A genome-wide differential expression of long noncoding RNAs (lncRNAs) was identified in blood specimens of autism spectrum disorder (ASD). A total of 3929 lncRNAs were found to be differentially expressed in ASD peripheral leukocytes, including 2407 that were upregulated and 1522 that were downregulated. Simultaneously, 2591 messenger RNAs (mRNAs), including 1789 upregulated and 821 downregulated, were also identified in ASD leukocytes. Functional pathway analysis of these lncRNAs revealed neurological pathways of the synaptic vesicle cycling, long-term depression and long-term potentiation to be primarily involved. Thirteen synaptic lncRNAs, including nine upregulated and four downregulated, and 19 synaptic mRNAs, including 12 upregulated and seven downregulated, were identified as being differentially expressed in ASD. Our identification of differential expression of synaptic lncRNAs and mRNAs suggested that synaptic vesicle transportation and cycling are important for the delivery of synaptosomal protein(s) between presynaptic and postsynaptic membranes in ASD. Finding of 19 lncRNAs, which are the antisense, bi-directional and intergenic, of HOX genes may lead us to investigate the role of HOX genes involved in the development of ASD. Discovery of the lncRNAs of SHANK2-AS and BDNF-AS, the natural antisense of genes SHANK2 and BDNF, respectively, indicates that in addition to gene mutations, deregulation of lncRNAs on ASD-causing gene loci presents a new approach for exploring possible epigenetic mechanisms underlying ASD. Our study also opened a new avenue for exploring the use of lncRNA(s) as biomarker(s) for the early detection of ASD.

Wnts-related signaling pathways have been reported to play roles in the pathogenesis of stress-induced depression-like behaviors. However, there is relatively few direct evidence to indicate the effect of Wnt ligands on this process. Here, we investigated the role of Wnts in mediating chronic restraint stress (CRS)-induced depression-like behaviors. We found that CRS induced a significant decrease in the expression of Wnt2 and Wnt3 in the ventral hippocampus (VH) but not in the dorsal hippocampus. Knocking down Wnt2 or Wnt3 in the VH led to impaired Wnt/β-catenin signaling, neurogenesis deficits and depression-like behaviors. In contrast, overexpression of Wnt2 or Wnt3 reversed CRS-induced depression-like behaviors. Moreover, Wnt2 and Wnt3 activated cAMP response element-binding protein (CREB) and there was CREB-dependent positive feedback between Wnt2 and Wnt3. Finally, fluoxetine treatment increased Wnt2 and Wnt3 levels in the VH and knocking down Wnt2 or Wnt3 abolished the antidepressant effect of fluoxetine. Taken together, our study indicates essential roles for Wnt2 and Wnt3 in CRS-induced depression-like behaviors and antidepressant.

Bacteria have two pathways to restart stalled replication forks caused by environmental stresses, error-prone translesion DNA synthesis (TLS) catalyzed by TLS polymerase and error-free template switching catalyzed by RecA, and their competition on the arrested fork affects bacterial SOS mutagenesis. DnaE2 is an error-prone TLS polymerase, and its functions require ImuA and ImuB. Here we investigated the function of imuA, imuB and dnaE2 in Myxococcus xanthus and found that imuA showed differences from imuB and dnaE2 in bacterial growth, resistance and mutation frequency. Transcriptomics analysis found that ImuA were associated with bacterial SOS response. Yeast-two-hybrid scanning revealed that ImuA interacted with RecA1 besides ImuB. Protein activity analysis proved that ImuA had no DNA binding activity, but inhibited the DNA binding and recombinase activity of RecA1. These findings highlight that ImuA not only participates in TLS by binding ImuB, but also inhibits the recombinase activity of RecA1 in M. xanthus, suggesting a role of ImuA in the two replication restart pathways.ImportanceDnaE2 is responsible for bacterial SOS mutagenesis in nearly one third of sequenced bacterial strains. However, its mechanism, especially the function of its accessory protein ImuA, is still unclear. Here we reported that M. xanthus ImuA might facilitate DnaE2 TLS by inhibiting the recombinase activity of RecA1, which helps to explain the mechanism of DnaE2-dependent TLS and the scientific problem of choosing one of the two restart pathways to repair the stalled replication fork.

BackgroundSalivary gland pleomorphic adenoma (SPA) is a common neoplasm of salivary glands that displays remarkable histological diversity. Previous studies have demonstrated the involvement of gene rearrangements and cytoskeleton‐remodeling‐related myoepithelial cells in SPA tumorigenesis. Cytoskeleton remodeling is necessary for epithelial‐mesenchymal transition (EMT), a key process in tumor progression. However, the heterogeneity of tumor cells and cytoskeleton remodeling in SPA has not been extensively investigated.MethodsAn analysis of single‐cell RNA sequencing (scRNA‐seq) was performed on 27 810 cells from two donors with SPA. Bioinformatic tools were used to assess differentially expressed genes, cell trajectories, and intercellular communications. Immunohistochemistry and double immunofluorescence staining were used to demonstrate FOXC1 and MYLK expression in SPA tissues.ResultsOur analysis revealed five distinct cell subtypes within the tumor cells of SPA, indicating a high level of intra‐lesional heterogeneity. Cytoskeleton‐remodeling‐related genes were highly enriched in subtype 3 of the tumor cells, which showed a close interaction with mesenchymal cells. We found that tumoral FOXC1 expression was closely related to MYLK expression in the tumor cells of SPA.ConclusionTumor cells enriched with cytoskeleton‐remodeling‐related genes play a crucial role in SPA development, and FOXC1 may partially regulate this process.