Communications Biology最新文献

Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-09 DOI: 10.1038/s42003-025-07970-8

Catherine E Oliver, Jonathan L Carter, James S Hong, Mingzhi Xu, William E Kraus, Kim M Huffman, George A Truskey

{"title":"Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls.","authors":"Catherine E Oliver, Jonathan L Carter, James S Hong, Mingzhi Xu, William E Kraus, Kim M Huffman, George A Truskey","doi":"10.1038/s42003-025-07970-8","DOIUrl":"https://doi.org/10.1038/s42003-025-07970-8","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting articular joints and skeletal muscle. To assess the role of cytokines upon muscle strength in RA, we developed an in vitro tissue-engineered human skeletal muscle model (myobundle). Myobundles were generated using primary skeletal muscle cells from the vastus lateralis muscle of RA patients and age-matched healthy controls. RA myobundles were more sensitive to 5 ng/mL IFN-γ, exhibiting reduced contractile force and altered contraction kinetics. Addition of IL-6 with or without IFN-γ led to a small but significant increase in striated fibers. Gene sets involved in the response to hypoxia, MTOR1 signaling, and the unfolded protein response were enriched in IFN-γ-treated RA myobundles, but not IFN-γ-treated controls. Tofacitinib increased contractile force, myosin heavy chain, and PIM1 protein levels in RA myobundles treated with IFN-γ. Thus, in RA muscle, low levels of IFN-γ selectively increase gene pathways that reduce contractile force.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"583"},"PeriodicalIF":5.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

METTL3 obstructs vascular smooth muscle cells osteogenic reprogramming by methylating Runx2 in chronic kidney disease.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-08 DOI: 10.1038/s42003-025-07972-6

Meijuan Cheng, Jingjing Jin, Dongxue Zhang, Mei Xiao, Hairong Zhao, Xiaoying Zhao, Shenglei Zhang, Yaling Bai, Jinsheng Xu

{"title":"METTL3 obstructs vascular smooth muscle cells osteogenic reprogramming by methylating Runx2 in chronic kidney disease.","authors":"Meijuan Cheng, Jingjing Jin, Dongxue Zhang, Mei Xiao, Hairong Zhao, Xiaoying Zhao, Shenglei Zhang, Yaling Bai, Jinsheng Xu","doi":"10.1038/s42003-025-07972-6","DOIUrl":"https://doi.org/10.1038/s42003-025-07972-6","url":null,"abstract":"The reprogrammed osteogenic phenotype of vascular smooth muscle cells (VSMCs) is considered a critical mechanism of vascular calcification (VC) in chronic kidney disease (CKD). Currently, the RNA N6-methyladenosine (m6A) modification is deciphered to be dynamically and reversibly participated in functional regulation of VSMCs. Here, we discover that serum m6A levels in RNA are dramatically reduced as VC progressed in patients with CKD, and this m6A demethylation is mainly due to the downregulation of methyltransferaselike-3 (METTL3). Functionally, METTL3 depletion exacerbates, whereas its overexpression attenuates calcification progression and osteogenic reprogramming. Mechanistically, Runx2, a crucial osteogenic gene, is identified as a key downstream target of METTL3-mediated m6A methylation. METTL3 negatively regulates Runx2 expression through the m6A modification. Overexpression of METTL3 exacerbates Runx2 mRNA degradation, which is orchestrated by the m6A reader YT521-B homology domain family 2 (YTHDF2) through specifically recognizing its m6A sites in the 3'UTR region. Finally, in vivo METTLs inhibitor SAH treatment aggravates VC and osteogenic conversion in aortas of CKD rats, accompanied by Runx2 expression upregulation. These above data reveal an underlying mechanism by which the m6A writer METTL3 regulates Runx2 expression through YTHDF2-mediated mRNA degradation and suggest a potential therapeutic strategy to reverse the osteogenic reprogramming of VSMCs.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"582"},"PeriodicalIF":5.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic and structural insights into the functional importance of the conserved gly-met-rich C-terminal tails in bacterial chaperonins.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-08 DOI: 10.1038/s42003-025-07927-x

C M Santosh Kumar, Aisha M Mai, Shekhar C Mande, Peter A Lund

{"title":"Genetic and structural insights into the functional importance of the conserved gly-met-rich C-terminal tails in bacterial chaperonins.","authors":"C M Santosh Kumar, Aisha M Mai, Shekhar C Mande, Peter A Lund","doi":"10.1038/s42003-025-07927-x","DOIUrl":"https://doi.org/10.1038/s42003-025-07927-x","url":null,"abstract":"E. coli chaperonin GroEL forms nano-cages for protein folding. Although the chaperonin-mediated protein folding mechanism is well understood, the role of the conserved glycine and methionine-rich carboxy-terminal residues remains unclear. Bacteria with multiple chaperonins always retain at least one paralogue having the gly-met-rich C-terminus, indicating an essential conserved function. Here, we observed a stronger selection pressure on the paralogues with gly-met-rich C-termini, consistent with their ancestral functional importance. E. coli GroEL variants having mutations in their C-termini failed to functionally replace GroEL, suggesting the functional significance of the gly-met-rich C-termini. Further, our structural modelling and normal mode analysis showed that the C-terminal region shuttles between two cavity-specific conformations that correlate with the client-protein-binding apical domains, supporting C-termini's role in client protein encapsulation. Therefore, employing phylogenetic, genetic, and structural tools, we demonstrate that the gly-met-rich C-termini are functionally significant in chaperonin-mediated protein folding function. Owing to the pathogenic roles of the chaperonins having non-canonical C-termini, future investigations on the client protein selectivity will enable understanding the disease-specific client protein folding pathways and treatment options.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"555"},"PeriodicalIF":5.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modelling the effects of diurnal temperature variation on malaria infection dynamics in mosquitoes.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-08 DOI: 10.1038/s42003-025-07949-5

Isaac J Stopard, Antoine Sanou, Eunho Suh, Lauren J Cator, Matthew B Thomas, W Moussa Guelbéogo, N'Falé Sagnon, Ben Lambert, Thomas S Churcher

{"title":"Modelling the effects of diurnal temperature variation on malaria infection dynamics in mosquitoes.","authors":"Isaac J Stopard, Antoine Sanou, Eunho Suh, Lauren J Cator, Matthew B Thomas, W Moussa Guelbéogo, N'Falé Sagnon, Ben Lambert, Thomas S Churcher","doi":"10.1038/s42003-025-07949-5","DOIUrl":"https://doi.org/10.1038/s42003-025-07949-5","url":null,"abstract":"Mosquito infection experiments that characterise how sporogony changes with temperature are increasingly being used to parameterise malaria transmission models. In these experiments, mosquitoes are exposed to a range of temperatures, with each group experiencing a single temperature. Diurnal temperature variation can, however, affect the sporogonic cycle of Plasmodium parasites. Mosquito dissection data is not available for all temperature profiles, so we investigate whether mathematical models of mosquito infection parameterised with constant temperature thermal performance curves can predict the effects of diurnal temperature variation. We use this model to predict two key parameters governing disease transmission: the human-to-mosquito transmission probability and extrinsic incubation period - and, embed this model into a malaria transmission model to simulate sporozoite prevalence with and without the effects of diurnal and seasonal temperature variation for a single site in Burkina Faso. Simulations incorporating diurnal temperature variation better predict changes in sporogony in laboratory mosquitoes, indicating that constant temperature experiments can be used to predict the effects of fluctuating temperatures. Including the effects of diurnal temperature variation, however, did not substantially improve the predictive ability of the transmission model to predict changes in sporozoite prevalence in wild mosquitoes, indicating further research is needed in more settings.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"581"},"PeriodicalIF":5.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights into the catalytic mechanism of the microcystin tailoring enzyme McyI.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-07 DOI: 10.1038/s42003-025-08008-9

Xiao Wang, Yue Yin, Wen-Long Cheng, Ya-Fei Duan, Yu-Shuai Li, Jia Wang, Mingzhu Wang, Huai-En Dai, Lin Liu

{"title":"Structural insights into the catalytic mechanism of the microcystin tailoring enzyme McyI.","authors":"Xiao Wang, Yue Yin, Wen-Long Cheng, Ya-Fei Duan, Yu-Shuai Li, Jia Wang, Mingzhu Wang, Huai-En Dai, Lin Liu","doi":"10.1038/s42003-025-08008-9","DOIUrl":"10.1038/s42003-025-08008-9","url":null,"abstract":"The most common cyanotoxin microcystin is a cyclic heptapeptide produced by non-ribosomal peptide-polyketide synthetases and tailoring enzymes. The tailoring enzyme McyI, a 2-hydroxyacid dehydrogenase, converts (3-methyl)malate into (3-methyl)oxaloacetate to produce the non-proteinogenic amino acid (3-methyl)aspartate. The reaction is NAD(P)-dependent but the catalytic mechanism remains unclear. Here we describe the crystal structures of McyI at three states: bound with copurified NAD, cocrystallized with NAD/NADP, and cocrystallized with malate or the substrate analogue citrate. An McyI protomer has unusual three nicotinamide cofactor-binding sites, named the NAD-prebound, NADP specific, and non-specific sites. Biochemical studies confirmed the NADP preference during oxidoreductase reaction. Molecular basis for McyI catalysis was revealed by the structures of McyI-NAD binary complex, McyI-NAD-NADP and McyI-NAD-malate ternary complexes, which demonstrate different opening angles between the substrate-binding domain and the nucleotide-binding domain. These findings indicate that McyI is a unique member of the 2-hydroxyacid dehydrogenase superfamily and provide detailed structural insights into its catalytic mechanism. In addition, the structural ensemble representing various binding states offers clues for designing enzyme for bioengineering applications.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"578"},"PeriodicalIF":5.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intronic RNAscope probes enable precise identification of cardiomyocyte nuclei and cell cycle activity.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-07 DOI: 10.1038/s42003-025-08012-z

Zhe Yu, Sen Zhang, Julius Bogomolovas, Ju Chen, Sylvia M Evans

{"title":"Intronic RNAscope probes enable precise identification of cardiomyocyte nuclei and cell cycle activity.","authors":"Zhe Yu, Sen Zhang, Julius Bogomolovas, Ju Chen, Sylvia M Evans","doi":"10.1038/s42003-025-08012-z","DOIUrl":"10.1038/s42003-025-08012-z","url":null,"abstract":"Cardiac regeneration studies have been plagued by technical challenges in unequivocally identifying cardiomyocyte (CM) nuclei in cardiac sections, crucial for accurate identification of cycling CMs. The use of antibodies to sarcomeric proteins is error-prone, the CM specificity of common nuclear markers is controversial, and utilizing genetically modified mouse models poses risk of inducing unintended cardiac phenotypes. The application of RNAscope intronic probes overcomes the above shortcomings. Intronic probes label intronic RNAs within nuclei and can therefore be utilized as a method for nuclear localization. A Tnnt2 intronic RNAscope probe highly colocalized with Obscurin-H2B-GFP in adult mouse hearts, demonstrating CM specificity. Studies in embryos demonstrated that the Tnnt2 intronic RNAscope probe labeled CM nuclei that had undergone DNA replication, and remained closely associated with CM chromatin at all stages of mitosis, even with nuclear envelope breakdown. The efficiency, accuracy, and perdurance of the Tnnt2 intronic RNAscope probe even with nuclear envelope breakdown facilitated reliable investigation of dynamics of DNA synthesis and potential mitoses in CMs in both border and infarct zones after myocardial infarction (MI). Furthermore, we designed Myl2 and Myl4 intronic RNAscope probes, which labeled ventricular and atrial CM nuclei, respectively, and may help identify CM subtypes generated in vitro.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"577"},"PeriodicalIF":5.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A structural and mechanistic model for BSEP dysfunction in PFIC2 cholestatic disease.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-07 DOI: 10.1038/s42003-025-07908-0

Clémence Gruget, Bharat G Reddy, Jonathan M Moore

{"title":"A structural and mechanistic model for BSEP dysfunction in PFIC2 cholestatic disease.","authors":"Clémence Gruget, Bharat G Reddy, Jonathan M Moore","doi":"10.1038/s42003-025-07908-0","DOIUrl":"10.1038/s42003-025-07908-0","url":null,"abstract":"BSEP (ABCB11) transports bile salts across the canalicular membrane of hepatocytes, where they are incorporated into bile. Biallelic mutations in BSEP can cause Progressive Familial Intrahepatic Cholestasis Type 2 (PFIC2), a rare pediatric disease characterized by hepatic bile acid accumulation leading to hepatotoxicity and, ultimately, liver failure. The most frequently occurring PFIC2 disease-causing mutations are missense mutations, which often display a phenotype with decreased protein expression and impaired maturation and trafficking to the canalicular membrane. To characterize the mutational effects on protein thermodynamic stability, we carried out biophysical characterization of 13 distinct PFIC2-associated variants using in-cell thermal shift (CETSA) measurements. These experiments reveal a cluster of residues localized to the NBD2-ICL2 interface, which exhibit severe destabilization relative to wild-type BSEP. A high-resolution (2.8 Å) cryo-EM structure provides a framework for rationalizing the CETSA results, revealing a novel, NBD2-localized mechanism through which the most severe missense patient mutations drive cholestatic disease. These findings suggest potential strategies for identifying mechanism-based small molecule correctors to address BSEP trafficking defects and advance novel therapies for PFIC2 and other cholestatic diseases.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"531"},"PeriodicalIF":5.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the early evolution of black corals.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-07 DOI: 10.1038/s42003-025-08022-x

Wenjing Hao, Jian Han, Andrzej Baliński, Mercer R Brugler, Deng Wang, Xin Wang, Bernhard Ruthensteiner, Tsuyoshi Komiya, Jie Sun, Yuanyuan Yong, Xikun Song

引用次数: 0

Diving back two hundred million years: yawn contagion in fish.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-07 DOI: 10.1038/s42003-025-08004-z

Alice Galotti, Gianluca Manduca, Matteo Digregorio, Sara Ambrosini, Donato Romano, Massimiliano Andreazzoli, Elisabetta Palagi

引用次数: 0

Targeting alveolar epithelial cells with lipid micelle-encapsulated necroptosis inhibitors to alleviate acute lung injury.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-04-06 DOI: 10.1038/s42003-025-08010-1

Zhi-Ying Kang, Nan-Xia Xuan, Qi-Chao Zhou, Qian-Yu Huang, Meng-Jia Yu, Gen-Sheng Zhang, Wei Cui, Zhao-Cai Zhang, Yang Du, Bao-Ping Tian

{"title":"Targeting alveolar epithelial cells with lipid micelle-encapsulated necroptosis inhibitors to alleviate acute lung injury.","authors":"Zhi-Ying Kang, Nan-Xia Xuan, Qi-Chao Zhou, Qian-Yu Huang, Meng-Jia Yu, Gen-Sheng Zhang, Wei Cui, Zhao-Cai Zhang, Yang Du, Bao-Ping Tian","doi":"10.1038/s42003-025-08010-1","DOIUrl":"10.1038/s42003-025-08010-1","url":null,"abstract":"Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS), represents a critical condition characterized by extensive inflammation within the airways. Necroptosis, a form of cell death, has been implicated in the pathogenesis of various inflammatory diseases. However, the precise characteristics and mechanisms of necroptosis in ARDS remain unclear. Thus, our study seeks to elucidate the specific alterations and regulatory factors associated with necroptosis in ARDS and to identify potential therapeutic targets for the disease. We discovered that necroptosis mediates the progression of ALI through the activation and formation of the RIPK1/RIPK3/MLKL complex. Moreover, we substantiated the involvement of both MYD88 and TRIF in the activation of the TLR4 signaling pathway in ALI. Furthermore, we have developed a lipid micelle-encapsulated drug targeting MLKL in alveolar type II epithelial cells and successfully applied it to treat ALI in mice. This targeted nanoparticle selectively inhibited necroptosis, thereby mitigating epithelial cell damage and reducing inflammatory injury. Our study delves into the specific mechanisms of necroptosis in ALI and proposes novel targeted therapeutic agents, presenting innovative strategies for the management of ARDS.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"573"},"PeriodicalIF":5.2,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0