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Transit time can be estimated thanks to natural tracers, but few of them are usable in the 0–6-month range. The main purpose of this work is to analyze the potential of the ratio of heavy- to light-weight organic compounds (the humification index (HIX); Ohno, 2002; Zsolnay et al., 1999) as a natural tracer of short transit time (Blondel et al., 2012). Critical analysis of former studies shows that although the link between HIX and transit time seems consistent, the whole methodological approach needs to be consolidated. Natural organic matter fluorescence from 289 groundwater samples from four springs and 10 flow points located in the unsaturated zone of the Vaucluse karst system is characterized by parallel factor analysis (PARAFAC) thanks to the excitation–emission matrix (EEM), thus (i) allowing for the identification of main fluorescent compounds of sampled groundwater and (ii) evidencing the inadequacy of HIX 2D emission windows to characterize groundwater organic matter. We then propose a new humification index called the Transit Time index (TTi) based on the Ohno (2002) formula but using PARAFAC components of heavy and light organic matter from our samples instead of 2D windows. Finally, we evaluate TTi relevance as a transit time tracer by (i) performing a detailed analysis of its dynamics on a selected spring (Millet) and (ii) comparing its mean value over karst springs of the Vaucluse karst system. Principal component analysis (PCA) of TTi and other hydrochemical parameters monitored at Millet spring put in relief the different ranges of transit time associated with the different organic matter compounds. PCA results also provide evidence that TTi can detect a small proportion of fast infiltration water within a mix, while other natural tracers of transit time provide no or less sensitive information. TTi distributions at monitored karst springs are consistent with relative transit times expected for the small-scale, short average transit time systems. TTi thus appears as a relevant qualitative tracer of transit time in the 0–6-month range where existing tracers fail and may remain applicable, even in the case of anthropic contamination thanks to PARAFAC modeling. Transforming it into quantitative information is a challenging task which may be possible thanks to intensive studies of organic matter degradation kinetics in natural waters with the help of radiogenic isotope usage or an artificial tracer test.

The Jovian plasma sheet is a key region of the Jovian magnetosphere populated by a mix of warm and hot plasma. It is the main channel for radial transport of mass and energy in the Jovian magnetosphere and provides a favorable environment for magnetic reconnection and wave–particle interactions although the understanding of its plasma properties is incomplete. This study combines observations from the Jovian Auroral Distributions Experiment and Juno Energetic Particle Detector Instrument on board the Juno spacecraft during its first 31 orbits to analyze the plasma properties of the Jovian plasma sheet from 20 R _J to 100 R _J . Our results indicate that the plasma number density decreases from 1 cm ^−3 at 20 R _J to 0.005 cm ^−3 at 100 R _J , while the plasma pressure decreases from 2 nPa at 20 R _J to 0.02 nPa at 100 R _J . The plasma pressure inside the plasma sheet is comparable to the magnetic pressure in the lobe region, suggesting a rough balance between the two. In the plasma sheet with r > 70 R _J , the H ^+ density and pressure remain relatively constant, likely due to other plasma sources such as the solar wind. Additionally, we find that the pressure (density) ratios for heavy ions between the center and the edge of the plasma sheet are generally an order of magnitude, while that for H ^+ decreases with radial distance. These findings contribute to a more comprehensive understanding of the plasma properties of the Jovian plasma sheet.

Abstract We characterize the precipitating electrons accelerated in the Europa‐magnetosphere interaction by analyzing in situ measurements and remote sensing observations recorded during 10 crossings of the flux tubes connected to Europa's auroral footprint tail by Juno. The electron downward energy flux, ranging from 34 to 0.8 mW/m2, exhibits an exponential decay as a function of downtail distance, with an e‐folding factor of 7.4°. Electrons are accelerated at energies between 0.3 and 25 keV, with a characteristic energy that decreases downtail. The electron distributions form non‐monotonic spectra in the near tail (i.e., within an angular separation of less than 4°) that become broadband in the far tail. The size of the interaction region at the equator is estimated to be 4.2 ± 0.9 Europa radii, consistent with previous estimates based on theory and UV observations.

We highlight the importance of magnetic reconnection at the heliopause, both as one of the key processes driving the interaction between solar and interstellar media, but also as an element of the definition of the heliopause itself. We highlight the main observations that have fed the current debates on the definition, location and shape of the heliopause. We explain that discriminating between the current interpretations of plasma and magnetic field structures near the heliopause necessitates appropriate measurements which are lacking on Voyager 1 and 2, and describe some of the ensuing requirements for thermal plasma measurements on a future Interstellar Probe. The content of this article was submitted as a white paper contribution to the Decadal Survey for Solar and Space Physics 2024–2033 of the National Academy of Sciences.

Abstract The accurate prediction of solar wind conditions in the interplanetary space is crucial in the context of both scientific research and technical applications. In this study, we simulate the solar wind throughout the heliosphere from 0.1 to 5.5 astronomical units (AU) with our improved heliospheric magnetohydrodynamics (MHD) model during the time period from 2007 to 2017. The model uses synoptic magnetogram maps as input to derive the inner boundary conditions based on a series of empirical relations such as the Wang‐Sheeley‐Arge (WSA) relation. To test the performance of this model, we compare the simulation results with in situ measurements from multiple spacecraft including ACE/WIND, Solar TErrestrial Relations Observatory, Ulysses, Juno, and MErcury Surface, Space ENvironment, GEochemistry, and Ranging at different latitudes and heliocentric distances. There is an overall agreement between the model results and solar wind observations at different latitudes and heliocentric distances. Statistical analysis for Year 2007 reveals that our model can predict most of the corotation interaction regions, high‐speed streams, and magnetic sector boundaries at 1 AU. In addition, the bimodal structure of the solar wind for different latitudes is well reproduced by the model which is consistent with Ulysses data. This study demonstrates the capabilities of our heliosphere model in the prediction of the large‐scale structures of the solar wind in the inner heliosphere, and the model can be used to predict the ambient solar wind at locations of planets in the solar system such as Earth and Jupiter.

A new fatigue testing device has been developed to test specimens under biaxial loading at 20 kHz. A flat smooth specimen with a disc geometry is placed on a torus frame and cyclically loaded at the center of its upper face. Disc bending generates a biaxial proportional stress state at the center of the lower face. Any positive loading ratio can be applied. A cast aluminum alloy (used to produce cylinder heads) has been tested under biaxial bending using this device in order to determine its fatigue strength at 109 cycles under high hydrostatic pressure. Self-heating is moderate but macroscopic fatigue cracks after testing are very long. First results in VHCF regime are consistent with literature results obtained under similar stress state but in HCF regime and at 20 Hz.

La relation entre la quantité de réserves adipeuses et la reproduction est connue depuis longtemps, mais le moyen par lequel les animaux sont capables d’estimer leur propre contenu en lipides corporels n’est connu que depuis peu. La leptine, une hormone principalement synthétisée et sécrétée par le tissu adipeux, identifiée en 1994, joue en grande partie ce rôle. Cette hormone agit sur des récepteurs spécifiques, présents dans de nombreux tissus. Chez les rongeurs, la leptine est impliquée dans la régulation centrale de l’ingestion alimentaire, de l’équilibre énergétique, de la thermorégulation, de l’activité reproductrice ainsi que dans la régulation de l’angiogenèse et des processus de cicatrisation. Pour la régulation de l’activité des neurones à LHRH (Luteinising Hormone-Releasing Hormone, le décapeptide hypothalamique qui contrôle la synthèse et la libération de LH et de FSH dans l’hypohyse), la leptine agit au niveau hypothalamique, sur la forme longue du récepteur. Son action, indirecte, passerait très probablement par des neuromédiateurs tels que le neuropeptide Y (NPY), la pro-opiomélanocortine (POMC), la sérotonine ou la galanine. Des récepteurs à la leptine se rencontrent également dans l’hypophyse, les gonades et le placenta. Chez les ruminants, la leptine et ses récepteurs n’ont été identifiés et clonés que récemment ; leurs rôles sont en cours de détermination.

Abstract Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth –/– mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth –/– mice compared to both WT and Slc7a11 –/– mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota.

ABSTRACT Helicobacter pylori colonizes a majority of the human population worldwide and can trigger development of a variety of gastric diseases. Since the bacterium is classified as a carcinogen, elucidation of the characteristics of H. pylori that influence gastric carcinogenesis is a high priority. To this end, the Mongolian gerbil infection model has proven to be an important tool to study gastric cancer progression. However, only a small number of H. pylori strains have been evaluated in the gerbil model. Thus, to identify additional strains able to colonize and induce disease in this model, several H. pylori strains were used to infect Mongolian gerbils, and stomachs were harvested at multiple timepoints to assess colonization and gastric pathology. The USU101 strain reproducibly colonized Mongolian gerbils and induced gastric inflammation in the majority of the animals 1 month after infection. Adenocarcinoma or dysplasia was observed in the majority of gerbils by 2 months post-infection. To define the contribution of key virulence factors to this process, isogenic strains lacking cagA or vacA, along with restorant strains containing a wild-type (WT) copy of the genes, were studied. The ΔcagA USU101 strain colonized gerbils at levels similar to WT, but did not induce comparable levels of inflammation or disease. In contrast, the ΔvacA USU101 strain did not colonize gerbils, and the stomach pathology resembled that of the mock-infected animals. The restorant USU101 strains expressed the CagA and VacA proteins in vitro, and in vivo experiments with Mongolian gerbils showed a restoration of colonization levels and inflammation scores comparable to those observed in WT USU101. Our studies indicate that the USU101 strain is a valuable tool to study H. pylori-induced disease.IMPORTANCEGastric cancer is the fifth leading cause of cancer-related death globally; the majority of gastric cancers are associated with Helicobacter pylori infection. Infection of Mongolian gerbils with H. pylori has been shown to result in induction of gastric cancer, but few H. pylori strains have been studied in this model; this limits our ability to fully understand gastric cancer pathogenesis in humans because H. pylori strains are notoriously heterogenous. Our studies reveal that USU101 represents a unique H. pylori strain that can be added to our repertoire of strains to study gastric cancer development in the Mongolian gerbil model.

Enteropathogenic Escherichia coli (EPEC) is a bacterium that causes attaching/effacing (A/E) lesions and serious diarrheal disease, a major health issue in developing countries. EPEC pathogenicity results from the effect of virulence factors and dysregulation of host responses. Polyamines, including spermidine, play a major role in intestinal homeostasis. Spermidine is the substrate for deoxyhypusine synthase (DHPS), which catalyzes the conjugation of the amino acid hypusine to eukaryotic translation initiation factor 5A (EIF5A); hypusinated EIF5A (EIF5AHyp) binds specific mRNAs and initiates translation. Our aim was to determine the role of hypusination during infection with A/E pathogens. We found that DHPS and EIF5AHyp levels are induced in i) a colonic epithelial cell line and human-derived colon organoids infected with EPEC, and ii) the colon of mice infected with Citrobacter rodentium, the rodent equivalent of EPEC. Specific deletion of Dhps in intestinal epithelial cells worsened clinical, histological, and pro-inflammatory parameters in C. rodentium-infected mice. These animals also exhibited an exacerbated pathogenic transcriptome in their colon. Furthermore, infected mice with specific Dhps deletion exhibited reduced levels of proteins involved in detoxification of tissue-damaging reactive aldehydes and consequently increased electrophile adducts in the colon. Thus, hypusination in intestinal epithelial cells protects from infectious colitis mediated by A/E pathogens.

Helicobacter pylori infection is the predominant risk factor for the development of gastric cancer. Risk is enhanced by specific H. pylori virulence factors, diet, and the inflammatory response. Chronic activation of T helper (Th) 1 and Th17 pathways contributes to prolonged inflammation; yet, higher expression of IL-17 receptor (IL-17RA) is a favorable prognostic marker for survival after gastric cancer diagnosis. The protective impact of IL-17RA signaling is not understood. To investigate if IL-17RA signaling protects during H. pylori-induced carcinogenesis, the transgenic InsGAStg/tg mouse, which is prone to H. pylori-induced gastric cancer, was utilized. InsGAStg/tg mice and InsGAStg/tgIl17ra-/- mice were infected with a cag type 4 secretion system (T4SS) positive H. pylori strain for up to 6 months. Six weeks post-infection, IL-17RA deficiency led to increased bacterial burden, increased gastritis, and development of lymphoid follicles. Increased inflammation was associated with heightened cellular proliferation and earlier loss of parietal and chief cells in InsGAStg/tgIl17ra-/- mice. Gastric cancers developed more frequently by 3- and 6-months post-infection in H. pylori-infected InsGAStg/tgIl17ra-/- mice compared to InsGAStg/tg mice. Chronic inflammation was exacerbated with IL-17RA deficiency, characterized by elevated Th1/Th17 cytokines, increased B cell infiltration, and enhanced IgA production, despite reduced expression of the polymeric immunoglobulin receptor. Further, paragastric lymph nodes of InsGAStg/tgIl17ra-/- mice were enlarged relative to controls and displayed altered gene expression profiles. Increased inflammation was accompanied by a significant increase in Cybb expression, which encodes NADPH oxidase 2, suggesting that increased oxidative damage may occur in the absence of IL-17RA. Further, there is increased phosphorylation of histone 2AX in IL-17RA deficient mice, indicating that the DNA damage response is highly activated. These data suggest that IL-17RA signaling activates a protective pathway to prevent excessive inflammation which otherwise can lead to increased oxidative stress, DNA damage, and drive gastric carcinogenesis after H. pylori infection.

Hypusine is an amino acid synthesized by the enzyme deoxyhypusine synthase (DHPS). It is critical for the activity of eukaryotic translation initiation factor 5A (EIF5A). We reported that hypusination i) in macrophages supports the innate response towards pathogenic bacteria and ii) in epithelial cells maintains intestinal homeostasis. Herein, we investigated the effect of myeloid hypusination on the outcome of colitis and colitis-associated cancer. We found that patients with Crohn's disease exhibit increased levels of DHPS and EIF5AHyp in cells infiltrating the colon lamina propria. However, the specific deletion of Dhps in myeloid cells had no impact on clinical, histological, or inflammatory parameters in mice treated with dextran sulfate sodium (DSS). Further, tumorigenesis and level of dysplasia were not affected by myeloid deletion of Dhps in the azoxymethane-DSS model. The composition of the fecal and the mucosa-associated microbiome was similar in animals lacking or not DHPS in myeloid cells. Thus, hypusination in myeloid cells does not regulate colitis associated with epithelial injury and colitis-associated cancer. Enhancement of the DHPS/hypusine pathway in patients with inflammatory bowel disease could have therapeutic impact through epithelial effects, but modulation of hypusination in myeloid cells will be unlikely to affect the disease.

Abstract The intestinal immune response is crucial in maintaining a healthy gut, but the enhanced migration of macrophages in response to pathogens is a major contributor to disease pathogenesis. Integrins are ubiquitously expressed cellular receptors that are highly involved in immune cell adhesion to endothelial cells while in the circulation and help facilitate extravasation into tissues. Here we show that specific deletion of the Tln1 gene encoding the protein talin-1, an integrin-activating scaffold protein, from cells of the myeloid lineage using the Lyz2-cre driver mouse reduces epithelial damage, attenuates colitis, downregulates the expression of macrophage markers, decreases the number of differentiated colonic mucosal macrophages, and diminishes the presence of CD68-positive cells in the colonic mucosa of mice infected with the enteric pathogen Citrobacter rodentium. Bone marrow-derived macrophages lacking expression of Tln1 did not exhibit a cell-autonomous phenotype; there was no impaired proinflammatory gene expression, nitric oxide production, phagocytic ability, or surface expression of CD11b, CD86, or major histocompatibility complex II in response to C. rodentium. Thus, we demonstrate that talin-1 plays a role in the manifestation of infectious colitis by increasing mucosal macrophages, with an effect that is independent of macrophage activation.

Abstract Invasive plant pathogenic fungi have a global impact, with devastating economic and environmental effects on crops and forests. Biosurveillance, a critical component of threat mitigation, requires risk prediction based on fungal lifestyles and traits. Recent studies have revealed distinct genomic patterns associated with specific groups of plant pathogenic fungi. We sought to establish whether these phytopathogenic genomic patterns hold across diverse taxonomic and ecological groups from the Ascomycota and Basidiomycota, and furthermore, if those patterns can be used in a predictive capacity for biosurveillance. Using a supervised machine learning approach that integrates phylogenetic and genomic data, we analyzed 387 fungal genomes to test a proof-of-concept for the use of genomic signatures in predicting fungal phytopathogenic lifestyles and traits during biosurveillance activities. Our machine learning feature sets were derived from genome annotation data of carbohydrate-active enzymes (CAZymes), peptidases, secondary metabolite clusters (SMCs), transporters, and transcription factors. We found that machine learning could successfully predict fungal lifestyles and traits across taxonomic groups, with the best predictive performance coming from feature sets comprising CAZyme, peptidase, and SMC data. While phylogeny was an important component in most predictions, the inclusion of genomic data improved prediction performance for every lifestyle and trait tested. Plant pathogenicity was one of the best-predicted traits, showing the promise of predictive genomics for biosurveillance applications. Furthermore, our machine learning approach revealed expansions in the number of genes from specific CAZyme and peptidase families in the genomes of plant pathogens compared to non-phytopathogenic genomes (saprotrophs, endo- and ectomycorrhizal fungi). Such genomic feature profiles give insight into the evolution of fungal phytopathogenicity and could be useful to predict the risks of unknown fungi in future biosurveillance activities.

In this work, we describe the phase behaviour and the dielectric and conductivity response of new light-responsive ionic liquid crystals, ILCs, which can be applied as controllable electrolytes. The materials include two different dicationic viologens, the asymmetric 6BP18 and the symmetric EV2ON(Tf)2, containing bistriflimide as the counterions, mixed with 5% and 50% molar, respectively, of one new photoresponsive mesogen called CNAzO14. These mixtures exhibit liquid crystal behaviour, light responsiveness through the E-Z photoisomerisation of the azobenzene groups in CNAzO14, and strong dielectric responses. The 5%-CNAzO14/Ev2ON(Tf)2 mixture displays direct current conductivities in the 10−7 S·cm−1 range, which can be increased by a two-fold factor upon the irradiation of UV light at 365 nm. Our findings set the grounds for designing new smart ionic soft materials with nanostructures that can be tuned and used for energy conversion and storage applications.

ABSTRACT Helicobacter pylori (H. pylori) causes a cascade from gastritis to gastric neoplasia. During the chronic stages, the oncogenic transcription factor forkhead box protein M1 (FOXM1) becomes increasingly expressed. Given certain strains of the gastric commensal Cutibacterium acnes (C. acnes) produce thiopeptides that directly inhibit FOXM1, we hypothesized that coinfection with thiopeptide-positive C. acnes would decrease Foxm1 expression and alter H. pylori-induced pathogenesis. C. acnes was isolated from 31% of gastric biopsies from Nicaraguan patients, and thiopeptide-positive strains were identified by whole genome sequencing. Germ-free INS-GAS mice were inoculated with thiopeptide-positive C. acnes, H. pylori SS1, H. pylori 1 week before C. acnes, C. acnes 2 weeks before H. pylori, or no bacteria. At 17 weeks post-infection, males dosed with C. acnes followed by H. pylori exhibited increased inflammation scores by histopathology; however, males dosed with H. pylori followed by C. acnes exhibited reduced gastric Foxm1, pro-inflammatory cytokine (Il-1β, Ifn-γ, Tnf-α, Il-17a, and iNOS), regulatory cytokine (Foxp3) gene expression, pro-inflammatory IgG2a antibodies, and gastric lymph node RORγT expression compared to H. pylori-monoinfected mice. Male mice coinfected with C. acnes followed by H. pylori exhibited reduced gastric inflammatory markers (IL-17, IL-10, GM-CSF, M-CSF, MCP-1, MIP-1α, MIP-2, RANTES, and VEGF) by cytokine array analysis and reduced H. pylori gastric colonization. These data show that thiopeptide-positive C. acnes exhibited anti-inflammatory and anti-FOXM1 properties in the context of H. pylori gastritis. IMPORTANCE H. pylori infects half of the world population and is the leading cause of gastric cancer. We previously demonstrated that gastric cancer risk is associated with gastric microbiota. Specifically, gastric urease-positive Staphylococcus epidermidis and Streptococcus salivarius had contrasting effects on H. pylori-associated gastric pathology and immune responses in germ-free INS-GAS mice. As gastritis progresses to gastric cancer, the oncogenic transcription factor Foxm1 becomes increasingly expressed. In this study, we evaluated the gastric commensal C. acnes, certain strains of which produce thiopeptides that directly inhibit FOXM1. Thiopeptide-positive C. acnes was isolated from Nicaraguan patient gastric biopsies and inoculated into germ-free INS-GAS mice with H. pylori. We, therefore, asked whether coinfection with C. acnes expressing thiopeptide and H. pylori would decrease gastric Foxm1 expression and pro-inflammatory cytokine mRNA and protein levels. Our study supports the growing literature that specific non-H. pylori gastric bacteria affect inflammatory and cancer biomarkers in H. pylori pathogenesis.