As the most abundant internal modification of mRNA, N 6 -methyladenosine (m 6 A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering-time control, microspore generation and fruit ripening, in plants. However, the cellular role of m 6 A in plant responses to environmental stimuli remains largely unexplored. In this study, we show that m 6 A methylation plays an important role in salt stress tolerance in Arabidopsis. All mutants of m 6 A writer components, including MTA, MTB, VIRILIZER (VIR) and HAKAI, displayed salt-sensitive phenotypes in an m 6 A-dependent manner. The vir mutant, in which the level of m 6 A was most highly reduced, exhibited salt-hypersensitive phenotypes. Analysis of the m 6 A methylome in the vir mutant revealed a transcriptomewide loss of m 6 A modification in the 3ʹ untranslated region (3ʹ-UTR). We demonstrated further that VIR-mediated m 6 A methylation modulates reactive oxygen species homeostasis by negatively regulating the mRNA stability of several salt stress negative regulators, including ATAF1, GI and GSTU17, through affecting 3ʹ-UTR lengthening linked to alternative polyadenylation. Our results highlight the important role played by epitranscriptomic mRNA methylation in the salt stress response of Arabidopsis and indicate a strong link between m 6 A methylation and 3ʹ-UTR length and mRNA stability during stress adaptation.
The American Society for Histocompatibility and Immunogenetics HLA common and well‐documented (CWD) catalog, CWD 2.0.0 catalog and European Federation for Immunogenetics (EFI) CWD catalog have been published, which are useful for improving the accuracy of HLA genotyping in laboratories. Here, we studied the Chinese HLA CWD catalog. A total of 812 211 unrelated volunteer donors from the China Marrow Donor Program (CMDP) were analyzed. Six hundred seventy‐six alleles at the HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 loci were defined as CWD alleles in the Chinese population, including 159 common and 517 well‐documented alleles. The distribution of HLA alleles in the Chinese CWD catalog is different from that in the EFI CWD catalog. Thirty‐two percent (215/676) of CWD alleles in the Chinese CWD catalog are shared with those in the EFI CWD catalog. Fifty‐six percent (380/676) of alleles in the Chinese CWD catalog are not found in the EFI CWD catalog, while 655 alleles in the EFI CWD catalog are neither common nor well‐documented alleles in the Chinese CWD catalog. The Chinese CWD catalog described in this study may help to improve high‐resolution histocompatibility testing for CMDP‐accredited laboratories in China. However, to accommodate an increasing number of HLA alleles, this Chinese CWD catalog should be regularly updated.
BackgroundBasic region/leucine zipper (bZIP) transcription factors perform as crucial regulators in ABA-mediated stress response in plants. Nevertheless, the functions for most bZIP family members in tomato remain to be deciphered.ResultsHere we examined the functional characterization of SlbZIP1 under salt and drought stresses in tomato. Silencing of SlbZIP1 in tomato resulted in reduced expression of multiple ABA biosynthesis- and signal transduction-related genes in transgenic plants. In stress assays, SlbZIP1-RNAi transgenic plants exhibited reduced tolerance to salt and drought stresses compared with WT plants, as are evaluated by multiple physiological parameters associated with stress responses, such as decreased ABA, chlorophyll contents and CAT activity, and increased MDA content. In addition, RNA-seq analysis of transgenic plants revealed that the transcription levels of multiple genes encoding defense proteins related to responses to abiotic stress (e.g. endochitinase, peroxidases, and lipid transfer proteins) and biotic stress (e.g. pathogenesis-related proteins) were downregulated in SlbZIP1-RNAi plants, suggesting that SlbZIP1 plays a role in regulating the genes related to biotic and abiotic stress response.ConclusionsCollectively, the data suggest that SlbZIP1 exerts an essential role in salt and drought stress tolerance through modulating an ABA-mediated pathway, and SlbZIP1 may hold potential applications in the engineering of salt- and drought-tolerant tomato cultivars.Electronic supplementary materialThe online version of this article (10.1186/s12870-018-1299-0) contains supplementary material, which is available to authorized users.
Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases.
Ribosomal RNA (rRNA) methylation is a pivotal process in the assembly and activity of ribosomes, which in turn play vital roles in the growth, development, and stress responses of plants. Although few methyltransferases responsible for rRNA methylation have been identified in plant chloroplasts, the nature and function of these enzymes in chloroplasts remain largely unknown. In this study, we characterized Arabidopsis RsmD (At3g28460), an ortholog of the methyltransferase responsible for N2-methylguanosine (m2G) modification of 16S rRNA in Escherichia coli. Confocal microscopic analysis of an RsmD-GFP fusion protein revealed that RsmD is localized to chloroplasts. Primer extension analysis indicated that RsmD is responsible for m2G methylation at position 915 in the 16S rRNA of Arabidopsis chloroplasts. Under cold stress, rsmd mutant plants exhibited retarded growth, i.e., had shorter roots, lower fresh weight, and pale-green leaves, compared with wild-type plants. However, these phenotypes were not detected in response to drought or salt stress. Notably, the rsmd mutant was hypersensitive to erythromycin or lincomycin and accumulated fewer chloroplast proteins compared with the wild type, suggesting that RsmD influences translation in chloroplasts. Complementation lines expressing RsmD in the rsmd mutant background recovered wild-type phenotypes. Importantly, RsmD harbored RNA methyltransferase activity. Collectively, the findings of this study indicate that RsmD is a chloroplast 16S rRNA methyltransferase responsible for m2G915 modification that plays a role in the adaptation of Arabidopsis to cold stress.
The purpose of this meta-analysis was to compare the effectiveness of mannitol and hypertonic saline for reducing intracranial pressure (ICP) after traumatic brain injury (TBI).PubMed, Cochrane, Embase, and ISI Web of Knowledge databases were searched until July 3, 2014 using the terms intracranial hypertension, mannitol, and hypertonic saline. Randomized controlled trials and 2-arm prospective studies in which elevated ICP was present after TBI treated with mannitol or hypertonic saline were included. The primary outcome was the change of ICP from baseline to termination of the infusion, while the secondary outcomes were change from baseline to 30, 60, and 120 minutes after terminating the infusion and change of osmolarity from baseline to termination.A total 7 studies with 169 patients were included. The mean age of patients receiving mannitol ranged from 30.8 to 47 years, and for patients receiving hypertonic saline ranged from 35 to 47 years. A pooled difference in means = −1.69 (95% confidence interval [CI]: −2.95 to −0.44, P = 0.008) indicated that hypertonic saline reduced ICP more effectively than mannitol when compared from the baseline value to the last measurement after treatment. At 30 minutes after intervention, there was no difference in the mean ICP change between the groups, whereas at 60 minutes after intervention (pooled difference in means = −2.58, 95% CI: −4.37 to −0.80, P = .005) and 120 min after intervention (pooled difference in means = −4.04, 95% CI: −6.75 to −1.32, P = .004) hypertonic saline resulted in a significantly greater decrease in ICP. The pooled difference in means = 1.84 (95% CI: −1.64 to 5.31, P = .301) indicated no difference in serum osmolarity between patients treated with hypertonic saline or mannitol.Hypertonic saline is more effective than mannitol for reducing ICP in cases of TBI.
BMI obesity and WC/WHR central obesity have a combined effect on cognitive impairment and WHR has a stronger association with cognitive impairment than WC.
In this systematic review and meta-analysis, the effectiveness and safety among different dosage of methotrexate protocols for the treatment of unruptured tubal ectopic pregnancy was evaluated. Six studies of randomized contorlled trials were identified through searches conducted on PubMed, Embase and Cochrane Library between January 1974 and March 2016. The overall success rate of multiple-dose protocol was similar to the single-dose protocol (RR 1.07, 95% CI 0.99 to 1.17, I = 0%). The difference between double-dose and single-dose groups was not significant (RR 1.09, 95% CI 0.98 and 1.20, I = 0%). The incidence of side-effects of double-dose regimen was similar with single-dose regimen. Side-effects, however, are more common in multiple-dose regimen (RR 1.64, 95% CI 1.15 to 2.34, P = 0.006, I = 0%). This meta-analysis indicated that the incidence of side-effects of multiple-dose protocol was significantly higher than single-dose protocol, and the success rates between them were similar. The double-dose regimen was an efficient and safe alternative to the single-dose protocol. Further high-quality researches are needed to confirm our findings and to develop the optimal protocol.
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