Next-generation sequencing technology may clarify microbiota that are as yet poorly understood in the soil, the rhizosphere, and the phyllosphere of vineyards. To provide new information on the interaction between grapevine and microorganisms, we focused on the endophytic microbiota in grapevine. We performed endophytic microbiome analysis of the shoot xylems of four cultivars,Vitis viniferacvs. Chardonnay, Pinot Noir, Cabernet Sauvignon, andVitissp. cv. Koshu, grown in eleven vineyards in Japan. The number of endophytic fungal species was small in the grapevine shoot xylems and could not be analyzed further, whereas a total of 7,019,600 amplicon sequences (46,642–285,003 per shoot xylem) and 1305 bacterial operational taxonomic units were obtained by analysis of the V3–V4 region of the bacterial 16S rRNA gene. Gammaproteobacteria was predominant in the shoot xylems at the shoot elongation stage irrespective of the cultivar, whereas Alphaproteobacteria and Oxyphotobacteria were predominant at véraison. Actinobacteria, Bacteroidia, Bacilli, and Clostridia were also detected in the shoot xylems. The endophytic bacterial microbiota in Koshu and Pinot Noir shoot xylems were similar irrespective of the grapevine-growing region. In contrast, the endophytic bacterial microbiota in Chardonnay and Cabernet Sauvignon showed diversity and complexity among grapevine-growing regions. Alpha diversity analysis revealed that Koshu shoot xylems had a higher diversity of endophytic bacterial microbiota than Pinot Noir, Chardonnay, and Cabernet Sauvignon shoot xylems, and that grapevine shoot xylems at the shoot elongation stage had a higher diversity of endophytic bacterial microbiota than those at véraison. Principal coordinate analysis (PCoA) demonstrated that the profiles of the endophytic bacterial microbiota in grapevine shoot xylems at véraison were relatively uniform compared with those at the shoot elongation stage. Multidimensional scaling analysis showed that the plots of all cultivars were generally apart from each other at the shoot elongation stage and then became close to each other at véraison. The plots of all grapevine-growing regions cultivating Koshu were close to each other, whereas those of grapevine-growing regions cultivating Chardonnay and Cabernet Sauvignon were apart from each other. The findings of this study suggest that the endophytic bacterial microbiota in grapevine shoot xylems varied depending on the cultivar and the grapevine-growing region even for the same cultivars, and that the microbiota fluctuated depending on the shoot growth stage.

DNA demethylation for hormone-induced transcriptional derepression

Molecular targeted therapy using poly (ADP-ribose) polymerase inhibitors has improved survival in patients with castration-resistant prostate cancer (CRPC). However, this approach is only effective in patients with specific genetic mutations, and additional drug discovery targeting epigenetic modulators is required. Here, we evaluated the involvement of the transcriptional coregulator ESS2 in prostate cancer. ESS2-knockdown PC3 cells dramatically inhibited proliferation in tumor xenografts in nude mice. Microarray analysis revealed that ESS2 regulated mRNA levels of chromodomain helicase DNA binding protein 1 (CHD1)-related genes and other cancer-related genes, such as PPAR-γ, WNT5A, and TGF-β, in prostate cancer. ESS2 knockdown reduced nuclear factor (NF)-κB/CHD1 recruitment and histone H3K36me3 levels on the promoters of target genes (TNF and CCL2). In addition, we found that the transcriptional activities of NF-κB, NFAT and SMAD2/3 were enhanced by ESS2. Tamoxifen-inducible Ess2-knockout mice showed delayed prostate development with hypoplasia and disruption of luminal cells in the ventral prostate. Overall, these findings identified ESS2 acts as a transcriptional coregulator in prostate cancer and ESS2 can be novel epigenetic therapeutic target for CRPC.

Patients with end-stage renal disease (ESRD) are at increased risk of acquired cystic kidney disease (ACKD) and renal tumors, but the molecular basis of such disorders remains elusive. In this study, we performed spatial immunogenomic analyses on 268 specimens from 43 patients with ACKD and associated tumors. The molecular landscape of ESRD-associated tumors is different from that of sporadic renal cell carcinoma. Single-cell and spatial analyses have shown that ACKD is under an inflammatory environment and that the renal cysts in ACKD are derived from proximal tubular cells that have survived the destructive effects of inflammation. Interestingly, we revealed that cysts are formed by clonal expansion and that paracrine activation of the MET tyrosine kinase pathway by the surrounding environment nurtures cysts. Collectively, our results identify the oncogenic mechanisms of ESRD-associated renal tumors and will pave the way for improving the prognosis of patients with ESRD. Significance: We elucidated the molecular basis of renal cancer arising in patients with ESRD and show that the inflammatory environment of ESRD gives rise to field cancerization. See related commentary by Sager et al., p. 426

A 33-year-old man was referred to our institution with papillary masses at the urethral meatus and difficulty urinating. Genital examination showed two piercings on the frenulum, which were penetrating the external urethra. Endoscopic examination revealed papillary tumours over the entire circumference of the penile urethra and the piercing site. The tumours were resected transurethrally. Microscopic examination revealed condylomata acuminata. Human papillomavirus types 6 and 66 were detected in the lesions. Retrograde urethral viral infection is rare because of the protection provided by the mucosal immune system. Genital piercing may have facilitated spread of the human papillomavirus into the urethra.