Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor.

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.

Vaginitis with purulent vaginal discharge caused by artificial insemination using frozen Histophilus somni-contaminated semen.

In April 2020, two cows in Japan, developed reproductive disorders accompanied by vaginitis with purulent discharge within 3 days of artificial insemination (AI) with the same lot of frozen semen. Histophilus somni was isolated from the vaginal swabs of both cows as well as from the same lot of frozen semen used for the AI. This incident marks the first reported case of H. somni infection in cattle through AI. The major outer membrane protein gene sequences and pulsed-field gel electrophoresis profiles of the isolates were identical. Moreover, we investigated the antimicrobial activity of 12 frozen semen straws against an H. somni isolate using a disk diffusion test. These straws were sourced from five AI centers and included the same lot of semen used for the AI. Although the composition of semen diluents from individual AI centers is not publicly available, both the same lot of frozen semen used in the AI and other lots produced by the same manufacturer showed lower antimicrobial activity than semen from other manufacturers. These results strongly suggest that the two vaginitis were caused by AI using H. somni-contaminated frozen semen because of insufficient antimicrobial activity to inhibit bacterial growth. The minimum inhibitory concentrations of the six antimicrobials recommended for addition to frozen semen in isolates were below the recommended concentrations, suggesting that proper addition could have prevented this incident. This highlights the importance of conducting periodical checks on the antibacterial activity of frozen semen to prevent the transmission of pathogens via AI.

Accumulation and biological effects of metals in wild rats in mining areas of Zambia.

The lead-zinc (Pb-Zn) mine in Kabwe City and the copper-cobalt (Cu-Co) mine in the Copperbelt Province are major mining areas in Zambia. To examine the effects of metal pollution on wildlife, wild black rats (Rattus rattus and Rattus tanezumi) were captured in Kabwe and Chingola (in the Copperbelt Province), and in Lusaka (a noncontaminated site). Wild black rats in Kabwe accumulated significantly higher concentrations of Pb and Cd in various organs than rats from Lusaka. In Chingola, significantly higher concentrations of Cu, Co, Pb, and Cd were accumulated in wild black rats than in rats from Lusaka. These results were in accordance with metal accumulation patterns in soil. From toxicological aspects, concentrations of Pb and Cd in rats were generally low. However, metallothionein-1 (MT-1) and metallothionein-2 (MT-2) mRNA expression levels in wild black rats from Kabwe were significantly higher than those in rats from Lusaka. A generalized linear model (GLM) showed that concentrations of Zn and Cu had positive effects on the MT-1 and MT-2 mRNA expression. These results suggest that wild black rats in Zambian mining sites were exposed to metals that accumulated in their organs, causing biological responses such as MT mRNA induction. GLM indicated that heme oxygenase-1 (HO-1) mRNA expression could be a marker for Cr exposure.

Draft genome sequence of Pasteurella multocida strain BD1769 with untypable capsular serotype isolated from a layer chicken.

We report the draft genome sequence of Pasteurella multocida strain BD1769 (GenBank accession numbers JARFTQ010000001-JARFTQ010000021) isolated in 2021 from a layer chicken in Japan. No gene locus for capsular biosynthesis was annotated in the genome of this strain.

Association between antimicrobial treatment and resistance of pathogenic Escherichia coli isolated from diseased swine in Kagoshima Prefecture, Japan.

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 ß-lactamase encoded by blaCTX-M-14, blaCTX-M-15, blaCTX-M-24, blaCTX-M-61, or blaSHV-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.

Metal and metalloid contamination in roadside soil and wild rats around a Pb-Zn mine in Kabwe, Zambia.

Metal (Cr, Co, Cu, Zn, Cd, Pb, Ni) and metalloid (As) accumulation was studied in roadside soil and wild rat (Rattus sp.) samples from near a Pb-Zn mine (Kabwe, Zambia) and the capital city of Zambia (Lusaka). The concentrations of the seven metals and As in the soil samples and Pb in the rat tissue samples were quantified using atomic absorption spectroscopy. The concentrations of Pb, Zn, Cu, Cd, and As in Kabwe soil were much higher than benchmark values. Geographic Information System analysis indicated the source of metal pollution was mining and smelting activity. Interestingly, the area south of the mine was more highly contaminated even though the prevailing wind flow was westward. Wild rats from Kabwe had much higher tissue concentrations of Pb than those from Lusaka. Their body weight and renal Pb levels were negatively correlated, which suggests that mining activity might affect terrestrial animals in Kabwe.