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We report the discovery of a candidate galaxy with a photo-z of z ∼ 12 in the first epoch of the James Webb Space Telescope (JWST) Cosmic Evolution Early Release Science Survey. Following conservative selection criteria, we identify a source with a robust z phot = 11.8 − 0.2 + 0.3 (1σ uncertainty) with m F200W = 27.3 and ≳7σ detections in five filters. The source is not detected at λ < 1.4 μm in deep imaging from both Hubble Space Telescope (HST) and JWST and has faint ∼3σ detections in JWST F150W and HST F160W, which signal a Lyα break near the red edge of both filters, implying z ∼ 12. This object (Maisie’s Galaxy) exhibits F115W − F200W > 1.9 mag (2σ lower limit) with a blue continuum slope, resulting in 99.6% of the photo-z probability distribution function favoring z > 11. All data-quality images show no artifacts at the candidate’s position, and independent analyses consistently find a strong preference for z > 11. Its colors are inconsistent with Galactic stars, and it is resolved (r h = 340 ± 14 pc). Maisie’s Galaxy has log M */M ⊙ ∼ 8.5 and is highly star-forming (log sSFR ∼ −8.2 yr−1), with a blue rest-UV color (β ∼ −2.5) indicating little dust, though not extremely low metallicity. While the presence of this source is in tension with most predictions, it agrees with empirical extrapolations assuming UV luminosity functions that smoothly decline with increasing redshift. Should follow-up spectroscopy validate this redshift, our universe was already aglow with galaxies less than 400 Myr after the Big Bang.

The 2016 law on prostitution in France introduced the so-called Swedish model approach to sex work, which, at the national level, criminalises those who purchase sex rather than the sex workers themselves. Alongside the repressive character of the law, lawmakers introduced a number of social policy measures through the implementation of a ‘prostitution exit programme’. Whilst some pioneering research has sought to evaluate the impact of penalising the clients of sex workers, no survey has yet focused on the outcomes of prostitution exit programmes. Based on qualitative data, including interviews with sex workers and grassroots organisations, this article aims to analyse how the programme was implemented and its overall outcomes. The interviews we conducted shed particular light on the fact that the implementation of the programme is impacted on by the application of restrictive migration policies.

IntroductionAmyloidosis typing is crucial to determine the best therapeutic strategy for patients. Since conventional histological techniques often fail, the identification of amyloid precursors by mass spectrometry became the new standard. However, without quantification, selecting the amyloid precursor from proteins that may be ubiquitous under non-pathological conditions may be equivocal. Therefore, we quantified protein enrichment in amyloid deposits to improve typing.MethodsProtein enrichment was measured by extracted ion chromatogram based label free quantification by comparing a microdissected amyloid area with a non-amyloid area. We assessed the discrimination ability of candidate precursors with this approach compared to the two practiced identification methods.ResultsAs proof of concept, we selected seven cases, 5 typical of the most common amyloidosis subtypes and typed by immunostainings, 2 inconclusive after immunohistochemistry. Proteins associated with amyloid deposits were identified in all samples confirming the pathology. When the routine clinical mass spectrometric identification techniques allowed unambiguous conclusions for 2/3 of 7 cases, quantification of the enrichment ratio in the amyloid deposit allowed unambiguous precursor selection in all cases.ConclusionQuantification of precursor enrichment in amyloid deposits is a promising optimization for amyloidosis typing. Incorporated into routine clinical processes, it will improve patient care in difficult diagnostic situations.

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PDF file - 52K, PCR primers used in this study

The molecular mechanisms and cellular targets of sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma (HCC), remain to be fully characterized. Recent studies have shown that sorafenib induces tumor cell death through the activation of endoplasmic reticulum stress signaling and/or autophagy in various cellular models. Using liver cancer–derived cell lines, we specifically show that the IRE1 and phosphorylated extracellular signal–regulated kinase arms of the unfolded protein response (UPR) become activated upon sorafenib treatment, whereas the ATF6 arm is inhibited. Our results also reveal that sorafenib treatment causes disruption to the secretory pathway, as witnessed by the fragmentation of the Golgi apparatus and the induction of autophagy. On the basis of these observations, we tested the relevance of the AAA+ ATPase p97/VCP as a potential functional target of sorafenib. Our results show that p97/VCP tyrosine phosphorylation is prevented upon sorafenib treatment, and that this can be correlated with enhanced membrane association. Moreover, we show that DBeQ, a recently discovered inhibitor of p97/VCP, enhances sorafenib-mediated toxicity in cultured cells. Our data show a novel mechanism for sorafenib-mediated cell death in HCC, which depends on the integrity of the secretory pathway; and we identify p97/VCP phosphorylation as a potential target for improved sorafenib treatment efficacy in patients. Mol Cancer Ther; 11(12); 2610–20. ©2012 AACR.

PDF file - 877K, Figure S1. (A) Quantification of Xbp1 mRNA splicing shown in Figure 2A. (B) Wild-type HepG2 cells were either not treated or treated with 10 μM Sorafenib for 2 h followed by staining for giantin, a Golgi complex marker, α-tubulin, as a marker for the microtubules and Hoechst 33342 as a nuclear marker. (C) Cells treated as above were immunostained against giantin and phalloidin was used to stain the actin cytoskeleton. Images were acquired by wide-field fluorescence microscopy. Scale bars correspond to 25 μm.

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PDF file - 510K, Figure S2. (A) HepG2 cells were either not treated or treated with 10 μM Sorafenib for 4 h, after which they were either fixed or Sorafenib removed from cells and fresh medium added for a further 2 h. Cells were then stained with anti Giantin (green). Scale bars correspond to 25 μm. (B) The number of cells containing fragmented Golgi complex was quantified. Between 200 and 400 cells were analyzed for each condition and results are represented as the means � SD. Student's t-test *: p < 0.03, compared to control, #: p < 0.03 HepG2 mock transfected compared to IRE1-DN transfected cells.

PDF file - 36K, Quantification of eiF2α phosphorylation upon sorafenib treatment. X-ray film were quantified using scanning densitometry and data are represented as arbitrary units � SD.

Cereal bran possesses enzymes and antinutrients which should be reduced for their usability as a food ingredient high in dietary fiber, minerals, and antioxidants. This study investigated the influence of high-intensity ultrasound on enzymatic and antioxidant activities, phytic acid content (PA), and functional and rheological properties of oat and barley bran. Ultrasonication was performed at three specific energies (87 kJ/kg, 217.5 kJ/kg, and 348 kJ/kg), without or with pulsation (5 s emission, 10 s pause). Bran was assessed for β-glucanase, phytase and antioxidant activities, PA and total phenolic content, hydration, and rheological properties. β-glucanase from oat bran was inactivated up to 82% and from barley bran up to 55%, depending on the ultrasound-specific energy and pulsation. PA and antioxidant activities were higher in native oat bran (PA 17.35 mg/g d.w., FRAP 6.96 μmol TE/g d.w., 3.30 μmol FAE/g d.w.) compared to barley bran (PA 11.53 mg/g d.w., FRAP 2.27 μmol TE/g d.w., 5.30 μmol FAE/g d.w.). In both bran types, phytase activity increased (40–44%) after treatments at 87 kJ/kg, and on average, PA was reduced by 17% in oat bran and by 39% in barley bran. Depending on the energy and pulsation, bran ultrasonication reduced total phenolic content (27–55%), antioxidant activity (by 28–48%), complex viscosity (62–71%), and maximum stress tolerance (46–68%) while increased water swelling (42–48%) and retention capacity (44–59%). Hence, high-intensity ultrasound is a useful technique in reducing antinutrients while altering the enzymatic activity and functional properties of the bran. These results could help the wider application of bran in food production.

We report on the host properties of five X-ray-luminous active galactic nuclei (AGN) identified at 3 < z < 5 in the first epoch of imaging from the Cosmic Evolution Early Release Science Survey. Each galaxy has been imaged with the JWST Near-Infrared Camera, which provides rest-frame optical morphologies at these redshifts. We also derive stellar masses and star formation rates for each host by fitting its spectral energy distribution using a combination of galaxy and AGN templates. We find that three of the AGN hosts have spheroidal morphologies, one is a bulge-dominated disk, and one is dominated by pointlike emission. None are found to show strong morphological disturbances that might indicate a recent interaction or merger event. When compared to a sample of mass-matched inactive galaxies, we find that the AGN hosts have morphologies that are less disturbed and more bulge-dominated. Notably, all four of the resolved hosts have rest-frame optical colors consistent with a quenched or poststarburst stellar population. The presence of AGN in passively evolving galaxies at z > 3 is significant because a rapid feedback mechanism is required in most semianalytic models and cosmological simulations to explain the growing population of massive quiescent galaxies observed at these redshifts. Our findings show that AGN can continue to inject energy into these systems after their star formation is curtailed, potentially heating their halos and preventing renewed star formation. Additional observations will be needed to determine what role this feedback may play in helping to quench these systems and/or maintain their quiescent state.

With the advent of globalization, family diversity is further advanced by the rates of marriage migration, which are rising in Europe, the Americas, and most prominently in South Korea, Japan, Taiwan, Singapore, and other countries of Northeast Asia. Hélène Le Bail explores the geography and routes of cross-border marriages along with the positive and adverse consequences of this trend. She highlights the contradictory discourse surrounding cross-border marriages, which on one hand is seen as a cultural threat to a homogenous society, and on the other hand as a favorable solution to declining fertility rates in places such as South Korea, where public policy now lends support to the “multicultural family.”

International audience; Temporal networks of face-to-face interactions between individuals are useful proxies of the dynamics of social systems on fast time scales. Several empirical statistical properties of these networks have been shown to be robust across a large variety of contexts. In order to better grasp the role of various mechanisms of social interactions in the emergence of these properties, models in which schematic implementations of such mechanisms can be carried out have proven useful. Here, we put forward a new framework to model temporal networks of human interactions, based on the idea of a co-evolution and feedback between (i) an observed network of instantaneous interactions and (ii) an underlying unobserved social bond network: social bonds partially drive interaction opportunities, and in turn are reinforced by interactions and weakened or even removed by the lack of interactions. Through this co-evolution, we also integrate in the model well-known mechanisms such as triadic closure, but also the impact of shared social context and non-intentional (casual) interactions, with several tunable parameters. We then propose a method to compare the statistical properties of each version of the model with empirical face-to-face interaction data sets, to determine which sets of mechanisms lead to realistic social temporal networks within this modeling framework.

Oat and barley bran are high in dietary fiber (β-glucans), minerals, and antioxidants, have high activity of enzymes, but possess also antinutrients. This study aimed to investigate the influence of high-intensity ultrasound on enzyme and antioxidant activities, phytic acid content, as well as functional and rheological properties of oat and barley bran. Ultrasonic treatment was performed at 24 kHz on a 15% bran water suspension, at three specific energies (87, 217.5, and 348 kJ/kg), with or without pulsation (5 sec every 10 sec). Bran was assessed for β-glucanase and phytase activity, phytic acid and total phenolic content, antioxidant activity, hydration, and rheological properties. β-glucanase from oat bran was inactivated up to 82% and from barley bran up to 55%, in dependence of ultrasound specific energy and pulsation. In both bran types, phytase activity increased by 40–44% after treatments with 87 kJ/kg but decreased by 89–94% at 348 kJ/kg. Phytic acid was reduced on average in oat bran by 17% and in barley bran by 39%. Depending on the energy and pulsation, the ultrasonication of both bran types reduced total phenolic content (27–55%), antioxidant activity (by 28–48%), complex viscosity (62–71%) and maximum stress tolerated by the sample (46–68%). In contrast, water swelling (42–48%) and water retention capacity (44–59%) increased for both bran types. Hence, high-intensity ultrasound is a useful technique in reducing antinutrients, while altering the enzyme activity and functional properties of the bran. These results could help wider application of bran in food production.

In response to the sustainability issues that agriculture faces in advanced economies, agroecology has gained increasing relevance in scientific, political, and social debates. This has promoted discussion about transitions to agroecology, which represents a significant advancement. Accordingly, it has become a growing field of research. We reviewed the literature on and in support of farm transitions to agroecology in advanced economies in order to identify key research challenges and suggest innovative research paths. Our findings can be summarized as follows: (1) Research that supports exploration and definition of desired futures, whether based on future-oriented modeling or expert-based foresight approaches, should more explicitly include the farm level. It should stimulate the creativity and design ability of farmers and other stakeholders, and also address issues of representation and power among them. (2) Research that creates awareness and assesses farms before, during or after transition requires more holistic and dynamic assessment frameworks. These frameworks need to be more flexible to adapt to the diversity of global and local challenges. Their assessment should explicitly include uncertainty due to the feedback loops and emergent properties of transitions. (3) Research that analyzes and supports farms during transition should focus more on the dynamics of change processes by valuing what happens on the farms. Research should especially give more credence to on-farm experiments conducted by farmers and develop new tools and methods (e.g., for strategic monitoring) to support these transitions. This is the first review of scientific studies of farm transitions to agroecology. Overall, the review indicates that these transitions challenge the system boundaries, temporal horizons, and sustainability dimensions that agricultural researchers usually consider. In this context, farm transitions to agroecology require changes in the current organization and funding of research in order to encourage longer term and more adaptive configurations.

The new realisation of the International Terrestrial Reference Frame, the ITRF2020, becamepublicly available in April 2022. For each of the four contributing space-geodetic techniques, it provides station positions and linear station velocities at a given epoch,as well as post-seismic deformation parametric models for stations subject to majorearthquakes, and annual and semi-annual periodic terms for all stations. Discontinuities areintroduced to take into consideration changes related to the equipment or to the station motion.During the evaluation of the ITRF2020, discrepancies were found in the temporal position modelling between two stations of the research facility of Ny-Ålesund on Svalbard (Norway). The possible impact that these discrepancies may have on the ITRF2020 is so far not well studied. In this study, we hypothesize that such discrepancies are the result of neglecting non-linear vertical motions resulting from contemporary ice cap melting in this area. The vertical motion at sites that only experience glacial isostatic adjustment (GIA) are well described by linear uplift rates. However, GNSS and GRACE time series show that several sites in polar areas that are still surrounded by ice caps experience accelerated rates of contemporary ice melting due to climate change.To be consistent with the idea of providing non-linear post-seismic deformation models at sites experiencing earthquakes, we suggest that sites experiencing non-linear motions due to contemporary ice-cap melting should also be provided with an adjusted uplift model. We assess the impact of this approach onterrestrial reference frameresults, focusing particularly on two geodetic techniques, VLBI and GNSS., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

The main objective was to assess the performance of the neutrophil-lymphocyte ratio (NLR) for early prediction of delayed neurological impairment and cerebral contusion worsening in patients with mild-to-moderate traumatic brain injury (TBI).Over a 3-year period, every adult patient triaged to our level 1 trauma center with brain contusion and Glasgow Coma Scale (GCS) of 10 or greater were retrospectively included. The main study outcome was the occurrence of delayed clinical deterioration, defined as a GCS10 and/or a secondary need for mechanical ventilation, within 5 days after TBI. The performance of NLR for prediction of delayed clinical deterioration was assessed by receiver operating characteristic (ROC) curve.Overall, 115 patients were included and 16 (14%) presented a delayed clinical deterioration. Overall, the NLR at ED admission was higher in patients who developed a delayed clinical deterioration (18 [12-29] vs 8 [5-13], p = 0.0003). The area under the ROC curves for NLR at ED admission in predicting delayed clinical deterioration was 0.79 [0.65-0.93] and NLR15 was found to be independently associated with the occurrence of delayed clinical deterioration (adjusted OR = 10.1 [95%CI: 2.3-45.6]).The NLR at ED admission was independently associated with the occurrence of delayed clinical deterioration, although limited by a poor discriminative value by itself. Further studies are needed to test the predictive value of composite scoring systems including NLR for prevention of under-triage of patients with mild-to-moderate TBI.

Jazz, the illustrated book by Henri Matisse, is a testament to the vitality of the artist in the last decade of his career. The book consists of twenty illustrations reproduced in 370 copies using a stencil-based printing technique and the same Linel gouaches the artist had used for the original maquettes. This study reports on the comprehensive analysis carried out to identify the pigments in the gouaches used in Jazz by transmitted and reflectance infrared, Raman, SERS, and X-ray fluorescence spectroscopies, and describes the lightfastness of these gouaches as evaluated by microfaedometry. This study also highlights the necessity of a multi-analytical approach for comprehensive identification of artist materials and investigates the suitability of portable and non-invasive techniques. The results were consistent across the three copies investigated: a portfolio in the collection of the Museum of Modern Art in New York and two books in the collection of the Musée National d’Art Moderne in Paris. In total, 39 distinct colors were characterized, with the magenta, pinks, and blues being the most fugitive.

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Immune checkpoint blockade primarily benefits patients with viral HCC. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by the emergence of high entropy myeloid cell states and myeloid-biased NK cell differentiation. We identify a discrete population of tumor-infiltrating myeloid cells, predominant in the steatohepatitis setting, that expresses a variety of myeloid lineage-affiliated genes, including granulocyte, macrophage and dendritic cell features, and can be identified in HCC tumors based on selective dual expression ofTREM1andCD163. Functional characterization reveals that TREM1+CD163+myeloid cells highly express TGFβ and IL-13RA, localize to HCC fibrotic lesions, and potently suppress T cell effector functionsex vivo, a function further potentiated by TREM1 engagement. We refer to this population as TREM1+CD163+regulatory myeloid cells (TREM1+CD163+Mreg). Deconvolution analyses in large cohorts of patients with HCC and other solid tumors reveals that the density of TREM1+CD163+Mregincreases in advanced stages, associates with poor prognosis, and therapeutic resistance to PD-1 blockade. Our data support myeloid subset-targeted immunotherapies to treat HCC and identify TREM1 as a therapeutic target.HIGHLIGHTSAtlas of hepatic innate immune cells (100,000 transcriptomes) from patients with HCCCore signatures to identify, discriminate and localize innate lymphoid and myeloid cellsA population of TREM1+CD163+myeloid cells, referred to as TREM1+CD163+Mreg, expands in steatohepatitis HCCTREM1+CD163+Mregexpress granulocyte- and macrophage/dendritic cell-lineage genesTREM1+CD163+Mregpotently suppress T cell effector functions, which is potentiated by TREM1 engagement by cognate ligandsTREM1+CD163+Mregproduce high levels of TGFβ and populate fibrotic lesionsThe density of TREM1+CD163+Mregincreases in advanced HCC and associate with poor patient survivalThe density of TREM1+CD163+Mregassociates with resistance to immune checkpoint blockade in other solid tumors

This study investigated the impacts of the complete substitution of sucrose by maltitol and/or sorbitol on the dough-crumb transition in biscuits. To this end, the phenomena of starch gelatinization/melting were studied at different moisture contents, both in the biscuit dough and model systems, by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and by environmental scanning electron microscopy (ESEM). Observation of doughs in ESEM revealed sorbitol had a structure very different from sucrose and maltitol crystals. After forming the dough pieces, it could be seen that at least some sugar and maltitol crystals were still present while sorbitol flakes were solubilized. At a limiting real water content (~20% dry basis), adding sweeteners to the mixture increased the gelatinization temperature, more markedly for sucrose and maltitol, as well as increasing the enthalpy. These results were confirmed by the model systems analyses. The calorimetric study with mixing batch cells revealed that sorbitol dissolved completely while maltitol and sucrose competed with the flour constituents to capture water. The proportion of water available for the sorption of the starch grain and its gelatinization was therefore different according to the affinity of the sweetener for water, and might influence the degree and temperature of starch gelatinization/melting.

Protocol

International audience; Background & aims: Noninvasive tests (NITs) of liver fibrosis have been suggested to be less accurate in type 2 diabetes mellitus (T2DM). We aimed to compare the accuracy of 6 NITs between patients with or without T2DM, explain any differences, and adapt diagnostic algorithms for clinical practice accordingly.Methods: We included 1051 patients with nonalcoholic fatty liver disease with liver biopsy, blood fibrosis tests (Nonalcoholic Fatty Liver Disease Fibrosis Score, FIB4, Fibrotest, FibroMeter), vibration-controlled transient elastography (VCTE), and the combinatory elasto-blood test FibroMeterVCTE. The study endpoint was advanced fibrosis on liver biopsy.Results: NIT areas under the receiver operating characteristic curve were significantly lower in patients with T2DM, mostly because of a decrease in specificity. For FIB4, this decrease in specificity was only related to the higher age of patients with T2DM enrolled. For Fibrotest, FibroMeter, and FibroMeterVCTE, the decrease in specificity was related to age but also to higher alpha2-macroglobulin level, which is known to increase in T2DM. Sensitivity was unaffected by T2DM, but it masked a doubled raw number of false negatives because of the 2-fold higher prevalence of advanced fibrosis in that setting. The sequential algorithm FIB4-vibration-controlled transient elastography had 90.3% accuracy in patients without T2DM vs 79.0% in those with (P < .001). Algorithms using first-line specialized tests maintained a low rate of false negatives and false positives in T2DM.Conclusions: The decrease in NIT accuracy observed in T2DM is partly biased by the different characteristics of the groups studied, but also linked to T2DM itself through modification of the levels of some NIT biomarkers. Specialized tests should be used first-line to diagnose advanced liver fibrosis in T2DM.

We present an investigation into the first 500 Myr of galaxy evolution from the Cosmic Evolution Early Release Science (CEERS) survey. CEERS, one of 13 JWST ERS programs, targets galaxy formation from z~0.5 to z>10 using several imaging and spectroscopic modes. We make use of the first epoch of CEERS NIRCam imaging, spanning 35.5 sq. arcmin, to search for candidate galaxies at z>9. Following a detailed data reduction process implementing several custom steps to produce high-quality reduced images, we perform multi-band photometry across seven NIRCam broad and medium-band (and six Hubble broadband) filters focusing on robust colors and accurate total fluxes. We measure photometric redshifts and devise a robust set of selection criteria to identify a sample of 26 galaxy candidates at z~9-16. These objects are compact with a median half-light radius of ~0.5 kpc. We present an early estimate of the z~11 rest-frame ultraviolet (UV) luminosity function, finding that the number density of galaxies at M_UV ~ -20 appears to evolve very little from z~9 to z~11. We also find that the abundance (surface density [arcmin^-2]) of our candidates exceeds nearly all theoretical predictions. We explore potential implications, including that at z>10 star formation may be dominated by top-heavy initial mass functions, which would result in an increased ratio of UV light per unit halo mass, though a complete lack of dust attenuation and/or changing star-formation physics may also play a role. While spectroscopic confirmation of these sources is urgently required, our results suggest that the deeper views to come with JWST should yield prolific samples of ultra-high-redshift galaxies with which to further explore these conclusions., 41 pages, 20 figures, 6 tables, submitted to ApJL. Key results in Figures 13-15, discussed in Sections 7 and 8

OBJECTIVE Our aim was to determine independent risk factors of clinical bleeding of hepatocellular adenoma (HCA) to define a better management strategy. SUMMARY BACKGROUND DATA HCA is a rare benign liver tumor with severe complications: malignant transformation that is rare (5%-8%) and more often, hemorrhage (20%-27%). To date, only size > 5 cm and histological subtype (possibly sonic hedgehog) are associated with bleeding, but these criteria are not clearly established. METHODS We retrospectively collected data from a cohort of 268 patients with HCA managed in our tertiary center, from 1984 to 2020 and focused on clinical bleeding. Hemorrhage was considered severe when it required intensive care and moderate when bleeding symptoms required a hospitalization. We included 261 patients, of whom 130 (49.8%) had multiple HCAs or liver adenomatosis. All surgical specimen and liver biopsy were reviewed by an experienced liver pathologist and reclassified in the light of the current immunohistochemistry. Mean duration of follow-up was 93.3 months (range 1-363). We analyzed type, frequency, consequences of bleeding, and risk factors among clinical data and HCA characteristics. RESULTS Eighty-three HCA (31.8%) were hemorrhagic. There were 4 pregnant women with 1 newborn death. One patient died before treatment. Surgery was performed in 78 (94.0%) patients. Mortality was nil and severe complications occurred in 11.5%. Multivariate analysis identified size (OR 1.02 [1.01-1.02], P < 0.001), shHCA (OR 21.02 [5.05-87.52], P < 0.001), b-catenin mutation on exon 7/8 (OR 6.47 [1.78-23.55], P = 0.0046), chronic alcohol consumption (OR 9.16 [2.47-34.01], P < 0.001) as independent risk factors of clinical bleeding. CONCLUSIONS This series, focused on the hemorrhagic risk of HCA, shows that size, but rather more molecular subtype is determinant in the natural history of HCA.

Background and Aims : Through an exploratory proteomic approach based on typical hepatocellular adenomas (HCAs), we previously identified a diagnostic biomarker for a distinctive subtype of HCA with high risk of bleeding, already validated on a multicenter cohort. We hypothesized that the whole protein expression deregulation profile could deliver much more informative data for tumor characterization. Therefore, we pursued our analysis with the characterization of HCA proteomic profiles, evaluating their correspondence with the established genotype/phenotype classification and assessing whether they could provide added diagnosis and prognosis values. Approach and Results : From a collection of 260 cases, we selected 52 typical cases of all different subgroups on which we built a reference HCA proteomics database. Combining laser microdissection and mass-spectrometry–based proteomic analysis, we compared the relative protein abundances between tumoral (T) and nontumoral (NT) liver tissues from each patient and we defined a specific proteomic profile of each of the HCA subgroups. Next, we built a matching algorithm comparing the proteomic profile extracted from a patient with our reference HCA database. Proteomic profiles allowed HCA classification and made diagnosis possible, even for complex cases with immunohistological or genomic analysis that did not lead to a formal conclusion. Despite a well-established pathomolecular classification, clinical practices have not substantially changed and the HCA management link to the assessment of the malignant transformation risk remains delicate for many surgeons. That is why we also identified and validated a proteomic profile that would directly evaluate malignant transformation risk regardless of HCA subtype. Conclusions : This work proposes a proteomic-based machine learning tool, operational on fixed biopsies, that can improve diagnosis and prognosis and therefore patient management for HCAs.

Despite beneficial effects in acute heart failure, recombinant relaxin-2 full therapeutic potential has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units. A multiparametric optimization of relaxin B-chain led to the identification of single chain lipidated peptide agonists of RXFP1 like SA10SC-RLX with subcutaneous bioavailability and extended half-life. SA10SC-RLX has sub nanomolar activity on cells expressing human RXFP1 and molecular modeling associated with study of different RXFP1 mutant were used to decipher the mechanism of SA10SC-RLX interaction with RXFP1. Telemetry was performed in rat where SA10SC-RLX was able to engage RXFP1 after subcutaneous administration and this, without tachyphylaxis after repeated dosing. Renal blood flow was then used as a translational model to evaluate RXFP1 activation. SA10SC-RLX increased renal blood flow and decreased renal vascular resistance in rats as reported with relaxin in humans. In conclusion, SA10SC-RLX mimics relaxin activity in in vitro and in vivo models of acute RXFP1 engagement. SA10SC-RLX represents a new class of long-lasting RXFP1 agonist, suitable for once daily subcutaneous administration in patients and potentially paving the way to new treatments for chronic fibrotic and cardiovascular diseases.

Malignant pleural mesothelioma, a tumor arising from the membrane covering the lungs and the inner side of the ribs, is a cancer in which genetic alterations of genes encoding proteins that act on or are part of the Hippo-YAP1 signaling pathway are frequent. Dysfunctional Hippo signaling may result in aberrant activation of the transcriptional coactivator protein YAP1, which binds to and activates transcription factors of the TEAD family. Recent studies have associated elevated YAP1 protein activity with a poor prognosis of malignant mesothelioma and its resistance to current therapies, but its role in tumor maintenance is unclear. In this study, we investigate the dependence of malignant mesothelioma on YAP1 signaling to maintain fully established tumors in vivo. We show that downregulation of YAP1 in a dysfunctional Hippo genetic background results in the inhibition of YAP1/TEAD-dependent gene expression, the induction of apoptosis, and the inhibition of tumor cell growth in vitro. The conditional downregulation of YAP1 in established tumor xenografts leads to the inhibition of YAP1-dependent gene transcription and eventually tumor regression. This effect is only seen in the YAP1-activated MSTO-211H mesothelioma xenograft model, but not in the Hippo-independent HCT116 colon cancer xenograft model. Our data demonstrate that, in the context of a Hippo pathway mutated background, YAP1 activity alone is enough to maintain the growth of established tumors in vivo, thus validating the concept of inhibiting the activated YAP1-TEAD complex for the treatment of malignant pleural mesothelioma patients.

International audience; Trophic support of species-rich tropical fish communities remains uncertain in small forest streams where dense and constant canopy cover strongly limits the solar radiation available to aquatic producers. We sampled >1300 fish from 80 species in 14 remote headwater streams during the dry season in French Guiana. Carbon and nitrogen stable isotope analyses and mixing models were run to estimate the trophic position (TP) of each species and its dependence on terrestrial organic carbon sources. Matching patterns were found between nitrogen stable isotope ratios and the literature on diets of species at the base and top of the food web. Nearly 60% of the species fed exclusively on animal prey (mean TP >3), including piscivorous and parasitic fish species. Phylogenetic analysis revealed that TP were distributed broadly along the phylogeny and changed gradually within lineages. Carbon stable isotope ratios differed strongly between herbivores that fed on aquatic primary producers and those that fed on terrestrial plants along banksides. Terrestrial carbon was dominant in nearly 90% of species, and most of them depended more or less exclusively on terrestrial carbon. Ancestral state reconstructions indicated that only a few lineages showed local changes toward the consumption of algal carbon. We conclude that fish in neotropical headwater streams shaded by a dense tree canopy depend strongly on terrestrial subsidies. Changes in this aquatic-terrestrial linkage would have major consequences for the remarkable fish biodiversity in these streams.; La contribution majoritaire du carbone algal aux réseaux trophiques d'eau douce a été démontrée, même dans la partie amont des bassins versants où les apports de carbone terrestre sont substantiels. Ces apports terrestres proviennent principalement de lignocellulose, une source de nourriture que les consommateurs n'assimilent pas bien sous les climats tempérés, contrairement aux algues de haute qualité nutritive. La prédominance de l'apport algal reste en questionnement dans les petits cours d'eau en forêt tropicale, qui diffèrent entre autre par un couvert forestier dense et constant limitant fortement le rayonnement solaire disponible pour les producteurs aquatiques, par les essences végétales elles même, et par les caractéristiques physicochimiques du sol et de l'eau. Nous avons étudié l'écologie trophique de 80 espèces de poissons (> 1300 individus) issues de 14 ruisseaux pauvres en nutriments dans un contexte de forêt tropicale préservée en Guyane Française. Nous avons rassemblé des informations sur leur alimentation, puis combiné ces connaissances avec l'analyse des isotopes stables C et N dans leur muscle et dans une variété d'aliments potentiels, aquatiques et terrestres. Nous avons calculé leur position trophique et leur dépendance vis‐à‐vis des sources de C terrestres ou aquatiques. Nos résultats montrent des profils trophiques concomitants entre les isotopes stables de l'azote et la littérature sur les régimes alimentaires des espèces à la base et au sommet du réseau trophique, validant la pertinence d'une telle approche combinée pour ces communautés de poissons. Nous constatons qu'une majorité des espèces (60%) se nourrit de proies animales, y compris des poissons strictement piscivores. Une grande majorité (près de 90%) dépend principalement de sources alimentaires terrestres (>50% de C terrestre dans leurs tissus), et 65% en dépendrait plus ou moins exclusivement (>75% de C terrestre). Leurs niveaux trophiques sont très variables, depuis l'herbivorie (Myloplus ternetzi) jusqu’à l'ichtyoparasitisme (Ituglanis nebulosus). Seules 9 espèces sont plus fortement liées aux sources de C aquatique, et elles ont majoritairement un niveau trophique bas (Farlowella reticulata, Cyphocharax helleri, Ancistrus temminckii, Ancistrus aff. hoplogenys, Satanoperca rhynchitis and Ancistrus cf. leucostictus). Ces traits trophiques ont été utilisés dans une analyse phylogénétique pour tester leur pertinence évolutive. Ceci révèle que les positions trophiques sont largement réparties le long de la phylogénie et changent progressivement au sein des lignées. Les reconstructions d'états ancestraux indiquent toutefois que quelques lignées montrent des changements ponctuels vers la consommation de carbone algal. Nous concluons que les poissons des petits cours d'eau néotropicaux ombragés par un couvert forestier dense dépendent très fortement des apports nutritifs terrestres. Des changements dans ce lien aquatique‐terrestre auraient des conséquences majeures sur la remarquable biodiversité des poissons de ces cours d'eau. Ces connaissances aideront les gestionnaires de l'environnement à mieux appréhender les impacts potentiels des projets d'exploitation des ressources naturelles, et à proposer des solutions de remédiations plus pertinentes dans les cas de réhabilitation de sites en fin d'exploitation.

L’épidémie de Covid-19 a été une nouvelle étape dans l’avènement d’une cause, celle de la mise en évidence et de la dénonciation d’actes et de discours racistes en France à l’égard des personnes d’origine chinoise, et plus largement d’origine asiatique. L’on ne peut comprendre la rapide circulation du hashtag #JeNeSuisPasUnVirus et la multiplication des interviews de Français d’origine asiatique dans la presse, fin janvier 2020, sans revenir sur une décennie de mobilisations collectives en faveur de cette cause. À partir des mobilisations des immigrés chinois depuis 2010, déjà bien documentées, cet article propose de se focaliser sur le rôle des descendants d’immigrés chinois et du Sud-Est asiatique, qui ont multiplié les espaces d’échange et les supports de communication, tout au long de la dernière décennie, pour mettre en place des actions collectives de lutte contre les « stéréotypes qui tuent » et pour faire reconnaître l’existence d’un « racisme anti-asiatique ».

Plan de l'article : - Une approche de l’intimité des immigrées chinoises par la sociologie clinique ; - Conflit de loyautés chez Ruguo, épouse et amante, mère dévouée et femme amoureuse ; - Interroger le passé pour mieux appréhender le présent ; - Le poids des surdéterminations sociales et psychiques au cours de la migration ; - Vivre pour les autres avant de penser à soi, singularité d’une génération de Chinois

Resume Consequence d’un dysfonctionnement metabolique, la steatose hepatique ou NAFLD (Non-Alcoholic Fatty Liver Disease) peut etre presente au cours de nombreuses maladies nutritionnelles ou metaboliques, au premier rang desquelles l’obesite. La steatose peut etre diagnostiquee dans le cadre d’un bilan ou du suivi d’une pathologie predisposante ou de decouverte fortuite sur une echographie abdominale. L’obesite est la cause principale de steatose (NAFLD), retrouvee chez environ 80 % des enfants ayant une steatose hepatique, notamment apres l’âge de 10 ans. Une composante inflammatoire (NASH) peut s’accompagner d’une fibrose mais le risque d’evolution vers une cirrhose est faible chez l’enfant. Toutefois, du fait de l’augmentation croissante de la prevalence de l’obesite, ce risque ne doit pas etre neglige et un diagnostic precoce est indispensable afin d’instaurer une prise en charge multidisciplinaire le plus tot possible. Par ailleurs, il faut savoir evoquer d’autres causes de steatose hepatique, nutritionnelles ou metaboliques, en particulier chez le jeune enfant.