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Abstract Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.

Abstract The Kramers escape problem is a paradigmatic model for the kinetics of rare events, which are usually characterized by Arrhenius law. So far, analytical approaches have failed to capture the kinetics of rare events in the important case of non-Markovian processes with long-term memory, as occurs in the context of reactions involving proteins, long polymers, or strongly viscoelastic fluids. Here, based on a minimal model of non-Markovian Gaussian process with long-term memory, we determine quantitatively the mean FPT to a rare configuration and provide its asymptotics in the limit of a large energy barrier E. Our analysis unveils a correction to Arrhenius law, induced by long-term memory, which we determine analytically. This correction, which we show can be quantitatively significant, takes the form of a second effective energy barrier $$E^{\prime} \, < \, E$$ E ′ < E and captures the dependence of rare event kinetics on initial conditions, which is a hallmark of long-term memory. Altogether, our results quantify the impact of long-term memory on rare event kinetics, beyond Arrhenius law.

Abstract High and low pathogenicity avian influenza viruses (HPAIV, LPAIV) are the primary causes of poultry diseases worldwide. HPAIV and LPAIV constitute a major threat to the global poultry industry. Therefore, early detection and well-adapted surveillance strategies are of the utmost importance to control the spread of these viruses. Volatile Organic Compounds (VOCs) released from living organisms have been investigated over the last decades as a diagnostic strategy. Mass spectrometry instruments can analyze VOCs emitted upon viral infection. Selected ion flow tube mass spectrometry (SIFT-MS) enables direct analysis of cell headspace in less than 20 min. As a proof-of-concept study, we investigated the ability of a SIFT-MS coupled sparse Partial Least Square-Discriminant Analysis analytical workflow to discriminate IAV-infected cells. Supernatants of HPAIV, LPAIV, and control cells were collected from 1 to 72 h post-infection and analyzed using our analytical workflow. At each collection point, VOCs' signatures were first identified based on four independent experiments and then used to discriminate the infectious status of external samples. Our results indicate that the identified VOCs signatures successfully discriminate, as early as 1-h post-infection, infected cells from the control cells and differentiated the HPAIV from the LPAIV infection. These results suggest a virus-dependent VOCs signature. Overall, the external samples' status was identified with 96.67% sensitivity, 100% specificity, and 97.78% general accuracy.

Abstract Meiotic rapid prophase chromosome movements (RPMs) require connections between the chromosomes and the cytoskeleton, involving SUN (Sad1/UNC-84)-domain-containing proteins at the inner nuclear envelope (NE). RPMs remain significantly understudied in plants, with respect to their importance in the regulation of meiosis. Here, we demonstrate that Arabidopsis thaliana meiotic centromeres undergo rapid (up to 500 nm/s) and uncoordinated movements during the zygotene and pachytene stages. These centromere movements are not affected by altered chromosome organization and recombination but are abolished in the double mutant sun1 sun2. We also document the changes in chromosome dynamics and nucleus organization during the transition from leptotene to zygotene, including telomere attachment to SUN-enriched NE domains, bouquet formation, and nucleolus displacement, all of which were defective in sun1 sun2. These results establish A. thaliana as a model species for studying the functional implications of meiotic RPMs and demonstrate the mechanistic conservation of telomere-led RPMs in plants.

Abstract Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

Abstract Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8+ T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster could enhance CD8+ T-cell cytotoxicity. Altogether, these data pave the way for therapy targeting YAP1 in ECM-myCAF in HGSOC.

Abstract In Apicomplexa, rhoptry discharge is essential for invasion and involves an apical vesicle (AV) docking one or two rhoptries to a macromolecular secretory apparatus. Toxoplasma gondii is armed with 10–12 rhoptries and 5-6 microtubule-associated vesicles (MVs) presumably for iterative rhoptry discharge. Here, we have addressed the localization and functional significance of two intraconoidal microtubule (ICMT)-associated proteins instrumental for invasion. Mechanistically, depletion of ICMAP2 leads to a dissociation of the ICMTs, their detachment from the conoid and dispersion of MVs and rhoptries. ICMAP3 exists in two isoforms that contribute to the control of the ICMTs length and the docking of the two rhoptries at the AV, respectively. This study illuminates the central role ICMTs play in scaffolding the discharge of multiple rhoptries. This process is instrumental for virulence in the mouse model of infection and in addition promotes sterile protection against T. gondii via the release of key effectors inducing immunity.

The Surface Water and Ocean Topography (SWOT) mission was launched on 16 December 2022 to measure water levels over both open ocean and inland waters. To achieve these objectives, the SWOT Payload contains an innovative Ka-band radar interferometer, called KaRIn, completed with a nadir altimeter called POSEIDON-3C that was switched on a month after launch and a few days before KaRIn. POSEIDON-3C measurements provide a link between large-scale phenomena and high resolution. The POSEIDON-3C design is based on POSEIDON-3B, its predecessor on board JASON-3. It is also a dual-frequency radar altimeter operating in C- and Ku-bands, but with some improvements to enhance its performance. Even though it is a Low Resolution Mode altimeter, its performance over open ocean, inland waters and coastal zones are indeed excellent. This paper first describes the POSEIDON-3C design and its modes with a focus on its new features and the Digital Elevation Model that drives its open-loop tracking mode. Then, we assess the in-flight performances of the altimeter from an instrumental point of view. For that purpose, special and routine calibrations have been realized. They show the good performance and stability of the radar. In-flight assessments thus provide confidence when it comes to ensuring excellent altimeter measurement stability throughout the mission duration.

Abstract Caspase recruitment-domain containing protein 9 (CARD9) is a key signaling pathway in macrophages but its role in atherosclerosis is still poorly understood. Global deletion of Card9 in Apoe -/- mice as well as hematopoietic deletion in Ldlr -/- mice increases atherosclerosis. The acceleration of atherosclerosis is also observed in Apoe -/- Rag2 -/- Card9 -/- mice, ruling out a role for the adaptive immune system in the vascular phenotype of Card9 deficient mice. Card9 deficiency alters macrophage phenotype through CD36 overexpression with increased IL-1β production, increased lipid uptake, higher cell death susceptibility and defective autophagy. Rapamycin or metformin, two autophagy inducers, abolish intracellular lipid overload, restore macrophage survival and autophagy flux in vitro and finally abolish the pro-atherogenic effects of Card9 deficiency in vivo. Transcriptomic analysis of human CARD9-deficient monocytes confirms the pathogenic signature identified in murine models. In summary, CARD9 is a key protective pathway in atherosclerosis, modulating macrophage CD36-dependent inflammatory responses, lipid uptake and autophagy.

Tyrosine kinase inhibitors (TKI) directed against MET have been recently approved to treat advanced non-small cell lung cancer (NSCLC) harbouring activating MET mutations. This success is the consequence of a long characterization of MET mutations in cancers, which we propose to outline in this review. MET, a receptor tyrosine kinase (RTK), displays in a broad panel of cancers many deregulations liable to promote tumour progression. The first MET mutation was discovered in 1997, in hereditary papillary renal cancer (HPRC), providing the first direct link between MET mutations and cancer development. As in other RTKs, these mutations are located in the kinase domain, leading in most cases to ligand-independent MET activation. In 2014, novel MET mutations were identified in several advanced cancers, including lung cancers. These mutations alter splice sites of exon 14, causing in-frame exon 14 skipping and deletion of a regulatory domain. Because these mutations are not located in the kinase domain, they are original and their mode of action has yet to be fully elucidated. Less than five years after the discovery of such mutations, the efficacy of a MET TKI was evidenced in NSCLC patients displaying MET exon 14 skipping. Yet its use led to a resistance mechanism involving acquisition of novel and already characterized MET mutations. Furthermore, novel somatic MET mutations are constantly being discovered. The challenge is no longer to identify them but to characterize them in order to predict their transforming activity and their sensitivity or resistance to MET TKIs, in order to adapt treatment.

Introduction: Although, there is an increasing focus on inactive or extinct seafloor massive sulfide (SMS) deposits driven by the possibility of marine mining, only few studies have been devoted to them so far. The Trans-Atlantic Geotraverse (TAG) hydrothermal field is probably one of the best-studied hydrothermal systems even if the relict SMS deposits known since the mid-1980s have not been thoroughly explored.Objectives: The main objective of this study was to describe the characteristics of these so-called inactive sites.Methods: During four different expeditions, we acquired high-resolution acoustic data and performed numerous human occupied vehicle (HOV) dive operations including extensive rock sampling and in-situ temperature measurements.Results and Discussion: We discovered thirteen new hydrothermal mounds including six large (i.e. > 5,000 m2) deposits making the TAG hydrothermal field one of the largest accumulation of hydrothermal materials (21.1 Mt) known on the seafloor. However, copper and zinc grades of the largest SMS deposits remain low (i.e. < 1.4 wt%) even compared to on-land volcanogenic massive sulfide deposits. Additionally, eight areas of diffuse hydrothermal fluid flow were identified challenging the presumed inactivity of these SMS deposits and, for the first time, emphasizing the importance of low temperature (LT) hydrothermal activity in whole the TAG field. Inactive and weakly active SMS deposits exhibit a large diversity of surface mineralization (e.g. sulfides, Fe-Mn mineralization, jasper) illustrating complexity of hydrothermal activities but also different ageing history. Several mounds no longer have visible sulfide chimneys and are covered by a widespread layer of manganese and iron oxyhydroxides attesting the longevity of diffuse fluid flow at specific locations even long after last high-temperature (HT) hydrothermal activity has ceased. This contrasts with SMS deposits that are devoid of extensive LT precipitates but characterized by standing or topped sulfide chimney indicating a relatively abrupt cessation of HT hydrothermal activity.Conclusion: Together these results allow us to propose evolution models to explain the diversity of active, weakly active and inactive SMS deposits in the TAG hydrothermal field.

Abstract Our goal was to investigate the effects of head-thorax elevation (HUP) during chest compressions (CC) on lung ventilation. A prospective study was performed on seven human cadavers. Chest was automatically compressed-decompressed in flat position and during progressive HUP from 18 to 35°. Lung ventilation was measured with electrical impedance tomography. In each cadaver, 5 sequences were randomly performed: one without CC at positive end-expiratory pressure (PEEP) 0cmH2O, 3 s with CC at PEEP0, 5 or 10cmH2O and 1 with CC and an impedance threshold device at PEEP0cmH2O. The minimal-to-maximal change in impedance (VTEIT in arbitrary unit a.u.) and the minimal impedance in every breathing cycle (EELI) the) were compared between flat, 18°, and 35° in each sequence by a mixed-effects model. Values are expressed as median (1st–3rd quartiles). With CC, between flat, 18° and 35° VTEIT decreased at each level of PEEP. It was 12416a.u. (10,689; 14,442), 11,239 (7667; 13,292), and 6457 (4631; 9516), respectively, at PEEP0. The same was true with the impedance threshold device. EELI/VTEIT significantly decreased from − 0.30 (− 0.40; − 0.15) before to − 1.13 (− 1.70; − 0.61) after the CC (P = 0.009). With HUP lung ventilation decreased with CC as compared to flat position. CC are associated with decreased in EELI.

Abstract A new sensitive method to determine polonium-210 (210Po) and lead-210 (210Pb) in a diversity of environmental samples was developed. For fresh and marine waters, Po was pre-concentrated using a titanium (III) hydroxide (Ti(OH)3) co-precipitation. Solid environmental samples were digested with nitric acid (HNO3) and hydrogen peroxide (H2O2). The alpha thin layer source was prepared using CuS micro-precipitation and 210Po was measured by alpha spectrometry. Lead-210 was left to decay for up to a year and indirectly measured via its progeny, 210Po. The chemical recoveries for 210Po and 210Pb were high, 90% and 97%, respectively, for a large variety of samples and a very low minimum detectable activity (MDA) was obtained. The method was validated using standardized solutions and certified reference materials.

Abstract The phylum Apicomplexa comprises important eukaryotic parasites that invade host tissues and cells using a unique mechanism of gliding motility. Gliding is powered by actomyosin motors that translocate host-attached surface adhesins along the parasite cell body. Actin filaments (F-actin) generated by Formin1 play a central role in this critical parasitic activity. However, their subcellular origin, path and ultrastructural arrangement are poorly understood. Here we used cryo-electron tomography to image motile Cryptosporidium parvum sporozoites and reveal the cellular architecture of F-actin at nanometer-scale resolution. We demonstrate that F-actin nucleates at the apically positioned preconoidal rings and is channeled into the pellicular space between the parasite plasma membrane and the inner membrane complex in a conoid extrusion-dependent manner. Within the pellicular space, filaments on the inner membrane complex surface appear to guide the apico-basal flux of F-actin. F-actin concordantly accumulates at the basal end of the parasite. Finally, analyzing a Formin1-depleted Toxoplasma gondii mutant pinpoints the upper preconoidal ring as the conserved nucleation hub for F-actin in Cryptosporidium and Toxoplasma. Together, we provide an ultrastructural model for the life cycle of F-actin for apicomplexan gliding motility.

Abstract Progress in sample preparation for scRNA-seq is reported based on RevGel-seq, a reversible-hydrogel technology optimized for samples of fresh cells. Complexes of one cell paired with one barcoded bead are stabilized by a chemical linker and dispersed in a hydrogel in the liquid state. Upon gelation on ice the complexes are immobilized and physically separated without requiring nanowells or droplets. Cell lysis is triggered by detergent diffusion, and RNA molecules are captured on the adjacent barcoded beads for further processing with reverse transcription and preparation for cDNA sequencing. As a proof of concept, analysis of PBMC using RevGel-seq achieves results similar to microfluidic-based technologies when using the same original sample and the same data analysis software. In addition, a clinically relevant application of RevGel-seq is presented for pancreatic islet cells. Furthermore, characterizations carried out on cardiomyocytes demonstrate that the hydrogel technology readily accommodates very large cells. Standard analyses are in the 10,000-input cell range with the current gelation device, in order to satisfy common requirements for single-cell research. A convenient stopping point after two hours has been established by freezing at the cell lysis step, with full preservation of gene expression profiles. Overall, our results show that RevGel-seq represents an accessible and efficient instrument-free alternative, enabling flexibility in terms of experimental design and timing of sample processing, while providing broad coverage of cell types.

Abstract Large earthquakes breaking the frontal faults of the Himalayan thrust system produce surface ruptures, quickly altered due to the monsoon conditions. Therefore, the location and existence of the Mw8.3 1934 Bihar–Nepal surface ruptures remain vividly disputed. Even though, previous studies revealed remnants of this surface rupture at the western end of the devastated zone, ruptures extent remains undocumented in its central part. Evidence for recent earthquakes is revealed along the frontal thrust in this region. The Khutti Khola river cuts an 8 m-high fault scarp exposing Siwalik siltstone thrusted over recent alluvial deposits, with faults sealed by a colluvial wedge and undeformed alluvial sediments. Detrital charcoals radiocarbon dating reveals that the last event occurred between the seventeenth century and the post-bomb era, advocating for the 1934 earthquake as the most recent event. In the hanging wall, fluvial terraces associated with fault scarps were abandoned after a penultimate event that happened after the tenth century, a rupture we associate with the historic earthquake of 1255CE. Slips of 11–17 m and 14–22 m for the 1934 and 1255 earthquakes, respectively, compare well with the ~ 10–15 m slip deficit accumulated between the two earthquakes, suggesting that most of the deformation along the front is accommodated by surface-rupturing earthquakes.

Abstract Pseudomonas aeruginosa is one of the leading causes of healthcare-associated infections. For this study, the susceptibility profiles to antipseudomonal antibiotics and a quaternary ammonium compound, didecyldimethylammonium chloride (DDAC), widely used as a disinfectant, were established for 180 selected human and environmental hospital strains isolated between 2011 and 2020. Furthermore, a genomic study determined resistome and clonal putative relatedness for 77 of them. During the ten-year study period, it was estimated that 9.5% of patients’ strains were resistant to carbapenems, 11.9% were multidrug-resistant (MDR), and 0.7% were extensively drug-resistant (XDR). Decreased susceptibility (DS) to DDAC was observed for 28.0% of strains, a phenotype significantly associated with MDR/XDR profiles and from hospital environmental samples (p

Studying human-animal interactions in domestic species and how they affect the establishment of a positive Human-Animal Relationship (HAR) may help us improve animal welfare and better understand the evolution of interspecific interactions associated with the domestication process. Understanding and describing the quality of an HAR requires information on several aspects of the animal biology and emotional states (social, spatial and postural behaviours, physiological and cognitive states). Growing evidence shows that acoustic features of animal vocalisations may be indicators of emotional states. Here, we tested the hypothesis that vocal structure may indicate the quality of HAR. At weaning, 30 piglets were positively handled by an experimenter who talked to and physically interacted with them three times a day, while 30 other piglets only received the contact necessary for proper husbandry. After two weeks, we recorded the behaviours and vocalisations produced in the presence of the static experimenter for 5 min. We repeated this test two weeks later, after a conditioning period during which human presence with additional positive contacts was used as a reward for all piglets. We hypothesized this conditioning period would lead to a positive human-piglet relationship for all piglets. As expected, piglets that were positively handled at weaning expressed a higher attraction toward the experimenter, and, after the conditioning, piglets that were not positively handled at weaning expressed a similar level of attraction than the positively handled ones. Piglets positively handled at weaning produced shorter grunts than the other ones, regardless of the context of recording, which may indicate a more positive affect. During reunions with the static experimenter, a more positive HAR was associated with a decrease in vocal reactivity to human proximity. However, during reunions with the experimenter providing additional positive contacts and over the conditioning, spatial proximity to the human systematically triggered shorter and higher pitched grunts, which may indicate a more positive emotional state. Results first show that changes in vocal structure are consistent with indicators of positive states in the presence of a human. Second, these changes are stronger when the human positively interact with the piglets, supposedly emphasizing a higher positive arousal state during these interactions. We show that vocalisation structure may be a promising indicator of the quality of human-pig relationship.

Seven IN Absentia (SINA) is a small family of genes coding for ubiquitin-ligases that play major roles in regulating various plant growth and developmental processes, as well as in plant response to diverse biotic and abiotic stresses. Here, we studied the SINA genes family in bread wheat Triticum aestivum which is a culture of major importance for food security worldwide. One hundred and forty-one SINA family genes have been identified in bread wheat and showed that their number is very high compared to other plant species such as A. thaliana or rice. The expansion of this family seems to have been more important in monocots than in eudicots. In bread wheat, the chromosome 3 distal region is the site of a massive amplification of the SINA family, since we found that 83 of the 141 SINA genes are located on this chromosome in the Chinese Spring variety. This amplification probably occurred as a result of local duplications, followed by sequences divergence. The study was then extended to 4856 SINA proteins from 97 plant species. Phylogenetic and structural analyses identified a group of putative ancestral SINA proteins in plants containing a 58 aminoacid specific signature. Based on sequence homology and the research of that "Ancestral SINA motif" of 58 amino acids, a methodological process has been proposed and lead to the identification of functional SINA genes in a large family such as the Triticae that might be used for other species. Finally, tis paper gives a comprehensive overview of wheat gene family organization and functionalization taken the SINA genes as an example.

Here we report on Neanderthal engravings on a cave wall at La Roche-Cotard (LRC) in central France, made more than 57±3 thousand years ago. Following human occupation, the cave was completely sealed by cold-period sediments, which prevented access until its discovery in the 19th century and first excavation in the early 20th century. The timing of the closure of the cave is based on 50 optically stimulated luminescence ages derived from sediment collected inside and from around the cave. The anthropogenic origin of the spatially-structured, non-figurative marks found within the cave is confirmed using taphonomic, traceological and experimental evidence. Cave closure occurred significantly before the regional arrival of H. sapiens, and all artefacts from within the cave are typical Mousterian lithics; in Western Europe these are uniquely attributed to H. neanderthalensis. We conclude that the LRC engravings are unambiguous examples of Neanderthal abstract design.

Did Neanderthal produce a bone industry? The recent discovery of a large bone tool assemblage at the Neanderthal site of Chagyrskaya (Altai, Siberia, Russia) and the increasing discoveries of isolated finds of bone tools in various Mousterian sites across Eurasia stimulate the debate. Assuming that the isolate finds may be the tip of the iceberg and that the Siberian occurrence did not result from a local adaptation of easternmost Neanderthals, we looked for evidence of a similar industry in the Western side of their spread area. We assessed the bone tool potential of the Quina bone-bed level currently under excavation at chez Pinaud site (Jonzac, Charente-Maritime, France) and found as many bone tools as flint ones: not only the well-known retouchers but also beveled tools, retouched artifacts and a smooth-ended rib. Their diversity opens a window on a range of activities not expected in a butchering site and not documented by the flint tools, all involved in the carcass processing. The re-use of 20% of the bone blanks, which are mainly from large ungulates among faunal remains largely dominated by reindeer, raises the question of blank procurement and management. From the Altai to the Atlantic shore, through a multitude of sites where only a few objects have been reported so far, evidence of a Neanderthal bone industry is emerging which provides new insights on Middle Paleolithic subsistence strategies.

Quantum control of lossy systems is known to be achieved by adiabatic passage via an approximate dark state relatively immune to loss, such as the emblematic example of stimulated Raman adiabatic passage (STIRAP) featuring a lossy excited state. By systematic optimal control study, via the Pontryagin maximum principle, we design alternative more efficient routes that, for a given admissible loss, feature an optimal transfer with respect to the cost defined as (i) the pulse energy (energy minimization) or (ii) the pulse duration (time minimization). The optimal controls feature remarkably simple sequences in the respective cases: (i) operating far from a dark state, of π-pulse type in the limit of low admissible loss, or (ii) close to the dark state with a counterintuitive pulse configuration sandwiched by sharp intuitive sequences, referred to as the intuitive/counterintuitive/intuitive (ICI) sequence. In the case of time optimization, the resulting stimulated Raman exact passage (STIREP) outperforms STIRAP in term of speed, accuracy, and robustness for low admissible loss.

We investigate the extent to which a two-level quantum system subjected to an external time-dependent drive can be characterized by supervised learning. We apply this approach to the case of bang-bang control and the estimation of the offset and the final distance to a given target state. For any control protocol, the goal is to find the mapping between the offset and the distance. This mapping is interpolated using a neural network. The estimate is global in the sense that no a priori knowledge is required on the relation to be determined. Different neural network algorithms are tested on a series of data sets. We show that the mapping can be reproduced with very high precision in the direct case when the offset is known, while obstacles appear in the indirect case starting from the distance to the target. We point out the limits of the estimation procedure with respect to the properties of the mapping to be interpolated. We discuss the physical relevance of the different results.

Accounting for temporal changes in carbon dioxide (CO _2 ) effluxes from freshwaters remains a challenge for global and regional carbon budgets. Here, we synthesize 171 site-months of flux measurements of CO _2 based on the eddy covariance method from 13 lakes and reservoirs in the Northern Hemisphere, and quantify dynamics at multiple temporal scales. We found pronounced sub-annual variability in CO _2 flux at all sites. By accounting for diel variation, only 11% of site-months were net daily sinks of CO _2 . Annual CO _2 emissions had an average of 25% (range 3%–58%) interannual variation. Similar to studies on streams, nighttime emissions regularly exceeded daytime emissions. Biophysical regulations of CO _2 flux variability were delineated through mutual information analysis. Sample analysis of CO _2 fluxes indicate the importance of continuous measurements. Better characterization of short- and long-term variability is necessary to understand and improve detection of temporal changes of CO _2 fluxes in response to natural and anthropogenic drivers. Our results indicate that existing global lake carbon budgets relying primarily on daytime measurements yield underestimates of net emissions.

We investigate the problem of population transfer in a two-states system driven by an external electromagnetic field featuring a few cycles, until the extreme limit of two or one cycle. Taking the physical constraint of zero-area total field into account, we determine strategies leading to ultrahigh-fidelity population transfer despite the failure of the rotating wave approximation. We specifically implement adiabatic passage based on adiabatic Floquet theory for a number of cycles as low as 2.5 cycles, finding and making the dynamics follow an adiabatic trajectory connecting the initial and targeted states. Nonadiabatic strategies with shaped or chirped pulses, extending the π-pulse regime to two- or single-cycle pulses, are also derived.

The terrestrial carbon and water cycles are strongly coupled. As atmospheric carbon dioxide concentration increases, climate and the coupled hydrologic cycle are modified, thus altering the terrestrial water cycle and the availability of soil moisture necessary for plants’ carbon dioxide uptake. Concomitantly, rising surface carbon dioxide concentrations also modify stomatal (small pores at the leaf surface) regulation as well as biomass, thus altering ecosystem photosynthesis and transpiration rates. Those coupled changes have profound implications for the predictions of the carbon and water cycles. This paper reviews the main mechanisms behind the coupling of the terrestrial water and carbon cycles. We especially focus on the key role of dryness (atmospheric dryness and terrestrial water availability) on carbon uptake, as well as the predicted impact of rising carbon dioxide on the water cycle. Challenges related to this coupling and the necessity to constrain it based on observations are finally discussed.

A quantum process encodes the causal structure that relates quantum operations performed in local laboratories. The process matrix formalism includes as special cases quantum mechanics on a fixed background space-time, but also allows for more general causal structures. Motivated by the interpretation of processes as a resource for quantum information processing shared by two (or more) parties, with advantages recently demonstrated both for computation and communication tasks, we investigate the notion of composition of processes. We show that under very basic assumptions such a composition rule does not exist. While the availability of multiple independent copies of a resource, e.g. quantum states or channels, is the starting point for defining information-theoretic notions such as entropy (both in classical and quantum Shannon theory), our no-go result means that a Shannon theory of general quantum processes will not possess a natural rule for the composition of resources.

In general relativity, the causal structure between events is dynamical, but it is definite and observer-independent; events are point-like and the membership of an event A in the future or past light-cone of an event B is an observer-independent statement. When events are defined with respect to quantum systems however, nothing guarantees that the causal relationship between A and B is definite. We propose to associate a causal reference frame corresponding to each event, which can be interpreted as an observer-dependent time according to which an observer describes the evolution of quantum systems. In the causal reference frame of one event, this particular event is always localised, but other events can be ‘smeared out’ in the future and in the past. We do not impose a predefined causal order between the events, but only require that descriptions from different reference frames obey a global consistency condition. We show that our new formalism is equivalent to the pure process matrix formalism (Araújo et al 2017 Quantum 1 10). The latter is known to predict certain multipartite correlations, which are incompatible with the assumption of a causal ordering of the events—these correlations violate causal inequalities. We show how the causal reference frame description can be used to gain insight into the question of realisability of such strongly non-causal processes in laboratory experiments. As another application, we use causal reference frames to revisit a thought experiment Zych et al (arXiv: 1708.00248 ) where the gravitational time dilation due to a massive object in a quantum superposition of positions leads to a superposition of the causal ordering of two events.

In patients with melanoma, increased RAS/mitogen-activated protein kinase (MAPK) pathway activity is known to drive chemotherapy resistance. Here, the authors identify CDK12 as a downstream effector of the RAS/MAPK pathway and therapeutic target which mediates chemotherapy resistance through increased expression of DNA repair associated genes.

The persistence of random walker can quantify the kinetics of transport limited reactions and predict the time to reach a target, but is challenging for non-stationary random processes with a large number of degrees of freedom. The authors introduce a method to determine the persistence exponent of random processes with general non-stationary dynamics.

Abstract The role of commensal birds in the epidemiology of pathogens in poultry farms remains unclear. Our study aimed to identify potential key species for interactions with domestic ducks on one free-range duck farm in southwest France. Methods combined direct individual observations on duck outdoor foraging areas, network analysis, and general linear mixed models of abundances. Results showed a wide diversity of wild bird species visiting foraging areas, heavily dominated in frequency by White wagtails (Motacilla alba) and Sparrows (Passer domesticus and Passer montanus). These also were the only species seen entering duck premises or perching on drinkers in the presence of ducks. Moreover, White wagtails were the species most frequently observed on the ground and in close proximity to ducks. Network analysis suggested the role of White wagtails and Sparrows in linking ducks to other wild birds on the farm. The abundance of White wagtails was positively associated with open vegetation, with the presence of ducks and particularly in the afternoon, while the abundance of Sparrows was positively associated only with the fall-winter season. By precisely characterising interactions, the study was able to identify few wild bird species which should be prioritized in infectious investigations at the interface with poultry.

Abstract Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. This bacterial species is subdominant in a healthy physiological state of the gut microbiota (eubiosis) in adults, but can become dominant and cause infections when the intestinal homeostasis is disrupted (dysbiosis). The relatively high concentrations of bile acids deoxycholate (DCA) and taurocholate (TCA) hallmark eubiosis and dysbiosis, respectively. This study aimed to better understand how E. faecalis adapts to DCA and TCA. We showed that DCA impairs E. faecalis growth and possibly imposes a continuous adjustment in the expression of many essential genes, including a majority of ribosomal proteins. This may account for slow growth and low levels of E. faecalis in the gut. In contrast, TCA had no detectable growth effect. The evolving transcriptome upon TCA adaptation showed the early activation of an oligopeptide permease system (opp2) followed by the adjustment of amino acid and nucleotide metabolisms. We provide evidence that TCA favors the exploitation of oligopeptide resources to fuel amino acid needs in limiting oligopeptide conditions. Altogether, our data suggest that the combined effects of decreased DCA and increased TCA concentrations can contribute to the rise of E. faecalis population during dysbiosis.

Abstract Vocal expression of emotions has been observed across species and could provide a non-invasive and reliable means to assess animal emotions. We investigated if pig vocal indicators of emotions revealed in previous studies are valid across call types and contexts, and could potentially be used to develop an automated emotion monitoring tool. We performed an analysis of an extensive and unique dataset of low (LF) and high frequency (HF) calls emitted by pigs across numerous commercial contexts from birth to slaughter (7414 calls from 411 pigs). Our results revealed that the valence attributed to the contexts of production (positive versus negative) affected all investigated parameters in both LF and HF. Similarly, the context category affected all parameters. We then tested two different automated methods for call classification; a neural network revealed much higher classification accuracy compared to a permuted discriminant function analysis (pDFA), both for the valence (neural network: 91.5%; pDFA analysis weighted average across LF and HF (cross-classified): 61.7% with a chance level at 50.5%) and context (neural network: 81.5%; pDFA analysis weighted average across LF and HF (cross-classified): 19.4% with a chance level at 14.3%). These results suggest that an automated recognition system can be developed to monitor pig welfare on-farm.

Abstract The mechanisms underlying movement sense alterations following repeated eccentric contractions remain unclear. This study concomitantly investigated the effects of unilateral eccentric contractions on movement sense and on neuromuscular function at the knee before, immediately after (POST), 24 (POST24) and 48 (POST48) h after the exercise. Twelve participants performed sets of submaximal knee extensors (KE) eccentric contractions until a 20% decrease in maximal voluntary isometric contraction (MVIC) torque was reached. Threshold to detect passive movement (TTDPM) tasks were used to assess movement sense during both knee flexion (TTDPMFLEX) and extension (TTDPMEXT). KE fatigability was assessed using the interpolated twitch technique. TTDPM values expressed in seconds and the percentage of unsuccessful trials only increased at POST during TTDPMFLEX and TTDPMEXT. The 20%-MVIC decrease was associated with significant decreases in voluntary activation level (− 12.7%, p

Abstract The insertion losses of miniature gold/silicon-on-insulator (SOI) coplanar waveguides (CPW) are rendered low, stable, and light insensitive when covered with a thin film (95 nm) fluoropolymer deposited by a trifluoromethane (CHF3) plasma. Microwave characterization (0–50 GHz) of the CPWs indicates that the fluoropolymer stabilizes a hydrogen-passivated silicon surface between the CPW tracks. The hydrophobic nature of the fluoropolymer acts as a humidity barrier, meaning that the underlying intertrack silicon surfaces do not re-oxidize over time—something that is known to increase losses. In addition, the fluoropolymer thin film also renders the CPW insertion losses insensitive to illumination with white light (2400 lx)—something potentially advantageous when using optical microscopy observations during microwave measurements. Capacitance–voltage (CV) measurements of gold/fluoropolymer/silicon metal–insulator-semiconductor (MIS) capacitors indicate that the fluoropolymer is an electret—storing positive charge. The experimental results suggest that the stored positive charge in the fluoropolymer electret and charge trapping influence surface-associated losses in CPW—MIS device modelling supports this. Finally, and on a practical note, the thin fluoropolymer film is easily pierced by commercial microwave probes and does not adhere to them—facilitating the repeatable and reproducible characterization of microwave electronic circuitry passivated by thin fluoropolymer.

Abstract The largest (M8+) known earthquakes in the Himalaya have ruptured the upper locked section of the Main Himalayan Thrust zone, offsetting the ground surface along the Main Frontal Thrust at the range front. However, out-of-sequence active structures have received less attention. One of the most impressive examples of such faults is the active fault that generally follows the surface trace of the Main Boundary Thrust (MBT). This fault has generated a clear geomorphological signature of recent deformation in eastern and western Nepal, as well as further west in India. We focus on western Nepal, between the municipalities of Surkhet and Gorahi where this fault is well expressed. Although the fault system as a whole is accommodating contraction, across most of its length, this particular fault appears geomorphologically as a normal fault, indicating crustal extension in the hanging wall of the MHT. We focus this study on the reactivation of the MBT along the Surkhet-Gorahi segment of the surface trace of the newly named Reactivated Boundary Fault, which is ~ 120 km long. We first generate a high-resolution Digital Elevation Model from triplets of high-resolution Pleiades images and use this to map the fault scarp and its geomorphological lateral variation. For most of its length, normal motion slip is observed with a dip varying between 20° and 60° and a maximum cumulative vertical offset of 27 m. We then present evidence for recent normal faulting in a trench located in the village of Sukhetal. Radiocarbon dating of detrital charcoals sampled in the hanging wall of the fault, including the main colluvial wedge and overlying sedimentary layers, suggest that the last event occurred in the early sixteenth century. This period saw the devastating 1505 earthquake, which produced ~ 23 m of slip on the Main Frontal Thrust. Linked or not, the ruptures on the MFT and MBT happened within a short time period compared to the centuries of quiescence of the faults that followed. We suggest that episodic normal-sense activity of the MBT could be related to large earthquakes rupturing the MFT, given its proximity, the sense of motion, and the large distance that separates the MBT from the downdip end of the locked fault zone of the MHT fault system. We discuss these results and their implications for the frontal Himalayan thrust system.

Abstract Performing the Roux-en-Y gastric bypass (RYGBP) in obese Yucatan minipigs provides an opportunity to explore the mechanisms behind the effects of this surgery in controlled environmental and nutritional conditions. We hypothesized that RYGBP in these minipigs would induce changes at multiple levels, as in obese humans. We sought to characterize RYGBP in a diet-induced obese minipig model, compared with a pair-fed sham group. After inducing obesity with an ad libitum high-fat/high-sugar diet, we performed RYGBP (n = 7) or sham surgery (n = 6). Oral glucose tolerance tests (OGTT) were performed before and after surgery. Histological analyses were conducted to compare the alimentary limb at sacrifice with tissue sampled during RYGBP surgery. One death occurred in the RYGBP group at postoperative day (POD) 3. Before sacrifice, weight loss was the same across groups. GLP-1 secretion (OGTT) was significantly higher at 15, 30 and 60 min at POD 7, and at 30 and 60 min at POD 30 in the RYGBP group. Incremental insulin area under the curve increased significantly after RYGBP (p = 0.02). RYGBP induced extensive remodeling of the alimentary limb. Results show that RYGBP can be safely performed in obese minipigs, and changes mimic those observed in humans.

Abstract In poultry, in vitro propagated primordial germ cells (PGCs) represent an important tool for the cryopreservation of avian genetic resources. However, several studies have highlighted sexual differences exhibited by PGCs during in vitro propagation, which may compromise their reproductive capacities. To understand this phenomenon, we compared the proteome of pregonadal migratory male (ZZ) and female (ZW) chicken PGCs propagated in vitro by quantitative proteomic analysis using a GeLC-MS/MS strategy. Many proteins were found to be differentially abundant in chicken male and female PGCs indicating their early sexual identity. Many of the proteins more highly expressed in male PGCs were encoded by genes localised to the Z sex chromosome. This suggests that the known lack of dosage compensation of the transcription of Z-linked genes between sexes persists at the protein level in PGCs, and that this may be a key factor of their autonomous sex differentiation. We also found that globally, protein differences do not closely correlate with transcript differences indicating a selective translational mechanism in PGCs. Male and female PGC expressed protein sets were associated with differential biological processes and contained proteins known to be biologically relevant for male and female germ cell development, respectively. We also discovered that female PGCs have a higher capacity to uptake proteins from the cell culture medium than male PGCs. This study presents the first evidence of an early predetermined sex specific cell fate of chicken PGCs and their sexual molecular specificities which will enable the development of more precise sex-specific in vitro culture conditions for the preservation of avian genetic resources.

The rhoptry is an apical secretory organelle of apicomplexan parasites that is essential for host cell invasion. Here, Mageswaran et al. provide in situ ultrastructures of rhoptries from two pathogens, revealing a conserved architecture including luminal filaments and a distinct docking mechanism.

Abstract Intestinal fibrosis is a frequent complication in inflammatory bowel diseases (IBD). It is a challenge to identify environmental factors such as diet that may be driving this risk. Intestinal fibrosis result from accumulation of extracellular matrix (ECM) proteins secreted by myofibroblasts. Factors promoting intestinal fibrosis are unknown, but diet appears to be a critical component in its development. Consumption of salt above nutritional recommendations can exacerbate chronic inflammation. So far, high salt diet (HSD) have not been thoroughly investigated in the context of intestinal fibrosis associated to IBD. In the present study, we analyze the role of dietary salt in TNBS chronic colitis induced in rat, an intestinal fibrosis model, or in human colon fibroblast cells. Here, we have shown that high-salt diet exacerbates undernutrition and promoted ECM-associated proteins in fibroblasts. Taken together, our results suggested that dietary salt can activate intestinal fibroblasts, thereby contributing to exacerbation of intestinal fibrosis. Dietary salt may be considered as a putative environmental factor that drives intestinal fibrosis risk.

Abstract Highly Pathogenic Avian Influenza viruses (HPAIVs) display a tissue pantropism, which implies a possible spread in feathers. HPAIV detection from feathers had been evaluated for H5N1 or H7N1 HPAIVs. It was suggested that viral RNA loads could be equivalent or higher in samples of immature feather compared to tracheal (TS) or cloacal swabs (CS). We investigated the suitability of feathers for the detection of clade 2.3.4.4b H5N8 HPAIV in ducks and geese field samples. In the six H5N8 positive flocks that were included in this study, TS, CS and immature wing feathers were taken from at least 10 birds. Molecular loads were then estimated using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) targetting H5 and M genes. In all flocks, viral loads were at least equivalent between feather and swab samples and in most cases up to 103 higher in feathers. Bayesian modelling confirmed that, in infected poultry, RT-qPCR was much more likely to be positive when applied on a feather sample only (estimated sensitivity between 0.89 and 0.96 depending on the positivity threshold) than on a combination of a tracheal and a cloacal swab (estimated sensitivity between 0.45 and 0.68 depending on the positivity threshold). Viral tropism and lesions in feathers were evaluated by histopathology and immunohistochemistry. Epithelial necrosis of immature feathers and follicles was observed concurrently with positive viral antigen detection and leukocytic infiltration of pulp. Accurate detection of clade 2.3.4.4b HPAIVs in feather samples were finally confirmed with experimental H5N8 infection on 10-week-old mule ducks, as viral loads at 3, 5 and 7 days post-infection were higher in feathers than in tracheal or cloacal swabs. However, feather samples were associated with lower viral loads than tracheal swabs at day 1, suggesting better detectability of the virus in feathers in the later course of infection. These results, based on both field cases and experimental infections, suggest that feather samples should be included in the toolbox of samples for detection of clade 2.3.4.4b HPAI viruses, at least in ducks and geese.

Abstract The main aim was to assess the short-term effects of active-tDCS (a-tDCS) in the primary motor cortex (anodal stimulation-M1) on sensorimotor variables. These variables included discriminative sensation through the two-point discrimination (2-PD) test, tactile acuity threshold and pressure pain threshold (PPT), and electromyographic (EMG) activity compared with a sham-tDCS (s-tDCS) in healthy individuals. A total of 100 participants were included. Fifty of the participants received the a-tDCS application of 2 mA for 20 min, whereas the remaining fifty received the s-tDCS. The 2-PD and tactile acuity threshold in thenar eminence of the hand and in the dorsal part of the foot and also, PPT and EMG activity during maximal voluntary contraction in the biceps brachii and rectus femoris were assessed before and after the tDCS application. The a-tDCS intervention was not significantly superior to the s-tDCS in any variable. However, significant within-group pre- and post-intervention differences were found in the a-tDCS, such as the tactile acuity threshold in thenar eminence of the hand, with a small effect size (p = .012, d = 0.20) and in the PPT of the rectus femoris, also with a small effect size (p = .001, d = − 0.17). Regarding EMG activity, a trend towards greater activity was observed in participants with a-tDCS compared with s-tDCS, which showed a trend towards decreased EMG activity. In fact, although no differences were found between the groups, within-group differences were statistically significant in the biceps brachii pre- and postintervention (p = .023, d = − 0.16, and p = .002, d = 0.18, respectively), and also in the rectus femoris, only in the a-tDCS, with a small effect size (p = .011, d = − 0.14). This study showed no significant between-group differences in sensorimotor outcomes. A single session of tDCS in isolation appears to produce immediate effects in healthy participants on sensorimotor function; however, these effects were very small.

Abstract Finger-tapping tasks are classically used to investigate sensorimotor synchronization in relation to neutral auditory cues, such as metronomes. However, music is more commonly associated with an entrained bodily response, such as toe tapping, or dancing. Here we report an experimental procedure that was designed to bridge the gap between timing and intervention studies by directly comparing the effects of metronome and musical cue types on motor timing abilities across the three naturalistic voluntary actions of finger tapping, toe tapping, and stepping on the spot as a simplified case of whole body movement. Both pacing cues were presented at slow, medium, and fast tempi. The findings suggested that the task of stepping on the spot enabled better timing performances than tapping both in younger and older adults (75+). Timing performances followed an inverse U shape with best performances observed in the medium tempi that were set close to the spontaneous motor tempo in each movement type. Finally, music provided an entrainment effect in addition to pace setting that enabled better motor timing and greater stability than classically reported using a metronome. By applying time-stamp analyses to kinetic data, we demonstrate that tapping and stepping engage different timing modes. This work details the importance of translational research for a better understanding of motor timing. It offers a simple procedure that strengthens the validity of applying academic work and contributes in knowledge towards a wide range of therapeutic interventions.

Ultrafast control of materials draws interest. Here, the authors extend X-ray powder diffraction to the femtosecond timescale to follow the photo-induced semiconductor to metal transition in titanium pentaoxide, observing a phase front that moves at the speed of sound and proposing a little explored mechanism.

Abstract The origin of funerary practices has important implications for the emergence of so-called modern cognitive capacities and behaviour. We provide new multidisciplinary information on the archaeological context of the La Ferrassie 8 Neandertal skeleton (grand abri of La Ferrassie, Dordogne, France), including geochronological data -14C and OSL-, ZooMS and ancient DNA data, geological and stratigraphic information from the surrounding context, complete taphonomic study of the skeleton and associated remains, spatial information from the 1968–1973 excavations, and new (2014) fieldwork data. Our results show that a pit was dug in a sterile sediment layer and the corpse of a two-year-old child was laid there. A hominin bone from this context, identified through Zooarchaeology by Mass Spectrometry (ZooMS) and associated with Neandertal based on its mitochondrial DNA, yielded a direct 14C age of 41.7–40.8 ka cal BP (95%), younger than the 14C dates of the overlying archaeopaleontological layers and the OSL age of the surrounding sediment. This age makes the bone one of the most recent directly dated Neandertals. It is consistent with the age range for the Châtelperronian in the site and in this region and represents the third association of Neandertal taxa to Initial Upper Palaeolithic lithic technocomplex in Western Europe. A detailed multidisciplinary approach, as presented here, is essential to advance understanding of Neandertal behavior, including funerary practices.

ASPICov was developed to provide a rapid, reliable and complete analysis of NGS SARS-Cov2 samples to the biologist. This broad application tool allows to process samples from either capture or amplicon strategy and Illumina or Ion Torrent technology. To ensure FAIR data analysis, this Nextflow pipeline follows nf-core guidelines and use Singularity containers. Pipeline is implemented and available at https://gitlab.com/vtilloy/aspicov.

The Infectious Diseases Data Observatory (IDDO, https://www.iddo.org) has launched a clinical data platform for the collation, curation, standardisation and reuse of individual participant data (IPD) on treatments for two of the most globally important neglected tropical diseases (NTDs), schistosomiasis (SCH) and soil-transmitted helminthiases (STHs). This initiative aims to harness the power of data-sharing by facilitating collaborative joint analyses of pooled datasets to generate robust evidence on the efficacy and safety of anthelminthic treatment regimens. A crucial component of this endeavour has been the development of a Research Agenda to promote engagement with the SCH and STH research and disease control communities by highlighting key questions that could be tackled using data shared through the IDDO platform. Here, we give a contextual overview of the priority research themes articulated in the Research Agenda—a ‘living’ document hosted on the IDDO website—and describe the three-stage consultation process behind its development. We also discuss the sustainability and future directions of the platform, emphasising throughout the power and promise of ethical and equitable sharing and reuse of clinical data to support the elimination of NTDs.