The DNA Methylome and Transcriptome of Different Brain Regions in Schizophrenia and Bipolar Disorder

Extensive changes in DNA methylation have been observed in schizophrenia (SC) and bipolar disorder (BP), and may contribute to the pathogenesis of these disorders. Here, we performed genome-scale DNA methylation profiling using methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) on two brain regions (including frontal cortex and anterior cingulate) in 5 SC, 7 BP and 6 normal subjects. Comparing with normal controls, we identified substantial differentially methylated regions (DMRs) in these two brain regions of SC and BP. To our surprise, different brain regions show completely distinct distributions of DMRs across the genomes. In frontal cortex of both SC and BP subjects, we observed widespread hypomethylation as compared to normal controls, preferentially targeting the terminal ends of the chromosomes. In contrast, in anterior cingulate, both SC and BP subjects displayed extensive gain of methylation. Notably, in these two brain regions of SC and BP, only a few DMRs overlapped with promoters, whereas a greater proportion occurs in introns and intergenic regions. Functional enrichment analysis indicated that important psychiatric disorder-related biological processes such as neuron development, differentiation and projection may be altered by epigenetic changes located in the intronic regions. Transcriptome analysis revealed consistent dysfunctional processes with those determined by DMRs. Furthermore, DMRs in the same brain regions from SC and BP could successfully distinguish BP and/or SC from normal controls while differentially expressed genes could not. Overall, our results support a major role for brain-region-dependent aberrant DNA methylation in the pathogenesis of these two disorders

Discovering Dysfunction of Multiple MicroRNAs Cooperation in Disease by a Conserved MicroRNA Co-Expression Network

MicroRNAs, a new class of key regulators of gene expression, have been shown to be involved in diverse biological processes and linked to many human diseases. To elucidate miRNA function from a global perspective, we constructed a conserved miRNA co-expression network by integrating multiple human and mouse miRNA expression data. We found that these conserved co-expressed miRNA pairs tend to reside in close genomic proximity, belong to common families, share common transcription factors, and regulate common biological processes by targeting common components of those processes based on miRNA targets and miRNA knockout/transfection expression data, suggesting their strong functional associations. We also identified several co-expressed miRNA sub-networks. Our analysis reveals that many miRNAs in the same sub-network are associated with the same diseases. By mapping known disease miRNAs to the network, we identified three cancer-related miRNA sub-networks. Functional analyses based on targets and miRNA knockout/transfection data consistently show that these sub-networks are significantly involved in cancer-related biological processes, such as apoptosis and cell cycle. Our results imply that multiple co-expressed miRNAs can cooperatively regulate a given biological process by targeting common components of that process, and the pathogenesis of disease may be associated with the abnormality of multiple functionally cooperative miRNAs rather than individual miRNAs. In addition, many of these co-expression relationships provide strong evidence for the involvement of new miRNAs in important biological processes, such as apoptosis, differentiation and cell cycle, indicating their potential disease links

MaxEnt Modeling and the Impact of Climate Change on Pistacia chinensis Bunge Habitat Suitability Variations in China

Climate change impacts the world’s biota, creating a critical issue for scientists, conservationists, and decision makers. Pistacia chinensis Bunge (Anacardiaceae) is an economical importantly species with strong drought resistance. Nevertheless, the characteristics of habitat distribution and the major eco-environmental variables affecting its suitability are poorly understood. By using 365 occurrence records along with 51 environmental factors, present and future suitable habitats were estimated using MaxEnt modeling, and the important environmental variables affecting its geographical distribution were analyzed. The results indicate that water vapor pressure, precipitation of wettest quarter, normalized difference vegetation index, and isothermality were the most influential environmental factors determining the existence of P. chinensis. In future climate change, MaxEnt predicted that inappropriate habitats of P. chinensis show a decreasing trend, whereas moderately and highly appropriate habitat areas exhibited an increasing trend. Furthermore, under this climate change scenario, the suitable habitat will geographically expand to higher latitude and altitude. Our results might be applied in a variety of contexts, including discovering previously unreported P. chinensis places where it may appear in the future, or possible areas where the species could be cultivated, thus contributing to the preservation and protection of this species

Seed Dormancy and Germination Requirements of Torilis scabra (Apiaceae)

The timing of seed germination significantly affects the fitness and life cycle of plants. Torilis scabra is a perennial medicinal herb occurring in mixed forests but the increasing use and modification of forestlands in recent decades has led to the degeneration of its natural habitat. Nonetheless, the requirements for germination in T. scabra remain unclear. The present study focused on identifying conditions necessary to break T. scabra seed dormancy and describing its seed dormancy type. By periodically collecting seeds that were sown in the field, germination phenology was studied. The impact of light, temperature, and warm/cold stratification on breaking seed dormancy and promoting germination was also determined through incubating seeds in laboratory conditions. Additionally, the effect of GA3 was explored to more accurately identify the type of dormancy present. The results demonstrated that the seeds of T. scabra possessed small, undeveloped embryos with physiological dormancy at the time of maturity. In the field, embryo growth initiated in early spring and the embryo–seed length ratio increased by ~300% before the radical emerged. In the laboratory, the embryo–seed length ratio increased from 0.24 to 0.82 when seeds were subjected to cold stratification at 4 °C and then transferred to 15/25 °C. Germination was observed across a broad temperature range after cold stratification. GA3 also helped to break dormancy but after-ripening did not. Taken together, the results suggest that seeds of T. scabra have non-deep simple morphophysiological dormancy

Intermediate complex morphophysiological dormancy in seeds of Aconitum barbatum (Ranunculaceae)

Abstract Background Seed dormancy and germination are key components of plant regeneration strategies. Aconitum barbatum is a plant commonly found in northeast China. Although it has potential for use in gardening and landscaping, its seed dormancy and regeneration strategy, which adapt to its natural habitat, are not well understood. Our aim was to identify conditions for breaking A. barbatum seed dormancy and determine its dormancy type. Embryo growth and germination were determined by collecting seeds over time in the field. Laboratory experiments that control light, temperature, and stratification period were conducted to assess dormancy breaking and germination, and GA3 was used to identify dormancy type. Results Seeds of A. barbatum have undeveloped embryos with physiological dormancy at maturity in autumn. The embryo-to-seed length ratio increases from 0.33 to 0.78 before the emergence of the radical. Under natural environmental conditions, embryo development begins in early winter. Laboratory experiments have shown that long-term incubation under 4 °C (cold stratification) promotes embryo development and seed dormancy break. With an extension of cold stratification, an increase in germination percentages was observed when seeds were transferred from 4 °C to warmer temperatures. Seeds exposed to light during incubation show a higher germination percentage than those kept in the dark. Seed germination can also be enhanced by a 100 mg/L GA3 concentration. Conclusions Seeds of A. barbatum display intermediate complex morphophysiological dormancy at maturity. In addition to the underdeveloped embryo, there are also physiological barriers that prevent the embryo from germinating. Dormancy breaking of A. barbatum seeds can be achieved by natural winter cold stratification, allowing seeds to germinate and sprout seedlings at the beginning of the following growing season. Our findings provide valuable insights into the seed dormancy and regeneration strategy of A. barbatum, which could facilitate its effective utilization in gardening and landscaping

Identification of multiple sclerosis-related genes regulated by EBV-encoded microRNAs in B cells

Abstract Background: Multiple sclerosis (MS) is driven by the interaction between genetic susceptibility and environmental triggers, particularly to Epstein-Barr virus (EBV) infection. EBV-encoded microRNAs (miRNAs) are abundantly expressed in all stages of EBV infection and latency, which can target both viral and host cellular mRNAs, allowing EBV-infected B cells to evade the host immune response. However, it remains a big gap to understand the roles of EBV miRNAs and their target genes in MS pathogenesis.Methods: We investigated the correlation between MS-related viruses infection and MS risk quantitatively by systematic analysis. All MS-related genes in B cells were obtained by integrating MS susceptibility genes and differentially expressed genes from B cells. In comparison with differentially expressed genes from B cells after EBV infection in vitro, we confirmed EBV-regulated, MS-related genes. Subsequently, we obtained target EBV miRNAs which can regulate these genes from several online databases. By constructing pathway-pathway, pathway-gene and protein-protein interaction networks, we further screened out MS-related genes and risk pathways regulated by EBV miRNAs. Finally, we identified target EBV miRNAs may directly regulate MS-related genes through bioinformatic prediction and experimental validation.Results: EBV infection showed the strongest correlation with MS risk. A total of 873 MS-related genes and 52 risk pathways in B cells were obtained. We then identified 150 MS-related genes and 18 associated risk pathways that EBV was involved in. In addition, 42 human target genes regulated by 36 EBV miRNAs overlapped with EBV-regulated, MS-related genes. Finally, 15 target EBV miRNAs and their regulated, 6 MS-related genes (MALT1, BCL10, IFNGR2, STAT3, CDK6 and FOXP1) have been confirmed as crucial pathogenic molecules, which could promote the initiation and development of MS through NF-kappa B (MALT1 and BCL10) and PD-L1/PD-1 (IFNGR2 and STAT3) pathways. Surprisingly, ebv-miR-BHRF1-2-5p directly targeting MALT1 was confirmed by our experiments, and FOXP1 was identified as a target gene of ebv-miR-BART11.Conclusions: This work identified the target EBV miRNAs and their regulated, MS-related genes and risk pathways, which may provide a novel insight into discovering diagnostic biomarkers and therapeutic targets for MS.</jats:p

A Comparison for Dimensionality Reduction Methods of Single-Cell RNA-seq Data

Single-cell RNA sequencing (scRNA-seq) is a high-throughput sequencing technology performed at the level of an individual cell, which can have a potential to understand cellular heterogeneity. However, scRNA-seq data are high-dimensional, noisy, and sparse data. Dimension reduction is an important step in downstream analysis of scRNA-seq. Therefore, several dimension reduction methods have been developed. We developed a strategy to evaluate the stability, accuracy, and computing cost of 10 dimensionality reduction methods using 30 simulation datasets and five real datasets. Additionally, we investigated the sensitivity of all the methods to hyperparameter tuning and gave users appropriate suggestions. We found that t-distributed stochastic neighbor embedding (t-SNE) yielded the best overall performance with the highest accuracy and computing cost. Meanwhile, uniform manifold approximation and projection (UMAP) exhibited the highest stability, as well as moderate accuracy and the second highest computing cost. UMAP well preserves the original cohesion and separation of cell populations. In addition, it is worth noting that users need to set the hyperparameters according to the specific situation before using the dimensionality reduction methods based on non-linear model and neural network.</jats:p