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

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

International Liver Transplantation Society Global Census:First Look at Pediatric Liver Transplantation Activity Around the World

Background. Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions. Methods. A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita. Results. One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P &lt; 0.001) compared to lower-middle-income countries. Conclusions. This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.</p

Living donor liver transplantation

PubMed ID: 28675358In 50 years after the first liver transplantation, the medical world has witnessed the liver transplantation to become one of the widely recognized and leading branches of surgery. In this period, liver transplantation combined with surgical technique, patient selection, advancements in anesthesia and postoperative care and increased experience has become the most effective treatment option in treatment of several acute and chronic liver diseases. Yet, the worldwide organ restriction and associated high mortality rates in organ transplantation waiting list has compelled referring to living donors in order to expand the donor pool. This paper explains liver transplantation indications from living donors, the surgical technique involved, the complications of the procedure and the medical treatments used. © Celsius

Linalool improve biochemical damage and fatty acids composition of testes on fasting male rats

The aim of this study was to evaluate fatty acids compositions, oxidative stress levels and some antioksidant levels in the testes of 24 h fasted rats and linalool application. Adult male Wistar albino rats were assigned as Control (C), 24 h fasted (24 h F) group and added linalool (120 mg kg-1) during 24 h fasted (24 h F+L) groups. After applications, the animals were killed and the testes were excised for determination of tissue malondialdehyde, Glutation Peroxidase (GSH-Px), the activity of superoxide dismutase and determination of tissue fatty acids compositions. The activites of Superoxide Dismutase (SOD), Glutathione peroxidase (GSH-Px) and the level of Malondialdehyde (MDA) in testicular tissue specimens were determined spectrophotometrically. The fatty acid compositons in the testes were analyzed as percent by gas chromatography (GC). Researchers calculated between C 16:0 (palmitic acid) andC22:6 (docosahexaenoic acid) fatty acids in the testes of all experimental groups. Treatment with fasted rats resulted in a significant reduction inC16:l (palmitoleate) fatty acids when compared to the control rats (p&lt;0.05). C16:l fatty acids were higher in linalool application than fasted groups (p&lt;0.05). C22:4 (docosatetraenoic Acid), C22:5 (docosapentaenoic acid), C22:6 n3 (docosahexaenoic acid) fatty acids were lower in the fasted group than the control group. In addition, C22:4, C22:5, C22:6 fatty acids compositions in the linalool treatment group were higher than the fasted group (p&lt;0.05). Saturated fatty acids levels in all experiment groups were not change as statistically (p&gt;0.05). SOD and GSH-Px levels in the fasted rats were statistically lower than control groups (p&lt;0.05). Both SOD and GSH-Px levels in the linalool application groups were not statistically a change compared to fasted groups (p&gt;0.05). In addition, MDA levels in the fasted groups were higher than control groups. Besides, MDA levels in the linalool application groups were lower compared to fasted groups (p&lt;0.05). These findings indicate that fasted state has oxidative effects on testicular tissue and linalool has protective effects on male reproductive system. © Medwell Journals, 2011

Effect of Heavy Metals and Antibiotics on Siderophores Producing Bacterial Isolates

2nd International Conference on Computational and Experimental Science and Engineering (ICCESEN) -- OCT 14-19, 2015 -- Kemer, TURKEYWOS: 000384810700047In this study, siderophore-producing bacterial species have been isolated from soils contaminated with diesel oil. In P. aeruginosa (P-7) production of siderophores was inhibited at concentrations of ZnSO4 and CoCl2 of 2000 mu M, while B. subtilis (BS-1) has increased siderophores production at similar concentrations of CoCl 2 and ZnSO4. The same bacteria have increased the production of siderophores in presence of streptomycine (512 mg/ml). In B. subtilis the production of siderophores was inhibited by cefuroxime. The results show the effect of metals on the efficiency of siderophore production by bacteria for potential application in bioremediation of metalcontaminated iron-deficient soils in the microbial assisted phytoremediation processes. The results include the effect of metals on siderophore production efficiency of the bacteria used for the bioremediation of metal-contaminated soils. In conclusion, it has been found that heavy metals and antibiotics significantly effect the production of siderophores by bacteria

Missed intra-abdominal malignancies after laparoscopic cholecystectomy [1]

PubMed ID: 15977702[No abstract available