Inhibition of ER stress attenuates kidney injury and apoptosis induced by 3-MCPD via regulating mitochondrial fission/fusion and Ca2+ homeostasis

Cell Biology and Toxicology - 3-Chloro-1, 2-propanediol (3-MCPD) is a food-borne toxic substance well-known for more than 40 years that is mainly associated with nephrotoxicity. A better...     

Divergent DNA methylation contributes to duplicated gene evolution and chilling response in tea plants

The tea plant (Camellia sinensis) is a thermophilic cash crop and contains a highly duplicated and repeat-rich genome. It is still unclear how DNA methylation regulates the evolution of duplicated genes and chilling stress in tea plants. We therefore generated a single-base-resolution DNA methylation map of tea plants under chilling stress. We found that, compared with other plants, the tea plant genome is highly methylated in all three sequence contexts, including CG, CHG and CHH (where H = A, T, or C), which is further proven to be correlated with its repeat content and genome size. We show that DNA methylation in the gene body negatively regulates the gene expression of tea plants, whereas non-CG methylation in the flanking region enables a positive regulation of gene expression. We demonstrate that transposable element-mediated methylation dynamics significantly drives the expression divergence of duplicated genes in tea plants. The DNA methylation and expression divergence of duplicated genes in the tea plant increases with evolutionary age and selective pressure. Moreover, we detect thousands of differentially methylated genes, some of which are functionally associated with chilling stress. We also experimentally reveal that DNA methyltransferase genes of tea plants are significantly downregulated, whereas demethylase genes are upregulated at the initial stage of chilling stress, which is in line with the significant loss of DNA methylation of three well-known cold-responsive genes at their promoter and gene body regions. Overall, our findings underscore the importance of DNA methylation regulation and offer new insights into duplicated gene evolution and chilling tolerance in tea plants.     

Target-specific mutations efficiency at multiple loci of CRISPR/Cas9 system using one sgRNA in soybean

Soybean has a palaeopolyploid genome with nearly 75% of the genes present in multiple copies. Although the CRISPR/Cas9 system has been employed in soybean to generate site-directed mutagenesis, a systematical assessment of mutation efficiency of the CRISPR/Cas9 system for the multiple-copy genes is still urgently needed. Here, we successfully optimize one sgRNA CRISPR/Cas9 system in soybean by testing the efficiency, pattern, specificity of the mutations at multiple loci of GmFAD2 and GmALS. The results showed that simultaneous site-directed mutagenesis of two homoeologous loci by one sgRNA, the mutation frequency in the T0 generation were 64.71% for GmPDS, 60.0% for GmFAD2 and 42.86% for GmALS, respectively. The chimeric and heterozygous mutations were dominant types. Moreover, association of phenotypes with mutation pattern at target loci of GmPDS11 and GmPDS18 could help us further demonstrate that the CRISPR/Cas9 system can efficiently generate target specific mutations at multiple loci using one sgRNA in soybean, albeit with a relatively low transformation efficiency.

     

Impact of genetic variants in IL-2RA and IL-2RB on breast cancer risk in Chinese Han women

The expression of IL-2RA and IL-2RB was correlated with breast cancer (BC) progression. However, there is no literature investigating the association of IL-2RA and IL-2RB polymorphisms with BC predisposition among Chinese Han Women. Seven SNPs in IL-2RA and IL-2RB were genotyped by Agena MassARRAY platform among 553 BC patients and 550 healthy controls. Odds ratios (OR) and 95% confidence interval (CI) adjusted for age were calculated for the effect of IL-2RA and IL-2RB variants on BC susceptibility. IL-2RA rs12722498 was a protective factor for BC occurrence (OR?=?0.70, p?=?0.019), especially in subjects with age?≤?52 years (OR?=?0.55, p?=?0.004). IL-2RA rs12569923 (OR?=?9.07, p?=?0.033), IL-2RB rs2281089 (OR?=?0.67, p?=?0.043) and rs9607418 (OR?=?0.59, p?=?0.012) were related to the incidence of estrogen receptor positive (ER?+) BC. IL-2RB rs3218264 (OR?=?1.38, p?=?0.010) and rs9607418 (OR?=?0.56, p?=?0.009) were associated with the risk of developing progesterone receptor positive (PR?+) BC. Rs2281089 (OR?=?1.54, p?=?0.012) and rs1573673 (OR?=?0.72, p?=?0.035) were correlated to Ki-67 level. Moreover, IL-2RB rs2281089 (OR?=?0.72, p?=?0.022) showed a reduced risk of BC metastasis, and IL-2RA rs12722498 (OR?=?0.54, p?=?0.030) had a lower frequency in BC patients with tumor size?>?2 cm. Our study identified the potential effect of genetic variations in IL-2RA and IL-2RB on BC susceptibility and/or BC clinicopathologic indicators among Chinese Han Women.