Role of reactive oxygen species in angiotensin II: induced receptor activator of nuclear factor-κB ligand expression in mouse osteoblastic cells

To assess the influence of monoclonal anti-Lewis b, anti-H type 1, and anti-sialyl Lewis x addition on interactions of sugar structures of MUC1 mucin with Helicobacter pylori. The investigations were carried out on gastric juices of 11 patients and 12 H. pylori strains. The levels of Lewis b and sialyl Lewis x antigens on MUC1 were assessed by sandwich ELISA tests. Anti-Lewis b, anti-H type 1 or anti-sialyl Lewis x monoclonal antibodies were added to MUC1 to determine whether the adhesion activities of H. pylori isolates to examined mucin would be affected. Binding of bacteria to MUC1 was assessed by ELISA test. Clear inhibitory effect of examined antibodies was revealed in 6 of 12 examined H. pylori isolates independently on babA2 status. In the rest of strains this effect was negligible. We confirmed participation of Lewis b, H type 1 and also sialyl Lewis x of MUC1 mucin in interactions with H. pylori independently on babA genopositivity. Not full inhibition and a lack of this effect in some strains suggest an existence of other mechanisms of H. pylori adherence to mucin.     

Sanguinarine synergistically potentiates aminoglycoside-mediated bacterial killing

Aminoglycosides are one of the oldest classes of antimicrobials that are being used in current clinical practice, especially on multi-drug resistant Gram-negative pathogenic bacteria. However, the serious side effects at high dosage such as ototoxicity, neuropathy and nephrotoxicity limit their applications in clinical practice. Approaches that potentiate aminoglycoside killing could lower down their effective concentrations to a non-toxic dosage for clinical treatment. In this research, we screened a compound library and identified sanguinarine that acts synergistically with various aminoglycosides. By checkerboard and dynamical killing assay, we found that sanguinarine effectively potentiated aminoglycoside killing on diverse bacterial pathogens, including Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa. The mechanistic studies showed an elevated intracellular ROS and DNA oxidative level in the bacterial cells treated by a combination of sanguinarine with aminoglycosides. Furthermore, an enhanced level of sanguinarine was observed in bacteria in the presence of aminoglycosides, suggesting that aminoglycosides promote the uptake of sanguinarine. Importantly, sanguinarine was shown to promote the elimination of persister cells and established biofilm cells both in vivo and in vitro. Our study provides a novel insight for approaches to lower down the clinical dosages of aminoglycosides.     

MoWhi2 regulates appressorium formation and pathogenicity via the MoTor signalling pathway in Magnaporthe oryzae

Magnaporthe oryzae causes rice blast disease, which seriously threatens the safety of food production. Understanding the mechanism of appressorium formation, which is one of the key steps for successful infection by M. oryzae, is helpful to formulate effective control strategies of rice blast. In this study, we identified MoWhi2, the homolog of Saccharomyces cerevisiae Whi2 (Whisky2), as an important regulator that controls appressorium formation in M. oryzae. When MoWHI2 was disrupted, multiple appressoria were formed by one conidium and pathogenicity was significantly reduced. A putative phosphatase, MoPsr1, was identified to interact with MoWhi2 using a yeast two-hybridization screening assay. The knockout mutant ΔMopsr1 displayed similar phenotypes to the ΔMowhi2 strain. Both the ΔMowhi2 and ΔMopsr1 mutants could form appressoria on a hydrophilic surface with cAMP levels increasing in comparison with the wild type (WT). The conidia of ΔMowhi2 and ΔMopsr1 formed a single appressorium per conidium, similar to WT, when the target of rapamycin (TOR) inhibitor rapamycin was present. In addition, compared with WT, the expression levels of MoTOR and the MoTor signalling activation marker gene MoRS3 were increased, suggesting that inappropriate activation of the MoTor signalling pathway is one of the important reasons for the defects in appressorium formation in the ΔMowhi2 and ΔMopsr1 strains. Our results provide insights into MoWhi2 and MoPsr1-mediated appressorium development and pathogenicity by regulating cAMP levels and the activation of MoTor signalling in M. oryzae.     

The PsbS protein controls the macro-organisation of photosystem II complexes in the grana membranes of higher plant chloroplasts

The PsbS protein is a critical component in the regulation of non-photochemical quenching (NPQ) in higher plant photosynthesis. Electron microscopy and image analysis of grana membrane fragments from wild type and mutant Arabidopsis plants showed that the semi-crystalline domains of photosystem II supercomplexes were identical in the presence and absence of PsbS. However, the frequency of the domains containing crystalline arrays was increased in the absence of PsbS. Conversely, there was a complete absence of such arrays in the membranes of plants containing elevated amounts of this protein. It is proposed that PsbS controls the macro-organisation of the grana membrane, providing an explanation of its role in NPQ.     

Suppression of tyrocidine production by purine nucleotides and related substances in Bacillus brevis

Bacillus brevis (ATCC 8185) produces an antibiotic peptide, tyrocidine. We found that adenosine or 5'-AMP suppressed the production of tyrocidine with half-maximum inhibition at 100-300 microM. This inhibition was specific to the production of tyrocidine since neither adenosine nor 5'-AMP showed any effect on bacterial growth. Cyclic nucleotides had no effect. These results suggest that adenosine, 5'-AMP or its metabolite was specifically involved in the regulation of tyrocidine production.     

Evolutionary Genomics of Structural Variation in Asian Rice (Oryza sativa) Domestication

Structural variants (SVs) are a largely unstudied feature of plant genome evolution, despite the fact that SVs contribute substantially to phenotypes. In this study, we discovered SVs across a population sample of 347 high-coverage, resequenced genomes of Asian rice (Oryza sativa) and its wild ancestor (O. rufipogon). In addition to this short-read data set, we also inferred SVs from whole-genome assemblies and long-read data. Comparisons among data sets revealed different features of genome variability. For example, genome alignment identified a large (∼4.3 Mb) inversion in indica rice varieties relative to japonica varieties, and long-read analyses suggest that ∼9% of genes from the outgroup (O. longistaminata) are hemizygous. We focused, however, on the resequencing sample to investigate the population genomics of SVs. Clustering analyses with SVs recapitulated the rice cultivar groups that were also inferred from SNPs. However, the site-frequency spectrum of each SV type—which included inversions, duplications, deletions, translocations, and mobile element insertions—was skewed toward lower frequency variants than synonymous SNPs, suggesting that SVs may be predominantly deleterious. Among transposable elements, SINE and mariner insertions were found at especially low frequency. We also used SVs to study domestication by contrasting between rice and O. rufipogon. Cultivated genomes contained ∼25% more derived SVs and mobile element insertions than O. rufipogon, indicating that SVs contribute to the cost of domestication in rice. Peaks of SV divergence were enriched for known domestication genes, but we also detected hundreds of genes gained and lost during domestication, some of which were enriched for traits of agronomic interest.