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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of molecular cell biology Sungkyunkwan University School of MedicineSuwonKorea Single cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms

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Journal of molecular cell biology 2024年第1期16卷 15-28页

作者： Te Li Min Liu Fan Yu Song Yang Weiwen Bu Kai Liu Jia Yang Hua Ni Mulin Yang Hanxiao Yin Renjie Hong Dengwen Li Huĳie Zhao Jun Zhou Haihe Laboratory of cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Protein ScienceCollege of Life SciencesNankai UniversityTianjin 300071China Laboratory of Tissue Homeostasis Haihe Laboratory of Cell EcosystemTianjin 300462China Center for cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongShandong Provincial Key Laboratory of Animal Resistance BiologyCollege of Life SciencesShandong Normal UniversityJinan 250014China

Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan ***,the mechanistic link of cilia to CMD complications is still poorly ***,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar ***,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl *** studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium *** vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm *** findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.

关键词： carbohydrate metabolism disorder aldose aldehyde cilium disassembly formyl group calcium influx HDAC6

Revealing Tissue Heterogeneity and Spatial Dark Genes from Spatially Resolved Transcriptomics by Multiview Graph Networks

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Research 2024年第2期6卷 629-645页

作者： Ying Li Yuejing Lu Chen Kang Peiluan Li Luonan Chen School of Mathematics and Statistics Henan University of Science and TechnologyLuoyang471023China Longmen Laboratory LuoyangHenan471003China Key Laboratory of Systems biology Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai201100China Key Laboratory of Systems Health Science of Zhejang Province Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou310000China School of Life Science and Technology ShanghaiTech UniversityShanghai201100.China

Spatially resolved transcriptomics(SRT)is capable of comprehensively characterizing gene expression patterns and providing an unbiased image of spatial *** fully understand the organizational complexity and tumor immune escape mechanism,we propose stMGATF,a multiview graph attention fusion model that integrates gene expression,histological images,spatial location,and gene *** better extract information,stMGATF exploits SimCLRv2 for visual feature exaction and employs edge feature enhanced graph attention networks for the learning potential embedding of each view.A global attention mechanism is used to adaptively integrate 3 views to obtain low-dimensional *** to diverse SRT datasets,stMGATF is robust and outperforms other methods in detecting spatial domains and denoising data even with different resolutions and *** particular,stMGATF contributes to the elucidation of tissue heterogeneity and extraction of 3-dimensional expression ***,considering the associations between genes in tumors,stMGATF can identify the spatial dark genes ignored by traditional methods,which can be used to predict tumor-driving transcription factors and reveal tumor immune escape mechanisms,providing theoretical evidence for the development of new immunotherapeutic strategies.

关键词： Spatial integrate driving

Regulation of aging by NELF-A and RNA polymerase Ⅱ elongation

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Neural Regeneration Research 2024年第7期19卷 1415-1416页

作者： Chin-Tong Ong Zhen-Kai Ngian Temasek Life Sciences Laboratory and Department of Biological Sciences National University of SingaporeSingaporeSingapore Department of Genetics Harvard Medical SchoolBostonMAUSA Institute of molecular and cell biology Agency for ScienceTechnology and ResearchSingaporeSingapore

Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and *** in different animal models have l... 详细信息

关键词： aging twelve integrity

A CRISPR/RfxC as13d-mediated strategy for efficient RNA knockdown in mouse embryonic development

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Science China Life Sciences 2024年

作者： Lin Zhang Shi-Meng Cao Hao Wu Meng Yan Jinsong Li Ling-Ling Chen State Key Laboratory of cell biology Shanghai Key Laboratory of Molecular Andrology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory of RNA Innovation Science and Engineering CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology University of Chinese Academy of Sciences Chinese Academy of Sciences Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences School of Life Science and Technology ShanghaiTech University New Cornerstone Science Laboratory Shenzhen

The growing variety of RNA classes, such as mRNAs, lncRNAs, and circRNAs, plays pivotal roles in both developmental processes and various pathophysiological conditions. Nonetheless, our comprehension of RNA functions in live organisms remains limited due to the absence of durable and effective strategies for directly influencing RNA levels. In this study, we combined the CRISPR-RfxCas13d system with spermlike stem cell-mediated semi-cloning techniques, which enabled the suppressed expression of different RNA species. This approach was employed to interfere with the expression of three types of RNA molecules: Sfmbt2 mRNA, Fendrr lncRNA, and circMan1a2(2,3,4,5,6). The results confirmed the critical roles of these RNAs in embryonic development, as their loss led to observable phenotypes, including embryonic lethality, delayed embryonic development, and embryo resorption. In summary, our methodology offers a potent toolkit for silencing specific RNA targets in living organisms without introducing genetic alterations.

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Targeted nanopore sequencing for the identification of novel PRMT1 circRNAs unveils a diverse transcriptional profile of this gene in breast cancer cells

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Genes & Diseases 2024年第2期11卷 589-592页

作者： Maria Papatsirou Andreas Scorilas Diamantis C.Sideris Christos K.Kontos Department of Biochemistry and molecular biology National and Kapodistrian University of AthensPanepistimiopolisAthens GR 15701Greece

Long-read sequencing with nanopore technology has been widely utilized for the identification of the full-length sequence of RNA molecules."It is especially suitable for the identification of circular RNAs(circRNAs),which are regulatory molecules that are regarded as promising non-invasive biomarkers for various human malignancies,including breast cancer.2 The impact of circRNAs derived from the protein arginine methyltransferase 1(PRMT1)gene has not been clarified yet,even though the effect of PRMT1-mediated methylation on breast cancer cell characteristics has been well established.

关键词： PRMT1 breast cancer

BFP1:One of 700 Arabidopsis F-box proteins mediates degradation of JA oxidases to promote plant immunity

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molecular Plant 2024年第3期17卷 375-376页

作者： Claus Wasternack Bettina Hause Department of molecular Signal Processing Leibniz Institute of Plant Biochemistry7 Weinberg 306120 Halle(Saale)Germany Department of cell and Metabolic biology Leibniz Institute of Plant Biochemistry06120 Halle(Saale)Germany

A switch off in jasmonate(JA)signaling by hydroxylation upon wounding was described in 2008(Miersch et al.,2008).This initiated the cloning of CYP450 enzymes involved in hydroxylation and carboxylation of JA and its amino acid conjugate JA-le,the most active form of JA compounds(reviewed by Wasternack and Feussner[2018]and Heitz et al.[2019]).Due to the central role of JA and JA-lle in plant stress responses and development(Wasternack and Hause,2013),catabolism of JA and its derivatives is an essential component in the sustainment of homeostasis of active JA compounds(Howe et al.,2018;Heitz et al.,2019).Catabolism of JA and JAIle takes place by JA-induced oxygenases(JOXs),also named JA-oxidases(JAOs),and by hydroxylation(CYP94B3/B1)followed by carboxylation(CYP94C1),respectively(Heitz et al.,2019).Another reaction performed by IAR3/ILL6 results in the deconjugation of JA-lle and 12-OH-JA-le to JA and 12-OH-JA,respectively(Heitz et al.,2019;Wasternack and Feussner,2018).

关键词： conjugate initiated media

Identification and functional characterization of fish IL‑17 receptors suggest important roles in the response to nodavirus infection

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Marine Life Science & Technology 2024年第2期6卷 252-265页

作者： Carmen González‑Fernández Miguel A.García‑Álvarez Alberto Cuesta Department of cell biology and Histology Faculty of BiologyUniversity of Murcia30100 MurciaSpain Laboratoire d’écotoxicologie Centre de Lyon-VilleurbanneINRAEUR RiverLy69625 VilleurbanneFrance

Th17 is a lymphocyte T helper(Th)subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin(IL)-*** crucial cytokine family acts through their binding to the IL-17 receptors(IL-17R),having up to six *** the biology of fish Th17 is well-recognized,the molecular and functional characterization of IL-17 and IL-17R has been ***,our aim was to identify and characterize the IL-17R repertory and regulation in the two main Mediterranean cultured fish species,the gilthead seabream(Sparus aurata)and the European sea bass(Dicentrarchus labrax).Our in silico results showed the clear identification of six members in each fish species,from IL-17RA to IL-17RE-like,with well-conserved gene structure and protein domains with their human *** of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues,namely skin,gill or *** leucocytes,T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most ***,in vivo nodavirus infection resulted in alterations on the transcription of il17 *** nodavirus infection led to some increments in the il17ra,il17rb,il17rc and il17rd transcripts in the susceptible European sea bass,many down-regulations were observed in the resistant gilthead *** data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection.

关键词： Th17 cells IL-17 receptors Immunity Teleost fish Nodavirus(NNV) Aquaculture

In-situ synthesis of quantum dots in the nucleus of live cells

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National Science Review 2024年第3期11卷 172-182页

作者： Yusi Hu Zhi-Gang Wang Haohao Fu Chuanzheng Zhou Wensheng Cai Xueguang Shao Shu-Lin Liu Dai-Wen Pang State Key Laboratory of Medicinal Chemical biology Frontiers Science Centre for New Organic MatterTianjin Key Laboratory of Biosensing and Molecular Recognition Research Centre for Analytical Sciences College of Chemistry School of Medicine and Frontiers Science Centre for Cell Responses Nankai University Haihe Laboratory of Sustainable Chemical Transformations

The cell nucleus is the main site for the storage and replication of genetic material, and the synthesis of substances in the nucleus is rhythmic, regular and strictly regulated by physiological processes. However,whether exogenous substances, such as nanoparticles, can be synthesized in situ in the nucleus of live cells has not been reported. Here, we have achieved in-situ synthesis of CdSxSe1-xquantum dots（QDs） in the nucleus by regulation of the glutathione（GSH） metabolic pathway. High enrichment of GSH in the nucleus can be accomplished by the addition of GSH with the help of the Bcl-2 protein. Then, high-valence Se is reduced to low-valence Se by glutathione-reductase-catalyzed GSH, and interacts with the Cd precursor formed through Cd and thiol-rich proteins, eventually generating QDs in the nucleus. Our work contributes to a new understanding of the syntheses of substances in the cell nucleus and will pave the way for the development of advanced ‘supercells’.

关键词： glutathione live cell nucleus quantum dot intracellular synthesis