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Learning Sequential and Structural Dependencies Between Nucleotides for rna N6-Methyladenosine Site Identification

IEEE/CAA Journal of Automatica Sinica 2024年第10期11卷 2123-2134页

作者： Guodong Li Bowei Zhao Xiaorui Su Dongxu Li Yue Yang Zhi Zeng Lun Hu Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of ScienceUrumqi 830011China College of Computer Xi’an Jiaotong UniversityXi’an 710049China IEEE

N6-methyladenosine(m6A)is an important rna methylation modification involved in regulating diverse biological processes across multiple ***,the identification of m6A modification sites provides valuable insight into the biological mechanisms of complex diseases at the post-transcriptional *** a variety of identification algorithms have been proposed recently,most of them capture the features of m6A modification sites by focusing on the sequential dependencies of nucleotides at different positions in rna sequences,while ignoring the structural dependencies of nucleotides in their threedimensional *** overcome this issue,we propose a cross-species end-to-end deep learning model,namely CR-NSSD,which conduct a cross-domain representation learning process integrating nucleotide structural and sequential dependencies for rna m6A site ***,CR-NSSD first obtains the pre-coded representations of rna sequences by incorporating the position information into single-nucleotide states with chaos game representation *** then constructs a crossdomain reconstruction encoder to learn the sequential and structural dependencies between *** minimizing the reconstruction and binary cross-entropy losses,CR-NSSD is trained to complete the task of m6A site *** experiments have demonstrated the promising performance of CR-NSSD by comparing it with several state-of-the-art m6A identification ***,the results of cross-species prediction indicate that the integration of sequential and structural dependencies allows CR-NSSD to capture general features of m6A modification sites among different species,thus improving the accuracy of cross-species identification.

关键词： Cross-domain reconstruction cross-species prediction N6-methyladenosine(m6A)modification site rna sequence sequential and structural dependencies

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Transcriptomic analysis of spinal cord regeneration after injury in Cynops orientalis

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Neural Regeneration Research 2023年第12期18卷 2743-2750页

作者： Di Wang Man Zhao Xiao Tang Man Gao Wenjing Liu Minghui Xiang Jian Ruan Jie Chen Bin Long Jun Li College of Life Sciences Anhui Normal UniversityWuhuAnhui ProvinceChina College of Animal Science and Technology Nanjing Agricultural UniversityNanjingJiangsu ProvinceChina Laboratory of Reproductive Medicine The Second People’s HospitalWuhuWuhuAnhui ProvinceChina

Cynops orientalis(***)has a pronounced ability to regenerate its spinal cord after ***,exploring the molecular mechanism of this process could provide new approaches for promoting mammalian spinal cord *** this study,we established a model of spinal cord thoracic transection injury in ***,which is an endemic species in *** performed rna sequencing of the contused axolotl spinal cord at two early time points after spinal cord injury–during the very acute stage(4 days)and the subacute stage(7 days)–and identified differentially expressed genes;additionally,we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses,at each time *** sequencing showed that 13,059 genes were differentially expressed during *** spinal cord regeneration compared with uninjured animals,among which 4273 were continuously downregulated and 1564 were continuously ***-regulated genes were most enriched in the Gene Ontology term“multicellular organismal process”and in the ribosome pathway at 10 days following spinal cord *** found that multiple genes associated with energy metabolism were down-regulated and multiple genes associated with the lysosome were up-regulated after spinal cord injury,indicating the importance of low metabolic activity during wound *** response-associated pathways were activated during the early acute phase(4 days),while the expression of extracellular matrix proteins such as glycosaminoglycan and collagen,as well as tight junction proteins,was lower at 10 days post-spinal cord injury than 4 days post-spinal cord ***,compared with 4 days post-injury,at 10 days post-injury neuroactive ligand-receptor interactions were no longer down-regulated,up-regulated differentially expressed genes were enriched in pathways associated with cancer and the cell cycle,and SHH,VIM,and Sox2 were prominently *** staining showed

关键词： Cynops orientalis extracellular matrix glial fibrillary acidic protein metabolism neuron rna sequence salamander spinal cord injury spinal cord regeneration Transcriptomics

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Transcript Profiling Reveals Abscisic Acid,Salicylic Acid and Jasmonic-Isoleucine Pathways Involved in High Regenerative Capacities of Immature Embryos Compared with Mature Seeds in japonica Rice

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Rice science 2018年第4期25卷 227-234页

作者： XIAO Kaizhuan MAO Xiaohui WANG Yingheng WANG Jinlan WEI Yidong CAI Qiuhua XIE Hua'an ZHANG Jianfu College of Life Sciences Fujian Normal UniversityFuzhou 350108China Rice Research Institute Fujian Academy of Agricultural SciencesFuzhou 350019China Key Laboratory of Germplasm Innovation and Molecular Breeding of Hybrid Rice for South China Ministry of Agriculture/Incubator of National Key Laboratory of Fujian Germplasm Innovation and Molecular Breeding Between Fujian and Ministry of Sciences&Technology/Fuzhou BranchNational Rice Improvement Center of China/Fujian Engineering Laboratory of Crop Molecular Breeding/Fujian Key Laboratory of Rice Molecular Breeding/Base of South ChinaState Key Laboratory of Hybrid Rice/National Rice Engineering LaboratoryFuzhou 350003China

Induced pluripotent cell mass plays a role in genetic transformation mediated by Agrobacterium. Mature seeds are more recalcitrant to the induction of suitable calli than immature embryos in rice, but the exact molecular mechanisms involved remain elusive. In this study, the morphological structure of calli induced from mature seeds and immature embryos were observed under a scanning electron microscope using a paraffin embedded technique. Meanwhile, a total of 2 173 up- and down-regulated genes were identified in calli induced from mature seeds and immature embryos by rna-seq technique and furtherly confirmed by quantitative real-time PCR. The results revealed the remarkable morphological differences in calli induced from mature seeds and immature embryos, and plant hormone signal transduction and hormone biosynthesis pathways, such as abscisic acid, salicylic acid and jasmonic-isoleucine, were found to play roles in somatic embryogenesis. This study provided comprehensive gene expression sets for mature seeds and immature embryos that were served as an important platform resource for further functional studies in plant embryogenesis.

关键词： callus immature embryo mature seed japonica rice rna sequence hormone

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Inhibition of hepatitis C virus replication by single-stranded rna structural mimics

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World Journal of Gastroenterology 2010年第17期16卷 2100-2108页

作者： Robert Smolic Martina Smolic John H Andorfer Catherine H Wu Robert M Smith George Y Wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health Center263 Farmington Ave.FarmingtonCT 06030-1845United States

AIM: To examine the effect of hepatitis C virus (HCV) structural mimics of regulatory regions of the genome on HCV ***: HCV rna structural mimics were constructed and tested in a HCV genotype 1b aBB7 replicon,and a Japanese fulminant hepatitis-1 (JFH-1) HCV genotype 2a infection *** sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral ***7.5 cells bearing the BB7 replicon or infected with JFH-1 virus were transfected with expression vectors generating HCV mimics and *** HCV rna and protein levels were quantified by real-time polymerase chain reaction and Western blotting,*** evaluate possible antisense effects,complementary rnas spanning a mimic were ***: In the BB7 genotype 1b replicon system,mimics of the polymerase (NS-5B),X and BA regions inhibited replication by more than 90%,50%,and 60%,*** the JFH-1 genotype 2 infection system,mimics that were only 74% and 46% identical in sequence relative to the corresponding region in JFH-1 inhibited HCV replication by 91.5% and 91.2%,respectively,as effectively as a mimic with complete identity to HCV genotype *** inhibitory effects were confirmed by NS3 protein *** rna molecules spanning the 74% identical mimic had no significant ***: HCV rna structural mimics can inhibit HCV rna replication in replicon and infectious HCV systems and do so independent of close sequence identity with the target.

关键词： Hepatitis C virus Japanese fulminant hepatitis virus Complementarity rna sequence Hybridization

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FMLP对电离辐射的防护作用及其机制研究

FMLP对电离辐射的防护作用及其机制研究

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作者：钱雯中国人民解放军海军军医大学

学位级别：硕士

研究背景近年,随着核技术发展,电离辐射成为社会发展过程中的污染因素之一,而人体暴露于大剂量的电离辐射后会引发各种不良生物学效应,因此研制针对电离辐射损伤的辐射防护药物便显得十分重要。近来研究发现,细菌自身的结构成分(如脂多... 详细信息

研究背景近年,随着核技术发展,电离辐射成为社会发展过程中的污染因素之一,而人体暴露于大剂量的电离辐射后会引发各种不良生物学效应,因此研制针对电离辐射损伤的辐射防护药物便显得十分重要。近来研究发现,细菌自身的结构成分(如脂多糖,鞭毛蛋白等)能够抑制辐射导致的细胞凋亡,增强机体对辐射的抵抗力。我们实验室前期研究发现给予野生型小鼠TLR4配体细菌脂多糖(lipopolysaccharide,简称LPS)刺激后能提高小鼠对辐射的耐受。LPS是革兰氏阴性杆菌细胞壁的主要成分之一,它能激活机体的免疫反应。LPS虽有较好的抗辐射效应,但LPS会使感染的机体产生毒性反应。我们通过预实验筛选了大量LPS类似物,发现白细胞趋化肽N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸(N-formyl-methionyl-leucyl-phenylalanine,简称FMLP)可以诱导机体产生与LPS刺激类似的炎症反应。有文献报道FMLP对中性粒细胞、单核细胞等细胞有重要作用,包括粘附,趋化和超氧化物阴离子释放等。这提示FMLP可能通过影响细胞功能、调节机体免疫功能,从而具有潜在的辐射防护作用。基于以上研究背景,我们开展了FMLP对电离辐射防护作用及其机制的初步研究。研究目的1.评价FMLP的毒性效应,并研究FMLP对体外细胞、辐射敏感组织和小鼠的辐射防护效应。2.开展FMLP辐射防护作用的机制研究,初步探寻FMLP抗辐射的分子机制。研究方法***的毒性及辐射防护效应研究(1)FMLP毒性效应研究。细胞水平:不同浓度的FMLP作用于人小肠上皮细胞系(HIEC)、C57BL/6小鼠骨髓原代细胞(BMC)、C57BL/6小鼠脾原代细胞(Spleen cell)后,利用CCK-8方法检测细胞活力。动物水平:不同浓度的FMLP经腹腔给药于C57BL/6小鼠,以WR-2721、LPS等已知辐射防护效果较好的试剂作为阳性对照试剂,评价FMLP对在体动物的毒性效果。(2)FMLP对体外细胞的防护效应。通过HIEC/BMC/Spleen cell照后采用CCK-8实验和流式细胞术两种检测方法,检测受照细胞的细胞活力和细胞凋亡率变化,评价FMLP对体外细胞的防护效应。(3)FMLP对辐射敏感组织的辐射防护效应。采用小鼠外周血白细胞计数、骨髓单个核细胞计数、脾脏系数、肠道组织病理切片染色评价FMLP对辐射敏感组织的辐射防护作用。(4)FMLP对在体动物的辐射防护效应。以WR-2721、LPS等已知辐射防护效果较好的试剂作为阳性对照试剂,记录C57BL/6小鼠经不同剂量辐照后的生存期和生存时间评价FMLP对整体动物的辐射防护作用。***的辐射防护初步分子机制研究(1)应用多种基因敲除小鼠初步研究FMLP的辐射防护机制。采用野生型(WT)、TLR2敲除(KO)、TLR4 KO、My D88 KO四种小鼠的原代脾细胞和骨髓病理切片研究FMLP的辐射防护作用是否依赖TLRs及其下游信号通路。(2)构建FPR1、FPR2敲低稳转细胞株研究FMLP辐射防护机制。(3)结合参考文献,运用定量PCR研究FMLP对受照小鼠脾脏原代细胞内骨髓造血相关细胞因子IL-6,IL-11,CCL-2,IL-12和GM-CSF等m rna水平的影响。(4)ELISA法检测小鼠体内细胞因子IL-6,IL-11,CCL-2,IL-12和GM-CSF的表达量。(5)通过rna sequence技术筛选可能的辐射防护差异基因,而后采取定量PCR等实验技术进一步检测相关基因的表达情况。研究结果***毒性及辐射防护效应研究结果(1)FMLP毒性效应研究。CCK-8显示FMLP在16μM以下浓度对HIEC、BMC以及Spleen cell等细胞均无明显毒性,且表现出轻度促进细胞活力的作用,并选取0.5-1μM为最佳给药剂量。在FMLP与WR-2721和LPS这两种辐射防护剂的毒性作用对比检测中,小鼠生存期实验结果表明FMLP的急性毒性介于LPS和WR-2721之间。(2)FMLP对体外细胞的辐射防护效应。细胞照后活力检测显示FMLP对HIEC、BMC、Spleen cell三种细胞活力都有提高;在多种防护剂的效果对比中,FMLP防护效果最好,细胞活力达到80%以上。在流式细胞术凋亡检测中,选取HIEC、BMC、Spleen cell三种细胞实验,结果显示FMLP对三种细胞的存活率都有一定程度提高,其中HIEC细胞的存活率提高20%-30%。(3)FMLP对辐射敏感组织的防护效应。FMLP可显著升高照射后小鼠的外周血白细胞数目和骨髓有核细胞数目,降低小鼠在体BMC凋亡率,提高照后小鼠脾脏脏器指数,FMLP还可以保护骨髓和肠道组织,降低骨髓和肠道细胞凋亡。(4)FMLP对在体动物的辐射防护效应。小鼠生存期结果证明,在不

关键词：电离辐射辐射防护 FMLP FPR1 rna sequence

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