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International audience; This study aims to investigate the ability of an imidazolium biobased Zwitterionic Ionic Liquids (ZILs) in enhancing the phytoavailability of copper from garden (G) and vineyard (V) soils using the model plant ryegrass. Uncontaminated and artificially contaminated CuSO4 soils, unamended and ZIL-amended soil modalities were designed. The copper/ZIL mo-lar ratio (1/4) introduced was rationally established based on molecular modeling and on the maximal copper concentration in artificially contaminated soil. Higher accumulation of copper in the shoots was detected for the uncontaminated and copper contaminated ZIL amended V soils (18.9 and 23.3 mg/kg, respectively) contrary to G soils together with a ZIL concentration of around 3% (W/W) detected by LC-MS analyses. These data evidenced a Cu-accumulation improvement of 38% and 66% compared to non-amended V soils (13.6 and 13.9 mg/kg respectively). ZIL would be mainly present under Cu(II)-ZIL4 complexes in the shoots. The impact on the chemical composition of shoot was also studied. The results show that depending on the soils modalitity, the presence of free copper and/or ZIL led to different chemical compositions in lignin and monomeric sugar contents. In the biorefinery context, performances of enzymatic hydrolysis of shoots were also related to the presence of both ZIL and copper under free or complex forms. Ecotoxicity assessment of the vineyard soil samples indicated that the quantity of copper and ZIL remaining in the soils had no sig-nificant toxicity. ZIL amendment in a copper-contaminated soil was demonstrated as being a promising way to promote the valorization of phytoremediation plants.

SUMMARY A series of models of the Earth magnetic field and core surface flow have been simultaneously and sequentially co-estimated from year 1999 to 2022. The models were derived from magnetic satellite and ground observatory data using a linear Kalman filter approach and prior statistics based on numerical dynamo simulations. The core field and secular variation model components present the same characteristics as the most recent core field models with slightly higher resolution in time. A principal component analysis of the core surface flow series of models shows that the largest flow variations are observed at high latitudes and under the western part of the Pacific Ocean. Filtering out the flow variation periods longer than ∼11.5 yr leads to a filtered azimuthal flow that presents ∼7 yr periodicities with patterns propagating westward by ∼60° longitude per year. These patterns are present mainly at mid- and equatorial latitudes. They are compatible with a perturbation of the main flow made of small columnar flows with rotation axis intersecting the core–mantle boundary between 10° and 15° latitudes, and flow speed of less than 5 km yr–1. Present at all longitudes, these columnar flows are particularly strong under the Pacific Ocean after 2013. They can also be clearly identified under the Atlantic Ocean from 2005 to 2015.

PURPOSE We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors. METHODS Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498 ) were included. Trajectories of QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C30 Summary Score) and associations with trajectory group membership were identified by iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively. RESULTS Four trajectory groups were identified (N = 4,131): excellent (51.7%), very good (31.7%), deteriorating (10.0%), and poor (6.6%) QOL. The deteriorating trajectory group reported fairly good baseline QOL (mean [95% CI], 78.3/100 [76.2 to 80.5]), which significantly worsened at year-1 (58.1/100 [56.4 to 59.9]) and never recovered to pretreatment values through year-4 (61.1/100 [59.0 to 63.3]) postdiagnosis. Healthy behaviors were associated with better performing trajectory groups. Obesity (adjusted odds ratio [aOR] v lean, 1.51 [95% CI, 1.28 to 1.79]; P < .0001) and current smoking (aOR v never, 1.52 [95% CI, 1.27 to 1.82]; P < .0001) at diagnosis were associated with membership to the deteriorating group, which was also characterized by a higher prevalence of patients with excess body weight and insufficient physical activity through year-4 and by frequent exposure to tobacco smoking during chemotherapy. Additional factors associated with membership to the deteriorating group included younger age (aOR, 1-year decrement 1.01 [95% CI, 1.01 to 1.02]; P = .043), comorbidities (aOR v no, 1.22 [95% CI, 1.06 to 1.40]; P = .005), lower income (aOR v wealthier households, 1.21 [95% CI, 1.07 to 1.37]; P = .002), and endocrine therapy (aOR v no, 1.14 [95% CI, 1.01 to 1.30]; P = .047). CONCLUSION This latent-class analysis identified some patients with upfront poor QOL and a high-risk cluster with severe, persistent postchemotherapy QOL deterioration. Screening relevant patient-level characteristics may inform tailored interventions to mitigate the detrimental impact of chemotherapy and preserve QOL, including early addressal of behavioral concerns and provision of healthy lifestyle support programs.

Sepsis is an archetype of distributive shock and combines different levels of alterations in preload, afterload, and often cardiac contractility. The use of hemodynamic drugs has evolved over the past few years, along with the invasive and non-invasive tools used to measure these components in real time. However, none of them is impeccable, which is why the mortality of septic shock remains too high. The concept of ventriculo-arterial coupling (VAC) allows for the integration of these three fundamental macroscopic hemodynamic components. In this mini review, we discuss the knowledge, tools, and limitations of VAC measurement, along with the evidence supporting ventriculo-arterial uncoupling in septic shock. Finally, the impact of recommended hemodynamic drugs and molecules on VAC is detailed.

International audience; Mondialement connu pour ses églises creusées dans la roche, Lalibela est l’un des principaux centres de pèlerinage chrétiens en Éthiopie. Lieu d’inhumation du saint roi Lālibalā mais aussi cimetière pour de nombreux anonymes, ce lieu de mémoire a été façonné par des vestiges funéraires. La découverte tout à fait exceptionnelle de sépultures à Qedemt, dans la ville actuelle à l’écart des églises, apporte des données inédites sur les occupations humaines à Lalibela, depuis l’époque antérieure à la création des églises rupestres jusqu’à la période contemporaine. Ce site constitue ainsi un référentiel unique sur l’évolution des pratiques funéraires et l’utilisation des espaces pour les morts en Éthiopie. Grâce à une étude pluridisciplinaire prenant en compte la diversité des vestiges et des sites, les résultats obtenus interrogent l’évolution des espaces funéraires à Lalibela mais aussi la christianisation des pratiques funéraires. En mettant en avant la diversité des gestes et les transformations qu’ont connues les espaces funéraires, ces données permettent de discuter en miroir l’évolution du site des églises.

Models of planet-disk interaction are mainly based on 2D and 3D viscous hydrodynamical simulations. Accretion is classically prescribed by an alpha parameter which characterizes the turbulent radial transport of angular momentum (AM) in the disk. This accretion scenario has been questioned for a few years and an alternative paradigm has been proposed that involves the vertical transport of AM by MHD winds. We revisit planet-disk interaction in such context, with a focus on the planet's ability to open a gap and produce meridional flows. Accretion, magnetic field and wind torque in the gap are also explored, as well as the gravitational torque exerted by the disk onto the planet. We carry out high-resolution 3D global non-ideal MHD simulations of a gaseous disk threaded by a large-scale vertical magnetic field harboring a planet in a fixed circular orbit using the GPU-accelerated code Idefix. We consider various planet masses and disk magnetizations. We find that gap-opening always occurs for sufficiently massive planets, with deeper gaps when the planet mass increases and when the initial magnetization decreases. We propose a gap opening criterion when accretion is dominated by MHD winds. We show that accretion is unsteady and comes from surface layers in the outer disk, bringing material directly towards the planet poles. A planet gap is a privileged region for magnetic field accumulation, leading to nearly sonic accretion stream through the gap. For massive planets, the wind torque induces an asymmetric gap, both in depth and in width, that gradually erodes the outer gap edge, reducing the outer Lindblad torque and potentially reversing the migration direction of Jovian planets in magnetized disks after a few hundreds of orbits. For low-mass planets, we find strongly fluctuating gravitational torques that are mostly positive on average, indicating a stochastic outward migration.

A series of models of the Earth magnetic field and core surface flow are presented. The models were derived sequentially from year 1999 to 2022, using magnetic satellite and ground observatory data. A linear Kalman filter approach and prior statistics based on numerical dynamo runs were used. The core field and secular variation models present the same characteristics as the most recent core field models with slightly higher resolution in time. The core surface flow series of models presents large variations at high latitudes and under the western part of the Pacific Ocean. Filtering out the flow variation periods longer than ∼11.5 years leads to a filtered azimuthal flow with ∼7 years periodicities and patterns propagating westward by ∼60o longitude per year. These patterns are present mainly at mid- and equatorial latitudes. They are compatible with a perturbation of the main flow made of small columnar flows with rotation axis intersecting the core-mantle boundary between 10o to 15o latitudes, and flow speed of less than 5km/y. These columnar flows can be identified at all longitudes, but are particularly strong under the Pacific Ocean or under the Atlantic Ocean from 2005 to 2015.

The World Digital Magnetic Anomaly Map is prepared under the auspices of IAGA and the CGMW (Commission for the Geological Map of the World) of UNESCO. A first version was released in 2007 (Korhonen et al., 2007), and a second one in 2015 (Dyment et al., 2015; Lesur et al., 2016) with the mandate to update the version 2.0 using the same methodology when the availability of new data would make it necessary. The present version 2.1, compiled at 5 km interval, at 5 km altitude above the continents and at sea-level over the oceans, includes new datasets: (1) the complete digital aeromagnetic map of Brasil made available by ANP; (2) an improved version of the aeromagnetic map of Russia prepared by V-SEGEI; (3) the second version of the Antarctic Digital Magnetic Anomaly maP (ADMAP; Golynsky et al., 2018) which results from a remarkable international effort during and after the Second International Polar Year; (4) a new map of the Caribbean plate and Gulf of Mexico resulting from the compilation and re-processing of existing marine and aeromagnetic data in the area (Garcia and Dyment, EPSL, 2021, 2022); (5) the updated Magnetic Anomaly Map of Eastern Asia prepared by the CCOP (MAMEA; Ishihara and Uchida, 2021); and (6) a new marine magnetic anomaly data compilation prepared by T. Ishihara and coworkers. The new map will be presented and its improvements over the previous version discussed.We try to characterize the magnetic signature of the different geological provinces at global scale by comparing WDMAM v.2.1 and the Geological Map of the World (Bouysse et al., 2014, CGMW). The latitudinal and directional dependences of the magnetic anomaly amplitude and shape prevent a direct global comparison. Instead, we examine the distribution of magnetic anomaly amplitudes within the geological provinces continent by continent. We build an histogram of the magnetic anomaly amplitudes for each type of geological province within each studied continent. The histograms resemble normal distributions from which we determine the average amplitude and its standard deviation. The latter reflects how wide is the range of amplitudes in the distribution: a small standard deviation means a narrow distribution and low amplitudes, a large one a wide distribution and high amplitudes. On land, our first investigation suggests that cratons exhibit stronger magnetic anomalies, whereas regions covered by a significant thickness of sediments present weaker anomalies. At sea, large igneous provinces show stronger anomalies, whereas continental platforms and the oceanic crust show similar amplitudes.

Charged particle velocity-space diffusion in a prescribed one-dimensional turbulent electric field is investigated through numerical trajectories in phase-space and compared against quasi-linear theory (QL), including resonance broadening (RB). A Gaussian spectrum electric field of variable amplitude E is studied in conjunction with two plasma dispersion relations, namely, the Langmuir and ion-acoustic dispersion. A first parameter scan shows that RB effects become significant for a Kubo number K of a few percent. A Kubo number scan shows that diffusion increases as a power law of D∝K3∝E3/2 for large Kubo numbers. Moreover, at large Kubo numbers, transport processes include significant diffusion measured at velocities much higher than the resonant region, where QL and RB predict negligible diffusion. For times much larger than the trapped particle flight time τb and the autocorrelation time τ0, the velocity distribution departs from a Gaussian. Nevertheless, measurements show that the variance increases linearly in time, with a Hurst parameter of H∼0.5, where the diffusion scales as K5/2∝E5/4 and K3/2∝E3/4 for small and large Kubo number, respectively.

BACKGROUND – Sepsis is characterized by an overwhelming systemic inflammatory response to infection that may lead to multiple organ failure and death in over 20% of the estimated 49 million annual cases worldwide. Because sepsis-related inflammatory processes disturbing cardiac and endothelial cells homeostasis are still poorly understood, only few therapeutic strategies reached added-value efficacy in terms of mortality reduction in the critical care units. Using an innovative transgenic mouse line to detect the acute changes of newly synthetized proteins, we propose to assess the protein expression profile of cardiomyocytes and endothelial cells in a murine model of polymicrobial sepsis. METHODS – The Cre-recombinase mediated expression of mutant L274G-methionyl-tRNA synthetase (MetRS*) in transgenic mouse crosses enables the selective in vivo incorporation of azidonorleucine (ANL), a non-canonical methionine analog, in newly synthetized proteins. MetRS* mice expressing CDH5-creERT2 (CDH5, endothelial cells) or αMHC-MerCreMer (MCM, cardiomyocytes) underwent CLP (cecal ligation and puncture). The sepsis model was validated by echocardiography, inflammatory cytokine profiling and histology. Labeling efficiency of nascent proteins from MCM and CDH5 cells (heart and lung) were visualized by FUNCAT (Fluorescence non-canonical amino acid tagging) or purified by BONCAT (bioorthogonal non-canonical amino acid tagging) for mass spectrometry analysis. RESULTS – Significant elevation of circulating inflammatory cytokines proves the systemic inflammatory state of mice submitted to CLP compared to SHAM mice. Our experimental model also displays a significant impairment of the LV function at both systolic (reduced cardiac index) and diastolic levels (increased E/A and isovolumic relaxation time) confirming hemodynamics alteration related to sepsis. Metascape analysis showed expression changes for several proteins involved in the acute response to stress in both MCM and CDH5 samples. Overall, nascent protein synthesis is mainly reduced in MCM samples in sepsis (14 up/98 down), something not observed in CDH5 samples both in the heart (69 up/97 down) and in the lungs (137 up/43 down). Alterations in metabolic pathways such as pyruvate metabolism and glycolysis/gluconeogenesis were only observed in MCM samples while protein associated with focal adhesion, for example, was observed in heart and lungs CDH5 samples. CONCLUSIONS – The results of this study provide a better understanding of which proteins are altered in specific cell types in a sepsis model. We confirmed previously identified markers of inflammatory response in tissues, while identifying new protein candidates and signaling pathways that may contribute to key steps of sepsis detrimental effects and thus, offering potential new therapeutic avenues to curb the fatal outcomes of this disease. Supported by Canadian Institute of Health Research (CIHR) - Project Grants (399567) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

19 Pág., Microgeographical adaptation occurs when the effects of directional selection persist despite gene flow. Traits and genetic loci under selection can then show adaptive divergence, against the backdrop of little differentiation at other traits or loci. How common such events are and how strong the selection is that underlies them remain open questions. Here, we discovered and analysed microgeographical patterns of genomic divergence in four European and Mediterranean conifers with widely differing life-history traits and ecological requirements (Abies alba MIll., Cedrus atlantica [Endl.] Manetti, Pinus halepensis Mill. and Pinus pinaster Aiton) by screening pairs from geographically close forest stands sampled along steep ecological gradients. We inferred patterns of genomic divergence by applying a combination of divergence outlier detection methods, demographic modelling, Approximate Bayesian Computation inferences and genomic annotation to genomic data. Surprisingly for such small geographical scales, we showed that selection is strong in all species but generally affects different loci in each. A clear signature of selection was systematically detected on a fraction of the genome, of the order of 0.1%-1% of the loci depending on the species. The novel modelling method we designed for estimating selection coefficients showed that the microgeographical selection coefficient scaled by population size (Ns) was 2-30. Our results convincingly suggest that selection maintains within-population diversity at microgeographical scales in spatially heterogeneous environments. Such genetic diversity is likely to be a major reservoir of adaptive potential, helping populations to adapt under fluctuating environmental conditions., Agence Nationale de la Recherche, Grant/ Award Number: FLAG project (ANR-12- ADAP-0007-01); European Commission, Grant/Award Number: TOPWOOD project (MSCA-RISE-2014-645654- TOPWOOD) and grant agreement No. 676876 (GenTree); Ministère de l'Écologie, du Développement Durable et de l'Énergie, Grant/Award Number: GRAAL project (10-MCGOT-GICC-8-CVS-139)

BACKGROUND: Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear. METHODS: Using a prospective design, 1075 breast cancer patients receiving neoadjuvant chemotherapy between March 2012 and February 2017 were studied. Physical activity was assessed using the Global Physical Activity Questionnaire [GPAQ-16], quantified in standardised MET-h/wk. Chemotherapy completion was defined as the proportion of patients completing planned treatment course, requiring dose reduction, or requiring dose delay. Response was evaluated by pathologic complete response (pCR). Associations between physical activity and primary outcomes were assessed using multivariable logistic regression models. RESULTS: There was no differences between any chemotherapy completion outcome on the basis of physical activity classification. The percent of patients not completing planned treatment was 5.7% for ≦0.33 MET-h/wk, compared with 6.8% for 0.34–16.65 MET-h/wk, and 4.6% for ≥16.6 MET-h/wk (p = 0.52). No significant relationships were observed between physical activity dose classification and pCR for the overall cohort or upon stratification by clinical subtype. CONCLUSION: Future studies are required to further investigate the relationship between pre-treatment levels of physical activity and function on treatment completion and response in breast and other cancer populations. CLINICAL TRIAL REGISTRATION: NCT01993498.

In dwarf nov{\ae} and low-mass X-ray binaries, the tidal potential excites spiral waves in the accretion disc. Spiral wave driven accretion may be important in quiescent discs, where the angular momentum transport mechanism has yet to be identified. Previous studies were limited to unrealistically high temperatures for numerical studies or to specific regimes for analytical studies. We perform the first numerical simulation of spiral wave driven accretion in the cold temperature regime appropriate to quiescent discs, which have Mach numbers > 100. We use the new GPU-accelerated finite volume code Idefix to produce global hydrodynamics 2D simulations of the accretion discs of dwarf nov{\ae} systems with a fine-enough spatial resolution to capture the short scale-height of cold, quiescent discs with Mach numbers ranging from 80 to 370. Running the simulations on timescales of tens of binary orbits shows transient angular momentum transport that decays as the disc relaxes from its initial conditions. We find the angular momentum parameter {\alpha} drops to values << 0.01 , too weak to drive accretion in quiescence.

The effect of toroidal rotation on both turbulent and neoclassical transport of tungsten (W) in tokamaks is investigated using the flux-driven, global, nonlinear 5D gyrokinetic code GYSELA. Nonlinear simulations are carried out with different levels of momentum injection that drive W to the supersonic regime, while the toroidal velocity of the main ions remains in the subsonic regime. The numerical simulations demonstrate that toroidal rotation induces centrifugal forces that cause W to accumulate in the outboard region, generating an in-out poloidal asymmetry. This asymmetry enhances neoclassical inward convection, which can lead to central accumulation of W in cases of strong plasma rotation. The core accumulation of W is mainly driven by inward neoclassical convection. However, as momentum injection continues, roto-diffusion, proportional to the radial gradient of the toroidal velocity, becomes significant and generate outward turbulent flux in the case of ion temperature gradient (ITG) turbulence. Overall, the numerical results from nonlinear GYSELA simulations are in qualitative agreement with the theoretical predictions for impurity transport, as well as experimental observations., 26 pages, 10 figures, to be published

International audience; The present work aims to better understand the relation between heat treatment (Ultra High Temperature - UHT), partial demineralization of casein micelles (CMs) dispersions and their corresponded rheological properties. A multiscale analysis (SAXS, solid state NMR and Asymmetrical Flow Field Flow Fractionation (A4F)), has been used. Different samples with different levels of calcium/phosphorous demineralization (up to −30% of calcium content) have been studied before and after UHT treatment. The present data show that CM dispersions, displaying a mild demineralization, display an important decrease in viscosity after UHT. NMR shows that, during UHT, mild demineralized samples display stronger calcium/phosphorus intake than both, the non-demineralized and the strong demineralized ones. SAXS and A4F show that UHT-dependent calcium intake, in mild demineralization dispersions, seems to be responsible for a transformation of large casein aggregates into small and denser ones. This decrease of the large aggregates is probably the main reason of the UHT-dependent decrease in viscosity. These data show that a sample with a rather small amount of demineralization can have a quite important susceptibility to UHT in terms of viscosity.

Supplementary Table S2. List of precursors and related fragment ions extracted from PRM acquisition.

Supplementary Table S1. Clinico-pathological characteristics of the 116 women enrolled in the study.

Supplementary Table S3. List of the Pearson correlation coefficients between the two peptides of each protein.

Supplementary legend

Supplementary Table S4. List of proteins showing statistical differences between patients diagnosed with endometrial hyperplasia (n=9) and the other non-EC controls (n=38) with adjusted p-value 2.

Supplementary Figure 2. CTNB1, XPO2 and CAPG study according to the TCGA classification.

Purpose: Endometrial cancer (EC) diagnosis relies on the observation of tumor cells in endometrial biopsies obtained by aspiration (i.e., uterine aspirates), but it is associated with 22% undiagnosed patients and up to 50% of incorrectly assigned EC histotype and grade. We aimed to identify biomarker signatures in the fluid fraction of these biopsies to overcome these limitations.Experimental Design: The levels of 52 proteins were measured in the fluid fraction of uterine aspirates from 116 patients by LC-PRM, the latest generation of targeted mass-spectrometry acquisition. A logistic regression model was used to assess the power of protein panels to differentiate between EC and non-EC patients and between EC histologic subtypes. The robustness of the panels was assessed by the "leave-one-out" cross-validation procedure performed within the same cohort of patients and an independent cohort of 38 patients.Results: The levels of 28 proteins were significantly higher in patients with EC (n = 69) compared with controls (n = 47). The combination of MMP9 and KPYM exhibited 94% sensitivity and 87% specificity for detecting EC cases. This panel perfectly complemented the standard diagnosis, achieving 100% of correct diagnosis in this dataset. Nine proteins were significantly increased in endometrioid EC (n = 49) compared with serous EC (n = 20). The combination of CTNB1, XPO2, and CAPG achieved 95% sensitivity and 96% specificity for the discrimination of these subtypes.Conclusions: We developed two uterine aspirate-based signatures to diagnose EC and classify tumors in the most prevalent histologic subtypes. This will improve diagnosis and assist in the prediction of the optimal surgical treatment. Clin Cancer Res; 23(21); 6458–67. ©2017 AACR.

Supplementary Table S5. Clinico-pathological characteristics of the 38 women from a previous study used to validate the robustness of the diagnostic panel.

Supplementary Figure 1. LC-PRM data quality control. A. Coefficient of variation (CV) of the peptide signals quantified in the 116 uterine aspirates processed and analyzed by LC-PRM in duplicates. B. Plot representing the Pearson correlation coefficients between the peptides coming from the same protein.

Background Global warming raises serious concerns about the persistence of species and populations locally adapted to their environment, simply because of the shift it produces in their adaptive landscape. For instance, the phenological cycle of tree species may be strongly affected by higher winter temperatures and late frost in spring. Given the variety of ecosystem services they provide, the question of forest tree adaptation has received increasing attention in the scientific community and catalyzed research efforts in ecology, evolutionary biology and functional genomics to study their adaptive capacity to respond to such perturbations. Results In the present study, we used an elevation gradient in the Pyrenees Mountains to explore the gene expression network underlying dormancy regulation in natural populations of sessile oak stands sampled along an elevation cline and potentially adapted to different climatic conditions mainly driven by temperature. By performing analyses of gene expression in terminal buds we identified genes displaying significant dormancy, elevation or dormancy-by-elevation interaction effects. Our Results highlighted that low- and high-altitude populations have evolved different molecular strategies for minimizing late frost damage and maximizing the growth period, thereby increasing potentially their respective fitness in these contrasting environmental conditions. More particularly, population from high elevation overexpressed genes involved in the inhibition of cell elongation and delaying flowering time while genes involved in cell division and flowering, enabling buds to flush earlier were identified in population from low elevation. Conclusion Our study made it possible to identify key dormancy-by-elevation responsive genes revealing that the stands analyzed in this study have evolved distinct molecular strategies to adapt their bud phenology in response to temperature.

Design and synthesis of the first sulfated thiodisaccharide, analog of a heparane sulfate sequence, which is able to inhibit heparanase with an IC50 in the micromolar range.

Throughout the metastatic cascade, cancer cells are faced with harsh metabolic environments and nutritional stresses which apply selection pressure leaving only the most metabolically resilient cells to survive and form metastases. Metabolic characterisation of such cell populationsin vitrois currently challenging. Using galactose as a tool compound to mimic glycolytic limitation within the tumour microenvironment of primary and secondary neoplastic sites, we were able to uncover metabolic flexibility and plasticity of cancer cellsin vitro. In contrast to the established idea that high glycolytic flux and expression of dimeric PKM2 redirects carbons towards anabolic routes such as the pentose phosphate pathway and serine synthesis pathway (SSP), we have discovered by using stable-isotope tracing that also glycolytic limitation results in metabolic rewiring. Surprisingly, despite limited carbon availability and energetic stress, cells induce a near complete block of pyruvate kinase isozyme M2 (PKM2) to divert carbons towards SSP. Simultaneously, TCA cycle flux is sustained and oxygen consumption is increased, both supported by glutamine. Glutamine not only supports TCA cycle flux but also SSP via distinct mechanisms. Due to PKM2 block, malic enzyme exclusively supports TCA cycle flux while mitochondrial phosphoenolpyruvate carboxykinase supports SSP. Moreover, by using genetic modifications of different one-carbon (1C) cycle enzymes, we are able to reverse the PKM2 block suggesting a link between mitochondrial 1C cycle and pyruvate kinase. Thus we show that PKM2 inhibition acts as a branching point to direct glycolytic and glutamine carbons into distinct routes, overall supporting the metabolic plasticity and flexibility of cancer cells.

Metabolic rewiring is essential to enable cancer onset and progression. One important metabolic pathway that is often hijacked by cancer cells is the one-carbon cycle, in which the third carbon of serine is oxidized to formate. We have previously shown that formate production in cancer cells often exceeds the anabolic demand, resulting in formate overflow. Furthermore, we observed that high extracellular formate promotes thein vitroinvasiveness of glioblastoma (GBM) cells. However, additional data supporting thisin vitroobservation and mechanistic details remained elusive so far.In the present study, we now demonstrate that inhibition of formate overflow results in a decreased invasiveness of GBM cellsex vivoandin vivo. Additionally, we observed that exposure to exogeneous formate can induce a transiently stable pro-invasive phenotype that results in increased metastasis formationin vivo. All in all, these results suggest that a local formate increase within the tumor microenvironment may be one factor that can promote cancer cell motility and dissemination.Mechanistically, we uncover a previously undescribed interplay where formate acts as a trigger to alter fatty acid metabolism and matrix metalloproteinase (MMP) activity which in turn impacts cancer cell invasiveness. We thus highlight the role of formate as a pro-invasive metabolite. Gaining a deeper understanding of formate overflow and how it promotes invasion in cancer, may open new therapeutic opportunities to prevent cancer cell dissmination.

The last version of the World Digital Magnetic Anomaly Map (WDMAM v. 2.0) was released in 2015 (Dyment et al., EPSL, 2015; Lesur et al., EPS, 2016) with the mandate to update it using the same methodology when new data become available. The new version 2.1, compiled at 5km interval, at 5km altitude above the continents and at sea-level over the oceans, includes new datasets: (1) the complete digital aeromagnetic map of Brasil made available by ANP; (2) an improved version of the aeromagnetic map of Russia prepared by V-SEGEI; (3) the second version of the Antarctic Digital Magnetic Anomaly maP (ADMAP; Golynsky et al., GRL, 2018) which results from a remarkable international effort during and after the Second International Polar Year; (4) a new map of the Caribbean Plate and Gulf of Mexico (Garcia and Dyment, EPSL, 2021, 2022); (5) the updated Magnetic Anomaly Map of Eastern Asia prepared by the CCOP (MAMEA; Ishihara and Uchida, 2021); and (6) a new marine magnetic anomaly data compilation prepared by T. Ishihara and coworkers. The remaining data gaps are filled with a satellite anomaly model (Thebault et al., GRL, 2021). Long wavelengths of degree and order lower than 120 are filtered and replaced by those computed between order and degree 16 and 120 using the same satellite magnetic anomaly model from CHAMP and Swarm data. The new map will be presented and its significant improvements over the previous version discussed., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

The magnetic observatory network of the “Institut de physique du globe de Paris” (IPGP) includes the French national magnetic observatory, and a series of 11 other observatories in the world, managed in collaboration with local institutions, in Algeria, Senegal, Cameroon, French Guyana, Easter Island, French Polynesia, Vietnam, China, La Réunion Island and Russia. This network includes also two variometer stations set in France. The status of the observatories composing this network will be presented. Three observatories are new and not yet part of the INTERMAGNET network: the EDA observatory near Edéa in Cameroon, the SOK observatory near Niakhar in Senegal, and the REU observatory on La Réunion Island, set in 2018, 2020 and 2022, respectively. The variometer stations have been set close to Clermont-Ferrand in central France, in 2021 and near Brest in Brittany, in 2023. They deliver vector and scalar measurements in quasi real-time. The data from these observatories and stations are already freely available on the “Bureau Central de Magnétisme Terrestre” (BCMT) website, along with data from other French observatories: http://www.bcmt.fr, The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

A series of models of the Earth magnetic field and core surface flow are presented. The models were derived sequentially from year 1999 to 2022, using magnetic satellite and ground observatory data. A linear Kalman filter approach and prior statistics based on numerical dynamo runs were used. The core field and secular variation models present the same characteristics as the most recent core field models with slightly higher resolution in time. The core surface flow series of models presents large variations at high latitudes and under the western part of the Pacific Ocean. Filtering out the flow variation periods longer than 11.5 years leads to a filtered azimuthal flow with ∼7 years periodicities and patterns propagating westward by ∼60º longitude per year. These patterns are present mainly at mid- and equatorial latitudes. They are compatible with a perturbation of the main flow made of small columnar flows with rotation axis intersecting the core-mantle boundary between 10º to 15º latitudes, and flow speed of less than 5km/y. These columnar flows can be identified at all longitudes, but are particularly strong under the Pacific Ocean or under the Atlantic Ocean from 2005 to 2015., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Context: FUors outbursts are a crucial stage of accretion in young stars. However a complete mechanism at the origin of the outburst still remains missing. Aims: We aim at constraining the instability mechanism in FU Orionis star itself, by directly probing the size and the evolution in time of the outburst region with near-infrared interferometry, and to confront it to physical models of this region. Methods: FU Orionis has been a regular target of near-infrared interferometry. In this paper, we analyze more than 20 years of interferometric observations to perform a temporal monitoring of the region of the outburst, and compare it to the spatial structure deduced from 1D MHD simulations. Results: We measure from the interferometric observations that the size variation of the outburst region is compatible with a constant or slightly decreasing size over time in the H and K band. The temporal variation and the mean sizes are consistently reproduced by our 1D MHD simulations. We find that the most compatible scenario is a model of an outburst occurring in a magnetically layered disk, where a Magneto-Rotational Instability (MRI) is triggered by a Gravitational Instability (GI) at the outer edge of a dead-zone. The scenario of a pure Thermal Instability (TI) fails to reproduce our interferometric sizes since it can only be sustained in a very compact zone of the disk, Accepted for publication in A&A

A large collection of photographic paper magnetograms, covering globally an entire century is preserved in the archives of Chambon-la-forêt magnetic observatory, France. It contains magnetograms from various instruments and observatories: the National magnetic observatory (it moved from Parc-Saint-Maur, to Val-Joyeux, to Chambon-la-forêt), Bangui (Central African Republic), M’bour (Senegal), Pamatai (French Polynesia), and other observatories in metropolitan France at the beginning of the 20th century. Only values from tables of hand-written hourly values from the National magnetic observatory and overseas observatories had been digitised and made available to the scientific community.In order to access additional information on the magnetic variations recorded on the magnetograms, we developed a recovering software: RECOV. It is based on MATLAB and can be run either as a MATLAB App, or as a standalone desktop application, with MATLAB Runtime. It provides an interface for manual selection of magnetic traces that are converted into magnetic variations and calibrated time series, if definitive hourly time series are available. The user can recover magnetograms of different quality, even cases when the magnetic traces cross the temporal axis, or wrap-around traces appear during the strongest storms. We aim obtaining recovered time-series with sampling every minute, with a reliability depending on the size and resolution of magnetic traces. We present results of recovered magnetic variations during magnetic storms of 1958 and comparisons between different instruments., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Trapped ion modes (TIMs) belong to the family of ion temperature gradient (ITG) modes, which are one of the important ingredients in heat turbulent transport at the ion scale in tokamak plasmas. A global linear analysis of a reduced gyro-bounce kinetic model for trapped particle modes is performed, and a spectral method is proposed to solve the dispersion relation. Importantly, the radial profile of the particle drift velocity is taken into account in the linear analysis by considering the magnetic flux ψ dependency of the equilibrium Hamiltonian H e q ( ψ ) in both the quasi-neutrality equation and equilibrium gyro-bounce averaged distribution function F e q . Using this spectral method, linear growth rates of TIM instability in the presence of different temperature profiles and precession frequencies of trapped ions, with an approximated constant Hamiltonian and the exact ψ dependent equilibrium Hamiltonian, are investigated. The growth rate depends on the logarithmic gradient of temperature κ T , density κ n and equilibrium Hamiltonian κ Λ . With the exact ψ dependent Hamiltonian, the growth rates and potential profiles are modified significantly, compared to the cases with an approximated constant Hamiltonian. All the results from the global linear analysis agree with a semi-Lagrangian based linear Vlasov solver with good accuracy. This spectral method is very fast and requires much less computation resources compared to a linear version of the Vlasov-solver based on a semi-Lagrangian scheme.

In dwarf novæ and low-mass X-ray binaries, the tidal potential excites spiral waves in the accretion disc. Spiral wave driven accretion may be important in quiescent discs, where the angular momentum transport mechanism has yet to be identified. Previous studies were limited to unrealistically high temperatures for numerical studies or to specific regimes for analytical studies. We perform the first numerical simulation of spiral wave driven accretion in the cold temperature regime appropriate to quiescent discs, which have Mach numbers > 100. We use the new GPU-accelerated finite volume code Idefix to produce global hydrodynamics 2D simulations of the accretion discs of dwarf novæ systems with a fine-enough spatial resolution to capture the short scale-height of cold, quiescent discs with Mach numbers ranging from 80 to 370. Running the simulations on timescales of tens of binary orbits shows transient angular momentum transport that decays as the disc relaxes from its initial conditions. We find the angular momentum parameter α drops to values << 0.01 , too weak to drive accretion in quiescence.

Exascale super-computers now becoming available rely on hybrid energy-efficient architectures that involve an accelerator such as Graphics Processing Units (GPU). Leveraging the computational power of these machines often means a significant rewrite of the numerical tools each time a new architecture becomes available. To address these issues, we present Idefix, a new code for astrophysical flows that relies on the Kokkos meta-programming library to guarantee performance portability on a wide variety of architectures while keeping the code as simple as possible for the user. Idefix is based on a Godunov finite-volume method that solves the non-relativistic HD and MHD equations on various grid geometries. Idefix includes a wide choice of solvers and several additional modules (constrained transport, orbital advection, non-ideal MHD) allowing users to address complex astrophysical problems. Idefix has been successfully tested on Intel and AMD CPUs (up to 131 072 CPU cores on Irene-Rome at TGCC) as well as NVidia and AMD GPUs (up to 1024 GPUs on Adastra at CINES). Idefix achieves more than 1e8 cell/s in MHD on a single NVidia V100 GPU and 3e11 cell/s on 256 Adastra nodes (1024 GPUs) with 95% parallelization efficiency (compared to a single node). For the same problem, Idefix is up to 6 times more energy efficient on GPUs compared to Intel Cascade Lake CPUs. Idefix is now a mature exascale-ready open-source code that can be used on a large variety of astrophysical and fluid dynamics applications., Comment: 18 pages, 18 figures, 3 tables, accepted for publication in Astronomy & Astrophysics

Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase-cyclohydrolase 1 and 2 (MTHFD1 and MTHFD2). TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2, and selectively kills cancer cells. Here, we reveal that, in cells, TH9619 targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow of formate from mitochondria continues in the presence of TH9619. TH9619 inhibits the activity of MTHFD1 occurring downstream of mitochondrial formate release, leading to the accumulation of 10-formyl-tetrahydrofolate, which we term a 'folate trap'. This results in thymidylate depletion and death of MTHFD2-expressing cancer cells. This previously uncharacterized folate trapping mechanism is exacerbated by physiological hypoxanthine levels that block the de novo purine synthesis pathway, and additionally prevent 10-formyl-tetrahydrofolate consumption for purine synthesis. The folate trapping mechanism described here for TH9619 differs from other MTHFD1/2 inhibitors and antifolates. Thus, our findings uncover an approach to attack cancer and reveal a regulatory mechanism in 1C metabolism.In this study, Green, Marttila, Kiweler et al. characterize one-carbon metabolism rewiring in response to a dual MTHFD1 and MTHFD2 inhibitor. This work provides insight into one-carbon fluxes, and reveals a previously uncharacterized vulnerability in cancer cells created by folate trapping.

Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and low reactivity to exogenous catecholamines with risk of sympathetic overstimulation is well documented in septic shock. In this context, apelinergics are efficient and safe inotrope and vasoregulator in rodents. However, their utility in a larger animal model as well as the limitations with regards to the enzymatic breakdown during sepsis, need to be investigated. The therapeutic potential and degradation of apelinergics in sepsis were tested experimentally and in a cohort of patients. (1) 36 sheep with or without fecal peritonitis-induced septic shock (a large animal experimental design aimed to mimic the human septic shock paradigm) were evaluated for hemodynamic and renal responsiveness to incremental doses of two dominant apelinergics: apelin-13 (APLN-13) or Elabela (ELA), and (2) 52 subjects (33 patients with sepsis/septic shock and 19 healthy volunteers) were investigated for early levels of endogenous apelinergics in the blood, the related enzymatic degradation profile, and data regarding sepsis outcome. APLN-13 was the only one apelinergic which efficiently improved hemodynamics in both healthy and septic sheep. Endogenous apelinergic levels early rose, and specific enzymatic breakdown activities potentially threatened endogenous apelin system reactivity and negatively impacted the outcome in human sepsis. Short-term exogenous APLN-13 infusion is helpful in stabilizing cardiorenal functions in ovine septic shock; however, this ability might be impaired by specific enzymatic systems triggered during the early time course of human sepsis. Strategies to improve resistance of APLN-13 to degradation and/or to overcome sepsis-induced enzymatic breakdown environment should guide future works.

Apelins are potential candidate therapeutic molecules for hemodynamic support. The objective of this study was to assess the hemodynamic impacts of apelin-13 in a neonatal lamb model of septic shock.Lambs were randomized to receive apelin-13 or normal saline. Septic shock was induced by injecting a fecal slurry into the peritoneal cavity. Lambs underwent volume repletion (30 mL/kg over 1 h) followed by intravenous administration of 5 incremental doses (D) of apelin-13 (D1 = 0.039 to D5 = 19.5 µg/kg/h) or normal saline.Following fecal injection, mean arterial pressure (MAP) and cardiac index (CI) dropped in both groups (p 0.05). The MAP decreased non-significantly from D1 to D5 (p = 0.12) in the saline group, while increasing significantly (p = 0.02) in the apelin group (-12 (-17; 12) vs. +15 (6; 23) % (p = 0.012)). Systemic vascular resistances were higher in the apelin-13 group at D5 compared to the saline group (4337 (3239, 5144) vs. 2532 (2286, 3966) mmHg/min/mL, respectively, p = 0.046). The CI increased non-significantly in the apelin-13 group.Apelin-13 increased MAP in a neonatal lamb septic shock model.Administration of apelin-13 stabilized hemodynamics during the progression of the sepsis induced in this neonatal lamb model. Systemic vascular resistances were higher in the apelin-13 group than in the placebo group. This suggests ontogenic differences in vascular response to apelin-13 and warrants further investigation. This study suggests that apelin-13 could eventually become a candidate for the treatment of neonatal septic shock.

Claudins are a family of transmembrane proteins expressed in epithelial tissues and are the major components of tight junctions (TJs), which define barrier properties in epithelia and maintain cell polarity. How claudins regulate the formation of TJs and which functions they exert outside of them is not entirely understood. Although the long and unstructured C-terminal tail is essential for regulation, it is unclear how it is involved in these functions beyond interacting with TJ-associated proteins such as TJ protein ZO-1 (TJP1). Here, we present an interactome study of the pan-claudin family in Madin-Darby canine kidney (MDCK)-C7 cells by combining two complementary mass spectrometry-based pull-down techniques creating an interaction landscape of the entire claudin family. The interaction partners of the claudins' C termini reveal their possible implications in localized biological processes in epithelial cells and their regulation by post-translational modifications (PTMs).

Background The French National Cancer Institute recommends the use of survivorship care plans (SCP) for all cancer survivors. Developing useful SCP's requires understanding of what survivors and their providers need and how SCP's can be implemented in practice. We conducted a study to assess the delivery of SCP comprehensive binders for breast cancer women (BCW) and their general practitioners (GP) in a Cancer center from January 2019. Methods SCP binders, containing a full range of information on topics related to post-cancer care to survivor-specific information and referrals, were given to BCW during a post-treatment dedicated consultation. Then a letter, containing the treatment summary and 5-year follow-up schedule, was sent to their GPs. Comprehensive binder delivery assessment was carried out using item checkbox, and anonymous open-answered, self-reported questionnaires were sent by email to BCW and their GPs. Results The questionnaire response rates were 81.3% for BCW (n = 109/134) and 48.6% for their GPs (n = 52/107). Most BCW (85%) reported that SCP binders provided useful and comprehensive information. However, some of them (18%) felt abandoned and anonymous during the post-treatment follow-up. Most GPs found SCP letters from our anti-cancer center physicians to be useful for their patients, 38% of them had used this information to assure transition of care with other care providers. In addition, GPs were unanimous to express their feeling that this SCP could improve the long-term surveillance of BCW. There was a high concordance between BCW survivors’ and PCP’ answers, especially regarding SCPs as a communication bridge between GPs and BCW survivors. Response results concerning use of the binders: to talk about them: 59% for BCW vs. 51% for GPs, and to show them: 35% for BCW vs. 31% for GPs. Conclusion The opinions of BCW survivors’ and PCP’ opinions about the use of SCP's by our Cancer Center seems to be favourable. It is essential to implement and develop SCP's as a key tool in long-term surveillance and support for cancer patient survivors and they are a useful instrument for care providers in communication and transition.