Sex-Interacting mRNA- and miRNA-eQTLs and Their Implications in Gene Expression Regulation and Disease

Despite sex being an important epidemiological and physiological factor, not much is known about how sex works to interact with genotypes to result in different phenotypes. Both messenger RNA (mRNA) and microRNA (miRNA) may be differentially expressed between the sexes in different physiological conditions, and both may be differentially regulated between males and females. Using whole transcriptome data on lymphoblastoid cell lines from 338 samples of European origin, we tried to uncover genes differentially expressed between the two sexes and sex-interacting expression quantitative trait loci (ss-eQTLs). Two miRNAs were found to be differentially expressed between the two sexes, both of which were found to be functionally implicated in breast cancer. Using two stage linear regression analysis, 21 mRNA ss-eQTL and 3 miRNA ss-eQTLs were discovered. We replicated two of the mRNA ss-eQTLs (p < 0.1) using a separate dataset of gene expression data derived from monocytes. Three mRNA ss-eQTLs are in high linkage disequilibrium with variants also found to be associated with sexually dimorphic traits. Taken together, we believe the ss-eQTLs presented will assist researchers in uncovering the basis of sex-biased gene expression regulation, and ultimately help us understand the genetic basis of differences in phenotypes between sexes

Ions-induced Epitaxial Growth of Perovskite Nanocomposites for Highly Efficient Light-Emitting Diodes with EQE Exceeding 30%

Cesium lead bromide (CsPbBr3) is a widely used emitter for perovskite light-emitting diodes (PeLEDs), benefiting from its large carrier mobility, high color purity and good thermal stability. However, the three-dimensional CsPbBr3 films encounter challenges due to their massive intrinsic defects and weak exciton binding effect, which limited their electroluminescence efficiency. To address this issue, the prevailing approach is to confine carriers by reducing dimensionality or size. Nonetheless, this method results in an increase in surface trap states due to the larger surface-to-volume ratio and presents difficulties in carrier injection and transport after reducing lattice splitting to smaller sizes. Here, we successfully achieved proper control over film crystallization by introducing sodium ions, which facilitate the epitaxial growth of zero-dimensional Cs4PbBr6 on the surface of CsPbBr3, forming large grain matrixes where CsPbBr3 is encapsulated by Cs4PbBr6. Notably, the ions-induced epitaxial growth enables the CsPbBr3 emitter with significantly reduced trap states, and generates coarsened nanocomposites of CsPbBr3&Cs4PbBr6 with grain size that surpass the average thickness of the thin perovskite film, resulting in a wavy surface conducive to light out-coupling. Additionally, another additive of formamidinium chloride was incorporated to assist the growth of nanocomposites with larger size and lower defects as well as better carrier injection and transportation. As a result, our demonstrated PeLEDs based on the coarsened nanocomposites exhibit low nonradiative recombination, enhanced light extraction and well-balanced carrier transportation, leading to high-performance devices. The champion device achieved an external quantum efficiency of 31.0% at the emission peak of 521 nm with a narrow full width at half-maximum (FWHM) of 18 nm

Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.This work is part of the ‘‘SpatioTemporal Omics Consortium’’ (STOC) paper package. A list of STOC members is available at: http://sto-consortium.org. We would like to thank the MOTIC China Group, Rongqin Ke (Huaqiao University, Xiamen, China), Jiazuan Ni (Shenzhen University, Shenzhen, China), Wei Huang (Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China), and Jonathan S. Weissman (Whitehead Institute, Boston, USA) for their help. This work was supported by the grant of Top Ten Foundamental Research Institutes of Shenzhen, the Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), and the Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011); Longqi Liu was supported by the National Natural Science Foundation of China (31900466) and Miguel A. Esteban’s laboratory at the Guangzhou Institutes of Biomedicine and Health by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), National Natural Science Foundation of China (92068106), and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075).S

Direct and indirect effects of climate on richness drive the latitudinal diversity gradient in forest trees

Data accessibility statement: Full census data are available upon reasonable request from the ForestGEO data portal, http://ctfs.si.edu/datarequest/ We thank Margie Mayfield, three anonymous reviewers and Jacob Weiner for constructive comments on the manuscript. This study was financially supported by the National Key R&D Program of China (2017YFC0506100), the National Natural Science Foundation of China (31622014 and 31570426), and the Fundamental Research Funds for the Central Universities (17lgzd24) to CC. XW was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB3103). DS was supported by the Czech Science Foundation (grant no. 16-26369S). Yves Rosseel provided us valuable suggestions on using the lavaan package conducting SEM analyses. Funding and citation information for each forest plot is available in the Supplementary Information Text 1.Peer reviewedPostprin

Regulatory and evolutionary signatures of sex-biased genes on both the X chromosome and the autosomes

Abstract Background Sex is an important but understudied factor in the genetics of human diseases. Analyses using a combination of gene expression data, ENCODE data, and evolutionary data of sex-biased gene expression in human tissues can give insight into the regulatory and evolutionary forces acting on sex-biased genes. Methods In this study, we analyzed the differentially expressed genes between males and females. On the X chromosome, we used a novel method and investigated the status of genes that escape X-chromosome inactivation (escape genes), taking into account the clonality of lymphoblastoid cell lines (LCLs). To investigate the regulation of sex-biased differentially expressed genes (sDEG), we conducted pathway and transcription factor enrichment analyses on the sDEGs, as well as analyses on the genomic distribution of sDEGs. Evolutionary analyses were also conducted on both sDEGs and escape genes. Results Genome-wide, we characterized differential gene expression between sexes in 462 RNA-seq samples and identified 587 sex-biased genes, or 3.2% of the genes surveyed. On the X chromosome, sDEGs were distributed in evolutionary strata in a similar pattern as escape genes. We found a trend of negative correlation between the gene expression breadth and nonsynonymous over synonymous mutation (dN/dS) ratios, showing a possible pleiotropic constraint on evolution of genes. Genome-wide, nine transcription factors were found enriched in binding to the regions surrounding the transcription start sites of female-biased genes. Many pathways and protein domains were enriched in sex-biased genes, some of which hint at sex-biased physiological processes. Conclusions These findings lend insight into the regulatory and evolutionary forces shaping sex-biased gene expression and their involvement in the physiological and pathological processes in human health and diseases

Additional file 2: Table S1. of Regulatory and evolutionary signatures of sex-biased genes on both the X chromosome and the autosomes

Linear regression of dN/dS, or the amount of selection pressure, as a function of the following variables. Estimate refers to the coefficient of the covariate, Std.Error referes to the standard error of that estimate. T value refers to the test statistic of the estimate and Pr(>|t|) refer to the P value of that covariate. XYpair refers to whether the gene is part of an XY homologous pair. XAR or XCR refers to whether the gene belongs on the X added region on the X chromosome or the X conserved region strata, escape status refers to whether the gene is classified as an escape gene, and gene expression refers to the average level of gene expression among 264 female samples. Table S2. Linear regression of dN/dS, or the amount of selection pressure, as a function of the following variables. Estimate refers to the coefficient of the covariate, Std.Error referes to the standard error of that estimate. T value refers to the test statistic of the estimate and Pr(>|t|) refer to the p value of that covariate. Average gene expression refers to average level of gene expression among 462 samples. Gene bias_female refers to whether the gene is classified as female-biased, and the coefficient refers to the change in dnds between female-biased genes to genes without sex bias. Gene bias_male refers similarly to genes classified as male-biased. Gene expression breadth refers to the number of tissues the gene is expressed in. Table S3. Sex-biased genes (sDEG) (587 genes) from LCL data and GTex data (1308) and their relationship to replication timing data in different cell lines, based on the Spearman’s Rho between replication timing values and log2fc of gene expression between females and males. Table S4(a). GSEA results for gene regions that are enriched in female biased sDEGs. Table S4(b). ToppFun results for gene regions that are enriched in male-biased sDEGs. Table S5(a). Disease gene sets enriched in sex biased genes, as found by ToppFun. Table S5(b). GO terms enriched in sex biased genes, as found by ToppFun. Table S5 (c). Pubmed gene sets enriched in sex biased genes, as found by ToppFun. Table S5 (d). Pathway analysis of sex biased genes using gene sets from MSigDBC2, as found by ToppFun. Table S5 (e). Gene families enriched in sex biased genes, as found by ToppFun. Table S6 (a). Domains enriched in female biased genes, as found by ToppFun. Table S6 (b). KEGG pathways enriched in female biased genes, as found by GSEA. Table S7. Pathway analysis of sex biased genes in GSEA, using custom gene sets from [26–28, 43]. Table S8 (a). Gene families enriched in male biased genes. Table S8 (b). MSigDB gene sets enriched in male biased genes, as found by ToppFUn. Table S9. Pathways enriched in transcription factors enriched for female biased genes. (DOCX 49 kb

Data from: Genomic dynamics of transposable elements in the Western Clawed Frog (Silurana tropicalis)

Transposable elements (TEs) are repetitive DNA sequences that can make new copies of themselves that are inserted elsewhere in a host genome. The abundance and distributions of TEs vary considerably among phylogenetically diverse hosts. With the aim of exploring the basis of this variation, we evaluated correlations between several genomic variables and the presence of TEs and non-TE repeats in the complete genome sequence of the Western clawed frog (Silurana tropicalis). This analysis reveals patterns of TE insertion consistent with gene disruption but not with the insertional preference model. Analysis of non-TE repeats recovered unique features of their genome-wide distribution when compared with TE repeats, including no strong correlation with exons and a particularly strong negative correlation with GC content. We also collected polymorphism data from 25 TE insertion sites in 19 wild-caught S. tropicalis individuals. DNA transposon insertions were fixed at eight of nine sites and at a high frequency at one of nine, whereas insertions of long terminal repeat (LTR) and non-LTR retrotransposons were fixed at only 4 of 16 sites and at low frequency at 12 of 16. A maximum likelihood model failed to attribute these differences in insertion frequencies to variation in selection pressure on different classes of TE, opening the possibility that other phenomena such as variation in rates of replication or duration of residence in the genome could play a role. Taken together, these results identify factors that sculpt heterogeneity in TE distribution in S. tropicalis and illustrate that genomic dynamics differ markedly among TE classes and between TE and non-TE repeats

Effects of predictive nursing intervention on cognitive impairment and neurological function in ischemic stroke patients

Abstract Background Ischemic stroke is a clinical emergency caused by insufficient intracranial blood supply, which eventually leads to brain tissue necrosis and neurological impairment. Predictive nursing intervention has achieved impressive success in the nursing of multiple surgeries. However, the role of predictive nursing intervention in the care of patients with ischemic stroke remains unclear. Methods This study was a randomized controlled trial. Based on the inclusion and exclusion criteria, 126 patients were randomly assigned into two groups, namely the control group and the predictive nursing intervention group. Both groups were treated with thrombolytic therapy with alteplase. The patients in the control group were given routine nursing intervention and the predictive nursing intervention group received additional predictive care. Neurologic functions and cognitive impairment were evaluated by National Institutes of Health Stroke Scale (NIHSS), Fugl‐Meyer assessment (FMA), Montreal cognitive assessment (MoCA), and mini‐mental state examination (MMSE) scales, respectively. Door‐to‐Needle Times, venous thromboembolism (VTE)‐related parameters, and complications were recorded. Results Predictive nursing intervention significantly shortened the Door‐to‐Needle Times and enhanced the peak/average femoral venous blood flow and femoral venous diameter. In addition, predictive nursing intervention improved the NIHSS, FMA, MMSE, and MoCA scores and remarkably reduced the recurrence of ischemic stroke, deep vein thrombosis and gingival bleeding. Conclusion Predictive nursing intervention is beneficial to improve the effects of thrombolytic therapy in patients with ischemic stroke, which improves the neurological, cognitive and motor functions of patients, and reduces the occurrence of complications, suggesting an important clinical application value

Miniaturization and Electromagnetic Reliability of Wearable Textile Antennas

The wearable textile antenna plays a decisive role in the currently increasingly wireless communication network area. To realize the miniaturization and electromagnetic reliability, a slotted full-textile microstrip antenna was designed and fabricated using the screen printing method. The measured return loss and radiation pattern were tested and compared with the simulated results. Additionally, the adhesion between the silver paste coating as the radiation element and the textile substrate was detected using sticking tape as well as observation by the microscope. To develop the designed antenna in the on-body application, the artificial magnetic conductor (AMC) was designed, optimized and fabricated. The antenna performance results showed that the existence of the AMC had a significant effect in reducing the body coupling and antenna backward radiation

Novel Mutations in X-Linked, USP26-Induced Asthenoteratozoospermia and Male Infertility

Male infertility is a multifactorial disease with a strong genetic background. Abnormal sperm morphologies have been found to be closely related to male infertility. Here, we conducted whole-exome sequencing in a cohort of 150 Han Chinese men with asthenoteratozoospermia. Two novel hemizygous mutations were identified in USP26, an X-linked gene preferentially expressed in the testis and encoding a deubiquitinating enzyme. These USP26 variants are extremely rare in human population genome databases and have been predicted to be deleterious by multiple bioinformatics tools. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring hemizygous USP26 variants showed a highly aberrant morphology and ultrastructure of the sperm heads and flagella. Real-time quantitative PCR and immunoblotting assays revealed obviously reduced levels of USP26 mRNA and protein in the spermatozoa from men harboring hemizygous deleterious variants of USP26. Furthermore, intracytoplasmic sperm injections performed on infertile men harboring hemizygous USP26 variants achieved satisfactory outcomes. Overall, our study demonstrates that USP26 is essential for normal sperm morphogenesis, and hemizygous USP26 mutations can induce X-linked asthenoteratozoospermia. These findings will provide effective guidance for the genetic and reproductive counseling of infertile men with asthenoteratozoospermia