Explore the vast range of titles available.

Small nucleolar RNAs (snoRNAs) are one of the most abundant and evolutionary ancient group of functional non-coding RNAs. They were originally described as guides of post-transcriptional rRNA modifications, but emerging evidence suggests that snoRNAs fulfil an impressive variety of cellular functions. To reveal the true complexity of snoRNA-dependent functions, we need to catalogue first the complete repertoire of snoRNAs in a given cellular context. While the systematic mapping and characterization of “snoRNAomes” for some species have been described recently, this has not been done hitherto for the zebrafish (Danio rerio). Using size-fractionated RNA sequencing data from adult zebrafish tissues, we created an interactive “snoRNAome” database for this species. Our custom-designed analysis pipeline allowed us to identify with high-confidence 67 previously unannotated snoRNAs in the zebrafish genome, resulting in the most complete set of snoRNAs to date in this species. Reanalyzing multiple previously published datasets, we also provide evidence for the dynamic expression of some snoRNAs during the early stages of zebrafish development and tissue-specific expression patterns for others in adults. To facilitate further investigations into the functions of snoRNAs in zebrafish, we created a novel interactive database, snoDanio, which can be used to explore small RNA expression from transcriptomic data.

Recent advances in sequencing technologies have made it significantly easier to find the genetic roots of rare hereditary pediatric diseases. These novel methods are not panaceas, however, and they often give ambiguous results, highlighting multiple possible causative mutations in affected patients. Furthermore, even when the mapping results are unambiguous, the affected gene might be of unknown function. In these cases, understanding how a particular genotype can result in a phenotype also needs carefully designed experimental work. Model organism genetics can offer a straightforward experimental setup for hypothesis testing. Containing orthologs for over 80% of the genes involved in human diseases, zebrafish (Danio rerio) has emerged as one of the top disease models over the past decade. A plethora of genetic tools makes it easy to create mutations in almost any gene of the zebrafish genome and these mutant strains can be used in high-throughput preclinical screens for active molecules. As this small vertebrate species offers several other advantages as well, its popularity in biomedical research is bound to increase, with “aquarium to bedside” drug development pipelines taking a more prevalent role in the near future.

Small nucleolar RNAs (snoRNAs) are one of the most abundant and evolutionary ancient group of functional non-coding RNAs. They were originally described as guides of post-transcriptional rRNA modifications, but emerging evidence suggests that snoRNAs fulfil an impressive variety of cellular functions, some of which are only being discovered. To reveal the true complexity of snoRNA-dependent functions, we need to catalogue first the complete repertoire of snoRNAs in a given cellular context. While the systematic mapping and characterization of “snoRNAomes” for some species have been described recently, this has not been done hitherto for the zebrafish (Danio rerio). Using size-fractionated RNA sequencing data from adult zebrafish tissues, we created an interactive “snoRNAome” database for this species. Our custom-designed analysis pipeline allowed us to identify with high-confidence 68 previously unannotated snoRNAs in the zebrafish genome, resulting in the most complete set of snoRNAs to date in this species. Reanalyzing multiple previously published datasets, we also provide evidence for the dynamic expression of some snoRNAs during the early stages of zebrafish development and tissue-specific expression patterns for others in adults. To facilitate further investigations into the functions of snoRNAs in zebrafish, we created a novel interactive database, snoDanio, which can be used to explore small RNA expression from transcriptomic data.

RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in DKC1, NOP10, or NHP2 cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. Females with heterozygous DKC1 p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin–NOP10 binding interface in a region distinct from those implicated in DC, impair the dyskerin–NOP10 interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafish dkc1 mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction.

Background: The standardized diagnostic categories defined by the World Health Organization (WHO) reporting system support the interdisciplinary interpretation of cytological findings in the management of pancreatic cancer. Objective: To compare this classification to the Papanicolaou Society of Cytopathology (PSC) system in terms of predictive value and risk of malignancy (ROM) in solid pancreatic lesions. Design: Retrospective cohort study. Methods: All consecutive patients with solid pancreatic lesions who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) sampling at the University of Szeged from 2014 to 2021 were retrospectively enrolled. The predictive value and ROM of cytological findings were determined with comparison to histologic outcome and/or clinical follow-up. Results: A total of 521 EUS-FNAs were performed with a malignancy rate of 81.76%. In both classification systems, the absolute ROM of “non-diagnostic,” “negative for malignancy,” “atypical,” “suspicious for malignancy,” and “malignant” categories were 48.2%, 2.3%, 78.1%, 100.0%, and 99.4%, respectively. Despite the heterogeneous nature of the “neoplastic: other” category of the PSC system, the absolute ROM for solid lesions was 100%. Pancreatic neoplasm: high-risk/grade category including only two endosonographically solid cases of high-grade intraductal papillary mucinous neoplasms showed 100% ROM. There were no differences between PSC and WHO systems in sensitivity, specificity, and negative and positive predictive values: excluding the “atypical” category, these were 99.7%, 95.6%, 97.7%, and 99.5%, respectively. The “atypical” category considered benign resulted in a higher decrease in validity and negative predictive value, compared to “atypical” considered true malignant (93.6% vs 97.7% and 65.8% vs 97.7%). Conclusion: For solid pancreatic lesions, the WHO system was identical to the PSC system in terms of ROM and predictive values.

Background The usage of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of solid pancreatic cancer is increasing, however mainly retrospective studies are available about the detailed methods of sampling. Methods To compare prospectively the diagnostic yield of EUS-FNA samples obtained with slow-pull (SP) and with standard suction technique (SS). Results EUS-FNA sampling was diagnostic in 72 of 92 cases (78.3%). Diagnostic yield was 67.4% in the SS and 65.2% in the SP group. The number of smear pairs (1.84 vs. 3.56; p  < 0.001) and blood contamination (1.50 vs. 2.19; p  < 0.001) were significantly higher in the SS group, which resulted in lower rate of diagnostic samples (41.8% vs. 30.0%; p  = 0.003). There was no difference in the cellularity (1.58 vs. 1.37; p  = 0.2554), or in the sensitivity and specificity in the identification of malignancy between SP and SS subgroups (69.9, 100% vs. 73.5, 100%). Histological samples were obtained in 60 cases (with SP: 49 cases; with SS: 46 cases). There was no difference in the diagnostic yield of histological samples between the groups (63 and 58.7%). Conclusion The diagnostic yield, the cellularity of smears and the rate of acquiring sufficient histological material are similar in the SP and SS group, but due to lower bloodiness and decreased number of slides, the pathological diagnosis is faster and more cost-effective.