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1.
Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9
LIUCHENG WU YI WANG LILI DU GUIQING JI RUI ZHOU ZEYI ZHAO JUN CHEN SHUNXING ZHU 《Biocell》2021,45(6):1501-1507
Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value. 相似文献
2.
Marc De Doncker Chloé De Graeve Dr. Jorick Franceus Dr. Koen Beerens Prof. Vladimír Křen Dr. Helena Pelantová Dr. Ronny Vercauteren Prof. Dr. Tom Desmet 《Chembiochem : a European journal of chemical biology》2021,22(23):3319-3325
The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis. 相似文献
3.
《全球能源互联网(英文)》2022,5(6):618-626
A novel image sequence-based risk behavior detection method to achieve high-precision risk behavior detection for power maintenance personnel is proposed in this paper. In this method, the original image sequence data is first separated from the foreground and background. Then, the free anchor frame detection method is used in the foreground image to detect the personnel and correct their direction. Finally, human posture nodes are extracted from each frame of the image sequence, which are then used to identify the abnormal behavior of the human. Simulation experiment results demonstrate that the proposed algorithm has significant advantages in terms of the accuracy of human posture node detection and risk behavior identification. 相似文献
4.
This paper proposes an approach to improve the performance of no-reference video quality assessment for sports videos with dynamic motion scenes using an efficient spatiotemporal model. In the proposed method, we divide the video sequences into video blocks and apply a 3D shearlet transform that can efficiently extract primary spatiotemporal features to capture dynamic natural motion scene statistics from the incoming video blocks. The concatenation of a deep residual bidirectional gated recurrent neural network and logistic regression is used to learn the spatiotemporal correlation more robustly and predict the perceptual quality score. In addition, conditional video block-wise constraints are incorporated into the objective function to improve quality estimation performance for the entire video. The experimental results show that the proposed method extracts spatiotemporal motion information more effectively and predicts the video quality with higher accuracy than the conventional no-reference video quality assessment methods. 相似文献
5.
Ziwen Wu Tianping Zhang 《International Journal of Adaptive Control and Signal Processing》2021,35(9):1768-1788
In this article, the issue of adaptive finite-time dynamic surface control (DSC) is discussed for a class of parameterized nonlinear systems with full state constraints. Using the property of logarithmic function, a one-to-one nonlinear mapping is constructed to transform a constrained system into an unconstrained system with the same structure. The nonlinear filter is constructed to replace the first-order linear filter in the traditional DSC, and the demand on the filter time constant is reduced. Based on finite-time stable theory and using modified DSC, the finite-time controller is designed via DSC. Theoretical analysis shows that all the signals in the closed-loop system are semiglobal practical finite-time stable. Furthermore, none of the states are outside the defined open set. In the end, simulation results are presented to demonstrate the effectiveness of the proposed control schemes with both linear filters and nonlinear filters. 相似文献
6.
Elham Shafiei Gol Mari-Klara Stein Michel Avital 《The Journal of Strategic Information Systems》2019,28(2):175-195
Crowdwork, a new form of digitally mediated employment and part of the so-called gig economy, has the capacity to change the nature of work organization and to provide strategic value to workers, job providers, and intermediary platform owners. However, because crowdwork is temporary, large-scale, distributed, and mediated, its governance remains a challenge that often casts a shadow over its strategic value. The objective of this paper is to shed light on the making of value-adding crowdwork arrangements. Specifically, the paper explores crowdwork platform governance mechanisms and the relationships between these mechanisms and organizational value creation. Building on a comprehensive review of the extant literature on governance and crowdwork, we construct an overarching conceptual model that integrates control system and coordination system as two complementary mechanisms that drive crowdwork platform governance effectiveness and the consequent job provider benefits. Furthermore, the model accentuates the role of the degree of centralization and the degree of routinization as critical moderators in crowdwork platform governance. Overall, the paper highlights the potential of crowdwork to contribute not only to inclusion, fair wages and flexible work arrangements for workers but also to organizations’ value and competitive edge. 相似文献
7.
This paper offers an overall picture of the importance of Strategic Environmental Assessment (SEA) in Romania and its opportunities and constraints. The role, scope and effectiveness of SEA in Romania are presented in two good practice examples and examined in order to highlight the strengths and weaknesses of the procedure at national and local scale. In practice, the number of SEA procedures is very high due to the legislation in force, and it is increasingly effective in decision-making about programmes and plans. SEA can be viewed as a great opportunity for the implementation of sustainable development in practice. It also continues to be an important procedural and decisional instrument for management and monitoring of socioeconomic development, spatial planning and environmental protection in Romania. 相似文献
8.
Facial Expression Recognition (FER) is an important subject of human–computer interaction and has long been a research area of great interest. Accurate Facial Expression Sequence Interception (FESI) and discriminative expression feature extraction are two enormous challenges for the video-based FER. This paper proposes a framework of FER for the intercepted video sequences by using feature point movement trend and feature block texture variation. Firstly, the feature points are marked by Active Appearance Model (AAM) and the most representative 24 of them are selected. Secondly, facial expression sequence is intercepted from the face video by determining two key frames whose emotional intensities are minimum and maximum, respectively. Thirdly, the trend curve which represents the Euclidean distance variations between any two selected feature points is fitted, and the slopes of specific points on the trend curve are calculated. Finally, combining Slope Set which is composed by the calculated slopes with the proposed Feature Block Texture Difference (FBTD) which refers to the texture variation of facial patch, the final expressional feature are formed and inputted to One-dimensional Convolution Neural Network (1DCNN) for FER. Five experiments are conducted in this research, and three average FER rates 95.2%, 96.5%, and 97% for Beihang University (BHU) facial expression database, MMI facial expression database, and the combination of two databases, respectively, have shown the significant advantages of the proposed method over the existing ones. 相似文献
9.
吐哈盆地葡北地区“两宽一高”地震勘探技术及应用效果 总被引:1,自引:0,他引:1
吐哈盆地台北凹陷圈闭落实的准确度和储层分布预测的精度一直是制约该区油气发现的关键因素。通过可控震源“两宽一高”地震采集、OVT域时间偏移、地质导向深度偏移初始模型建立及各向异性深度偏移迭代处理,在地震资料的信噪比、频带宽度和分辨率等方面明显提高的基础上,以高精度层序地层学为指导,基于高分辨率地震资料与钻井、测井资料的综合分析,识别出侏罗系6个三级层序,在三级层序格架内将研究区七克台组底部和三间房组顶部砂体识别为两个连续上升半旋回四级层序;通过构造几何属性分析及精细构造分析,揭示了本区“四带、两凹”的构造格局及形成机制;以宽频带多种反演技术为手段,对含油气层段的七克台组和三间房组砂体分布进行了预测;在综合构造分析、储层分析和油藏成藏规律分析的基础上,提出本区油气沿构造带脊线聚集,断裂系统是油气运移的优势路径,七克台组、三间房组储层在葡北构造带发育,向玉果构造带和胜北次凹减薄尖灭,葡北构造带与玉果构造带结合部位的,具有鼻状构造背景的岩性圈闭是获得油气突破的有利地区。 相似文献
10.