Tetraploid cells from cytokinesis failure induce aneuploidy and spontaneous transformation of mouse ovarian surface epithelial cells

Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced an intermediate tetraploid cell stage, before evolving to aneuploid (mainly near-tetraploid) cells. Using long-term live-cell imaging followed by fluorescence in situ hybridization (FISH), we demonstrated that tetraploid cells originally arose from cytokinesis failure of bipolar mitosis in diploid cells, and gave rise to aneuploid cells through chromosome mis-segregation during both bipolar and multipolar mitoses. Injection of the late passage aneuploid MOSECs resulted in tumor formation in C57BL/6 mice. Therefore, we reveal a pathway for the evolution of diploid to aneuploid MOSECs and elucidate a mechanism for the development of near-tetraploid ovarian cancer cells

Comparative Assessment of Three Nonlinear Approaches for Landslide Susceptibility Mapping in a Coal Mine Area

Landslide susceptibility mapping is the first and most important step involved in landslide hazard assessment. The purpose of the present study is to compare three nonlinear approaches for landslide susceptibility mapping and test whether coal mining has a significant impact on landslide occurrence in coal mine areas. Landslide data collected by the Bureau of Land and Resources are represented by the X, Y coordinates of its central point; causative factors were calculated from topographic and geologic maps, as well as satellite imagery. The five-fold cross-validation method was adopted and the landslide/non-landslide datasets were randomly split into a ratio of 80:20. From this, five subsets for 20 times were acquired for training and validating models by GIS Geostatistical analysis methods, and all of the subsets were employed in a spatially balanced sample design. Three landslide models were built using support vector machine (SVM), logistic regression (LR), and artificial neural network (ANN) models by selecting the median of the performance measures. Then, the three fitted models were compared using the area under the receiver operating characteristics (ROC) curves (AUC) and the performance measures. The results show that the prediction accuracies are between 73.43% and 87.45% in the training stage, and 67.16% to 73.13% in the validating stage for the three models. AUCs vary from 0.807 to 0.906 and 0.753 to 0.944 in the two stages, respectively. Additionally, three landslide susceptibility maps were obtained by classifying the range of landslide probabilities into four classes representing low (0–0.02), medium (0.02–0.1), high (0.1–0.85), and very high (0.85–1) probabilities of landslides. For the distributions of landslide and area percentages under different susceptibility standards, the SVM model has more relative balance in the four classes compared to the LR and the ANN models. The result reveals that the SVM model possesses better prediction efficiency than the other two models. Furthermore, the five factors, including lithology, distance from the road, slope angle, elevation, and land-use types, are the most suitable conditioning factors for landslide susceptibility mapping in the study area. The mining disturbance factor has little contribution to all models, because the mining method in this area is underground mining, so the mining depth is too deep to affect the stability of the slopes

The γ-tubulin complex protein GCP6 is crucial for spindle morphogenesis but not essential for microtubule reorganization in Arabidopsis

γ-Tubulin typically forms a ring-shaped complex with 5 related γ-tubulin complex proteins (GCP2 to GCP6), and this γ-tubulin ring complex (γTuRC) serves as a template for microtubule (MT) nucleation in plants and animals. While the γTuRC takes part in MT nucleation in most eukaryotes, in fungi such events take place robustly with just the γ-tubulin small complex (γTuSC) assembled by γ-tubulin plus GCP2 and GCP3. To explore whether the γTuRC is the sole functional γ-tubulin complex in plants, we generated 2 mutants of the GCP6 gene encoding the largest subunit of the γTuRC in Arabidopsis thaliana. Both mutants showed similar phenotypes of dwarfed vegetative growth and reduced fertility. The gcp6 mutant assembled the γTuSC, while the wild-type cells had GCP6 join other GCPs to produce the γTuRC. Although the gcp6 cells had greatly diminished γ-tubulin localization on spindle MTs, the protein was still detected there. The gcp6 cells formed spindles that lacked MT convergence and discernable poles; however, they managed to cope with the challenge of MT disorganization and were able to complete mitosis and cytokinesis. Our results reveal that the γTuRC is not the only functional form of the γ-tubulin complex for MT nucleation in plant cells, and that γ-tubulin-dependent, but γTuRC-independent, mechanisms meet the basal need of MT nucleation. Moreover, we show that the γTuRC function is more critical for the assembly of spindle MT array than for the phragmoplast. Thus, our findings provide insight into acentrosomal MT nucleation and organization

Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing

Abstract Liquid biopsy by genotyping circulating tumor DNA (ctDNA) has provided a non-invasive approach in assessing tumor genomic alterations in clinical oncology. However, emerging evidence in clinical settings has shown significant discordance in the genomic alterations between matched tumor tissue and blood ctDNA samples, and even between the same set of blood samples analyzed on different testing platforms. Thus, it is necessary to study underlying causes of discrepancies in these studies by genotyping tumor tissue and ctDNA in parallel using next generation sequencing (NGS) panels based on the same technology. Here we enrolled 56 non-small-cell lung cancer (NSCLC) patients and evaluated tumor tissue genotyping and ctDNA based liquid biopsy by parallel NGS panel testing and compared different sample preparation conditions. Somatic mutations in plasma cell-free DNA (cfDNA) were detected in 63.6% patients with early-stage NSCLC and 60% patients with advanced-stage NSCLC. The overall concordance between matched formalin-fixed paraffin-embedded sample and cfDNA was 54.6% in early-stage NSCLC patients and 80% in advanced-stage NSCLC patients. The positive concordance rate was 44.4% and 71.4% in early-stage and advanced-stage patients, respectively. Using fresh frozen tumor samples did not improve the overall concordance rate between matched tumor tissue and cfDNA. Processing blood samples beyond 4 h after blood draw significantly decreased the detection rate of somatic mutations in cfDNA. Thus, the concordance rate between tumor tissue-based and ctDNA-based genotyping in clinical samples can be affected by multiple pre-analytical, analytical and biologic factors. Parallel NGS panel testing on both sample types for each patient may be warranted for effective guidance of cancer targeted therapies and possible early detection of cancer

The Potential of Alternaria Toxins Production by A. alternata in Processing Tomatoes

As a filamentous and spoilage fungus, Alternaria spp. can not only infect processing tomatoes, but also produce a variety of mycotoxins which harm the health of human beings. To explore the production of Alternaria toxins in processing tomatoes during growth and storage, four main Alternaria toxins and four conjugated toxins were detected by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and ultra-performance liquid chromatography-ion mobility quadrupole time-of-flight mass spectrometry (UPLC-IMS QToF MS) in processing tomatoes on different days after being inoculated with A. alternata. The results show that the content of Alternaria toxins in an in vivo assay is higher than that under field conditions. Tenuazonic acid (TeA) is the predominant toxin detected in the field (205.86~41,389.19 μg/kg) and in vivo (7.64~526,986.37 μg/kg) experiments, and the second-most abundant toxin is alternariol (AOH). In addition, a small quantity of conjugated toxins, AOH-9-glucoside (AOH-9-Glc) and alternariol monomethyl ether-3-glucoside (AME-3-Glc), were screened in the in vivo experiment. This is the first time the potential of Alternaria toxins produced in tomatoes during the harvest period has been studied in order to provide data for the prevention and control of Alternaria toxins

Cytokine profiling reveals increased serum inflammatory cytokines in idiopathic choroidal neovascularization

Abstract Background The exact pathogenesis of idiopathic choroidal neovascularization (ICNV) remains unclear. Cytokine-mediated inflammation has been thought to be involved in the pathophysiology of ICNV. The purpose of this study was to investigate serum cytokine profiles in patients with ICNV and to explore the relationship between serum cytokine levels and ICNV severity. Methods This case-control study was conducted in 32 ICNV patients and 30 healthy volunteers. Clinical and demographic information was obtained from the medical data platform and the serum was analysed with a multiplex assay to determine the levels of seven cytokines: interleukin (IL)-2, IL-10, IL-15, IL-17, basic fibroblast growth factor (basic FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). Results Serum levels of IL-2, IL-10, IL-17, basic FGF, and VEGF were elevated in ICNV patients compared to controls. Serum GM-CSF levels were positively related to central retinal thickness, and serum IL-17 levels were positively related to CNV lesion area. Conclusion Serum inflammatory cytokines were significantly elevated in ICNV patients compared to controls. This suggests that systemic inflammation may play a critical role in the physiopathology of ICNV