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Novel heterozygous USH1C mutation impacts hair cell mechanotransduction and causes progressive hearing loss

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Science Bulletin 2024年第2期69卷 167-172页

作者： Yanyan Jia Gaogan Jia Luo Guo Nan Song Yu-Meng Wang Luoying Jiang Yilai Shu Yan Chen Shujia Zhu Huawei Li Wenyan Li ENT Institute and Otorhinolaryngology Department of Eye&ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China institutes of Biomedical sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of Hearing Medicine(Fudan University) Shanghai 200031China The institutes of brain Science and the Collaborative Innovation Center for brain Science Fudan UniversityShanghai 200032China Shanghai Center for brain Science and brain-Inspired Intelligence Technology Shanghai 201210China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Department of Cardiology and Institute for Developmental and Regenerative Cardiovascular MedicineXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200092China

Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.

关键词： mec hearing approximate

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National Science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao Zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu Pengcheng Zhou Guo-Qiang Bi Institute of Artiflcial Intelligence Hefei Comprehensive National Science Center Department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Faculty of Life and Health sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of Life sciences University of Science and Technology of China Institute of Semiconductors Chinese Academy of Sciences Department of Modern Life sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong Institute of brain Science-Shenzhen Fundamental Research Institutions Suzhou Institute for Advanced Research University of Science and Technology of China

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment.Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice.Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

Prediction of cell-cell communication patierns of dorsal root ganglion cells: single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna Lian Cheng Wu Li Liu Xiangyao Li National Health Commission and Chinese Academy of Medical sciences Key Laboratory of Medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration School of Brain Science and Brain Medicine Zhejiang University International institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University-University of Edinburgh Institute Zhejiang University School of Medicine Zhejiang University 4. Biomedical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh Core Facilities of the School of Medicine Zhejiang University

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing(scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

Comparative transcriptome analysis between rhesus macaques(Macaca mulatta) and crab-eating macaques(M. fascicularis)

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Zoological Research 2024年第2期45卷 299-310页

作者： Yu-Xiang Mao Yamei Li Zikun Yang Ning Xu Shilong Zhang Xuankai Wang Xiangyu Yang Qiang Sun Yafei Mao Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science&Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai Center for brain Science and brain-Inspired Intelligence Technology Shanghai 201210China University of Chinese Academy of sciences Beijing 100049China Key Laboratory of Genetic Evolution&Animal Models Chinese Academy of SciencesKunmingYunnan 650201China Bio-X institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200030China Zhiyuan College Shanghai Jiao Tong UniversityShanghai 200240China Center for Genomic Research International Institutes of MedicineFourth Affiliated HospitalZhejiang UniversityYiwuZhejiang 322000China

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

关键词： Crab-eating macaques Rhesus macaques Comparative transcriptomics Biomedical models Nonhuman primates RNA-seq Duplicated genes

Structures and ion transport mechanisms of plant high-affinity potassium transporters

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Molecular Plant 2024年第3期17卷 409-422页

作者： Jiangqin Wang Yanping Luo Fan Ye Zhong Jie Ding Shao Jian Zheng Shuai Qiao Yong Wang Jiangtao Guo Wei Yang Nannan Su international institutes of Medicine the Fourth Affiliated HospitalZhejang University School of MedicineYiwuZhejiang 322000China Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital Zhejiang University School of MedicineHangzhouZhejang 310058China State Key Laboratory of Plant Environmental Resilience College of Life SciencesZhejang UniversityHangzhouZhejang 310058China College of Life sciences Zhejiang UniversityHangzhouZhejiang 310058China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Science and Brain-machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310058China Nanhu brain-computer Interface Institute Hangzhou.Zheiang 311100.China

Plant high-affinity K^(+) transporters(HKTs)mediate Na^(+) and K^(+) uptake,maintain Na^(+)/K^(+) homeostasis,and therefore play crucial roles in plant salt tolerance.In this study,we present cryoelectron microscopy structures of HKTs from two classes,classI HKT1;1 from Arabidopsis thaliana(AtHKT1;1)and class II HKT2;1 from Triticum aestivum(TaHKT2;1),in both Na^(+) -and K^(+) -bound states at 2.6-to 3.0-A resolutions.BothAtHKT1;1and TaHKT2;1function ashomodimers.Each HKT subunit consists of four tan-dem domain units(D1-D4)with a repeated K^(+) -channel-like M-P-M topology.In each subunit,D1-D4 assemble into an ion conduction pore with a pseudo-four-fold symmetry.Although both TaHKT2;1and AtHKT1;1 have only one putative Na^(+) ion bound in the selectivity filter with a similar coordination pattern,the two HKTs display different K^(+) binding modes in the filter.TaHKT2;1 has three K^(+) ions bound in the selec-tivity filter,but AtHKT1;1 has only two K^(+) ions bound in the filter,which has a narrowed external entrance due to the presence of a Ser residue in the first filter motif.These structures,along with compu-tational,mutational,and electrophysiological analyses,enable us to pinpoint key residues that are critical for the ion selectivity of HKTs.The findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.

关键词： HKTs structure ion selectivity mechanism salt tolerance

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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World Journal of Clinical Cases 2024年第3期12卷 474-478页

作者： Yusuf Tutar Department of Basic Pharmaceutical sciences Faculty of PharmacyDivision of BiochemistryUniversity of Health SciencesIstanbul 34668Turkey Health sciences Faculty Recep Tayyip Erdogan UniversityRize 53350Turkey Molecular Oncology Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey Molecular Medicine Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weig

关键词： Network pharmacology Metabologenomics Genome Pathways Cancer

Nuclear phylogenomics of angiosperms and insights into their relationships and evolution

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Journal of Integrative Plant Biology 2024年第3期66卷 546-578页

作者： Guojin Zhang Hong Ma College of Life sciences Hunan Normal UniversityChangsha 410081China Department of Biology 510 Mueller LaboratoryHuck Institutes of the Life SciencesThe Pennsylvania State UniversityUniversity ParkPA 16802USA

Angiosperms(flowering plants) are by far the most diverse land plant group with over 300,000 species. The sudden appearance of diverse angiosperms in the fossil record was referred to by Darwin as the “abominable mystery,”hence contributing to the heightened interest in angiosperm evolution. Angiosperms display wide ranges of morphological, physiological,and ecological characters, some of which have probably influenced their species richness. The evolutionary analyses of these characteristics help to address questions of angiosperm diversification and require well resolved phylogeny. Following the great successes of phylogenetic analyses using plastid sequences,dozens to thousands of nuclear genes from next-generation sequencing have been used in angiosperm phylogenomic analyses, providing well resolved phylogenies and new insights into the evolution of angiosperms. In this review we focus on recent nuclear phylogenomic analyses of large angiosperm clades, orders, families,and subdivisions of some families and provide a summarized Nuclear Phylogenetic Tree of Angiosperm Families. The newly established nuclear phylogenetic relationships are highlighted and compared with previous phylogenetic results. The sequenced genomes of Amborella,Nymphaea, Chloranthus, Ceratophyllum, and species of monocots, Magnoliids, and basal eudicots, have facilitated the phylogenomics of relationships among five major angiosperms clades. All but one of the 64 angiosperm orders were included in nuclear phylogenomics with well resolved relationships except the placements of several orders. Most families have been included with robust and highly supported placements, especially for relationships within several large and important orders and families.Additionally, we examine the divergence time estimation and biogeographic analyses of angiosperm on the basis of the nuclear phylogenomic frameworks and discuss the differences compared with previous analyses. Furthermore,we discuss the implications of nuclear phylogenomic analyses on ancestral

关键词： angiosperms evolution flowering plants nuclear gene phylogenomics phylogeny

Vision-based docking system for an aromatic-hydrocarbon-inspired reconfigurable robot

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Science China Technological sciences 2024年第6期67卷 1798-1816页

作者： XING FangYi XU Cheng LIU JinGuo XUE ZhiHui State Key Laboratory of Robotics Shenyang Institute of AutomationChinese Academy of Sciences School of Automation and Electrical Engineering Shenyang Ligong University institutes for Robotics and Intelligent Manufacturing Chinese Academy of Sciences University of Chinese Academy of sciences

Aromatic hydrocarbons generally refer to compounds containing benzene rings. Many types of isomers can be formed by replacing hydrogen atoms on the benzene ring. In this paper, an aromatic-hydrocarbon-inspired modular robot(AHIMR) is proposed.The robot can be reassembled into different configurations suitable for various task requirements. A vision-based docking system is designed for the AHIMR. The system primarily consists of two stages: a remote guidance stage and a precise docking stage.During the remote guidance stage, an object module is identified using an illumination adaptive target recognition algorithm,and then the active module moves to the docking area through communication with ZigBee. In the precise docking stage, the active module calculates the relative pose with the object module using a perspective-n-point method and dynamically adjusts its posture to dock. In this process, a Kalman filter is used to reduce target occlusion and jitter interference. In addition, the docking system feasibility is verified via several simulation experiments. The module docking accuracy is controlled within 0.01 m, which meets the reconfiguration task requirements of the AHIMR. In the AHIMR submodule docking experiment, the active module accurately moves to the expected position with a docking success rate of 95%.

关键词： modular robot reconfiguration aromatic hydrocarbon autonomous docking visual identification

RACK1A promotes hypocotyl elongation by scaffolding light signaling components in Arabidopsis

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Journal of Integrative Plant Biology 2024年第5期66卷 956-972页

作者： Yajuan Fu Wei Zhu Yeling Zhou Yujing Su Zhiyong Li Dayan Zhang Dong Zhang Jinyu Shen Jiansheng Liang Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education institutes Department of BiologySchool of Life SciencesInstitute of Plant and Food SciencesSouthern University of Science and TechnologyShenzhen 518055China

Plants deploy versatile scaffold proteins to intricately modulate complex cell signaling.Among these,RACK1A(Receptors for Activated C Kinase 1A)stands out as a multifaceted scaffold protein functioning as a central integrative hub for diverse signaling pathways.However,the precise mechanisms by which RACK1A orchestrates signal transduction to optimize seedling development remain largely unclear.Here,we demonstrate that RACK1A facilitates hypocotyl elongation by functioning as a flexible platform that connects multiple key components of light signaling pathways.RACK1A interacts with PHYTOCHROME INTERACTING FACTOR(PIF)3,enhances PIF3 binding to the promoter of BBX11 and down-regulates its transcription.Furthermore,RACK1A associates with ELONGATED HYPOCOTYL 5(HY5)to repress HY5 biochemical activity toward target genes,ultimately contributing to hypocotyl elongation.In darkness,RACK1A is targeted by CONSTITUTIVELY PHOTOMORPHOGENIC(COP)1 upon phosphorylation and subjected to COP1-mediated degradation via the 26 S proteasome system.Our findings provide new insights into how plants utilize scaffold proteins to regulate hypocotyl elongation,ensuring proper skoto-and photo-morphogenic development.

关键词： Arabidopsis hypocotyl development light signaling components RACK1 scaffoldprotein