12 results on '"Linnan Zhao"'
Search Results
2. Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.
- Author
-
Jun Li, Linnan Zhao, Yang You, Tianlan Lu, Meixiang Jia, Hao Yu, Yanyan Ruan, Weihua Yue, Jing Liu, Lin Lu, Dai Zhang, and Lifang Wang
- Subjects
Medicine ,Science - Abstract
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic component. Many lines of evidence indicated that ASD shares common genetic variants with other psychiatric disorders (for example, schizophrenia). Previous studies detected that calcium channels are involved in the etiology of many psychiatric disorders including schizophrenia and autism. Significant association between CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit) and schizophrenia was detected. Furthermore, rare mutation in CACNA1C is suggested to cause Timothy syndrome, a multisystem disorder including autism-associated phenotype. However, there is no evidence for association between CACNA1C and autism in Chinese Han population. To investigate the association between single nucleotide polymorphisms (SNP) in CACNA1C and autism, we first performed a family-based association study between eighteen SNPs in CACNA1C and autism in 239 trios. All SNPs were genotyped by using Sequenom genotyping platform. Two SNPs (rs1006737 and rs4765905) have a trend of association with autism. To further confirm the association between these two SNPs with autism, we expanded the sample size to 553 trios by adding 314 trios. Association analyses for SNPs and haplotype were performed by using family-based association test (FBAT) and Haploview software. Permutation tests were used for multiple testing corrections of the haplotype analyses (n=10,000). The significance level for all statistical tests was two-tailed (p
- Published
- 2015
- Full Text
- View/download PDF
3. The evidence for association of ATP2B2 polymorphisms with autism in Chinese Han population.
- Author
-
Wen Yang, Jing Liu, Fanfan Zheng, Meixiang Jia, Linnan Zhao, Tianlan Lu, Yanyan Ruan, Jishui Zhang, Weihua Yue, Dai Zhang, and Lifang Wang
- Subjects
Medicine ,Science - Abstract
BACKGROUND:Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca(2+) from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. METHODS:We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses. RESULTS:This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = -2.482, p = 0.013; Z = -2.591, p = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180-rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = -2.037, p = 0.042; Global p = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = -2.206, p = 0.027; Global p = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032). These results were still significant after using the permutation method to obtain empirical p values. CONCLUSIONS:Our research suggested that ATP2B2 might play a role in the etiology of autism in Chinese Han population.
- Published
- 2013
- Full Text
- View/download PDF
4. Auts2 deletion involves in DG hypoplasia and social recognition deficit: The developmental and neural circuit mechanisms
- Author
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Jun Li, Xiaoxuan Sun, Yang You, Qiongwei Li, Chengwen Wei, Linnan Zhao, Mengwen Sun, Hu Meng, Tian Zhang, Weihua Yue, Lifang Wang, and Dai Zhang
- Subjects
Multidisciplinary - Abstract
The involvement of genetic risk and the underlying developmental and neural circuit mechanisms in autism-related social deficit are largely unclear. Here, we report that deletion of AUTS2 , a high-susceptibility gene of ASDs, caused postnatal dentate gyrus (DG) hypoplasia, which was closely relevant to social recognition deficit. Furthermore, a previously unknown mechanism for neural cell migration in postnatal DG development was identified, in which Auts2-related signaling played a vital role as the transcription repressor. Moreover, the supramammillary nucleus (SuM)–DG-CA3 neural circuit was found to be involved in social recognition and affected in Auts2 -deleted mice due to DG hypoplasia. Correction of DG-CA3 synaptic transmission by using a pharmacological approach or chemo/optogenetic activation of the SuM-DG circuit restored the social recognition deficit in Auts2 -deleted mice. Our findings demonstrated the vital role of Auts2 in postnatal DG development, and this role was critical for SuM-DG-CA3 neural circuit-mediated social recognition behavior.
- Published
- 2022
5. Activatable fluorescence molecular imaging and anti-tumor effects investigation of GSH-sensitive BRD4 ligands
- Author
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Hang Zhang, Mingliang Zhang, Yujie Zhang, Han Wang, Linnan Zhao, and Haiwei Xu
- Subjects
Sulfonamides ,Organic Chemistry ,Optical Imaging ,Nuclear Proteins ,Antineoplastic Agents ,Cell Cycle Proteins ,Ligands ,Biochemistry ,Glutathione ,Molecular Imaging ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Humans ,Molecular Biology ,Cell Proliferation ,Transcription Factors - Abstract
Overexpression of bromodomain 4 (BRD4) is closely correlated with a variety of human cancers by regulating the histone post-translational modifications, which renders BRD4 a promising target for pharmacological discoveries of novel therapeutic agents for cancer therapy. We herein present the design, chemical synthesis, cellular imaging and biological assessment of a novel tumor-sensitive BRD4 ligand (compound 4) by introducing anticancer BRD4 inhibitor into naphthalimide moiety (fluorescent reporter) via a sulfonamide unit as glutathione (GSH)-specific cleavable linker. Upon reaction with abundant intramolecular GSH in cancer cells or free GSH in aqueous solution (pH = 7.4), sulfonamide cleavage of 4 occurs, leading to the release of BRD4 inhibitor and concomitant fluorescence-on. This activatable fluorescence molecular imaging was demonstrated to preferentially occur in tumor cells. Moreover, towards cancer cell lines MGC-803 cells and THP-1, compound 4 was identified to show better antitumor efficacy than net BRD4 inhibitor. Collectively, this study presents a drug delivery strategy, wherein the drug release can be directly monitored in the cellular content by fluorescence imaging, and provides a valuable compound 4 as a potential antitumor agent. Compound 4 may represent a useful tool for explorative studies of BRD4 inhibition, such as an improved understanding of BRD4 inhibitor release-related information.
- Published
- 2021
6. Determination of Organochlorine Pesticides in Green Leafy Vegetable Samples via Fe3O4 Magnetic Nanoparticles Modified QuEChERS Integrated to Dispersive Liquid-Liquid Microextraction Coupled with Gas Chromatography-Mass Spectrometry
- Author
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Fang Wang, Guo Guiquan, Yu Ling, Linnan Zhao, Jun Zhao, Xu He, Cuijuan Xing, Lili Dong, and Aiqing Xia
- Subjects
Detection limit ,Chromatography ,Chloroform ,QD71-142 ,Article Subject ,Chemistry ,General Chemical Engineering ,010401 analytical chemistry ,Carbon black ,010501 environmental sciences ,Mass spectrometry ,Quechers ,01 natural sciences ,0104 chemical sciences ,Computer Science Applications ,Solvent ,chemistry.chemical_compound ,Adsorption ,Gas chromatography–mass spectrometry ,Instrumentation ,Analytical chemistry ,0105 earth and related environmental sciences - Abstract
A fast method based on Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) modified QuEChERS integrated to dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass spectrometry was established for the determination of 8 organochlorine pesticides (OCPs) in green leafy vegetables. The factors involved in the purification by QuEChERS and concentration by DLLME were optimized. In the QuEChERS process, Fe3O4 MNPs were used as a new impurity adsorbent after the sample extraction procedure by acetonitrile, which achieved phase separation rapidly. Carbon black was used as an alternative to costly graphitized carbon black without affecting the recovery. In the process of DLLME, 1 mL of the extract obtained by QuEChERS was used as the dispersive solvent, 40 μL of chloroform was used as the extractive solvent, and 4 mL of water was added. Making them mix well, then the dispersed liquid-liquid microextraction concentration was subsequently carried out. The enrichment factors of 8 OCPs ranged from 22.8 to 36.6. The recoveries of the proposed method ranged from 78.6% to 107.7%, and the relative standard deviations were not more than 7.5%. The limits of detection and limits of quantification were 0.15–0.32 μg/kg and 0.45–0.96 μg/kg, respectively. The method has been successfully applied to the determination of OCPs in green leafy vegetable samples.
- Published
- 2021
7. Determination of Organochlorine Pesticides in Green Leafy Vegetable Samples via Fe
- Author
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Ling, Yu, Guiquan, Guo, Jun, Zhao, Linnan, Zhao, Aiqing, Xia, Xu, He, Cuijuan, Xing, Lili, Dong, and Fang, Wang
- Subjects
Research Article - Abstract
A fast method based on Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) modified QuEChERS integrated to dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass spectrometry was established for the determination of 8 organochlorine pesticides (OCPs) in green leafy vegetables. The factors involved in the purification by QuEChERS and concentration by DLLME were optimized. In the QuEChERS process, Fe3O4 MNPs were used as a new impurity adsorbent after the sample extraction procedure by acetonitrile, which achieved phase separation rapidly. Carbon black was used as an alternative to costly graphitized carbon black without affecting the recovery. In the process of DLLME, 1 mL of the extract obtained by QuEChERS was used as the dispersive solvent, 40 μL of chloroform was used as the extractive solvent, and 4 mL of water was added. Making them mix well, then the dispersed liquid-liquid microextraction concentration was subsequently carried out. The enrichment factors of 8 OCPs ranged from 22.8 to 36.6. The recoveries of the proposed method ranged from 78.6% to 107.7%, and the relative standard deviations were not more than 7.5%. The limits of detection and limits of quantification were 0.15–0.32 μg/kg and 0.45–0.96 μg/kg, respectively. The method has been successfully applied to the determination of OCPs in green leafy vegetable samples.
- Published
- 2020
8. Destabilizing LSD1 by Jade-2 Promotes Neurogenesis: An Antibraking System in Neural Development
- Author
-
Jing Liang, Xia Yi, Linnan Zhao, Wenhua Yu, Ruorong Yan, Yan Wang, Lifang Li, Xiaohan Yang, Xiao Han, Yi E. Sun, Jianguo Yang, Bin Gui, Yongfeng Shang, Wanjin Li, Di Zhang, Dai Zhang, Anming Meng, Luyang Sun, Cong Xiong, and Wenzhe Si
- Subjects
animal structures ,Cellular differentiation ,Neurogenesis ,Ubiquitin-Protein Ligases ,Biology ,Epigenesis, Genetic ,Mice ,Neuroblastoma ,Cell Line, Tumor ,Animals ,Humans ,Epigenetics ,Molecular Biology ,Embryonic Stem Cells ,Zebrafish ,Genetics ,Regulation of gene expression ,Histone Demethylases ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Oxidoreductases, N-Demethylating ,Cell Biology ,Zebrafish Proteins ,Embryonic stem cell ,Ubiquitin ligase ,Cell biology ,biology.protein ,Demethylase ,Neural development ,HeLa Cells - Abstract
Histone H3K4 demethylase LSD1 plays an important role in stem cell biology, especially in the maintenance of the silencing of differentiation genes. However, how the function of LSD1 is regulated and the differentiation genes are derepressed are not understood. Here, we report that elimination of LSD1 promotes embryonic stem cell (ESC) differentiation toward neural lineage. We showed that the destabilization of LSD1 occurs posttranscriptionally via the ubiquitin-proteasome pathway by an E3 ubiquitin ligase, Jade-2. We demonstrated that Jade-2 is a major LSD1 negative regulator during neurogenesis in vitro and in vivo in both mouse developing cerebral cortices and zebra fish embryos. Apparently, Jade-2-mediated degradation of LSD1 acts as an antibraking system and serves as a quick adaptive mechanism for re-establishing epigenetic landscape without more laborious transcriptional regulations. As a potential anticancer strategy, Jade-2-mediated LSD1 degradation could potentially be used in neuroblastoma cells to induce differentiation toward postmitotic neurons.
- Published
- 2014
- Full Text
- View/download PDF
9. Association study between genes in Reelin signaling pathway and autism identifies DAB1 as a susceptibility gene in a Chinese Han population
- Author
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Tianlan Lu, Dai Zhang, Yuanlin Ma, Weihua Yue, Yanyan Ruan, Qizhai Li, Linnan Zhao, Jing Liu, Lifang Wang, Jun Li, and Meixiang Jia
- Subjects
Male ,Genotype ,Cell Adhesion Molecules, Neuronal ,Nerve Tissue Proteins ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Adapter molecule crk ,Neurodevelopmental disorder ,Reeler ,Asian People ,medicine ,Humans ,Genetic Predisposition to Disease ,Reelin ,Autistic Disorder ,Child ,Genetic Association Studies ,Biological Psychiatry ,Adaptor Proteins, Signal Transducing ,Pharmacology ,Genetics ,Extracellular Matrix Proteins ,Serine Endopeptidases ,medicine.disease ,DAB1 ,CRKL ,Reelin Protein ,nervous system ,biology.protein ,Autism ,Female ,CUL5 ,Signal Transduction - Abstract
Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. The genetic factors might play an important role in its pathogenesis. Previous studies revealed that Reelin ( RELN ) polymorphisms were associated with autism. However, the roles of genes in Reelin signaling pathway for autism are largely unknown. As several knockout mice models in which the Reelin pathway genes (i.e. DAB1 , VLDLR / APOER2 , FYN / SRC and CRK / CRKL ) are deficient have the similar phenotype as the reeler mice ( Reelin −/− ), we hypothesized that the Reelin signaling pathway genes might play roles in the etiology of autism. Therefore, we conducted a family-based association study. Sixty-two tagged single nucleotide polymorphisms (SNPs) covering 15 genes in Reelin pathway were genotyped in 239 trios, and 14 significant SNPs were further investigated in the additional 188 trios. In the total 427 trios, we found significant genetic association between autism and four SNPs in DAB1 (rs12035887 G: p = 0.0006; rs3738556 G: p = 0.0044; rs1202773 A: p = 0.0048; rs12740765 T: p = 0.0196). After the Bonferroni correction, SNP rs12035887 remained significant. Furthermore, the haplotype constructed with rs1202773 and rs12023109 in DAB1 showed significant excess transmission in both individual and global haplotype analyses ( p = 0.0052 and 0.0279, respectively). Our findings suggested that variations in DAB1 involved in the Reelin signaling pathway might contribute to genetic susceptibility to autism with Chinese Han decent, supporting the defect in the Reelin signaling pathway as a predisposition factor for autism.
- Published
- 2013
10. Ezh2 is involved in radial neuronal migration through regulating Reelin expression in cerebral cortex
- Author
-
Jiutao Wang, Wen Pan, Kai Gao, Jun Li, Linnan Zhao, Tianlan Lu, Yuanlin Ma, Zhengrong Zhang, Weihua Yue, Yanyan Ruan, Dai Zhang, Lifang Wang, and Shanting Zhao
- Subjects
Cell Adhesion Molecules, Neuronal ,Nerve Tissue Proteins ,macromolecular substances ,Article ,Cell Movement ,medicine ,Animals ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Reelin ,Enhancer ,Cerebral Cortex ,Neurons ,Extracellular Matrix Proteins ,Gene knockdown ,Multidisciplinary ,biology ,Serine Endopeptidases ,EZH2 ,Polycomb Repressive Complex 2 ,Anatomy ,DAB1 ,Reelin Protein ,Corticogenesis ,medicine.anatomical_structure ,nervous system ,Cerebral cortex ,Histone methyltransferase ,biology.protein ,Neuroscience - Abstract
Radial migration of pyramidal neurons is an important event during the development of cerebral cortex. Neurons experience series of morphological and directional transitions to get to their final laminar positions. Here we report that the histone methyltransferase enhancer of zest homolog 2 (Ezh2) is involved in the regulation of cortical radial migration. We show that Ezh2 knockdown leads to disturbed neuronal orientation, which results in the impairment of radial migration. Further results reveal that this migration deficiency may be due to the derepression of Reelin transcription in the migrating neurons. Our study provides evidence that epigenetic regulation of Reelin by Ezh2 maintains appropriate Reelin expression pattern to fulfill proper orientation of migrating neurons.
- Published
- 2015
11. Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism
- Author
-
Lin Lu, Linnan Zhao, Weihua Yue, Tianlan Lu, Jing Liu, Hao Yu, Yanyan Ruan, Lifang Wang, Yang You, Jun Li, Dai Zhang, and Meixiang Jia
- Subjects
Male ,China ,Adolescent ,Calcium Channels, L-Type ,Genotype ,Autism Spectrum Disorder ,Haploview ,Timothy syndrome ,lcsh:Medicine ,Single-nucleotide polymorphism ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,behavioral disciplines and activities ,Asian People ,mental disorders ,medicine ,Humans ,Genetic Predisposition to Disease ,Heritability of autism ,lcsh:Science ,Child ,Alleles ,Genetic Association Studies ,Genetics ,Multidisciplinary ,lcsh:R ,Haplotype ,medicine.disease ,3. Good health ,Haplotypes ,Schizophrenia ,Autism spectrum disorder ,Child, Preschool ,Autism ,lcsh:Q ,Female ,Research Article - Abstract
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic component. Many lines of evidence indicated that ASD shares common genetic variants with other psychiatric disorders (for example, schizophrenia). Previous studies detected that calcium channels are involved in the etiology of many psychiatric disorders including schizophrenia and autism. Significant association between CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit) and schizophrenia was detected. Furthermore, rare mutation in CACNA1C is suggested to cause Timothy syndrome, a multisystem disorder including autism-associated phenotype. However, there is no evidence for association between CACNA1C and autism in Chinese Han population. To investigate the association between single nucleotide polymorphisms (SNP) in CACNA1C and autism, we first performed a family-based association study between eighteen SNPs in CACNA1C and autism in 239 trios. All SNPs were genotyped by using Sequenom genotyping platform. Two SNPs (rs1006737 and rs4765905) have a trend of association with autism. To further confirm the association between these two SNPs with autism, we expanded the sample size to 553 trios by adding 314 trios. Association analyses for SNPs and haplotype were performed by using family-based association test (FBAT) and Haploview software. Permutation tests were used for multiple testing corrections of the haplotype analyses (n=10,000). The significance level for all statistical tests was two-tailed (p
- Published
- 2015
12. The Evidence for Association of ATP2B2 Polymorphisms with Autism in Chinese Han Population
- Author
-
Jing Liu, Linnan Zhao, Tianlan Lu, Yanyan Ruan, Weihua Yue, Lifang Wang, Wen Yang, Jishui Zhang, Fanfan Zheng, Dai Zhang, and Meixiang Jia
- Subjects
Male ,Linkage disequilibrium ,Spatial Epidemiology ,Epidemiology ,lcsh:Medicine ,Developmental and Pediatric Neurology ,Linkage Disequilibrium ,Neurodevelopmental disorder ,Ethnicity ,Heritability of autism ,Child ,lcsh:Science ,Psychiatry ,Child Psychiatry ,Genetics ,Multidisciplinary ,Mental Health ,Neurology ,Autism spectrum disorder ,Genetic Epidemiology ,Child, Preschool ,Medicine ,Female ,Research Article ,China ,Adolescent ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,behavioral disciplines and activities ,Plasma Membrane Calcium-Transporting ATPases ,Asian People ,mental disorders ,otorhinolaryngologic diseases ,medicine ,Humans ,Genetic Predisposition to Disease ,Autistic Disorder ,Allele ,Genetic Association Studies ,Population Biology ,lcsh:R ,Haplotype ,Human Genetics ,medicine.disease ,Haplotypes ,Genetic Polymorphism ,Autism ,lcsh:Q ,Population Genetics - Abstract
BACKGROUND:Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca(2+) from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. METHODS:We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses. RESULTS:This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = -2.482, p = 0.013; Z = -2.591, p = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180-rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = -2.037, p = 0.042; Global p = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = -2.206, p = 0.027; Global p = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032). These results were still significant after using the permutation method to obtain empirical p values. CONCLUSIONS:Our research suggested that ATP2B2 might play a role in the etiology of autism in Chinese Han population.
- Published
- 2013
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