Relevance of iron metabolic genes in biofilm and infection in uropathogenic Proteus mirabilis.

The microorganisms are found in the environment, forming sessile communities embedded in an extracellular matrix of their own production, called biofilm. These communities have a great relevance in the clinical context, since they are associated with infections caused by biofilm in medical implants, such as urinary catheters. The development of biofilms is a complex process where a great diversity of genes participate. The present work is based on the study of genes related to iron metabolism and its implication in the development of P. mirabilis biofilms and pathogenicity. For this study, two mutant strains defective in biofilm formation were selected, generated by the interruption of genes that encoded non-heme ferritin and TonB-dependent receptor. The mutations influence on the development of the biofilm was evaluated by different approaches. The complexity of the biofilm was analyzed using Confocal Laser Microscopy and image analysis. The mutants infectivity potential was assessed in two experimental mice models of urinary tract infection. The results obtained in the present work show us the role of the ferritin and a TonB-associated porin protein over the initial and later stages of biofilm development. Moreover, in the ascending UTI mouse model, both mutants failed to colonize the urinary tract. In CAUTI models, ferritin mutant damaged the bladder similarly to wild type but the Ton-B mutant was unable to generate infection in the urinary tract. The results obtained in the present work confirm the relevant role that iron metabolism genes have in P. mirabilis biofilm development and for infection in the urinary tract.

Kinin B2 receptor can play a neuroprotective role in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline, presence of amyloid-beta peptide (Aß) aggregates and neurofibrillary tangles. Kinins act through B1 and B2 G-protein coupled receptors (B1R and B2R). Chronic infusion of Aß peptide leads to memory impairment and increases in densities of both kinin receptors in memory processing areas. Similar memory impairment was observed in C57BL/6 mice (WTAß) but occurred earlier in mice lacking B2R (KOB2Aß) and was absent in mice lacking B1R (KOB1Aß). Thus, the aim of this study was to evaluate the participation of B1R and B2R in Aß peptide induced cognitive deficits through the evaluation of densitiesof kinin receptors, synapses, cell bodies and number of Aß deposits in brain ofWTAß, KOB1Aß and KOB2Aß mice. An increase in B2R density was observed in both WTAß and KOB1Aß in memory processing related areas. KOB1Aß showed a decrease in neuronal density and an increase in synaptic density and, in addition, an increase in Aß deposits in KOB2Aß was observed. In conclusion, memory preservation in KOB1Aß, could be due to the increase in densities of B2R, suggesting a neuroprotective role for B2R, reinforced by the increased number of Aß plaques in KOB2Aß. Our data point to B2R as a potential therapeutic target in AD.

Characterization and validation of a Portuguese natural reference soil to be used as substrate for ecotoxicological purposes.

This study describes the first attempt to validate a Portuguese natural soil (PTRS1) to be used as reference soil for ecotoxicological purposes, aimed to both: (i) obtain ecotoxicological data for the derivation of Soil Screening Values (SSVs) with regional relevance, acting as a substrate to be spiked with ranges of concentrations of the chemicals under evaluation and (ii) act as control and as substrate for the dilution of contaminated soils in ecotoxicological assays performed to evaluate the ecotoxicity of contaminated soils, in tier 2 of risk assessment frameworks, applied to contaminated lands. The PTRS1 is a cambisol from a granitic area integrated in the Central Iberian Zone. After chemical characterization of the soil in terms of pseudo-total metals, PAHs, PCBs and pesticide contents, it was possible to perceive that some metals (Ba, Be, Co, Cr and V) surpass the Dutch Target Values (Dtvs) corrected for the percentage of organic matter and clay of the PTRS1. Nevertheless, these metals displayed total concentrations below the background total concentrations described for Portuguese soils in general. The same was observed for aldrin, endosulfan I, endosulfan II, heptachlor epoxide, and heptachlor; however the Dtvs corrected become negligible. The performance of invertebrate and plant species, commonly used in standard ecotoxicological assays, was not compromised by both soil properties and soil metal contents. The results obtained suggest that the PTRS1 can be used as a natural reference soil in ecotoxicological assays carried out under the scope of ecological risk assessment.