137 research outputs found

    Analysis of the Problems and Influencing Factors in Dubbing Actors’ Role Shaping

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    In recent years, with the rapid development of the Internet, dubbing has gradually gone out of the loop, and dubbing industry is being known by more and more people. Dubbing products such as radio dramas are also favored by more and more listeners. However, the understanding of dubbing by many dubbing enthusiasts and dubbing actors is only superficial, and the mechanical streamline of character creation does not show the real charm of dubbing performance. According to the basic skills of actors, this paper will discuss the basic skills of dubbing performance, voice makeup, how to shape roles, dubbing mentality and dubbing problems

    Analysis of immunogenic cell death in ascending thoracic aortic aneurysms based on single-cell sequencing data

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    BackgroundAt present, research on immunogenic cell death (ICD) is mainly associated with cancer therapy. Little is known about the role of ICD in cardiovascular disease, especially in ascending thoracic aortic aneurysms (ATAA).MethodATAA single-cell RNA (scRNA) sequencing data were analyzed to identify the involved cell types and determine their transcriptomic characteristics. The chi-square test, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Gene Set Enrichment Analysis (GSEA), and CellChat for cell-to-cell communication analysis from the Gene Expression Omnibus (GEO) database were used.ResultA total of 10 cell types were identified, namely, monocytes, macrophages, CD4 T/NK (CD4+ T cells and natural killer T cells), mast cells, B/Plasma B cells, fibroblasts, endothelial cells, cytotoxic T cells (CD8+ T cells, CTLs), vascular smooth muscle cells (vSMCs), and mature dendritic cells (mDCs). A large number of inflammation-related pathways were present in the GSEA results. A large number of ICD-related pathways were found in the KEGG enrichment analysis of differentially expressed genes in endothelial cells. The number of mDCs and CTLs in the ATAA group was significantly different from that in the control group. A total of 44 pathway networks were obtained, of which 9 were associated with ICD in endothelial cells (CCL, CXCL, ANNEXIN, CD40, IL1, IL6, TNF, IFN-II, GALECTIN). The most important ligand−receptor pair by which endothelial cells act on CD4 T/NK cells, CTLs and mDCs is CXCL12-CXCR4. The most important ligand−receptor pair by which endothelial cells act on monocytes and macrophages is ANXA1-FPR1. The most important ligand−receptor pair by which CD4 T/NK cells and CTLs act on endothelial cells is CCL5-ACKR1. The most important ligand−receptor pair that myeloid cells (macrophages, monocytes and mDCs) act on endothelial cells is CXCL8-ACKR1. Moreover, vSMCs and fibroblasts mainly promote inflammatory responses through the MIF signaling pathway.ConclusionICD is present in ATAA and plays an important role in the development of ATAA. The target cells of ICD may be mainly endothelial cells, in which the aortic endothelial cell ACKR1 receptor can not only promote T-cell infiltration through the CCL5 ligand but also promote myeloid cell infiltration through the CXCL8 ligand. ACKR1 and CXCL12 may become target genes for ATAA drug therapy in the future

    MBASED: allele-specific expression detection in cancer tissues and cell lines

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    Allele-specific gene expression, ASE, is an important aspect of gene regulation. We developed a novel method MBASED, meta-analysis based allele-specific expression detection for ASE detection using RNA-seq data that aggregates information across multiple single nucleotide variation loci to obtain a gene-level measure of ASE, even when prior phasing information is unavailable. MBASED is capable of one-sample and two-sample analyses and performs well in simulations. We applied MBASED to a panel of cancer cell lines and paired tumor-normal tissue samples, and observed extensive ASE in cancer, but not normal, samples, mainly driven by genomic copy number alterations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0405-3) contains supplementary material, which is available to authorized users

    Dl-3-n-Butylphthalide Reduces Cognitive Deficits and Alleviates Neuropathology in P301S Tau Transgenic Mice

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    Alzheimer’s disease (AD) is a destructive and burdensome neurodegenerative disease, one of the most common characteristics of which are neurofibrillary tangles (NFTs) that are composed of abnormal tau protein. Animal studies have suggested that dl-3-n-butylphthalide (dl-NBP) alleviates cognitive impairment in mouse models of APP/PS1 and SAMP8. However, the underlying mechanisms related to this remain unclear. In this study, we examined the effects of dl-NBP on learning and memory in P301S transgenic mice, which carry the human tau gene with the P301S mutation. We found that dl-NBP supplementation effectively improved behavioral deficits and rescued synaptic loss in P301S tau transgenic mice, compared with vehicle-treated P301S mice. Furthermore, we also found that it markedly inhibited the hyperphosphorylated tau at the Ser262 site and decreased the activity of MARK4, which was associated with tau at the Ser262 site. Finally, dl-NBP treatment exerted anti-inflammatory effects and reduced inflammatory responses in P301S mice. In conclusion, our results provide evidence that dl-NBP has a promising potential for the therapy of tauopathies, including AD

    Vulto-van Silfhout-de Vries syndrome caused by de novo variants of DEAF1 gene: a case report and literature review

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    Vulto-van Silfhout-de Vries syndrome (VSVS; MIM 615828) is an extremely rare autosomal dominant disorder with unknown incidence. It is always caused by de novo heterozygous pathogenic variants in the DEAF1 gene, which encodes deformed epidermal autoregulatory factor-1 homology. VSVS is characterized by mild to severe intellectual disability (ID) and/or global developmental delay (GDD), seriously limited language expression, behavioral abnormalities, somnipathy, and reduced pain sensitivity. In this study, we present a Chinese boy with moderate GDD and ID, severe expressive language impairment, behavioral issues, autism spectrum disorder (ASD), sleeping dysfunction, high pain threshold, generalized seizures, imbalanced gait, and recurrent respiratory infections as clinical features. A de novo heterozygous pathogenic missense variant was found in the 5th exon of DEAF1 gene, NM_021008.4 c.782G>C (p. Arg261Pro) variant by whole exome sequencing (WES). c.782G>C had not been previously reported in genomic databases and literature. According to the ACMG criteria, this missense variant was considered to be “Likely Pathogenic”. We diagnosed the boy with VSVS both genetically and clinically. At a follow-up of 2.1 years, his seizures were well controlled after valproic acid therapy. In addition, the child’s recurrent respiratory infections improved at 3.5 years of age, which has not been reported in previous individuals. Maybe the recurrent respiratory infections like sleep problems reported in the literature are not permanent but may improve naturally over time. The literature review showed that there were 35 individuals with 28 different de novo pathogenic variants of DEAF1-related VSVS. These variants were mostly missense and the clinical manifestations were similar to our patient. Our study expands the genotypic and phenotypic profiles of de novo DEAF1

    PoolHap: Inferring Haplotype Frequencies from Pooled Samples by Next Generation Sequencing

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    With the advance of next-generation sequencing (NGS) technologies, increasingly ambitious applications are becoming feasible. A particularly powerful one is the sequencing of polymorphic, pooled samples. The pool can be naturally occurring, as in the case of multiple pathogen strains in a blood sample, multiple types of cells in a cancerous tissue sample, or multiple isoforms of mRNA in a cell. In these cases, it's difficult or impossible to partition the subtypes experimentally before sequencing, and those subtype frequencies must hence be inferred. In addition, investigators may occasionally want to artificially pool the sample of a large number of individuals for reasons of cost-efficiency, e. g., when carrying out genetic mapping using bulked segregant analysis. Here we describe PoolHap, a computational tool for inferring haplotype frequencies from pooled samples when haplotypes are known. The key insight into why PoolHap works is that the large number of SNPs that come with genome-wide coverage can compensate for the uneven coverage across the genome. The performance of PoolHap is illustrated and discussed using simulated and real data. We show that PoolHap is able to accurately estimate the proportions of haplotypes with less than 2% error for 34-strain mixtures with 2X total coverage Arabidopsis thaliana whole genome polymorphism data. This method should facilitate greater biological insight into heterogeneous samples that are difficult or impossible to isolate experimentally. Software and users manual are freely available at http://arabidopsis.gmi.oeaw.ac.at/quan/poolhap/

    Seasonal variation in oxygenated organic molecules in urban Beijing and their contribution to secondary organic aerosol

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    Oxygenated organic molecules (OOMs) are crucial for atmospheric new particle formation and secondary organic aerosol (SOA) growth. Therefore, understanding their chemical composition, temporal behavior, and sources is of great importance. Previous studies on OOMs mainly focus on environments where biogenic sources are predominant, yet studies on sites with dominant anthropogenic emissions, such as megacities, have been lacking. Here, we conducted long-term measurements of OOMs, covering four seasons of the year 2019, in urban Beijing. The OOM concentration was found to be the highest in summer (1.6 x 10(8) cm(-3)), followed by autumn (7.9 x 10(7) cm(-3)), spring (5.7 x 10(7) cm(-3)) and winter (2.3 x 10(7) cm(-3)), suggesting that enhanced photo-oxidation together with the rise in temperature promote the formation of OOMs. Most OOMs contained 5 to 10 carbon atoms and 3 to 7 effective oxygen atoms (nO(eff) = nO - 2 x nN). The average nO(eff )increased with increasing atmospheric photo-oxidation capacity, which was the highest in summer and the lowest in winter and autumn. By performing a newly developed workflow, OOMs were classified into the following four types: aromatic OOMs, aliphatic OOMs, isoprene OOMs, and monoterpene OOMs. Among them, aromatic OOMs (29 %-41 %) and aliphatic OOMs (26 %-41 %) were the main contributors in all seasons, indicating that OOMs in Beijing were dominated by anthropogenic sources. The contribution of isoprene OOMs increased significantly in summer (33 %), which is much higher than those in the other three seasons (8 %-10 %). Concentrations of isoprene (0.2-5.3 x 10(7) cm(-3)) and monoterpene (1.1-8.4 x 10(6) cm(-3)) OOMs in Beijing were lower than those reported at other sites, and they possessed lower oxygen and higher nitrogen contents due to high NO, levels (9.5-38.3 ppbv - parts per billion by volume) in Beijing. With regard to the nitrogen content of the two anthropogenic OOMs, aromatic OOMs were mainly composed of CHO and CHON species, while aliphatic OOMs were dominated by CHON and CHON2 ones. Such prominent differences suggest varying formation pathways between these two OOMs. By combining the measurements and an aerosol dynamic model, we estimated that the SOA growth rate through OOM condensation could reach 0.64, 0.61, 0.41, and 0.30 mu g m(-3) h(-1) in autumn, summer, spring, and winter, respectively. Despite the similar concentrations of aromatic and aliphatic OOMs, the former had lower volatilities and, therefore, showed higher contributions (46 %-62 %) to SOA than the latter (14 %-32 %). By contrast, monoterpene OOMs and isoprene OOMs, limited by low abundances or high volatilities, had low contributions of 8 %-12 % and 3 %-5 %, respectively. Overall, our results improve the understanding of the concentration, chemical composition, seasonal variation, and potential atmospheric impacts of OOMs, which can help formulate refined restriction policy specific to SOA control in urban areas.Peer reviewe

    Do leaders matter? : Chinese politics, leadership transition and the 17th Party Congress

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    The opaque nature of decision making in China has generated considerable interest in the internecine machinations of elite politics. Particularly, but not only, when it comes to issues of leadership transition, considerations of factional formation and conflict come to the fore. This is partly to explain the transition process itself, but also out of concern for how new leaders might change the direction of Chinese policy. This paper suggests that whilst leaders and leadership changes do matter, they matter less than they once did. This is partly a result of the de-ideologicization and increasing diverse nature of elite interests and group formation. But it is also partly a result of the changed nature of China’s political economy; in short, there is less desire and less ability for new leaders to impose a clear paradigm shift
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