Evolutionary processes of melanomas from giant congenital melanocytic nevi

Melanoma can develop in a congenital melanocytic nevus (CMN). In fact, a large CMN is associated with a high risk of developing melanoma. Although melanomas arising from CMNs are thought to have a pathogenesis distinct from conventional melanomas, no studies have been conducted on the evolution or tumor heterogeneity of CMN melanomas. We applied multi‐region whole‐exome sequencing to investigate the clonal nature of driver events and evolutionary processes in CMNs and melanomas arising from CMNs. In two patients, we observed an independent subclonal evolution in cancerized fields of CMNs and chromosome 8q amplification in both melanomas arising from CMNs. The amplification of MYC, located in chromosome 8q, was correlated with the percentage of tumor cells expressing high levels of MYC protein detected in melanoma cells by immunohistochemistry. Our analysis suggests that each CMN cell may evolve sporadically and that amplification of MYC might be a key event for melanoma development in CMNs.     

Anaerocolumna sedimenticola sp. nov., isolated from fresh water sediment

Strain CBA3638^T was isolated from the Geum River sediment, Republic of Korea. The cells of strain CBA3638^T were Gram-stain-positive, strictly anaerobic, rod-shaped, and 0.5–1.0 μm wide, and 4.0–4.5 μm long. Optimal growth occurred at 37 °C, pH 7.0, and 1.0% (w/v) NaCl. Based on the 16S rRNA gene sequence, the phylogenetic analysis showed that strain CBA3638^T belongs to the genus Anaerocolumna in the family Lachnospiraceae, and is most closely related to Anaerocolumna cellulosilytica (94.6–95.0%). The DDH value with A. cellulosilytica SN021^T showed 15.0% relatedness. The genome of strain CBA3638^T consisted of one circular chromosome that is 5,500,435 bp long with a 36.7 mol% G?+?C content. The genome contained seven 16S-5S-23S rRNA operons and one antibiotic resistance-related transporter gene (mefA). Quinones were not detected. The predominant cellular fatty acids were C_16:0 and C_14:0 and the polar lipids were diphosphatidylglycerol, phosphatidylcholine, and uncharacterised polar lipids. Based on the polyphasic taxonomic analysis, we propose strain CBA3638^T as a novel species in the genus Anaerocolumna, with the name Anaerocolumna sedimenticola sp. nov. The type strain is CBA3638^T (=?KACC 21652^T?=?DSM 110663^T).

     

O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport

Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear transport receptors (NTRs). FG-repeat domains in NPCs are a major site of O-linked N-acetylglucosamine (O-GlcNAc) modification, but the functional role of this modification in nucleocytoplasmic transport is unclear. We developed high-throughput assays based on optogenetic probes to quantify the kinetics of nuclear import and export in living human cells. We found that increasing O-GlcNAc modification of the NPC accelerated NTR-facilitated transport of proteins in both directions, and decreasing modification slowed transport. Superresolution imaging revealed strong enrichment of O-GlcNAc at the FG-repeat barrier. O-GlcNAc modification also accelerated passive permeation of a small, inert protein through NPCs. We conclude that O-GlcNAc modification accelerates nucleocytoplasmic transport by enhancing the nonspecific permeability of the FG-repeat barrier, perhaps by steric inhibition of interactions between FG repeats.     

Antiviral and Antimicrobial Nucleoside Derivatives: Structural Features and Mechanisms of Action

Molecular Biology - The emergence of new viruses and resistant strains of pathogenic microorganisms has become a powerful stimulus in the search for new drugs. Nucleosides are a promising class of...     

Suppression of DRR1 results in the accumulation of insoluble ubiquitinated proteins,which impairs drought stress tolerance

Drought stress has detrimental effects on plants. Although the abscisic acid (ABA)‐mediated drought response is well established, defensive mechanisms to cope with dehydration‐induced proteotoxicity have been rarely studied. DRR1 was identified as an Arabidopsis drought‐induced gene encoding an ER‐localized RING‐type E3 Ub ligase. Suppression of DRR1 markedly reduced tolerance to drought and proteotoxic stress without altering ABA‐mediated germination and stomatal movement. Proteotoxicity‐ and dehydration‐induced insoluble ubiquitinated protein accumulation was more obvious in DRR1 loss‐of‐function plants than in wild‐type plants. These results suggest that DRR1 is involved in an ABA‐independent drought stress response possibly through the mitigation of dehydration‐induced proteotoxic stress.     

Differential requirement of Oryza sativa RAR1 in immune receptor-mediated resistance of rice to Magnaporthe oryzae

The required for Mla12 resistance (RAR1) protein is essential for the plant immune response. In rice, a model monocot species, the function of Oryza sativa RAR1 (OsRAR1) has been little explored. In our current study, we characterized the response of a rice osrar1 T-DNA insertion mutant to infection by Magnaporthe oryzae, the causal agent of rice blast disease. osrar1 mutants displayed reduced resistance compared with wild type rice when inoculated with the normally virulent M. oryzae isolate PO6-6, indicating that OsRAR1 is required for an immune response to this pathogen. We also investigated the function of OsRAR1 in the resistance mechanism mediated by the immune receptor genes Pib and Pi5 that encode nucleotide binding-leucine rich repeat (NB-LRR) proteins. We inoculated progeny from Pib/osrar1 and Pi5/osrar1 heterozygous plants with the avirulent M. oryzae isolates, race 007 and PO6-6, respectively. We found that only Pib-mediated resistance was compromised by the osrar1 mutation and that the introduction of the OsRAR1 cDNA into Pib/osrar1 rescued Pib-mediated resistance. These results indicate that OsRAR1 is required for Pib-mediated resistance but not Pi5-mediated resistance to M. oryzae.