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Research on nonlinear error compensation method for interferometers based on tracker

Journal of Information and Computational Science 2013年第11期10卷 3285-3294页

作者： zhao, suwen Zhu, Shaolan Wen, Desheng Xi'an Institute of Optics and Precision Mechanics Chinese Academy of Science Xi'an 710119 China Graduate School of the Chinese Academy of Sciences Beijing 100039 China

A dynamic nonlinear error compensation method for the interferometers is proposed to meet the design demands of the tracker. It makes the system reach high precise measurement when the target is moving with high speed. With the passive compensation method of the optical path, part of the errors are eliminated. Thus, the periods of the signals could be counted accurately. A dynamic compensation method is proposed for the displacement in less than one period. By tracking the peak values and valley values of the interference signals in one cycle, the zero offsets error and unequal amplitude error can be compensated;then the quadrature phase shift error could be compensated by tracking the intersection of the two compensated signals. By tracking the signals and renewing the compensation parameters, the signals even with random nonlinear errors can get high-precision subdivision. Experiment results show that the system can get nanometer accuracy even the target is moving at high velocity. The system has better adaptability to different environment and anti-jamming capability. © 2013 Binary Information Press.

关键词： Interferometers

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噬菌体Z基因组生物合成通路的研究进展

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遗传 2023年第10期45卷 887-903页

作者：陈荟玉赵素文上海科技大学iHuman研究所与生命科学与技术学院上海201210

噬菌体基因组中存在丰富的碱基修饰,主要用于逃避宿主内切酶的切割。40多年前,在蓝藻噬菌体S-2L的DNA中,研究者发现2-氨基腺嘌呤(Z)完全取代腺嘌呤(A),与胸腺嘧啶(T)形成具有三根氢键的互补配对,形成了特殊的Z基因组。近年来,研究者在... 详细信息

噬菌体基因组中存在丰富的碱基修饰,主要用于逃避宿主内切酶的切割。40多年前,在蓝藻噬菌体S-2L的DNA中,研究者发现2-氨基腺嘌呤(Z)完全取代腺嘌呤(A),与胸腺嘧啶(T)形成具有三根氢键的互补配对,形成了特殊的Z基因组。近年来,研究者在多个噬菌体中发现并证实了噬菌体Z基因组生物合成通路。该通路是一个多酶系统,其中包含由噬菌体DNA编码的2-氨基脱氧腺苷琥珀酸合成酶(PurZ)、脱氧腺苷三磷酸水解酶(dATPase/DatZ)、脱氧腺苷/脱氧鸟苷三磷酸的焦磷酸水解酶(DUF550/MazZ)和DNA聚合酶(DpoZ)。本文在简述噬菌体中各种修饰核苷发现历史的基础上,详细介绍了Z基因组生物合成通路中多种酶的研究进展,最后对Z基因组及其合成通路中多种酶的应用进行了展望,以期为该领域的研究提供借鉴和参考。

关键词： Z基因组噬菌体 DNA修饰 2-氨基腺嘌呤生物合成通路

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Association analysis between novel variants in LEPR gene and litter size in Mongolia and ujimqin sheep breeds

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THERIOGENOLOGY 2022年 183卷 79-89页

作者： Ma, Shujiao Ji, Xuewen Cang, Ming Wang, Jianguo Yu, Haiquan Liu, Yongbin Zhang, Wenguang Wu, Yiran zhao, suwen Cao, Guifang Tong, Bin Inner Mongolia Univ Sch Life Sci State Key Lab Reprod Regulat & Breeding Grassland Hohhot Peoples R China Inner Mongolia Acad Agr & Anim Husb Sci Inst Anim Sci Hohhot Peoples R China Inner Mongolia Agr Univ Coll Anim Sci Hohhot Peoples R China ShanghaiTech Univ Sch Life Sci & Technol iHuman Inst Shanghai Peoples R China Inner Mongolia Agr Univ Dept Vet Hohhot Peoples R China

Prolificacy is an important trait of livestock, especially for species with multiple births, such as sheep. The leptin receptor (LEPR) is considered as a major candidate gene that affects the reproductive traits of sheep. The known R62H mutation in the LEPR gene is associated with the hyperprolific phenotype of Davisdale sheep. However, studies identifying novel variations and seeking breed-specific markers associated with litter size in other sheep breeds are rare. In this study, we sequenced all coding regions of the LEPR gene of Mongolia sheep, and nine novel variants of the LEPR gene were detected by direct sequencing. Among them, the synonymous c.240C > T and c.279C > T mutations were significantly associated with the litter sizes of Mongolia ewes (P < 0.05 and P < 0.01, respectively) and Ujimqin ewes (P < 0.05 and P < 0.01, respectively). The silent c.240C > T and c.279C > T mutations are predicted to change the stability of the mRNA secondary structure by reducing the minimum free energy and are predicted to change the mRNA secondary structure of LEPR. Our findings may provide potentially useful genetic markers for increasing litter size in sheep. (c) 2022 Elsevier Inc. All rights reserved.

关键词： Association LEPR Litter size Novel mutation Mongolia sheep Ujimqin sheep

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Disulfide-Containing Detergents (DCDs) for the Structural Biology of Membrane Proteins

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CHEMISTRY-A EUROPEAN JOURNAL 2019年第50期25卷 11635-11640页

作者： Xue, Dongxiang Xu, Tiandan Wang, Huixia Wu, Meng Yuan, Ya Wang, Wei Tan, Qiwen zhao, Fei Zhou, Fang Hu, Tao Jiang, Zhongxing Liu, Zhi-Jie zhao, suwen Liu, Dongsheng Wuthrich, Kurt Tao, Houchao ShanghaiTech Univ iHuman Inst Ren Bldg393 Middle Huaxia Rd Shanghai 201210 Peoples R China Chinese Acad Sci Shanghai Inst Mat Med 555 Zuchongzhi Rd Shanghai 201203 Peoples R China Univ Chinese Acad Sci 19A Yuquan Rd Beijing 100049 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Chinese Acad Sci CAS Ctr Excellence Mol Cell Sci Shanghai Inst Biochem & Cell Biol Shanghai 200031 Peoples R China Wuhan Univ Hubei Prov Engn & Technol Res Ctr Fluorinated Pha Sch Pharmaceut Sci Wuhan 430071 Hubei Peoples R China

Disulfide-containing detergents (DCDs) are introduced, which contain a disulfide bond in the hydrophobic tail. DCDs form smaller micelles than corresponding detergents with linear hydrocarbon chains, while providing good solubilization and reconstitution of membrane proteins. The use of this new class of detergents in structural biology is illustrated with solution NMR spectra of the human G protein-coupled receptor A(2A)AR, which is an alpha-helical protein, and the beta-barrel protein OmpX from E. coli.

关键词： detergents disulfides membrane proteins micelle size NMR spectroscopy

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Delineating, Imaging, and Assessing Pulmonary Fibrosis Remodeling via Collagen Hybridization

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ACS NANO 2024年第41期18卷 27997-28011页

作者： zhao, Jie Yu, Wenjun Zhou, Daoning Liu, Yinghua Wei, Jingyue Bi, Lei zhao, suwen He, Jianzhong Liu, Jing Su, Jin Jin, Hongjun Liu, Ye Shan, Hong Li, Man Zhang, Yaqin Li, Yang Sun Yat Sen Univ Guangdong Hong Kong Macao Univ Joint Lab Intervent Affiliated Hosp 5 Guangdong Prov Engn Res Ctr Mol Imaging Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Radiol Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Biobank Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Informat Technol Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Data Ctr Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Pathol Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Pulm & Crit Care Med Zhuhai 519000 Peoples R China Guangzhou Med Univ Affiliated Hosp 1 Guangzhou Inst Resp Hlth State Key Lab Resp DisNatl Clin Res Ctr Resp Dis Guangzhou 510000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Intervent Med Zhuhai 519000 Peoples R China

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening disease with no early detection, few treatments, and dismal outcomes. Although collagen overdeposition is a hallmark of lung fibrosis, current research mostly focuses on the cellular aspect, leaving collagen, particularly its dynamic remodeling (i.e., degradation and turnover), largely unexplored. Here, using a collagen hybridizing peptide (CHP) that specifically binds unfolded collagen chains, we reveal vast collagen denaturation in human IPF lungs and delineate the spatiotemporal progression of collagen denaturation three-dimensionally within fibrotic lungs in mice. Transcriptomic analyses support that lung collagen denaturation is strongly associated with up-regulated collagen catabolism in mice and patients. We thus show that CHP probing differentiates remodeling responses to antifibrotics and highlights the resolution of established fibrosis by agents up-regulating collagen catabolism. We further develop a radioactive CHP that detects fibrosis in vivo in mice as early as 7 days postlung-injury (Ashcroft score: 2-3) by positron emission tomography (PET) imaging and ex vivo in clinical lung specimens. These findings establish collagen denaturation as a promising marker of fibrotic remodeling for the investigation, diagnosis, and therapeutic development of pulmonary fibrosis.

关键词： pulmonary fibrosis extracellular matrix remodeling positron emission tomography imaging collagen catabolism transcriptomic analysis therapeutic assessment light sheet fluorescence microscopy

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Structure-Activity Relationship Studies of Hydantoin-Cored Ligands for Smoothened Receptor

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CHEMISTRYOPEN 2021年第10期10卷 1028-1032页

作者： Liu, Yang Zhou, Fang Ding, Kang Xue, Dongxiang Zhu, Zhihao Li, Cuixia Li, Fei Xu, Yueming Xu, Fei Le, Zhiping zhao, suwen Tao, Houchao ShanghaiTech Univ iHuman Inst 393 Middle Huaxia Rd Shanghai 201210 Peoples R China Nanchang Univ Dept Chem 999 Xuefu Ave Nanchang 330031 Jiangxi Peoples R China ShanghaiTech Univ Sch Life Sci & Technol 393 Middle Huaxia Rd Shanghai 201210 Peoples R China

An underside binding site was recently identified in the transmembrane domain of smoothened receptor (SMO). Herein, we report efforts in the exploration of new insights into the interactions between the ligand and SMO. The hydantoin core in the middle of the parent compound was found to be highly conservative in chirality, ring size, and substituents. On each benzene at two ends, a plethora of variations, particularly halogen substitutions, were introduced and investigated. Analysis of the structure-activity relationship revealed miscellaneous halogen effects. The ligands with double halogen substituents exhibit remarkably enhanced potency, providing promising candidates that potentially overcome the common drug resistance and useful heavy-atom labeled chemical tools for co-crystallization studies of SMO.

关键词： anti-cancer halogen bonding molecular dynamics smoothened receptor structural biology

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Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement

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JOURNAL OF MEDICINAL CHEMISTRY 2021年第18期64卷 13830-13840页

作者： zhao, Fei Wu, Yiran Zhou, Fang Xue, Dongxiang zhao, Simeng Lu, Wanglong Liu, Xiaoyan Hu, Tao Qiu, Yanli Li, Rongyan Gu, Tangjie Xu, Yueming Xu, Fei Zhong, Guisheng Jiang, Zhongxing zhao, suwen Tao, Houchao ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China Wuhan Univ Sch Pharmaceut Sci Wuhan 430071 Hubei Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Phys Sci & Technol Shanghai 201210 Peoples R China

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven alpha-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.

关键词： Soil organic matter Ligands Cholesterol Conformation Conjugate acid-base pairs

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The structural study of mutation-induced inactivation of human muscarinic receptor M4

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IUCRJ 2020年第2期7卷 294-305页

作者： Wang, Jingjing Wu, Meng Wu, Lijie Xu, Yueming Li, Fei Wu, Yiran Popov, Petr Wang, Lin Bai, Fang zhao, suwen Liu, Zhi-Jie Hua, Tian ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Chinese Acad Sci CAS Ctr Excellence Mol Cell Sci Shanghai Inst Biochem & Cell Biol Shanghai Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Skolkovo Inst Sci & Technol Moscow Russia ShanghaiTech Univ Shanghai Inst Adv Immunochem Studies Shanghai 201210 Peoples R China

Human muscarinic receptor M4 belongs to the class A subfamily of the G-protein-coupled receptors (GPCRs). M4 has emerged as an attractive drug target for the treatment of Alzheimer's disease and schizophrenia. Recent results showed that M4-mediated cholinergic transmission is related to motor symptoms in Parkinson's disease. Selective ligand design for the five muscarinic acetylcholine receptor (mAchR) subtypes currently remains challenging owing to the high sequence and structural similarity of their orthosteric binding pockets. In order to obtain M4-selective antagonists, a new approach was tried to lock M4 into an inactive form by rationally designing an N449(7.49)R mutation, which mimics the allosteric sodium binding in the conserved sodium site usually found in class A GPCRs. In addition, the crystal structure of the mutation-induced inactive M4 was determined. By comparative analysis with other mAchR structures, followed by functional assays, the N449(7.49)R mutation was shown to stabilize M4 into an inactive state. Virtual screening of a focused ligand library using the crystal structure showed that the inactive M4 prefers antagonists much more than agonists. This study provides a powerful mutation strategy to stabilize GPCRs in inactive states and facilitate their structure determination.

关键词： muscarinic acetylcholine receptors G-protein-coupled receptors M4 mutation design ligand screening Parkinson's disease Alzheimer's disease GPCRs

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Cryo-EM structure of Z-genome phage and ZTCG DNA

Cryo-EM structure of Z-genome phage and ZTCG DNA

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第二十次中国暨国际生物物理大会

作者： Jing Lin suwen zhao iHuman Institute ShanghaiTech University School of Life Science and Technology ShanghaiTech University

2-aminoadenine (Z) fully replaces adenine in the genomes of hundreds of bacteriophages. It is known that Z genome DNA (ZTCG DNA) has different physical, chemical and mechanical properties since Z pairs with T through three hydrogen bonds. However, the structural details behind the special properties of Z-genome phage and ZTCG DNA remain elusive. Here, we present cryo-EM structures of Z-genome phage SH-Ab 15497, including its capsid, portal, major tail protein and the ZTCG DNA located within the portal.

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A Novel G Protein-Biased and Subtype-Selective Agonist for a G Protein-Coupled Receptor Discovered from Screening Herbal Extracts

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ACS CENTRAL SCIENCE 2020年第2期6卷 213-225页

作者： Zhang, Bingjie zhao, Simeng Yang, Dehua Wu, Yiran Xin, Ye Cao, Haijie Huang, Xi-Ping Cai, Xiaoqing Sun, Wen Ye, Na Xu, Yueming Peng, Yao zhao, suwen Liu, Zhi-Jie Zhong, Guisheng Wang, Ming-Wei Shui, Wenqing ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Chinese Acad Sci Natl Ctr Drug Screening Shanghai 201203 Peoples R China Chinese Acad Sci Shanghai Inst Mat Med CAS Key Lab Receptor Res Shanghai 201203 Peoples R China Univ N Carolina Dept Pharmacol NIMH Psychoact Drug Screening Program Sch Med Chapel Hill NC 27599 USA Univ Chinese Acad Sci Beijing 100049 Peoples R China Soochow Univ Jiangsu Key Lab Neuropsychiat Dis Suzhou 215123 Peoples R China Soochow Univ Coll Pharmaceut Sci Suzhou 215123 Peoples R China

Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal extracts to identify active ligands of a GPCR, the 5-HT2C receptor. Using this method, we discovered a naturally occurring aporphine 1857 that displayed strong selectivity for activating 5-HT2C without activating the 5-HT2A or 5-HT2B receptors. Remarkably, this novel ligand exhibited exclusive bias toward G protein signaling for which key residues were identified, and it showed comparable in vivo efficacy for food intake suppression and weight loss as the antiobesity drug, lorcaserin. Our study establishes an efficient approach to discovering novel GPCR ligands by exploring the largely untapped chemical space of natural products.

关键词： Agonists Ligands Genetics Assays Receptors

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