RESUMO
Primary hyperoxaluria type 1 (PH1) is a rare inherited metabolic disorder characterized by oxalate overproduction in the liver, resulting in renal damage. It is caused by mutations in the AGXT gene. Combined liver and kidney transplantation is currently the only permanent curative treatment. We combined locus-specific gene correction and hepatic direct cell reprogramming to generate autologous healthy induced hepatocytes (iHeps) from PH1 patient-derived fibroblasts. First, site-specific AGXT corrected cells were obtained by homology directed repair (HDR) assisted by CRISPR-Cas9, following two different strategies: accurate point mutation (c.731T>C) correction or knockin of an enhanced version of AGXT cDNA. Then, iHeps were generated, by overexpression of hepatic transcription factors. Generated AGXT-corrected iHeps showed hepatic gene expression profile and exhibited in vitro reversion of oxalate accumulation compared to non-edited PH1-derived iHeps. This strategy set up a potential alternative cellular source for liver cell replacement therapy and a personalized PH1 in vitro disease model.
RESUMO
Economic surveillance for securing water projects driven by non-conventional energy sources is a challenge. The carrying out of these initiatives in economies based on liberalized markets faces governments against the need for guaranteed profits. As water availability has become a relevant global problem, and desalination an energy-intensive demand solution, it is common to combine both kinds of technologies, renewable energy systems and desalination plants. This research investigates the influence of grants, investment rates, and energy and water sales on the commercialization of two desalination technologies. A performance analysis has been carried out taking into account different scenarios. Following this approach, a simulated reverse osmosis desalination plant has been compared with respect to an already granted novel pilot plant. Results show a better fulfilment of the non-economic objectives, and economically profitable not only under certain conditions of conceded grants, and investor's expected benefits but also of sales of water-energy, that highlighted as a limiting factor. The Levelized Cost of Energy might be similar than the Spanish generation means, depending on the cost escalation rate of the loans, and conceded grants. It was found a reduction of 11 euro cents under the average price that could be achieved, for the standard scenario.
