Restructuring a Water Distribution Network through the Reactivation of Decommissioned Water Tanks

Water resource management is a topic of great environmental and social relevance, since water must be preserved and managed to avoid waste, providing high quality service at fair tariffs for the consumer, as imposed by the European Water Directive (2000/CE). In the rehabilitation of a water distribution network, it may be suitable to recover decommissioned water tanks, if any, rather than afford high construction costs to build new ones. In this case, the assessment of the residual service life of these concrete structures affected by steel bar corrosion is the premise for the design of new pipeline routes, connecting them. For this aim, rather than carrying tests that can accurately determine mechanical properties of the dismissed water tanks, it is possible to empirically estimate their level of degradation. Their conditions infer on the expected life of the restructured water distribution network. However, they allow the aqueduct to be used for its technical duration, assumed to be equal to the decommissioned water tanks residual service life in the case they do not require maintenance. Here, a simplified model for the assessment of the residual service life of decommissioned water tanks is first proposed and then applied to a case study, consisting of a part of the water network managed by “Ausino S.p.A. Servizi Idrici Integrati”, Cava de’ Tirreni, Italy. Once the service life is assessed, the QEPANET plugin is used in QGIS to speed up the design of the new pipeline routes in the georeferenced space, thus overcoming the limits offered by the classic EPANET solver

Analysis of the interactome of ribosomal protein S19 mutants

Diamond–Blackfan anemia, characterized by defective erythroid progenitor maturation, is caused in one-fourth of cases by mutations of ribosomal protein S19 (RPS19), which is a component of the ribosomal 40S subunit. Our previous work described proteins interacting with RPS19 with the aim to determine its functions. Here, two RPS19 mutants, R62W and R101H, have been selected to compare their interactomes versus the wild-type protein one, using the same functional proteomic approach that we employed to characterize RPS19 interactome. Mutations R62W and R101H impair RPS19 ability to associate with the ribosome. Results presented in this paper highlight the striking differences between the interactomes of wild-type and mutant RPS19 proteins. In particular, mutations abolish interactions with proteins having splicing, translational and helicase activity, thus confirming the role of RPS19 in RNA processing/metabolism and translational control. The data have been deposited to the ProteomeXchange with identifier PXD00064

The proteome of methylmalonic acidemia (MMA): elucidation of altered pathways in patient livers

Methylmalonic acidemia (MMA) is a heterogeneous and severe autosomal recessive inborn error of metabolism most commonly caused by the deficient activity of the vitamin B12 dependent enzyme, methylmalonyl-CoA mutase (MUT). The main treatment for MMA patients is the dietary restriction of propiogenic amino acids and carnitine supplementation. Despite treatment, the prognosis for vitamin B12 non-responsive patients remains poor and is associated with neonatal lethality, persistent morbidity and decreased life expectancy. While multi-organ pathology is a feature of MMA, the liver is severely impacted by mitochondrial dysfunction which likely underlies the metabolic instability experienced by the patients. Liver and/or combined liver/kidney transplantation is therefore sometimes performed in severely affected patients. Using liver specimens from donors and MMA patients undergoing elective liver transplantation collected under a dedicated natural history protocol (clinicaltrials.gov: NCT00078078), we employed proteomics to characterize the liver pathology and impaired hepatic metabolism observed in the patients. Pathway analysis revealed perturbations of enzymes involved in energy metabolism, gluconeogenesis and Krebs cycle anaplerosis. Our findings identify new pathophysiologic and therapeutic targets that could be valuable for designing alternative therapies to alleviate clinical manifestations seen in this disorder

Fatty acid acylated peptide therapeutics: discovery of omega-n oxidation of the lipid chain as a novel metabolic pathway in preclinical species

International audienceWe recently described C18 fatty acid acylated peptides as a new class of potent long-lasting single-chain RXFP1 agonists that displayed relaxin-like activities in vivo. Early pharmacokinetics and toxicological studies of these stearic acid acylated peptides revealed a relevant oxidative metabolism occurring in dog and minipig, and also seen at a lower extent in monkey and rat. Mass spectrometry combined to NMR spectroscopy studies revealed that the oxidation occurred, unexpectedly, on the stearic acid chain at ω-1, ω-2 and ω-3 positions. Structure-metabolism relationship studies on acylated analogues with different fatty acids lengths (C15-C20) showed that the extent of oxidation was higher with longer chains. The oxidized metabolites could be generated in vitro using liver microsomes and engineered bacterial CYPs. These systems were correlating poorly with in vivo metabolism observed across species; however, the results suggest that this biotransformation pathway might be catalyzed by some unknown CYP enzymes