Genomic analysis of three cheese-borne pseudomonas lactis with biofilm and spoilage-associated behavior

Psychrotrophic pseudomonads cause spoilage of cold fresh cheeses and their shelf-life reduction. Three cheese-borne Pseudomonas sp., ITEM 17295, ITEM 17298, and ITEM 17299 strains, previously isolated from mozzarella cheese, revealed distinctive spoilage traits based on molecular determinants requiring further investigations. Genomic indexes (ANI, isDDH), MLST-based phylogeny of four housekeeping genes (16S rRNA, gyrB, rpoB and rpoD) and genome-based phylogeny reclassified them as Pseudomonas lactis. Each strain showed distinctive phenotypic traits at 15 and 30◦C: ITEM 17298 was the highest biofilm producer at both temperatures, whilst ITEM 17295 and ITEM 17299 showed the strongest proteolytic activity at 30◦C. A wider pattern of pigments was found for ITEM 17298, while ITEM 17295 colonies were not pigmented. Although the high genomic similarity, some relevant molecular differences supported this phenotypic diversity: ITEM 17295, producing low biofilm amount, missed the pel operon involved in EPS synthesis and the biofilm-related Toxin-Antitoxin systems (mqsR/mqsA, chpB/chpS); pvdS, required for the pyoverdine synthesis, was a truncated gene in ITEM 17295, harboring, instead, a second aprA involved in milk proteolysis. This work provided new insight into the food spoiler microbiota by identifying these mozzarella cheese spoilers as P. lactis; molecular targets to be exploited in the development of novel preservative strategies were also revealed

Synthesis and characterisation of a new benzamide-containing nitrobenzoxadiazole as a GSTP1-1 inhibitor endowed with high stability to metabolic hydrolysis

The antitumor agent 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (1) is a potent inhibitor of GSTP1-1, a glutathione S-transferase capable of inhibiting apoptosis by binding to JNK1 and TRAF2. We recently demonstrated that, unlike its parent compound, the benzoyl ester of 1 (compound 3) exhibits negligible reactivity towards GSH, and has a different mode of interaction with GSTP1-1. Unfortunately, 3 is susceptible to rapid metabolic hydrolysis. In an effort to improve the metabolic stability of 3, its ester group has been replaced by an amide, leading to N-(6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexyl)benzamide (4). Unlike 3, compound 4 was stable to human liver microsomal carboxylesterases, but retained the ability to disrupt the interaction between GSTP1-1 and TRAF2 regardless of GSH levels. Moreover, 4 exhibited both a higher stability in the presence of GSH and a greater cytotoxicity towards cultured A375 melanoma cells, in comparison with 1 and its analog 2. These findings suggest that 4 deserves further preclinical testing

Quantifying the unknown: issues in simulation validation and their experimental impact

The assessment of the reliability of Monte Carlo simulations is discussed, with emphasis on uncertainty quantification and the related impact on experimental results. Methods and techniques to account for epistemic uncertainties, i.e. for intrinsic knowledge gaps in physics modeling, are discussed with the support of applications to concrete experimental scenarios. Ongoing projects regarding the investigation of epistemic uncertainties in the Geant4 simulation toolkit are reported.Comment: To be published in the Proceedings of the 13th ICATPP Conference on Astroparticle, Particle, Space Physics and Detectors for Physics Applications, Villa Olmo, Como, 3-7 October 201

Geant4-related R&D for new particle transport methods

A R&D project has been launched in 2009 to address fundamental methods in radiation transport simulation and revisit Geant4 kernel design to cope with new experimental requirements. The project focuses on simulation at different scales in the same experimental environment: this set of problems requires new methods across the current boundaries of condensed-random-walk and discrete transport schemes. An exploration is also foreseen about exploiting and extending already existing Geant4 features to apply Monte Carlo and deterministic transport methods in the same simulation environment. An overview of this new R&D associated with Geant4 is presented, together with the first developments in progress.Comment: 4 pages, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

New models for PIXE simulation with Geant4

Particle induced X-ray emission (PIXE) is a physical effect that is not yet adequately modelled in Geant4. The current status as in Geant4 9.2 release is reviewed and new developments are described. The capabilities of the software prototype are illustrated in application to the shielding of the X-ray detectors of the eROSITA telescope on the upcoming Spectrum-X-Gamma space mission.Comment: To be published in the Proceedings of the CHEP (Computing in High Energy Physics) 2009 conferenc

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity.

In syngeneic mice, the H5V polyoma middle-T oncogene-transformed endothelioma cell line induces Kaposi's sarcoma-like cavernous haemangiomas that regress transiently, probably because of an anti-tumour immune response, but eventually grow progressively and kill the host. To evaluate the generation of tumour-specific cytotoxic T lymphocytes (CTLs), spleen cells of tumour-bearing mice were restimulated with irradiated H5V cells in mixed leucocyte-tumour cell cultures. Tumour-specific CTLs were demonstrable only when low numbers of H5V stimulator cells were used (<1 H5V cell per 50 splenocytes). We found that H5V cells secrete immunosuppressive mediators because CTL generation was blocked when H5V cells culture supernatants were added to allogeneic mixed leucocyte cultures. As numerous tumour-derived immunosuppressive mediators may interfere with interleukin 12 (IL-12) production, we tested whether IL-12 treatment of the tumour-bearing mice would augment their immune response and thus suppress tumour growth. Indeed, IL-12 inhibited tumour growth and prevented mortality, but did not increase anti-H5V CTL generation either in vitro or in vivo. Moreover, the anti-tumour activity in IL-12-treated mice was abrogated by anti-interferon (IFN)-gamma monoclonal antibody (MAb) co-administration. These results strongly suggest that the anti-tumour effect of IL-12 is principally mediated by IFN-gamma release that in turn blocks H5V cell proliferation and induces the release of factors that suppress angiogenesis