that U accumulation in this wetland has lasted for several thousand years. We propose that the wetland acts as an active reactor where U has been massively accumulating for ∼14500 years, especially as U(VI) forms associated to organic matter, and is further partly exported to the lake through soil erosion., Published by Elsevier, New York, NY [u.a.]

International audience; The sedimentary processes in the deep basin of large peri-Alpine lakes have not been studied much on long timescales due to high coring complexity of such lake systems. In 2018, a 15.5 m long sediment section was retrieved from the deep basin of Lake Iseo (Italy) at 251 m water depth. A seismic survey associated with a multi-proxy approach using sedimentological and geochemical analyses, reveals that event deposits correspond to 61.4% of the total sedimentation during the last 2000 years. The great heterogeneity of textures, colours and grain-size distribution between the different types of event layers can be explained by the high number of potential sources of sediment in this large lake system. By combining a proxy of sediment sources with proxies of transport processes, flood events were distinguished from destabilizations of the slopes and the main delta. The three thickest mass wasting deposits correspond to major regional earthquakes events of 1222 CE, 1117 CE and around 700 CE. From a thorough comparison with regional climatic fluctuations and human activities in the watershed, it appears that periods of high sediment remobilization can be linked to a preceding increase in erosion in the watershed mainly under human forcing. Hence, even in large catchments, human activities play a key role on erosion processes and on sediment availability, disrupting the recording of extreme events in lacustrine archive