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Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain

Neural Regeneration Research 2020年第2期15卷 270-276页

作者： Xiao-He Gu Heng Li Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao Department of Anatomy and Neurobiology Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurosurgery First Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016.

关键词： Δ78 locus brain region dopaminergic neurons glial cell line-derived neurotrophic factor mouse brain precursor protein α-pro-GDNF β-pro-GDNF sorting protein-related receptor with A-type repeats splice variants

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The antigenicity of SARS-CoV-2 Delta variants aggregated 10 high-frequency mutations in RBD has not changed sufficiently to replace the current vaccine strain

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Signal Transduction and Targeted Therapy 2022年第2期7卷 492-501页

作者： Jiajing Wu Jianhui Nie Li Zhang Hao Song Yimeng An Ziteng Liang Jing Yang Ruxia Ding Shuo Liu Qianqian Li Tao Li Zhimin Cui Mengyi Zhang Peng He Youchun Wang Xiaowang Qu Zhongyu Hu Qihui Wang Weijin Huang Division of HIV/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)102629 BeijingChina Research Network of Immunity and Health(RNIH) Beijing Institutes of Life ScienceChinese Academy of Sciences100101 BeijingChina CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyCenter for Influenza Research and Early-warning(CASCIRE)CAS-TWAS Center of Excellence for Emerging Infectious Diseases(CEEID)Chinese Academy of Sciences100101 BeijingChina Division of Hepatitis and Enteric Viral Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)and Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products102629 BeijingChina Translational Medicine Institute First People’s Hospital of ChenzhouUniversity of South ChinaChenzhouChina CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences100101 BeijingChina

Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and *** determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine,the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was *** neutralization activities of Alpha,Beta and Gamma variants’spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant,which were constructed using pseudotyped ***,the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta *** HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–*** results indicate that the antigenicity changes of possible Delta variants were mostly within four folds,whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–*** analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization *** study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.

关键词： vaccine antigenicity variants

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Development of Oligo-GISH kits for efficient detection of chromosomal variants in peanut

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The Crop Journal 2023年第1期11卷 238-246页

作者： Pei Du Liuyang Fu Qian Wang Tao Lang Hua Liu Suoyi Han Chenyu Li Bingyan Huang Li Qin Xiaodong Dai Wenzhao Dong Xinyou Zhang Henan Academy of Crop Molecular Breeding/State Industrial Innovation Center of Biological Breeding/The Shennong Laboratory/Key Laboratory of Oil Crops in Huang-Huai-Hai Plains Ministry of Agriculture/Henan Provincial Key Laboratory for Oil Crops ImprovementHenan Academy of Agricultural SciencesGraduate T&R Base of Zhengzhou UniversityZhengzhou 450002HenanChina Institute of Biotechnology and Nuclear Technology Sichuan Academy of Agricultural SciencesChengdu 610061SichuanChina

Oligo probe staining is a low-cost and efficient chromosome identification *** this study,oligo genomic in situ hybridization(Oligo-GISH)technology was established in *** A and B subgenome-specific interspersed repeat(IR)oligo probe sets were developed based on clustering and electronic localization of tandem repeat sequences in the reference genome of *** OligoGISH kit was then used to perform staining of 15 Arachis *** A-subgenome probe set stained the chromosomes of A-and E-genome Arachis species,the B-subgenome probe set stained those of B-,F-,K-,and E-genome species,and neither set stained those of H-genome *** results indicate the relationships among the genomes of these Arachis *** Oligo-GISH kit was also used for batch staining of the chromosomes of 389 seedlings from the irradiated M1generation,allowing 67 translocation and deletion lines to be *** Oligo-FISH karyotyping,FISH using single-copy probe libraries,and trait investigation identified seven homozygous chromosomal variants from the M3generation and suggested that there may be genes on chromosome 4B controlling seed number per *** findings demonstrate that the IR probe sets and method developed in this study can facilitate research on distant hybridization and genetic improvement in peanut.

关键词： Peanut Oligo-GISH Genomic relationship variants Chromosome identification

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Rare inherited missense variants of POGZ associate with autism risk and disrupt neuronal development

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Journal of Genetics and Genomics 2019年第5期46卷 247-257页

作者： Wenjing Zhao Jieqiong Tan Tengfei Zhu Jianjun Ou Ying Li Lu Shen Huidan Wu Lin Han Yanling Liu Xiangbin Jia Ting Bai Honghui Li Xiaoyan Ke Jingping Zhao Xiaobing Zou Zhengmao Hu Hui Guo Kun Xia Center of Medical Genetics & Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangsha410078China Mental Health Institute of the Second Xiangya Hospital Central South UniversityChangsha410011China Key Laboratory of Developmental Disorders in Children Liuzhou Maternity and Child Healthcare HospitalLiuzhou545001China Child Mental Health Research Center Nanjing Brain Hospital Affiliated of Nanjing Medical UniversityNanjing210029China Children Development Behavior Center of the Third Affiliated Hospital of Sun Yat-sen University Guangzhou510630China School of Life Sciences and Technology Xinjiang UniversityUrumqi830046China CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT) Chinese Academy of SciencesShanghai200030China

Excess de novo likely gene-disruptive and missense variants within dozens of genes have been identified in autism spectrum disorder(ASD)and other neurodevelopmental ***,many rare inherited missense variants of these high-risk genes have not been thoroughly *** this study,we analyzed the rare missense variant burden of POGZ in a large cohort of ASD patients from the Autism Clinical and Genetic Resources in China(ACGC)and further dissected the functional effect of diseaseassociated missense variants on neuronal *** results showed a significant burden of rare missense variants in ASD patients compared to the control population(P=4.6×10-5,OR=3.96),and missense variants in ASD patients showed more severe predicted functional outcomes than those in ***,by leveraging published large-scale sequencing data of neurodevelopmental disorders(NDDs)and sporadic case reports,we identified 8 de novo missense variants of POGZ in NDD *** analysis revealed that two inherited,but not de novo,missense variants influenced the cellular localization of POGZ and failed to rescue the defects in neurite and dendritic spine development caused by Pogz knockdown in cultured mouse primary cortical ***,L1CAM,an autism candidate risk gene,is differentially expressed in POGZ deficient cell *** expression of L1cam was able to partially rescue the neurite length defects caused by Pogz *** study showed the important roles of rare inherited missense variants of POGZ in ASD risk and neuronal development and identified the potential downstream targets of POGZ,which are important for further molecular mechanism studies.

关键词： Autism POGZ Neuronal development Missense variants

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Novel MSX1 variants identified in families with nonsyndromic oligodontia

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International Journal of Oral Science 2021年第1期13卷 42-51页

作者： Jinglei Zheng Miao Yu Haochen Liu Tao Cai Hailan Feng Yang Liu Dong Han Department of Prosthodontics Peking University School and Hospital of Stomatology&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital StomatologyBeijingChina National Institute of Dental and Craniofacial Research NIHBethesdaMDUSA

The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these ***-exome sequencing(WES)and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia,and a series of bioinformatics databases were used for variant confirmation and functional *** characterization of the members of these families was described,and an in vitro analysis was performed for functional *** novel MSX1 heterozygous variants were identified:three missense variants[c.662A>C(p.Q221P),c.670C>T(p.R224C),and c.809C>T(p.S270L)],one nonsense variant[c.364G>T(p.G122*)],and one frameshift variant[c.277delG(p.A93Rfs*67)].Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P,p.R224C,p.G122*,and p.A93Rfs*67 variants compared to the wild *** variants(p.Q221P,p.G122*,and p.A93Rfs*67)were classified as pathogenic or likely pathogenic,while p.S270L and p.R224C were of uncertain significance in the current ***,we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth *** results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.

关键词： MSX1 variants likely

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A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3645-3652页

作者： Zhenlin Yang Yulu Wang Yujia Jin Yuanfei Zhu Yanling Wu Cheng Li Yu Kong Wenping Song Xiaolong Tian Wuqiang Zhan Ailing Huang Shanshan Zhou Shuai Xia Xiaoxu Tian Chao Peng Cuicui Chen Yibing Shi Gaowei Hu Shujuan Du Yuyan Wang Youhua Xie Shibo Jiang Lu Lu Lei Sun Yuanlin Song Tianlei Ying Department of Pulmonary Medicine Zhongshan HospitalFudan UniversityShanghai 200032China Shanghai Engineering Research Center for Synthetic Immunology Shanghai 200032China Shanghai Key Laboratory of Lung Inflammation and Injury Shanghai 200032China MOE/NHC Key Laboratory of Medical Molecular Virology Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China The Fifth People’s Hospital of Shanghai Fudan University and Shanghai Key Laboratory of Medical EpigeneticsInstitutes of Biomedical SciencesFudan UniversityShanghai 200032China National Facility for Protein Science in Shanghai Zhangjiang LabShanghai Advanced Research InstituteChinese Academy of ScienceShanghai 201210China Department of Pulmonary Medicine Shanghai Respiratory Research InstituteShanghai 200032China

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for *** frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 *** we show that the bivalency of an affinity maturated fully human singledomain antibody(n3113.1-Fc)exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus,and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2(ACE2)humanized *** crystal structure of n3113 in complex with the receptor-binding domain(RBD)of SARS-CoV-2,combined with the cryo-EM structures of n3113 and spike ecto-domain,reveals that n3113 binds to the side surface of up-state RBD with no competition with *** binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion,expanding our recognition of neutralization by antibodies against *** assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages,including Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),and Delta(B.1.617.2)for n3113.1-Fc with Y58L mutation,demonstrating the potential of n3113.1-Fc(Y58L)as a promising candidate for clinical development to treat COVID-19.

关键词： ACE2 variants authentic

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SARS-CoV-2 variants:a new challenge to convalescent serum and mRNA vaccine neutralization efficiency

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1402-1403页

作者： Maochen Li Fuxing Lou Huahao Fan Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina

The spike protein of SARS-CoV-2 is the target of antibodies in convalescent and vaccine sera,and 23 mutations in spike protein were reported in the variants B.1.1.7,B.1.351,and P.1(Fig.1a).Recently,several groups evaluated the effects of convalescent and mRNA vaccine sera on two major circulating SARS-CoV-2 variants B.1.1.7 and B.1.351(Fig.1b),1,2,3,4,5 which leads to concerns about the immune escape of these variants from the human acquired immunity stimulated by previous infections and mRNA vaccines.

关键词： immunity vaccine variants

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Engineering SpyCatcher variants with Proteolytic Sites for Less-Trace Ligation

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Chinese Journal of Chemistry 2019年第2期37卷 113-118,I0002页

作者： Xue-Jian Zhang Xia-Ling Wu Dong Liu Xiao-Di Da Xiao-Wei Wang Shuguang Yang Wen-Bin Zhang State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Center for Advanced Low-dimension MaterialsCollege of Material Science and EngineeringDonghua UniversityShanghai 201620China Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and EngineeringCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

Summary of main observation and conclusion The SpyTag/SpyCatcher reaction is a powerful tool for bioconjugation, but it leaves a complex of considerable size after ligation. To facilitate removal of the catalytic fragment, proteolytic recog nit ion sites (such as DDDDK, AVLQ, and WELQ) were directly engineered into the first or second loop of SpyCatcher at locations after the reactive lysine to give a set of cleavable SpyCatcher variants. Among them, SpyCatcherDDDDK exhibits excellent reactivity with SpyTag and could still be cleaved proteolytically by enterokinase after ligation. Notably, SpyCatcherDDDDK is disordered in solution and forms an ordered complex upon reaction with SpyTag with a second order rate constant of 99.2 ± 0.1M^-1·S^-1 which is comparable to, if not faster than, most click reactions. The results demonstrate the high sequence plasticity of SpyCatcher and suggest that covalent bond formation may confer robustness on the folded structure against extensive mutation. These variants add to the expanding toolbox of genetically-encoded peptide-protein chemistry with diverse features.

关键词： SpyCatcher variants Proteolytic

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Chromatin conformation of human oral epithelium can identify orofacial cleft missing functional variants

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International Journal of Oral Science 2022年第4期14卷 497-508页

作者： Yao Xiao Shengbo Jiao Miao He Da Lin Huanyan Zuo Jiahao Han Yonghua Sun Gang Cao Zhi Chen Huan Liu The State Key Laboratory Breeding Base of Basic Science of Stomatology&Key Laboratory for Oral Biomedicine of Ministry of Education School and Hospital of StomatologyWuhan University237 Luoyu RoadWuhanChina Department of Stomatology Nanfang HospitalSouthern Medical UniversityGuangzhouChina State Key Laboratory of Freshwater Ecology and Biotechnology Hubei Hongshan LaboratoryInstitute of HydrobiologyInnovation Academy for Seed DesignChinese Academy of SciencesWuhanChina College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijingChina State Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhanChina Taikang Center for Life and Medical Sciences Wuhan UniversityWuhanChina

Genome-wide association studies(GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts(OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability,suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line(HIOEC) using RNA-seq, ATAC-seq,H3K27ac Ch IP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only(NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification *** total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epitheliumexpressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.

关键词： epithelium functional variants

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Parallel profiling of antigenicity alteration and immune escape of SARS-CoV-2 Omicron and other variants

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Signal Transduction and Targeted Therapy 2022年第3期7卷 770-779页

作者： Cong Sun Yin-Feng Kang Yuan-Tao Liu Xiang-Wei Kong Hui-Qin Xu Dan Xiong Chu Xie Yi-Hao Liu Sui Peng Guo-Kai Feng Zheng Liu Mu-Sheng Zeng State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineDepartment of Experimental ResearchSun Yat-sen University Cancer CenterSun Yat-sen UniversityGuangzhou 510060P.R.China Cryo-electron Microscopy Center Southern University of Science and TechnologyShenzhen 518000 GuangdongP.R.China Medical Laboratory of the Third affiliated Hospital of Shenzhen University Shenzhen 518000 GuangdongP.R.China Institute of Precision Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongP.R.China Clinical Trials Unit The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongP.R.China Department of Endocrinology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongP.R.China

SARS-CoV-2 variants have evolved a variety of critical mutations,leading to antigenicity changes and immune *** recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance t... 详细信息

关键词： variants antigenicity Omi

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