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Dating recent sediment archives (< 150 years) constitutes a prerequisite for environmental and climatic reconstructions. Radiocaesium (137Cs) emitted during thermonuclear bomb testing (∼ 1950–1980) and nuclear accidents and the decrease in excess lead-210 (210Pbxs) with depth are often combined to establish sediment core chronology. Although these methods have been widely used during the last several decades, there is a lack of structured and comprehensive worldwide synthesis of fallout radionuclide analyses used for dating sediment cores in environmental and Earth sciences. The current literature overview was based on the compilation of 573 articles published between 1977 and 2020, reporting the collection of 1351 individual dating sediment cores (the dataset can be accessed at 10.1594/PANGAEA.931493; Foucher et al., 2021). This review was conducted in order to map the locations where137Cs fallout events were detected. These included the thermonuclear bomb testing peak in 1963, the Chernobyl accident in 1986, the Fukushima accident in 2011, and 24 additional events identified at 112 sites that led to local or regional radioactive releases (e.g., Sellafield accidents, Chinese nuclear tests). When 210Pbxs records were used along with137Cs data, detailed information on the 210Pbxs age–depth models were also synthesized.With the current growing number of studies analyzing sediment cores and the increasing interest in the deployment of sediment fingerprinting techniques including radionuclides as potential discriminant properties, this spatialized synthesis provides a unique worldwide compilation for characterizing fallout radionuclide sources and levels at the global scale. This synthesis provides in particular a reference of 137Cs peak attribution for improving the sediment core dating, and it outlines the main questions that deserve attention in future research as well as the regions where additional 137Cs fallout investigations should be conducted in priority.

Mass spectrometry (MS)-based proteomics workflows typically involve complex, multi-step processes, presenting challenges with sample losses, reproducibility, requiring substantial time and financial investments, and specialized skills. Here we introduce One-Tip, a proteomics methodology that seamlessly integrates efficient, one-pot sample preparation with precise, narrow-window data-independent acquisition (nDIA) analysis. One-Tip substantially simplifies sample processing, enabling the reproducible identification of >9000 proteins from ~1000 HeLa cells. The versatility of One-Tip is highlighted by nDIA identification of ~6000 proteins in single cells from early mouse embryos. Additionally, the study incorporates the Uno Single Cell Dispenser™, demonstrating the capability of One-Tip in single-cell proteomics with >3000 proteins identified per HeLa cell. We also extend One-Tip workflow to analysis of extracellular vesicles (EVs) extracted from blood plasma, demonstrating its high sensitivity by identifying >3000 proteins from 16 ng EV preparation. One-Tip expands capabilities of proteomics, offering greater depth and throughput across a range of sample types. Traditional proteomics methods are complex and resource-intensive. Here, the authors develop One-Tip, a highly simplified approach that enables efficient, sensitive, and comprehensive analysis across various sample types, from blood plasma to single cells.

Event deposits in lake sediments provide invaluable chronicles of geodynamic and climatic natural hazards on multi-millennial timescales. Sediment archives are particularly useful for reconstructing high-impact, low-frequency events, which are rarely observed in instrumental or historical data. However, attributing a trigger mechanism to event deposits observed in lake sediments can be particularly challenging as different types of events can produce deposits with very similar lithological characteristics, such as turbidites. In this review paper, we summarize the state of the art on event deposits in paleolimnology. We start by describing the sedimentary facies typical of floods, glacial lake outburst floods, avalanches, hurricanes, earthquakes, tsunamis, volcanic eruptions, and spontaneous delta collapses. We then describe the most indicative methods that can be applied at the scale of lake basins (geophysical survey, multiple coring) and on sediment cores (sedimentology, inorganic and organic geochemistry, biotic approach). Finally, we provide recommendations on how to obtain accurate chronologies on sediment cores containing event deposits, and ultimately date the events. Accurately identifying and dating event deposits has the potential to improve hazard assessments, particularly in terms of the return periods, recurrence patterns, and maximum magnitudes, which is one of the main geological challenges for sustainable worldwide development.

Deconvolution of targets and action mechanisms of anticancer compounds is fundamental in drug development. Here, we report on ProTargetMiner as a publicly available expandable proteome signature library of anticancer molecules in cancer cell lines. Based on 287 A549 adenocarcinoma proteomes affected by 56 compounds, the main dataset contains 7,328 proteins and 1,307,859 refined protein-drug pairs. These proteomic signatures cluster by compound targets and action mechanisms. The targets and mechanistic proteins are deconvoluted by partial least square modeling, provided through the website http://protargetminer.genexplain.com . For 9 molecules representing the most diverse mechanisms and the common cancer cell lines MCF-7, RKO and A549, deep proteome datasets are obtained. Combining data from the three cell lines highlights common drug targets and cell-specific differences. The database can be easily extended and merged with new compound signatures. ProTargetMiner serves as a chemical proteomics resource for the cancer research community, and can become a valuable tool in drug discovery. Anticancer drugs often have widespread effects on the cellular proteome. Here, the authors generate a proteome signature library of drug-treated cancer cell lines and develop a software tool to deconvolute drug targets and gain insights into their mechanisms of action.

A major feature of the Anthropocene is the drastic increase in global soil erosion. Soil erosion is threatening Earth habitability not only as soils are an essential component of the Earth system but also because societies depend on soils. However, proper quantification of the impact of human activities on erosion over thousands of years is still lacking. This is particularly crucial in mountainous areas, where the highest erosion rates are recorded. Here we use the Lake Bourget catchment, one of the largest in the European Alps, to estimate quantitatively the impact of human activities on erosion. Based on a multi-proxy, source-to-sink approach relying on isotopic geochemistry, we discriminate the effects of climate fluctuations from those of human activities on erosion over the last 10,000 years. We demonstrate that until 3800 years ago, climate is the only driver of erosion. From that time on, climate alone cannot explain the measured rates of erosion. Thanks to an unprecedented regional paleoenvironmental reconstruction, we highlight that the development of pastoralism at high altitudes from the Bronze Age onwards and the extension of agriculture starting in the Middle Ages were key factors in the drastic increase in erosion observed in the Alps. Using a lake sediment core taken from the European Alps and combining a source-sink approach with isotope geochemistry, it has been established that the effects of human activities have outweighed those of climate on erosion for more than 3800 years.

G protein-coupled receptors are important drug targets that engage and activate signaling transducers in multiple cellular compartments. Delineating therapeutic signaling from signaling associated with adverse events is an important step towards rational drug design. The glucagon-like peptide-1 receptor (GLP-1R) is a validated target for the treatment of diabetes and obesity, but drugs that target this receptor are a frequent cause of adverse events. Using recently developed biosensors, we explored the ability of GLP-1R to activate 15 pathways in 4 cellular compartments and demonstrate that modifications aimed at improving the therapeutic potential of GLP-1R agonists greatly influence compound efficacy, potency, and safety in a pathway- and compartment-selective manner. These findings, together with comparative structure analysis, time-lapse microscopy, and phosphoproteomics, reveal unique signaling signatures for GLP-1R agonists at the level of receptor conformation, functional selectivity, and location bias, thus associating signaling neighborhoods with functionally distinct cellular outcomes and clinical consequences. Agonists of the glucagon-like peptide-1 receptor are used to treat diabetes and obesity. Here, Wright et al. investigate the subcellular location of the receptor’s signaling events and uncover associations between signaling profiles and adverse drug reactions.

Despite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery. The global identification of enzyme substrates is still challenging. Here, the authors develop a method based on proteome-wide thermal shift assays to discover enzyme substrates directly from cell lysates, identifying known and novel oxidoreductase, kinase and poly-(ADP-ribose) polymerase substrates.

Agricultural pesticide use has increased worldwide during the last several decades, but the long-term fate, storage, and transfer dynamics of pesticides in a changing environment are poorly understood. Many pesticides have been progressively banned, but in numerous cases, these molecules are stable and may persist in soils, sediments, and ice. Many studies have addressed the question of their possible remobilization as a result of global change. In this article, we present a retro-observation approach based on lake sediment records to monitor micropollutants and to evaluate the long-term succession and diffuse transfer of herbicides, fungicides, and insecticide treatments in a vineyard catchment in France. The sediment allows for a reliable reconstruction of past pesticide use through time, validated by the historical introduction, use, and banning of these organic and inorganic pesticides in local vineyards. Our results also revealed how changes in these practices affect storage conditions and, consequently, the pesticides' transfer dynamics. For example, the use of postemergence herbicides (glyphosate), which induce an increase in soil erosion, led to a release of a banned remnant pesticide (dichlorodiphenyltrichloroethane, DDT), which had been previously stored in vineyard soil, back into the environment. Management strategies of ecotoxicological risk would be well served by recognition of the diversity of compounds stored in various environmental sinks, such as agriculture soil, and their capability to become sources when environmental conditions change. Significance A record of lake sediment spanning approximately 100 years allowed us to reconstruct the long-term succession of herbicide, fungicide, and insecticide treatments in a vineyard catchment in France. This record of pesticide deposition is consistent with the historical onset and banning of these chemical substances by French and European environmental agencies. We also present evidence of the effects of postemergence herbicides, such as glyphosate, on soil erosion and evidence of the release of banned remnant pesticides, such as dichlorodiphenyltrichloroethane (DDT), that are stored in vineyard soil back into the environment. These results indicate that the sink–source dynamics of pesticides, which are crucial in ecotoxicological risk assessment, should take into account the effects of a changing environment on pesticide storage.

Detailed characterization of cell type transitions is essential for cell biology in general and particularly for the development of stem cell-based therapies in regenerative medicine. To systematically study such transitions, we introduce a method that simultaneously measures protein expression and thermal stability changes in cells and provide the web-based visualization tool ProteoTracker. We apply our method to study differences between human pluripotent stem cells and several cell types including their parental cell line and differentiated progeny. We detect alterations of protein properties in numerous cellular pathways and components including ribosome biogenesis and demonstrate that modulation of ribosome maturation through SBDS protein can be helpful for manipulating cell stemness in vitro. Using our integrative proteomics approach and the web-based tool, we uncover a molecular basis for the uncoupling of robust transcription from parsimonious translation in stem cells and propose a method for maintaining pluripotency in vitro. To characterize molecular changes during cell type transitions, the authors develop a method to simultaneously measure protein expression and thermal stability changes. They apply this approach to study differences between human pluripotent stem cells, their progenies, parental and allogeneic cells.