Evaluation of rhodamine B as an orally delivered biomarker for rodents and a feed-through transtadial biomarker for phlebotomine sand flies (Diptera: Psychodidae)

The purpose of this study was to evaluate the use of rhodamine B as an orally delivered biomarker for rodents and a feed-through transtadial biomarker for phlebotomine sand flies (Diptera: Psychodidae ). Rhodamine B-treated hamsters were visibly marked for up to 8 wk, and their feces were fluorescent when examined under a fluorescence microscope. The development and survival of sand fly larvae fed feces of rhodamine B-treated hamsters were not significantly different from control sand flies. Adult male and female sand flies, that had been fed as larvae the feces of rhodamine B-treated hamsters, were fluorescent when examined using fluorescent microscopy and could be distinguished from control sand flies. Adult female sand flies that took bloodmeals from rhodamine B-treated hamsters were fluorescent when examined immediately after feeding. Rhodamine B incorporated rodent baits could be used to detect adult male and female sand flies that fed on the feces of baited rodents as larvae, or adult female sand flies that have taken a bloodmeal from bait-fed rodents. This would allow the delineation of specific foci with rodent-sand fly associations that would be susceptible to control by using feed-through or systemic insecticides. © 2009 Entomological Society of America

Evaluation of juvenile hormone analogues as rodent feed-through insecticides for control of immature phlebotomine sandflies

The juvenile hormone analogues methoprene and pyriproxyfen were evaluated as rodent feed-through insecticides for control of immature stages of the sandfly Phlebotomus papatasi Scopoli (Diptera: Psychodidae). The development and survival of P. papatasi second-instar larvae fed faeces from Syrian hamsters, Mesocricetus auratus, that had been fed a diet containing methoprene (0, 9.788, 97.88 or 978.8 p.p.m.) or pyriproxyfen (0, 9.82, 98.2 or 982 p.p.m.) were evaluated. The faeces of methoprene-treated hamsters greatly reduced the percentage of larvae that pupated at all concentrations tested and prevented adult emergence at all but the lowest concentration (9.788 p.p.m.). Pyriproxyfen prevented both pupation and adult emergence at all concentrations tested. The results of this study suggest that a control strategy using rodent baits containing juvenile hormone analogues to control phlebotomine sandflies that live in rodent burrows and feed on rodent faeces may be possible. As rodent reservoirs and vectors of Leishmania major live in close association in many parts of the Middle East, control of the transmission of the agent of zoonotic cutaneous leishmaniasis may also be possible. © 2010 The Authors. Medical and Veterinary Entomology © 2010 The Royal Entomological Society

Third Yearly Activity Report

The calculation work performed during the 3rd project year in WP2 as well as the R&D activities carried out in WP3, WP4 and WP5 are described in this report. In addition, the work dedicated to the project management (WP1) as well as to WP6 regarding the dissemination/communication activities and the education/training program (e.g. the follow-up of the mobility program between different organizations in the consortium, training on simulation tools and activities accomplished by PhD/post-doctoral students) is also reported

Main outcomes of the Phebus FPT1 uncertainty and sensitivity analysis in the EU-MUSA project

The Management and Uncertainties of Severe Accidents (MUSA) project was funded in HORIZON 2020 and is coordinated by CIEMAT (Spain). The project aims at consolidating a harmonized approach for the analysis of uncertainties and sensitivities associated with Severe Accidents (SAs) analysis, focusing on source term figures of merit. The Application of Uncertainty Quantification (UQ) Methods against Integral Experiments (AUQMIE – Work Package 4 (WP4)), led by ENEA (Italy), was devoted to apply and test UQ methodologies adopting the internationally recognized PHEBUS FPT1 test. FPT1 was chosen to test UQ methodologies because, even though it is a simplified SA scenario, it was representative of the in-vessel phase of a severe accident initiated by a break in the cold leg of a PWR primary circuit. WP4 served as a platform to identify and discuss the issues encountered in the application of UQ methodol ogies to SA analyses (e.g. discuss the UQ methodology, perform the coupling between the SA codes and the UQ tools, define the results post-processing methods, etc.). The purpose of this paper is to describe the MUSA PHEBUS FPT1 uncertainty application exercise with the related specifications and the methodologies used by the partners to perform the UQ exercise. The main outcomes and lessons learned of the analysis are: scripting was in general needed for the SA code and uncertainty tool coupling and to have more flexibility; particular attention should be devoted to the proper choice of the input uncertain parameters; outlier values of figures of merit should be carefully analyzed; the computational time is a key element to perform UQ in SA; the large number of uncertain input parameters may complicate the interpretation of correlation or sensitivity analysis; there is the need for a statistically solid handling of failed calculations

First outcomes from the PHEBUS FPT1 uncertainty application done in the EU MUSA project

The Management and Uncertainties of Severe Accidents (MUSA) project, founded in HORIZON 2020 and coordinated by CIEMAT (Spain), aims to consolidate a harmonized approach for the analysis of uncertainties and sensitivities associated with Severe Accidents (SAs) by focusing on Source Term (ST) Figure of Merits (FOM). In this framework, among the 7 MUSA WPs the Application of Uncertainty Quantification (UQ) Methods against Integral Experiments (AUQMIE – Work Package 4 (WP4)), led by ENEA (Italy), looked at applying and testing UQ methodologies, against the internationally recognized PHEBUS FPT1 test. Considering that FPT1 is a simplified but representative SA scenario, the main target of the WP4 is to train project partners to perform UQ for SA analyses. WP4 is also a collaborative platform for highlighting and discussing results and issues arising from the application of UQ methodologies, already used for design basis accidents, and in MUSA for SA analyses. As a consequence, WP4 application creates the technical background useful for the full plant and spent fuel pool applications planned along the MUSA project, and it also gives a first contribution for MUSA best practices and lessons learned. 16 partners from different world regions are involved in the WP4 activities. The purpose of this paper is to describe the MUSA PHEBUS FPT1 uncertainty application exercise, the methodologies used by the partners to perform the UQ exercise, and the first insights coming out from the calculation phase

Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB

Staphylococcus aureus (S. aureus) pathogenesis is a complex process involving a diverse array of extracellular and cell wall components. ClfB, an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family surface protein, described as a fibrinogen-binding clumping factor, is a key determinant of S. aureus nasal colonization, but the molecular basis for ClfB-ligand recognition remains unknown. In this study, we solved the crystal structures of apo-ClfB and its complexes with fibrinogen α (Fg α) and cytokeratin 10 (CK10) peptides. Structural comparison revealed a conserved glycine-serine-rich (GSR) ClfB binding motif (GSSGXGXXG) within the ligands, which was also found in other human proteins such as Engrailed protein, TCF20 and Dermokine proteins. Interaction between Dermokine and ClfB was confirmed by subsequent binding assays. The crystal structure of ClfB complexed with a 15-residue peptide derived from Dermokine revealed the same peptide binding mode of ClfB as identified in the crystal structures of ClfB-Fg α and ClfB-CK10. The results presented here highlight the multi-ligand binding property of ClfB, which is very distinct from other characterized MSCRAMMs to-date. The adherence of multiple peptides carrying the GSR motif into the same pocket in ClfB is reminiscent of MHC molecules. Our results provide a template for the identification of other molecules targeted by S. aureus during its colonization and infection. We propose that other MSCRAMMs like ClfA and SdrG also possess multi-ligand binding properties