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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.

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.

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.

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)

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

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

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.

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.

High genetic variation and extensive gene flow may help forest trees with adapting to ongoing climate change, yet the genetic bases underlying their adaptive potential remain largely unknown. We investigated range-wide patterns of potentially adaptive genetic variation in 64 populations of European beech (Fagus sylvatica L.) using 270 SNPs from 139 candidate genes involved either in phenology or in stress responses. We inferred neutral genetic structure and processes (drift and gene flow) and performed differentiation outlier analyses and gene-environment association (GEA) analyses to detect signatures of divergent selection.Beech range-wide genetic structure was consistent with the species’ previously identified postglacial expansion scenario and recolonization routes. Populations showed high diversity and low differentiation along the major expansion routes. A total of 52 loci were found to be putatively under selection and 15 of them turned up in multiple GEA analyses. Temperature and precipitation related variables were equally represented in significant genotype-climate associations. Signatures of divergent selection were detected in the same proportion for stress response and phenology-related genes. The range-wide adaptive genetic structure of beech appears highly integrated, suggesting a balanced contribution of phenology and stress-related genes to local adaptation, and of temperature and precipitation regimes to genetic clines. Our results imply a best-case scenario for the maintenance of high genetic diversity during range shifts in beech (and putatively other forest trees) with a combination of gene flow maintaining within-population neutral diversity and selection maintaining between-population adaptive differentiation.

Hexokinase 2 (Hxk2) of Saccharomyces cerevisiae is a dual function hexokinase, acting as a glycolytic enzyme and being involved in the transcriptional regulation of glucose-repressible genes. Relief from glucose repression is accompanied by phosphorylation of Hxk2 at serine 15, which has been attributed to the protein kinase Tda1. To explore the role of Tda1 beyond Hxk2 phosphorylation, the proteomic consequences of TDA1 deficiency were investigated by difference gel electrophoresis (2D-DIGE) comparing a wild type and a Δtda1 deletion mutant. To additionally address possible consequences of glucose repression/derepression, both were grown at 2% and 0.1% (w/v) glucose. A total of eight protein spots exhibiting a minimum twofold enhanced or reduced fluorescence upon TDA1 deficiency was detected and identified by mass spectrometry. Among the spot identities are—besides the expected Hxk2—two proteoforms of hexokinase 1 (Hxk1). Targeted proteomics analyses in conjunction with 2D-DIGE demonstrated that TDA1 is indispensable for Hxk2 and Hxk1 phosphorylation at serine 15. Thirty-six glucose-concentration-dependent protein spots were identified. A simple method to improve spot quantification, approximating spots as rotationally symmetric solids, is presented along with new data on the quantities of Hxk1 and Hxk2 and their serine 15 phosphorylated forms at high and low glucose growth conditions. The Δtda1 deletion mutant exhibited no altered growth under high or low glucose conditions or on alternative carbon sources. Also, invertase activity, serving as a reporter for glucose derepression, was not significantly altered. Instead, an involvement of Tda1 in oxidative stress response is suggested.

The sense of a bodily self is thought to depend on adaptive weighting and integration of bodily afferents and prior believes. While the physical body changes in shape, size and functionality across the lifespan, the sense of body ownership remains relatively stable. Yet, little is known about how multimodal integration underlying such sense of ownership is altered in ontogenetic periods of strong physical changes. We aimed to study this link both for the motor and the tactile domain in a mixed-realty paradigm where participants ranging from 7 to 80 years old will see their own body with temporally mismatching multimodal signals. Participants will either see their hand being stroked or move it in multiple trials with different visual delays. For each trial, they will judge the visuo-motor/tactile synchrony and rate the sense of ownership for the seen hand. Visual dominance which has been related to susceptibility ownership illusions and vary across lifespan, and proprioceptive acuity will be additionally assessed.

A classic example of embodied cognition is the functional connection between numeric cognition and egocentric space. It has been proposed that the representation of numbers is processed by the same functional areas of the brain as “left” and “right “. In Western culture, numbers are allegedly represented on a “number line” from left (small numbers) to right (large numbers) in mental space. Here, we aim to study how subjects’ generation of random numbers is influenced by lateral head turns. Loetscher et al. (2008) established that during a random number generation task, more small numbers were produced when turning leftwards than turning rightwards. The present experiment aims at employing the head-turning paradigm to further explore the interactions between physical and number space. Specifically, we would like to differentiate the contribution of visual versus vestibular/proprioceptive signals to the number line by visually inverting the horizontal axis during head-rotation. If the egocentric perspective relies stronger on visual signals, the effect of generating more small numbers when turning left and vice versa will be reduced when the axis is inverted (inverted condition) compared to when it’s not (natural condition), while there should be no difference if the vestibular/proprioceptive cues are more dominant. To further investigate the dependency of this effect on individual weighting strategies we will assess visual dependency through a rod-and-frame task adapted from Rothacher et al. (2008). Proprioceptive sensitivity, which includes vestibular and proprioceptive signals, will be assessed using a newly developed proprioceptive sensitivity task. We expect that the difference in small numbers generated when turning left between conditions will be correlated with participants’ visual-dependency. We also predict an inverted pattern for the exploratory measure of participants’ proprioceptive sensitivity.

We investigate the potential of embodied virtual reality for enhancing imagery rescripting, a well-validated therapy for treating aversive memories (Wild & Clark, 2011; Morina et al., 2017). In a mixed design paradigm, healthy participants with a mildly distressing social aversive memory will either undergo a traditional imagery rescripting (IR) session based on pure imagery with an in-sensu self compassion component or such session with an embodied self-compassion component involving virtual reality (embodied rescripting: ER). We will compare affective and physiological aspects related to the aversive memory before, right after and one week after the intervention for each group and between them. We hypothesize that the inclusion of multisensory embodied self compassion (ER group) will improve the affective relation to the aversive memory as reflected by our measures.

Direkli Cave, located in the Taurus Mountains of southern Turkey, was occupied by Late Epipaleolithic hunters-gatherers for the seasonal hunting and processing of game including large numbers of wild goats. We report genomic data from new and published

Abnormal uterine bleeding (AUB) is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women's health, since all women presenting with bleeding will undergo sequential invasive tests, avoidable in 90-95% of those women who do not have EC. This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of EC diagnostic protein biomarkers. Samples collected with a Rovers Cervex Brush ® and the HC2 DNA collection device, Digene, were the most suitable for EC proteomic studies. A clinical retrospective study assessing the expression of 52 EC-related proteins in 41 patients (22 EC; 19 non-EC), by targeted proteomics, identified SERPINH1, VIM, TAGLN, PPIA, CSE1L, and CTNNB1 as potential EC protein biomarkers in cervical fluids (AUC > 0.8). This study opens an avenue for developing non-invasive protein-based EC diagnostic tests, which will improve the standard of care for gynecological patients. Background: Abnormal uterine bleeding is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women's health since all women presenting with bleeding will undergo sequential invasive tests, which are avoidable for 90-95% of those women who do not have EC. Methods: This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of protein biomarkers to diagnose EC. We evaluated the protein quantity and the proteome composition of five cervical sampling methods. Results: Samples collected with a Rovers Cervex Brush ® and the HC2 DNA collection device, Digene, were the most suitable samples for EC proteomic studies. Most proteins found in uterine fluids were also detected in both cervical samples. We then conducted a clinical retrospective study to assess the expression of 52 EC-related proteins in 41 patients (22 EC; 19 non-EC), using targeted proteomics. We identified SERPINH1, VIM, TAGLN, PPIA, CSE1L, and CTNNB1 as potential protein biomarkers to discriminate between EC and symptomatic non-EC women with abnormal uterine bleeding in cervical fluids (AUC > 0.8). Conclusions: This study opens an avenue for developing non-invasive protein-based EC diagnostic tests, which will improve the standard of care for gynecological patients.

n northeastern Africa, the beginning of the Holocene is characterized by major technical and sociocultural changes that particularly affected food management: the invention of pottery, and the intensive exploitation of grasses and wild bovids in a humid climatic phase. However, the first evidence for food production appears in desert contexts and during increasing aridification. Although its local or exogenous origin is still debated, the adoption of cattle herding in this region at the end of the seventh millennium BC appears to have been in response to this limited environment, with sev- eral head of livestock providing greater food security. Overall, herding took more than 6,000 years to diffuse across the continent in a variety of ways: migration, technology transfer, and acculturation. Ultimately, herding economies took on many forms, combining or alternating animal husbandry with the use of wild and domestic resources. Within herding, strong relationships developed between humans and domesticates. Cattle in particular are an excel- lent example of this. From the fifth millennium BC onward, certain livestock farming societies developed close links with cattle, extending well beyond the food sphere. In many pastoral cultures from northeastern Africa, the role of bovines continued to expand throughout the millennia. In addition to acting as a food source, they also acquired a social func- tion, materialized in funerary and ritual practices, and by the physical transformations applied to them.

Drought and waterlogging impede tree growth and may even lead to tree death. Oaks, an emblematic group of tree species, have evolved a range of adaptations to cope with these constraints. The two most widely distributed European species, pedunculate (PO; Quercus robur L.) and sessile oak (SO; Quercus petraea Matt. Lieb), have overlapping ranges, but their respective distribution are highly constrained by local soil conditions. These contrasting ecological preferences between two closely related and frequently hybridizing species constitute a powerful model to explore the functional bases of the adaptive responses in oak. We exposed oak seedlings to waterlogging and drought, conditions typically encountered by the two species in their respective habitats, and studied changes in gene expression in roots using RNA-seq. We identified genes that change in expression between treatments differentially depending on species. These “species × environment”-responsive genes revealed adaptive molecular strategies involving adventitious and lateral root formation, aerenchyma formation in PO, and osmoregulation and ABA regulation in SO. With this experimental design, we also identified genes with different expression between species independently of water conditions imposed. Surprisingly, this category included genes with functions consistent with a role in intrinsic reproductive barriers. Finally, we compared our findings with those for a genome scan of species divergence and found that the expressional candidate genes included numerous highly differentiated genetic markers between the two species. By combining transcriptomic analysis, gene annotation, pathway analyses, as well as genome scan for genetic differentiation among species, we were able to highlight loci likely involved in adaptation of the two species to their respective ecological niches.

The continuous technical improvement in sensitivity and specificity placed mass spectrometry as an alternative method for analyzing clinical samples. In parallel to the rapid development of discovery proteomics, targeted acquisition has been implemented as a complementary option for measuring a small set of proteins with high sensitivity and robustness in a large sample cohort. The combination of trapped ion mobility with a rapid time-of-flight (TOF) mass spectrometer improves the sensitivity even further and triggers the development of prm-PASEF.This article discusses the development of prm-PASEF and its advantages over the existing targeted and discovery methods for analyzing clinical samples. We are also highlighting the different requirements for the use of prm-PASEF on clinical samples.prm-PASEF takes advantage of a dual ion-mobility trap enabling highly multiplexed targeted acquisition. It allows the implementation of a short chromatographic separation setup without sacrificing the number of targeted peptides. Analyzing clinical samples by prm-PASEF holds the promise to significantly improve throughput while maintaining sensitivity to detect the selected target proteins.