Shiga toxin production and translocation during microaerobic human colonic infection with Shiga toxin-producing E. coli O157:H7 and O104:H4

Haemolytic uraemic syndrome caused by Shiga toxin-producing E. coli (STEC) is dependent on release of Shiga toxins (Stxs) during intestinal infection and subsequent absorption into the bloodstream. An understanding of Stx-related events in the human gut is limited due to lack of suitable experimental models. In this study, we have used a vertical diffusion chamber system with polarized human colon carcinoma cells to simulate the microaerobic (MA) environment in the human intestine and investigate its influence on Stx release and translocation during STEC O157:H7 and O104:H4 infection. Stx2 was the major toxin type released during infection. Whereas microaerobiosis significantly reduced bacterial growth as well as Stx production and release into the medium, Stx translocation across the epithelial monolayer was enhanced under MA versus aerobic conditions. Increased Stx transport was dependent on STEC infection and occurred via a transcellular pathway other than macropinocytosis. While MA conditions had a similar general effect on Stx release and absorption during infection with STEC O157:H7 and O104:H4, both serotypes showed considerable differences in colonization, Stx production, and Stx translocation which suggest alternative virulence strategies. Taken together, our study suggests that the MA environment in the human colon may modulate Stx-related events and enhance Stx absorption during STEC infection

Une entreprise hagiographique au XIe siècle dans l'abbaye de Fontenelle : le renouveau du culte de saint Vulfran

Au XIe siècle, au lendemain de la restauration de leur abbaye, les moines de Fontenelle se lancent dans une vaste entreprise hagiographique destinée à remédier à la pénurie de reliques à laquelle ils sont confrontés. Privés du corps de saint Wandrille, leur choix se porte sur saint Vulfran, archevêque de Sens et moine fontenellien, qui bénéficiait déjà d’un culte, à Fontenelle, avant les invasions scandinaves. Deux textes sont alors composés : l’Inventio et miracula sancti Vulfranni ainsi que les Miracula sancti Vulfranni. À travers leur examen, le présent article se propose d’étudier les motivations qui président à leur rédaction et d’identifier les enjeux qui entourent le soin apporté à la mémoire de saint Vulfran.In the XIth century, after the restoration of the abbey of Fontenelle, its monks launched a large hagiographical project in order to remedy the shortage of relics which they faced. Deprived of saint Wandrille’s body, their choice fell on saint Vulfran, archbishop of Sens and monk of Fontenelle, who had already benefited from a cult, in Fontenelle, before the Scandinavian invasions. Two texts were written: the Inventio et miracula sancti Vulfranni and the Miracula sancti Vulfranni. By examinating both texts, the author proposes to explore the monks’ motivations behind their writing and the significance of the monks’ appropriation of saint Vulfran’s memory

De l’usage politique du Précieux Sang dans l’Europe médiévale

Au cours du Moyen Âge, les reliques du Précieux Sang font l’objet de nombreuses translations entre Orient et Occident puis dans l’ensemble de l’Europe. Bien souvent, les grands y jouent un rôle majeur. Ce constat doit conduire à s’interroger sur l’intérêt qu’ils portent à ces restes du Christ. Comme on le verra, ceux-ci revêtent une lourde signification politique.In the Middle Ages, Holy blood relics were frequently translated, first between the Orient and the West, later throughout Europe. Quite often the aristocracy played a major role in the process of translation. This observation prompts the question as to the nature of the aristocracy's interest in Christ's remains. As shall be discussed, at the time such remains were imbued with considerable political meaning

A Bi-enzymatic Whole-Cell Algal Biosensor for Monitoring Waste Water Pollutants

International audienceTwo algal whole cells biosensors are developed to measure specific toxicity of freshwater pollutants. Both optical and conductometric biosensors are based on inhibition of algal alkaline phosphatase (AP) and esterase activities. Chlorella vulgaris cells are immobilised on a membrane placed in front of an optical fiber bundle for optical sensing or deposited on the surface of an electrode for conductometric sensing. Phosphatase activity of the biosensor is strongly inhibited by heavy metal ions (60% loss of activity is obtained after 10 ppb Cd2+ and Zn2+ with 20 min exposure time), as equally observed with a microplate reader. Inhibition of esterase activity (EA) is actually achieved with organophosphorous pesticides such as methyl paraoxon. The biosensors exhibit a response time of about 5 min. These pollutants can be detected down to 10 ppb after being in contact with the biosensor for 30 min. The biosensor can be used up to 20 days with 90% remaining activity

Algal biosensors for aquatic ecosystems monitoring

International audienceThe harmful effect of toxic chemicals on natural ecosystems has led to an increasing demand for early-warning systems to detect those toxicants at very low concentrations levels. Whole-cell biosensors based either on chlorophyll fluorescence or enzyme (phosphatase and esterase) inhibition are constructed for real-time detection and on-line monitoring. Results show that these devices are sensitive to heavy metals and pesticides. The system allows the cells to operate in their natural environment which favours long term stability and reflects the toxic action mechanism providing therefore an ecological interest

Development of a DSO support tool for congestion forecast

This paper presents a novel DSO support tool with visualisation capability for forecasting network congestion in distribution systems with a high level of renewables. To incorporate the uncertainties in the distribution systems, the probabilistic power flow framework has been utilised. An advanced photovoltaic production forecast based on sky images and a load forecast using an artificial neural network is used as the input to the tool. In addition, advanced load models and operating modes of photovoltaic inverters have been incorporated into the tool. The tool has been applied in case studies to perform congestion forecasts for two real distribution systems to validate its usability and scalability. The results from case studies demonstrated that the tool performs satisfactorily for both small and large networks and is able to visualise the cumulative probabilities of nodes voltage deviation and network components (branches and transformers) congestion for a variety of forecast horizons as desired by the DSO. The results have also shown that explicit inclusion of load-voltage dependency models would improve the accuracy of the congestion forecast. For demonstrating the applicability of the tool, it has been integrated into an existing distribution management system via the IoT platform of a DMS vendor, Atos Worldgrid

The Immunogenicity of the Tumor-Associated Antigen α-Fetoprotein Is Enhanced by a Fusion with a Transmembrane Domain

Aim. To investigate the ability of recombinant modified vaccinia virus Ankara (rMVA) vector to induce an immune response against a well-tolerated self-antigen. Methods. rMVA vectors expressing different form of α-fetoprotein (AFP) were produced and characterized. Naïve mice were vaccinated with MVA vectors expressing the AFP antigen in either a secreted, or a membrane-bound, or an intracellular form. The immune response was monitored by an IFNΓ ELISpot assay and antibody detection. Results. Vaccination with the membrane-associated form of AFP induced a stronger CD8+ T-cell response compared to the ones obtained with the MVA encoding the secreted or the intracellular forms of AFP. Moreover, the vaccination with the membrane-bound AFP elicited the production of AFP-specific antibodies. Conclusions. The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen

Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as being upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License