检索结果-南通市图书馆

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

Zoological Research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan Dong Lixing Zhang Suling Liu Fudan University shanghai Cancer center&institutes of biomedical sciences/State Key Laboratory of Genetic Engineering/Cancer institutes/Department of Oncology/Key Laboratory of Breast Cancer in shanghai/shanghai Key Laboratory of Medical Epigenetics/shanghai Key Laboratory of Radiation Oncology/International Co-laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and *** cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and *** have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast *** tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ***,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer *** this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory ***,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during ***,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem Tumor microenvironment Mouse model

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

引用

Signal Transduction and Targeted Therapy 2024年第3期9卷 1209-1220页

作者： Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang Lu Linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei Luo Hao Lu Zilun Wei Jian Wu Peng Yu Li Shen Xiaochun Zhang Aijun Sun Junbo Ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key Laboratory of Cardiology Zhongshan HospitalFudan UniversityShanghaiChina Key Laboratory of Viral Heart Diseases National Health CommissionShanghaiChina Key Laboratory of Viral Heart Diseases Chinese Academy of Medical SciencesShanghaiChina National clinical Research center for Interventional Medicine ShanghaiChina Department of cardiac surgery Zhongshan HospitalFudan UniversityShanghaiChina institutes of biomedical sciences Fudan UniversityShanghaiChina shanghai Institute of Hypertension Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure *** TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 ***1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 ***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

关键词： TEAD1 expression Wnt4

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

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

引用

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

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Ischemia-reperfusion injury:molecular mechanisms and therapeutic targets

引用

Signal Transduction and Targeted Therapy 2024年第2期9卷 558-596页

作者： Meng Zhang Qian Liu Hui Meng Hongxia Duan Xin Liu Jian Wu Fei Gao Shijun Wang Rubin Tan Jinxiang Yuan The Collaborative Innovation center Jining Medical UniversityJiningShandong 272067China clinical Medical College Jining Medical UniversityJiningShandong 272067China Second clinical Medical College Jining Medical UniversityJiningShandong 272067China shanghai Institute of Cardiovascular Diseases Zhongshan Hospital and Institutes of Biomedical SciencesFudan UniversityShanghaiChina Institute of Zoology Chinese Academy of SciencesBeijingChina Department of Physiology Basic medical schoolXuzhou Medical UniversityXuzhou 221004China

Ischemia-reperfusion(I/R)injury paradoxically occurs during reperfusion following ischemia,exacerbating the initial tissue *** limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic *** Wnt signaling pathway exhibits extensive crosstalk with various other pathways,forming a network system of signaling pathways involved in I/R *** review article elucidates the underlying mechanisms involved in Wnt signaling,as well as the complex interplay between Wnt and other pathways,including Notch,phosphatidylinositol 3-kinase/protein kinase B,transforming growth factor-β,nuclear factor kappa,bone morphogenetic protein,N-methyl-D-aspartic acid receptor-Ca2+-Activin A,Hippo-Yes-associated protein,toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β,and hepatocyte growth factor/mesenchymal-epithelial transition *** particular,we delve into their respective contributions to key pathological processes,including apoptosis,the inflammatory response,oxidative stress,extracellular matrix remodeling,angiogenesis,cell hypertrophy,fibrosis,ferroptosis,neurogenesis,and blood-brain barrier damage during I/R *** comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery,while activation of the non-canonical Wnt pathways exacerbates ***,we explore novel therapeutic approaches based on these mechanistic findings,incorporating evidence from animal experiments,current standards,and clinical *** objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction,to facilitate the development of innovative therapeutic agents for I/R injury.

关键词： therapeutic reperfusion damage

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

引用

biomedical and Environmental sciences 2024年第2期37卷 170-177页

作者： GU Wen Fei SHI Xia MA Xin YU Jun Lei XU Jin Chuan QIAN Cheng Cheng HU Zhi Dong ZHANG Hui shanghai public health clinical center Fudan UniversityShanghai 201508China School of Laboratory Medicine and Life Science Wenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of Laboratory Medicine Zhejiang Putuo HospitalZhoushan 316100ZhejiangChina Zhongshan Hospital Fudan UniversityShanghai 200032China

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the shanghai public health clinical center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological *** assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),*** on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),*** examination showed the highest sensitivity but lowest ***,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of *** with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower *** combination of histopathology with Xpert showed the best performance characteristics.

关键词： Extrapulmonary tuberculosis Diagnosis Biopsy Histopathological examination Puncture samples

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Harnessing innate immune pathways for therapeutic advancement in cancer

引用

Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng Liao Hui Yang Ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of Medical Neurobiology and MOE Frontiers center for Brain Science and MOE Frontiers center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer *** pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal *** targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical ***,to date,the clinical success of drugs targeting the innate immune pathway remains ***,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor *** uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate *** this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell *** propose that within the TME,the innate immune pathway exhibits multidimensional *** diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling *** pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative *** our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases

引用

The Innovation 2024年第2期5卷 27-41页

作者： Zheyan Fang Gang Zhao Shuang Zhao Xueting Yu Runyang Feng You-en Zhang Haomin Li Lei Huang Zhenyang Guo Zhentao Zhang Mukaddas Abdurahman Hangnan Hong Peng Li Bing Wu Jinhang Zhu Xin Zhong Dong Huang Hao Lu Xin Zhao Zhaoyang Chen Wenbin Zhang Junjie Guo Hongchao Zheng Yue He Shengying Qin Haojie Lu Yun Zhao Xiangdong Wang Junbo Ge Hua Li Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032China Department of Cardiology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Medical Examination Shanghai Xuhui District Central HospitalShanghai 200031China Department of Cardiology and Institute of clinical Medicine Renmin HospitalHubei University of MedicineShiyan 442000China clinical Data center Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Molecular Celland Cancer BiologyUniversity of Massachusetts Chan Medical SchoolWorcesterMA 01605USA Bio-X Institute Key Laboratory for The Genetics of Developmental and Neuropsychiatric DisordersShanghai Jiao Tong UniversityShanghai 200030China Department of Cardiology Heart Center of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Department of Cardiology Sir Run Run Shaw Hospitalaffiliated with Zhejiang University School of MedicineHangzhou 310020China Department of Cardiology The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Cardiology Shanghai Xuhui District Central HospitalShanghai 200031China Department of Cardiology Shanghai Eighth People’s HospitalShanghai 200235China Department of Chemistry and institutes of biomedical sciences Fudan UniversityShanghai 200032China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China School of Life Science and Technology Shanghai Tech University100 Haike RoadShanghai 201210China Key Laboratory of Systems health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Pulmonary and Critical Care Medicine Zhongshan Hospital

Partial endothelial-to-mesenchymal transition(EndMT)is an intermediate phenotype observed in endothelial cells(ECs)undergoing a transition toward a mesenchymal state to support neovascularization during(patho)physiological ***,we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4(GTF2H4)as a positive regulator of this *** addition,we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3(ERCC3)to co-regulate partial ***,by using phosphorylation proteomics and site-directed mutagenesis,we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3(NCOA3)at serine 1330,which promoted the interaction between NCOA3 and p65,resulting in the transcriptional activation of NF-κB and the NF-kB/Snail signaling axis during partial *** vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic ***,our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

关键词： ischemic activation GTF

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Biomolecular condensates and disease pathogenesis

引用

Science China Life sciences 2024年第9期67卷 1792-1832页

作者： Ke Ruan Ge Bai Yanshan Fang Dan Li Tingting Li Xingguo Liu Boxun Lu Qing Lu Zhou Songyang Shuguo Sun Zheng Wang Xin Zhang Wen Zhou Hong Zhang Neurology Department at Huashan Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science School of Life Sciences Fudan University Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education Bio-X Institutes Shanghai Jiao Tong University State Key Laboratory of Biocontrol MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging Research School of Life Sciences Sun Yat-sen Memorial HospitalSun Yat-sen University Department of Human Anatomy Histology and Embryology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology The Second Affiliated Hospital School of Basic Medical Sciences Institute of Biomedical Innovation Jiangxi Medical College Nanchang University Westlake Laboratory of Life sciences and Biomedicine Department of Immunology and Microbiology School of Life Sciences Southern University of Science and Technology National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences College of Life sciences University of Chinese Academy of Sciences The First Affiliated Hospital & School of Life sciences Ministry of Education Key Laboratory for Membrane-less Organelles & Cellular Dynamics Hefei National Research Center for Interdisciplinary Sciences at the Microscale Center for Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Sciences and Medicine University of Science and Technology of China Nanhu Brain-computer Interface Institute Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Interdisciplinary Research center on Biology and Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences University of Chinese Academy of sciences Bio-X institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of

Biomolecular condensates or membraneless organelles(MLOs) formed by liquid-liquid phase separation(LLPS) divide intracellular spaces into discrete compartments for specific functions. Dysregulation of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration, tumorigenesis, and many other pathological processes. Herein, we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase separation. We then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders, hearing loss, cancers, and immunological diseases. Finally, we describe the emerging discovery of chemical modulators of phase separation.

关键词： liquid-liquid phase separation biomolecular condensate membraneless organelle

来源：

同方期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

2024 Adult Compendium of Physical Activities:A third update of the energy costs of human activities

引用

Journal of Sport and health Science 2024年第1期13卷 6-12页

作者： Stephen D.Herrmann Erik A.Willis Barbara E.Ainsworth Tiago V.Barreira Mary Hastert Chelsea L.Kracht John M.Schuna Jr. Zhenghui Cai Minghui Quan Catrine Tudor-Locke Melicia C.Whitt-Glover David R. Jacobs Jr. Kansas center for Metabolism and Obesity Research University of Kansas Medical CenterKansas CityKS 66160USA Division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA center for health Promotion and Disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA College of health Solutions Arizona State UniversityPhoenixAZ 85003USA School of Exercise and health Shanghai University of SportShanghai 200438China Exercise Science Department Syracuse UniversitySyracuseNY 13244USA clinical sciences Division Pennington Biomedical Research CenterBaton RougeLA 70808USA School of Exercise and Sport Science Oregon State UniversityCorvallisOR 97331USA College of health and Human Services University of North Carolina at CharlotteCharlotteNC 28223USA Gramercy Research Group KnightdaleNC 27545USA Division of Epidemiology and Community health School of Public HealthUniversity of MinnesotaMinneapolisMN 55454USA

Background:The Compendium of Physical Activities was published in 1993 to improve the comparability of energy expenditure values assigned to self-reported physical activity(PA)across *** original version was updated in 2000,and again in 2011,and has been widely used to support PA research,practice,and public health ***:This 2024 update was tailored for adults 19-59 years of age by removing data from those≥60 *** a systematic review and supplementary searches,we identified new activities and their associated measured metabolic equivalent(MET)values(using indirect calorimetry)published since *** replaced estimated METs with measured values when ***:We screened 32,173 abstracts and 1507 full-text papers and extracted 2356 PA energy expenditure values from 701 *** added303 new PAs and adjusted 176 existing MET values and descriptions to reflect the addition of new data and removal of METs for older *** added a Major Heading(Video Games).The 2024 Adult Compendium includes 1114 PAs(912 with measured and 202 with estimated values)across 22 Major ***:This comprehensive update and refinement led to the creation of The 2024 Adult Compendium,which has utility across research,public health,education,and healthcare domains,as well as in the development of consumer health *** new website with the complete lists of PAs and supporting resources is available at https://***.

关键词： Adults Energy expenditure Exercise MET Physical Activities

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Biallelic variants in RBM42 cause a multisystem disorder with neurological,facial,cardiac,and musculoskeletal involvement

引用

Protein & Cell 2024年第1期15卷 52-68页

作者： Yiyao Chen Bingxin Yang Xiaoyu Merlin Zhang Songchang Chen Minhui Wang Liya Hu Nina Pan Shuyuan Li Weihui Shi Zhenhua Yang Li Wang Yajing Tan Jian Wang Yanlin Wang Qinghe Xing Zhonghua Ma Jinsong Li He-Feng Huang Jinglan Zhang Chenming Xu institutes of biomedical sciences Fudan UniversityShanghai 200032China bstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China Intermational Peace Matermity and Child health Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200030China shanghai Key Laboratory of Embryo Original Diseases Shanghai 200030China State Key Laboratory of Cell Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China State Key Laboratory of Rice Biology the Key Laboratory of Molecular Biology of Crop Pathogens and InsectsInstitute of BiotechnologyZhejiang UniversityHangzhou 310058China Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of MedicineHoustonTX 77030USA Children's hospital of Fudan University Shanghai 201102China School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024ZhejiangChina Research Units of Embryo Original Diseases Chinese Academy of Medical Sciences(No.2019RU056)Shanghai 200011China

Here,we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 *** patient is a 2-year-old female with severe central nervous system(CNs)abnormalities,hypotonia,hearing loss,congenital heart defects,and dysmorphic facial *** whole-exome sequencing(WEs)reveals that the patient has two compound heterozygous variants,c.304C>T(p.R102*)and c.1312G>A(p.A438T),in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein *** p.A438T variant is in the RRM domain which impairs RBM42 pro-tein stability in ***,p.A438T disrupts the interaction of RBM42 with hnRNP K,which is the causa-tive gene for Au-Kline syndrome with overlapping disease characteristics seen in the index *** human R102*or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout△FgRbp1 in Fusarium while it was rescued by the wild-type(WT)human RBM42.A mouse model carying Rbm42 compound heterozygous variants,c.280C>T(p.Q94*)and c.1306_1308delinsACA(p.A436T),demonstrated gross fetal develop-mental defects and most of the double mutant animals died by ***-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing(As).Overall,we present clinical,genetic,and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

关键词： RBM42 gene RNA-binding protein neurodevelopmental disorder Au-Kline syndrome alternative splicing

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：