Pathogenic Escherichia coli is an important cause of diarrhea, edema disease, and septicemia in swine. In Japan, the volume of antimicrobial drugs used for animals is highest in swine, but information about the prevalence of antimicrobial-resistant bacteria is confined to apparently healthy animals. In the present study, we determined the O serogroups, virulence factors, and antimicrobial resistance of 360 E. coli isolates from swine that died of disease in Kagoshima Prefecture, Japan, between 1999 and 2017. The isolates of the predominant serogroups O139, OSB9, O149, O8, and O116 possessed virulence factor genes typically found in diarrheagenic E. coli . We further found five strains of third-generation cephalosporin-resistant E. coli that each produced an extended-spectrum β-lactamase encoded by bla CTX-M-14 , bla CTX-M-15 , bla CTX-M-24 , bla CTX-M-61 , or bla SHV-12 . In 218 swine with a clear history of antimicrobial drug use, we further analyzed associations between the use of antimicrobials for the treatment of diseased swine and the isolation of resistant E. coli . We found significant associations between antimicrobial use and selection of resistance to the same class of antimicrobials, such as the use of ceftiofur and resistance to cefotaxime, cefazolin, or ampicillin, the use of aminoglycosides and resistance to streptomycin, and the use of phenicols and resistance to chloramphenicol. A significant association between antimicrobial use and the resistance of E. coli isolates to structurally unrelated antimicrobials, such as the use of ceftiofur and resistance to chloramphenicol, was also observed.

R 4 Ni 3 O 8 (R: rare-earth) is a candidate for high-T c superconductor because its crystal structure and electronic state are very similar to high-T c cuprates. Our recent works have pointed out that, by intercalation-deintercalation treatment with sulfur, the additional oxygen which impedes the metallic conduction is removed and the metallic behavior shows up in Nd 3.5 Sm 0.5 Ni 3 O 8. However, the semiconducting tendency remains below about 20-40 K, suggesting that the removal of additional oxygen is not complete. In this study, Pr-doping to Nd site in Nd 4 Ni 3 O 8 was performed in order to completely remove additional oxygen. By Pr-substitution, the electrical resistivity decreases and maintains metallic behavior down to low temperature (2 K). Next, we performed carrier tuning by chemical substitution to Ni sites in order to bring the electronic states of Ni closer to that of Cu in high-T c cuprates. Although the resistivity increases by doping, metallic behavior is maintained, suggesting that the dopants might occupy the specific Ni sites. However, superconductivity is not observed down to 2 K.

The epidermal growth factor receptor (EGFR) is the most intensively investigated receptor tyrosine kinase. Several EGFR mutations and modifications have been shown to lead to abnormal self-activation, which plays a critical role in carcinogenesis. Environmental air pollutants, which are associated with cancer and respiratory diseases, can also activate EGFR. Specifically, the environmental electrophile 1,2-naphthoquinone (1,2-NQ), a component of diesel exhaust particles and particulate matter more generally, has previously been shown to impact EGFR signaling. However, the detailed mechanism of 1,2-NQ function is unknown. Here, we demonstrate that 1,2-NQ is a novel chemical activator of EGFR but not other EGFR family proteins. We found that 1,2-NQ forms a covalent bond, in a reaction referred to as N -arylation, with Lys80, which is in the ligand-binding domain. This modification activates the EGFR–Akt signaling pathway, which inhibits serum deprivation–induced cell death in a human lung adenocarcinoma cell line. Our study reveals a novel mode of EGFR pathway activation and suggests a link between abnormal EGFR activation and environmental pollutant–associated diseases such as cancer.

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