Recurrence of primary sclerosing cholangitis after liver transplantation – analysing the European Liver Transplant Registry and beyond

Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4–18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9–9.1) and patient survival (HR 2.3; 95% CI 1.5–3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7–4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival

Alternative Splicing at a NAGNAG Acceptor Site as a Novel Phenotype Modifier

Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides. We identified such a mechanism as the origin of the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation (2623G>T) in the CFTR gene. Analyses performed on nasal epithelial cell mRNA detected three distinct isoforms, a considerably more complex situation than expected for a single nucleotide substitution. Structure-function studies and in silico analyses provided the first experimental evidence of an indel of a stop codon by alternative splicing at a NAGNAG acceptor site. In addition to contributing to proteome plasticity, alternative splicing at a NAGNAG tandem site can thus remove a disease-causing UAG stop codon. This molecular study reveals a naturally occurring mechanism where the effect of either modifier genes or epigenetic factors could be suspected. This finding is of importance for genetic counseling as well as for deciding appropriate therapeutic strategies

Biosynthesis of silver nanoparticles from Aeromonas sobria and antibacterial activity against fish pathogens

4th International Conference on Computational and Experimental Science and Engineering (ICCESEN) -- OCT 04-08, 2017 -- Kemer, TURKEYWOS: 000478894500021Fish diseases are a major obstacle to the development of the fisheries industry. Aeromonas sobria is an infectious waterborne bacterium that causes ulcers, tail rot and hemorrhagic septicemia in fishes and resistant to many existing antibiotics. In this context, A. sobria-AgNPs were synthesized by A. sobria using AgNO3. A. sobria-AgNPs were characterized using UV-Vis spectroscopy, and a peak was obtained at a range of 420-480 nm. A. sobria-AgNPs were evaluated for antibacterial activities against different fish pathogens. The highest antibacterial activity was observed against A. hydrophila, E. cloacae and E. coli. The lower activity was found against C. braakii and E. hermannii, but against H. alvei, P. rettger and M. morganii subsp. sibonii no zone of inhibition was recorded. The results indicated that the A. sobria-AgNPs can be used to develop antibacterial agent and as a therapeutic agent in the fishing industry and water disinfection. The antibacterial efficacy against the fish pathogen A. hydrophila of silver nanoparticles is a hope for possible application as a disinfectant or antimicrobial agent for better fish health management.Ahi Evran University Scientific Research Projects Coordination UnitAhi Evran University [FEF.E2.17.038]This work was supported by the Ahi Evran University Scientific Research Projects Coordination Unit. Project Number FEF.E2.17.038