Quantification of low abundance Yersinia pestis markers in dried blood spots by immuno-capture and quantitative high-resolution targeted mass spectrometry

International audiencePlague, caused by the bacterium Yersinia pestis, is still present in several countries worldwide. Besides, Y. pestis has been designated as Tier 1 agent, the highest rank of bioterrorism agents. In this context, reliable diagnostic methods are of great importance. Here, we have developed an original workflow based upon dried blood spot for simplified sampling of clinical specimens, and specific immuno-mass spectrometry monitoring of Y. pestis biomarkers. Targeted proteins were selectively enriched from dried blood spot extracts by multiplex immunocapture using antibody-coated magnetic beads. After accelerated on-beads digestion, proteotypic peptides were monitored by multiplex LC-MS/MS through the parallel reaction monitoring mode. The DBS-IC-MS assay was designed to quantify both F1 and LcrV antigens, although 10-fold lower sensitivity was observed with LcrV. The assay was successfully validated for F1 with a lower limit of quantification at 5 ng·mL−1 in spiked blood, corresponding to only 0.1 ng on spots. In vivo quantification of F1 in blood and organ samples was demonstrated in the mouse model of pneumonic plague. The new assay could help to simplify the laboratory confirmation of positive point of care F1 dipstick

HTS insert magnet design study

International audienceFuture accelerator magnets will need to reach higher field in the range of 20 T. This field level is very difficult to reach using only Low Temperature Superconductor materials whereas High Temperature Superconductors (HTS) provide interesting opportunities. High current densities and stress levels are needed to design such magnets. YBCO superconductor indeed carries large current densities under high magnetic field and provides good mechanical properties especially when produced using the IBAD approach. The HFM EUCARD program studies the design and the realization of an HTS insert of 6 T inside a dipole of 13 T at 4.2 K. In the HTS insert, engineering current densities higher than 250 under 19 T are required to fulfill the specifications. The stress level is also very severe. YBCO IBAD tapes theoretically meet these challenges from presented measurements. The insert protection is also a critical because HTS materials show low quench propagation velocities and the coupling with the magnet makes the problem even more challenging. The magnetic and mechanical designs of the HTS insert as well as some protection investigation ways will be presented

EuCARD-HFM dipole model design options

The EuCARD-HFM task aims at realizing a 13 T dipole magnet with an aperture of 100 mm, which is a challenging step towards very high field accelerator magnets. This dipole, utilizing Nb$_{3}$Sn superconductor, will be used in the Fresca test facility at CERN. A preliminary design study has compared two possible design layouts for the EuCARD-HFM magnet: the cos-θ and the block. This report summarizes the conclusions of this study and justifies, on the base of quantitative and qualitative arguments, our decision to pursue the detailed design with the block layout

The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system

Posté sur BioRxiv le 29 juillet 2019 : https://www.biorxiv.org/content/10.1101/718288v1Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota, but causality remains yet to be established. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that the UCMS mice display phenotypic alterations — characterized by an altered gut microbiota composition, a reduced adult hippocampal neurogenesis and a depressive-like behaviors — which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota on adult neurogenesis and behavior in naïve recipient mice were alleviated by selectively enhancing the central eCB tone or by adding arachidonic acid, a fatty acid precursor of eCB ligands, to the diet. In the gut of both UCMS donors and recipients, the microbiota composition was characterized by a relative decrease in Lactobacilli abundance, and complementation of the UCMS recipient microbiota with a strain of the Lactobacilli genus was sufficient to restore normal eCB brain levels, hippocampal neurogenesis and to alleviate depressive-like behaviors. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota dysbiosis generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system

Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

International audienceDepression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that UCMS mice display phenotypic alterations, which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota were alleviated by selectively enhancing the central eCB or by complementation with a strain of the Lactobacilli genus. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system

Eradications as scientific experiments: first attempt to eradicate two major invasive taxa, <em>Rattus rattus</em> and <em>Carpobrotus spp</em>. from a Mediterranean island

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Eradications as scientific experiments : progress in simultaneous eradications of two major invasive taxa from a Mediterranean island

BACKGROUNDBlack rats, Rattus rattus, and mat-forming iceplants, Carpobrotus aff. acinaciformis and Carpobrotus edulis, are pervasive pests on Mediterranean islands. Their cumulative impacts on native biotas alter the functioning of island ecosystems and threaten biodiversity. A report is given here of the first attempt to eradicate both taxa from a protected nature reserve in south-eastern France (Bagaud Island). In order to minimise unwanted hazardous outcomes and produce scientific knowledge, the operations were embedded in a four-step strategy including initial site assessment, planning, restoration and monitoring. RESULTSTrapping, which resulted in the removal of 1923 rats in 21045 trap-nights, made it possible to eliminate a substantial proportion of the resident rat population and to reduce the amount of rodenticide delivered in the second stage of the operation. Forty tons of Carpobrotus spp. were manually uprooted from a total area of 18000 m(2); yet careful monitoring over a decade is still required to prevent germinations from the seed bank. CONCLUSIONTwo years after the beginning of the interventions, both eradication operations are still ongoing. Biosecurity measures have been implemented to reduce reinvasion risks of both taxa. With the long-term monitoring of various native plants and animals, Bagaud Island will become a reference study site for scientific purposes