Monazite Alteration in H2O +/- HCl +/- NaCl +/- CaCl2 Fluids at 150 degrees C and p(sat): Implications for Uranium Deposits

International audienceSpectacular alteration of monazite by diagenetic/hydrothermal brines is well documented in some Proterozoic sedimentary basins in close relationship with high-grade uranium (U) deposits. Hence, monazite has been proposed as a viable source for some U deposits. However, monazite alteration remains enigmatic with regard to its high stability in relatively low temperature hydrothermal conditions. Here, the results of batch experiments in which 10 mg of natural monazite grains were reacted with 15 mL of Na-Ca-Cl (6 molal Cl) solutions as well as in pure water at 150 degrees C and saturated vapor pressure (p(sat)) for one and six months are reported. The influence of pH (pH = 1, 3, 7) and relative molar proportions of Na and Ca (Na/(Na + Ca) = 0, 0.5, 1), were tested. Discrete alteration features (etch pits and roughened surfaces) appear in a minority of the one month experiments and are more developed in the six months experiments, especially at pH = 1 and 3. Although spectacular alteration of monazite, as seen around U deposits, could not be reproduced here, this study shows that monazite is unstable in the presence of fluids analogous to acidic deep basinal brines

True 2-D resistivity imaging from vertical electrical soundings to support more sustainable rural water supply borehole siting in Malawi

To improve borehole siting for rural water supply, an advanced resistivity method was adapted for developing country use and demonstrated in Malawi. The method was designed to be low cost, developing-country accessible, efficient. It allows single or multiple operators to acquire the multiple vertical electrical soundings (VESs) required that are inverted together in 2-D, to give a true cross-section of subsurface resistivity. Application at four sites generated true cross-sections of subsurface resistivity to around 100 m depth relevant to groundwater-resource investigation. A wide range of (hydro)geological features was identified, including fractured/weathered basement, gneiss domes, well-developed fault zones and several types of deltaic deposits. Imaging performance appears comparable to that of 2-D surface ERT (electrical resistivity tomography) that uses more expensive equipment, often unaffordable in developing countries. Based on the subsurface configurations determined and hydrogeological conceptualisation subsequently undertaken, the local aquifer potential could be evaluated, thereby providing a decision-making basis for future borehole siting at the sites surveyed. The technology is far superior to conventional 1-D VES, electromagnetic profiling or magnetic profiling currently used for borehole siting in Malawi. Technology adoption currently under consideration nationally would make use of existing VES capacity and permit much improved targeting of aquifer resource, more sustainable siting of boreholes and greater future resilience of Malawi’s rural water-supply infrastructure

Acute and subchronic treatments with selective serotonin reuptake inhibitors increase Nociceptin/Orphanin FQ (NOP) receptor density in the rat dorsal raphe nucleus; interactions between nociceptin/NOP system and serotonin

International audienceNociceptin/Orphanin FQ is the endogenous ligand of NOP receptor, formerly referred to as the Opioid Receptor-Like 1 receptor. We have previously shown that NOP receptors were located on serotonergic neurons in the rat dorsal raphe nucleus, suggesting possible direct interactions between nociceptin and serotonin in this region, which is a target for antidepressant action. In the present study, we investigated further the link between Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant treatments and the nociceptin/NOP receptor system. Intraperitoneal administration of the SSRI citalopram induced an increase in NOP-receptor density, measured by autoradiographic [3H] nociceptin binding, in the rat dorsal raphe nucleus, from the first to the 21st day of treatment. This effect was also observed with other SSRIs (sertraline, fluoxetine), but not with two tricyclic antidepressants (imipramine, clomipramine) and was abolished by pre-treatment with para-chlorophenylalanine, an inhibitor of serotonin synthesis. Using microdialysis experiments, we demonstrated that NOP-receptor activation by infusion of nociceptin 10−6 M or 10−5 M increased the level of extracellular serotonin in the dorsal raphe nucleus. This effect was abolished by co-infusion of the NOP-receptor antagonist UFP 101. These results confirm the existence of reciprocal interactions between serotonin and nociceptin/NOP transmissions in the dorsal raphe nucleus

Projet RhamnoSol : Influence du sol sur la capacité des rhamnolipides à induire une résistance systémique chez Arabidopsis thaliana

International audienceL'étude de la résistance systémique induite d'A. thaliana contre Pseudomonas syringae pv. tomato DC3000 a été menée suite à l'application de RLs au niveau racinaire avant inoculation des feuilles avec la bactérie. Cette étude montre que seules les plantes cultivées sur terreau présentent une résistance à la bactérie accrue par le traitement aux RLs

Exposure to wild-type AAV drives distinct capsid immunity profiles in humans

International audienceRecombinant adeno-associated virus (AAV) vectors have been broadly adopted as a gene delivery tool in clinical trials, owing to their high efficiency of transduction of several host tissues and their low immunogenicity. However, a considerable proportion of the population is naturally exposed to the WT virus from which AAV vectors are derived, which leads to the acquisition of immunological memory that can directly determine the outcome of gene transfer. Here, we show that prior exposure to AAV drives distinct capsid immunity profiles in healthy subjects. In peripheral blood mononuclear cells (PBMCs) isolated from AAV-seropositive donors, recombinant AAV triggered TNF-α secretion in memory CD8+ T cells, B cell differentiation into antibody-secreting cells, and anti-capsid antibody production. Conversely, PBMCs isolated from AAV-seronegative individuals appeared to carry a population of NK cells reactive to AAV. Further, we demonstrated that the AAV capsid activates IL-1β and IL-6 cytokine secretion in monocyte-related dendritic cells (moDCs). IL-1β and IL-6 blockade inhibited the anti-capsid humoral response in vitro and in vivo. These results provide insights into immune responses to AAV in humans, define a possible role for moDCs and NK cells in capsid immunity, and open new avenues for the modulation of vector immunogenicity

Packaging tradeoff for high speed device integrations

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Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

International audienceGene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a promising treatment for systemic monogenic diseases. However, vector immunogenicity represents a major limitation to gene transfer with AAV vectors, particularly for vector re-administration. Here, we demonstrate that synthetic vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV vectors, prevents the induction of anti-capsid humoral and cell-mediated responses. This allows successful vector re-administration in mice and nonhuman primates. SVP[Rapa] dosed with AAV vectors reduces B and T cell activation in an antigen-selective manner, inhibits CD8+ T cell infiltration in the liver, and efficiently blocks memory T cell responses. SVP[Rapa] immunomodulatory effects can be transferred from treated to naive mice by adoptive transfer of splenocytes, and is inhibited by depletion of CD25+ T cells, suggesting a role for regulatory T cells. Co-administration of SVP[Rapa] with AAV vector represents a powerful strategy to modulate vector immunogenicity and enable effective vector re-administration

Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase

International audienceLiver delivery of engineered GAA transgenes to mice with Pompe disease rescued glycogen accumulation in multiple tissues