Primary Culture of Mycobacterium ulcerans from Human Tissue Specimens after Storage in Semisolid Transport Medium▿

Tissue specimens collected from patients with clinically suspected Buruli ulcer treated in two Buruli ulcer treatment centers in Benin between 1998 and 2004 were placed in semisolid transport medium and transported at ambient temperature for microbiological analysis at the Institute of Tropical Medicine in Antwerp, Belgium. The impact of the delay before microbiological analysis on primary culture of Mycobacterium ulcerans was investigated. The length of storage in semisolid transport medium varied from 6 days to 26 weeks. Of the 1,273 tissue fragments positive for M. ulcerans DNA by an IS2404-specific PCR, 576 (45.2%) yielded positive culture results. The sensitivity of direct smear examination was 64.6% (822/1,273 tissue fragments). The median time required to obtain a positive culture result was 11 weeks. Positive cultures were obtained even from samples kept for more than 2 months at ambient temperatures. Moreover, there was no reduction in the viability of M. ulcerans, as detected by culture, when specimens remained in semisolid transport medium for long periods of time (up to 26 weeks). We can conclude that the method with semisolid transport medium is very robust for clinical specimens from patients with Buruli ulcer that, due to circumstances, cannot be analyzed in a timely manner. This transport medium is thus very useful for the confirmation of a diagnosis of Buruli ulcer with specimens collected in the field

Dioxin-like compounds in porpoises and seals from the southern North Sea: relationship with biological and ecological factors

The North Sea represents a major ecosystem for the harbour porpoise (Phocoena phocoena) and the harbour seal (Phoca vitulina). The grey seal (Halichoerus grypus) occurs more occasionally in the southern part of the North Sea. Their population over this last decade has experienced major fluctuations likely linked to prey availability and seal epizootics. Despite being banned more than 30 years ago, levels of polychlorinated biphenyls (PCBs) in marine mammals are still of concern due to historical contamination of the North Sea

Arginine-selective modulation of the lysosomal transporter PQLC2 through a gate-tuning mechanism

International audienceLysosomes degrade excess or damaged cellular components and recycle their building blocks through membrane transporters. They also act as nutrient-sensing signaling hubs to coordinate cell responses. The membrane protein PQ-loop repeat-containing protein 2 (PQLC2; “picklock two”) is implicated in both functions, as it exports cationic amino acids from lysosomes and serves as a receptor and amino acid sensor to recruit the C9orf72/SMCR8/WDR41 complex to lysosomes upon nutrient starvation. Its transport activity is essential for drug treatment of the rare disease cystinosis. Here, we quantitatively studied PQLC2 transport activity using electrophysiological and biochemical methods. Charge/substrate ratio, intracellular pH, and reversal potential measurements showed that it operates in a uniporter mode. Thus, PQLC2 is uncoupled from the steep lysosomal proton gradient, unlike many lysosomal transporters, enabling bidirectional cationic amino acid transport across the organelle membrane. Surprisingly, the specific presence of arginine, but not other substrates (lysine, histidine), in the discharge (“ trans ”) compartment impaired PQLC2 transport. Kinetic modeling of the uniport cycle recapitulated the paradoxical substrate-yet-inhibitor behavior of arginine, assuming that bound arginine facilitates closing of the transporter’s cytosolic gate. Arginine binding may thus tune PQLC2 gating to control its conformation, suggesting a potential mechanism for nutrient signaling by PQLC2 to its interaction partners

Successful Prediction of Substrate-binding Pocket in SLC17 Transporter Sialin

International audienc

Methodology for the integration of process studies and development of a decision support tool (FRAC-WECO Project Deliverable D1.2)

This deliverable allows one to clarify the objectives of the different partners involved in the FRAC-WECO project and how they are going to interact, to exchange data, research results and knowledge in order to meet the ambitious objectives of the project. Particularly, the complex interactions between researches dealing with physical processes and with socio-economic aspects have been described in details. The modelling applications will constitute the key interacting tools as they are going to integrate all the information on water and contaminant mass fluxes and on biogeochemical processes affecting the fate of contaminant in the field and they are also going to be used to produce all data required for risk assessment and for the socio-economic analysis which are two of the most important expected outcomes of the project. The deliverable also clarifies the use of flux-based concepts through the definition of risk assessment indicators in the form of contaminant mass fluxes and discharge at the various considered receptors. Finally, this document has also allowed one to clarify the scope and the limits of the researches foreseen in the FRAC-WECO project that will focus on the risk of contaminant leaching to groundwater, of contaminant dispersion through groundwater and on the impact of contaminant on groundwater and surface water as affected by groundwater discharge and on the impact on aquatic ecosystems.Flux-based Risk Assessment of the impact of Contaminants on Water resources and ECOsystems (FRAC-WECO

Multi-Objective Optimization of the Nanocavities Diffusion in Irradiated Metals

International audienceMaterials in fission reactors or fusion tokamaks are exposed to neutron irradiation, which creates defects in the microstructure. With time, depending on the temperature, defects diffuse and form, among others, nanocavities, altering the material performance. The goal of this work is to determine the diffusion properties of the nanocavities in tungsten. We combine (i) a systematic experimental study in irradiated samples annealed at different temperatures up to 1800 K (the created nanocavities diffuse, and their coalescence is studied by transmission electron microscopy); (ii) our object kinetic Monte Carlo model of the microstructure evolution fed by a large collection of atomistic data; and (iii) a multi-objective optimization method (using model inversion) to obtain the diffusion of nanocavities, input parameters of our model, from the comparison with the experimental observations. We simplify the multi-objective function, proposing a projection into the parameter space. Non-dominated solutions are revealed: two “valleys” of minima corresponding to the nanocavities density and size objectives, respectively, which delimit the Pareto optimal solution. These “valleys” are found to be the upper and lower uncertainties on the diffusion beyond the uncertainties on the experimental and simulated results. The nanocavity diffusion can be split in three domains: the mono vacancy and small vacancy clusters, for which atomistic models are affordable, the small nanocavities for which our approach is decisive, and the nanocavities larger than 1.5 nm for which the classical surface diffusion theory is valid