Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and ...leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants.
We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific.
Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.
Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, ...suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer.
In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival.
We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% 95% CI 73·5–87·1 vs 64·5% 56·8–73·3; univariate hazard ratio 0·47 95% CI 0·30–0·75, p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% 66·5–79·9 in patients who received chemotherapy plus surgery vs 72·5% 65·8–79·9 in patients who only had surgery; 0·93 0·62–1·38, p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort.
The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted.
Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.
Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their ...sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very longchain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
The chemotherapeutic use of cisplatin is limited by its severe side effects. In this study, by conducting different omics data analyses, we demonstrated that cisplatin induces cell death in a ...proximal tubular cell line by suppressing glycolysis- and tricarboxylic acid (TCA)/mitochondria-related genes. Furthermore, analysis of the urine from cisplatin-treated rats revealed the lower expression levels of enzymes involved in glycolysis, TCA cycle, and genes related to mitochondrial stability and confirmed the cisplatin-related metabolic abnormalities. Additionally, an increase in the level of p53, which directly inhibits glycolysis, has been observed. Inhibition of p53 restored glycolysis and significantly reduced the rate of cell death at 24 h and 48 h due to p53 inhibition. The foremost reason of cisplatin-related cytotoxicity has been correlated to the generation of mitochondrial reactive oxygen species (ROS) that influence multiple pathways. Abnormalities in these pathways resulted in the collapse of mitochondrial energy production, which in turn sensitized the cells to death. The quenching of ROS led to the amelioration of the affected pathways. Considering these observations, it can be concluded that there is a significant correlation between cisplatin and metabolic dysfunctions involving mROS as the major player.
TGFam-Finder Kim, Seungill; Cheong, Kyeongchae; Park, Jieun ...
New phytologist,
September 2020, Letnik:
227, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Whole-genome annotation error that omits essential protein-coding genes hinders further research.
We developed Target Gene Family Finder (TGFam-Finder), an alternative tool for the structural ...annotation of protein-coding genes containing target domain(s) of interest in plant genomes. TGFam-Finder took considerably reduced annotation run-time and improved accuracy compared to conventional annotation tools.
Large-scale re-annotation of 50 plant genomes identified an average of 150, 166 and 86 additional far-red-impaired response 1, nucleotide-binding and leucine-rich-repeat, and cytochrome P450 genes, respectively, that were missed in previous annotations. We detected significantly higher number of translated genes in the new annotations using mass spectrometry data from seven plant species compared to previous annotations.
TGFam-Finder along with the new gene models can provide an optimized platform for comprehensive functional, comparative, and evolutionary studies in plants.
To discover functional gene clusters across cancers, we performed a systematic pan-cancer analysis of 33 cancer types. We identified genes that were associated with somatic mutations and were the ...cores of a co-expression network. We found that multiple cancer types have relatively exclusive hub genes individually; however, the hub genes cooperate with each other based on their functional relationship. When we built a protein-protein interaction network of hub genes and found nine functional gene clusters across cancer types, the gene clusters divided not only the region of the network map, but also the function of the network by their distinct roles related to the development and progression of cancer. This functional relationship between the clusters and cancers was underpinned by the high expression of module genes and enrichment of programmed cell death, and known candidate cancer genes. In addition to protein-coding hub genes, non-coding hub genes had a possible relationship with cancer. Overall, our approach of investigating cancer genes enabled finding pan-cancer hub genes and common functional gene clusters shared by multiple cancer types based on the expression status of the primary tumour and the functional relationship of genes in the biological network.
Telomerase has attracted much attention as a universal cancer biomarker because telomerase is overexpressed in more than 85% of human cancer cells while suppressed in normal somatic cells. Since a ...strong association exists between telomerase activity and human cancers, the development of effective telomerase activity assay is critically important. Here, a nanogap‐rich Au nanowire (NW) surface‐enhanced Raman scattering (SERS) sensor is reported for detection of telomerase activity in various cancer cells and tissues. The nanogap‐rich Au NWs are constructed by deposition of nanoparticles on single‐crystalline Au NWs and provided highly reproducible SERS spectra. The telomeric substrate (TS) primer‐attached nanogap‐rich Au NWs can detect telomerase activity through SERS measurement after the elongation of TS primers, folding into G‐quadruplex structures, and intercalation of methylene blue. This sensor enables us to detect telomerase activity from various cancer cell lines with a detection limit of 0.2 cancer cells mL−1. Importantly, the nanogap‐rich Au NW sensor can diagnose gastric and breast cancer tissues accurately. The nanogap‐rich Au NW sensors show strong SERS signals only in the presence of tumor tissues excised from 16 tumor‐bearing mice, while negligible signals in the presence of heated tumor tissues or normal tissues. It is anticipated that nanogap‐rich Au NW SERS sensors can be used for a universal cancer diagnosis and further biomedical applications including a diverse biomarker sensing.
A nanogap‐rich Au nanowire (NW) surface‐enhanced Raman scattering (SERS) sensor is developed for ultrasensitive and specific detection of telomerase activity. The optimized nanogap‐rich Au NW can provide highly reproducible and strong SERS signals. Using nanogap‐rich Au NW SERS sensors, telomerase activities of cancer cells and tumor tissues are successfully detected, suggesting the potential applicability of nanogap‐rich Au NW SERS sensor in cancer diagnosis.
The purpose of this study was to compare the cytotoxic effects and mineralization activity of three calcium silicate-based root canal sealers to those of a conventional resin-based sealer. ...Experiments were performed using human dental pulp stem cells grown in a monolayer culture. The root canal sealers tested in this study were EndoSequence BC Sealer (Brasseler), BioRoot RCS (Septodont), Endoseal MTA (Maruchi), and AH Plus (Dentsply DeTrey). Experimental disks 6 mm in diameter and 3 mm in height were made and stored in a 100% humidity chamber at 37 °C for 72 h to achieve setting. The cytotoxicity of various root canal sealers was evaluated using a methyl-thiazoldiphenyl-tetrazolium (MTT) assay. To evaluate cell migration ability, a scratch wound healing method was used, and images of the scratch area were taken using a phase-contrast microscope. Cell morphology was evaluated by a scanning electron microscope after direct exposure for 72 h to each sealer disk. In the cell viability assay, there were no significant differences between the EndoSequence BC, BioRoot RCS, Endoseal MTA, and control groups in any experimental period (
> 0.05). In the cell migration assay, there were no significant differences between the EndoSequence BC, Endoseal MTA, and control groups in any experimental period (
> 0.05). BioRoot RCS exhibited slower cell migration relative to EndoSequence BC and Endoseal MTA for up to 72 h (
< 0.05). Conversely, it showed a similar wound healing percentage at 96 h (
> 0.05). In an evaluation of cell morphology, cells in direct contact with EndoSequence BC, BioRoot RCS, and Endoseal MTA disks showed superior spreading compared to those in contact with the AH Plus disk. In an Alizarin red staining assay, EndoSequence BC, BioRoot RCS, and Endoseal MTA showed a significant increase in mineralized nodule formation compared to the AH Plus group (
< 0.05). In conclusion, all calcium silicate-based root canal sealers tested in this study showed good biological properties and mineralization activity compared to conventional resin-based sealer.
PDF
