Communications Biology最新文献_第8页

Author Correction: Nuclear factor interleukin 3 and metabolic dysfunction-associated fatty liver disease development. 作者更正：核因子白介素3与代谢功能障碍相关的脂肪肝疾病的发展。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-29 DOI: 10.1038/s42003-025-08902-2

Yung-Ni Lin, Jia-Rou Hsu, Chih-Lin Wang, Yi-Chen Huang, Jzy-Yu Wang, Chun-Ying Wu, Li-Ling Wu

引用次数: 0

Adjuvant activity of a small molecule TLR4 agonist discovered via structure-based virtual screening. 通过基于结构的虚拟筛选发现小分子TLR4激动剂的佐剂活性。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-29 DOI: 10.1038/s42003-025-08582-y

Mohammad Kadivella, Vivek P Varma, Jusail Cp, Sridhar Kavela, Sarwar Azam, Syed M Faisal

{"title":"Adjuvant activity of a small molecule TLR4 agonist discovered via structure-based virtual screening.","authors":"Mohammad Kadivella, Vivek P Varma, Jusail Cp, Sridhar Kavela, Sarwar Azam, Syed M Faisal","doi":"10.1038/s42003-025-08582-y","DOIUrl":"10.1038/s42003-025-08582-y","url":null,"abstract":"Monophosphoryl lipid A (MPLA), a TLR4 agonist, is a clinically approved vaccine adjuvant, but its complex structure and occasional toxicity limit broader use. Synthetic small-molecule TLR4 agonists offer advantages such as ease of synthesis, lower cost, and reduced toxicity. In this study, we conducted structure-based virtual screening of the ZINC database to identify novel TLR4-targeting small molecules across human, murine, and bovine species. Three lead compounds-NSF-418, NSF-501, and NSF-951-were selected based on favorable binding interactions and subjected to in vitro and in vivo evaluation. NSF-951 emerged as a potent TLR4 agonist, inducing strong proinflammatory cytokine responses (IL-6, TNF-α), upregulating CD80 and CD86 expression, and promoting macrophage maturation. Conversely, NSF-418 and NSF-501 acted as antagonists by suppressing MPLA-induced responses. In murine immunization studies, NSF-951, alone or with Alum (AF007), significantly enhanced OVA-specific antibody and T-cell responses without observable toxicity. These findings suggest that NSF-951 is a promising, cost-effective TLR4 agonist with strong immunostimulatory and adjuvant potential. Further studies are warranted to assess its performance with other antigens and adjuvant combinations, supporting its development as a next-generation adjuvant for veterinary and human vaccines.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1382"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191275","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

Deciphering conformational dynamics in AFM data using fast nonlinear NMA and FFT-based search with AFMFit. 利用快速非线性NMA和基于fft的AFMFit搜索来解密AFM数据中的构象动力学。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-29 DOI: 10.1038/s42003-025-08365-5

Rémi Vuillemot, Jean-Luc Pellequer, Sergei Grudinin

{"title":"Deciphering conformational dynamics in AFM data using fast nonlinear NMA and FFT-based search with AFMFit.","authors":"Rémi Vuillemot, Jean-Luc Pellequer, Sergei Grudinin","doi":"10.1038/s42003-025-08365-5","DOIUrl":"10.1038/s42003-025-08365-5","url":null,"abstract":"Atomic Force Microscopy (AFM) offers a unique opportunity to study the conformational dynamics of proteins in near-physiological conditions at the single-molecule level. However, interpreting the two-dimensional molecular surfaces of multiple molecules measured in AFM experiments as three-dimensional conformational dynamics of a single molecule poses a significant challenge. Here, we present AFMfit, a flexible fitting procedure that deforms an input atomic model to match multiple AFM observations. The fitted models form a conformational ensemble that unambiguously describes the AFM experiment. Our method uses a new fast fitting algorithm based on the nonlinear Normal Mode Analysis (NMA) method NOLB to associate each molecule with its conformational state. AFMfit processes conformations of hundreds of AFM images of a single molecule in a few minutes on a single workstation, enabling analysis of larger datasets, including high-speed (HS)-AFM. We demonstrate the applications of our methods to synthetic and experimental AFM/HS-AFM data that include activated factor V and a membrane-embedded transient receptor potential channel TRPV3. AFMfit is an open-source Python package available at https://gricad-gitlab.univ-grenoble-alpes.fr/GruLab/AFMfit/ .","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1381"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191342","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

Botulinum neurotoxin Light Chain/A1 uses fast synaptic vesicle cycling to cleave plasma membrane bound SNAP-25. 肉毒杆菌神经毒素轻链/A1利用快速突触囊泡循环裂解结合SNAP-25的质膜。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-29 DOI: 10.1038/s42003-025-08633-4

Alexander Gardner, Molly Sneller, William H Tepp, Joseph T Barbieri, Sabine Pellett

{"title":"Botulinum neurotoxin Light Chain/A1 uses fast synaptic vesicle cycling to cleave plasma membrane bound SNAP-25.","authors":"Alexander Gardner, Molly Sneller, William H Tepp, Joseph T Barbieri, Sabine Pellett","doi":"10.1038/s42003-025-08633-4","DOIUrl":"10.1038/s42003-025-08633-4","url":null,"abstract":"Botulinum neurotoxins (BoNT) are the most potent protein toxins for humans, yet how BoNT-Light Chain/A1 (LC/A1) journeys to cleave intracellular SNAP-25 is understudied. Here we use a cell-based assay to measure cytosolic EGFP-LC/A1 intracellular trafficking and SNAP-25 cleavage in Neuro-2A cells. Intracellular LC/A1 associated on microtubules and co-localized with Rab GTPases involved in fast synaptic vesicles and endosome recycling. Multiple Dominant Negative (DN) Rabs GTPases involved in fast synaptic vesicles or endosome recycling inhibited LC/A1 trafficking to the intracellular plasma membrane and SNAP-25 cleavage. A cytosolic LC/A1 variant that bound the plasma membrane from the cytosol was insensitive to DNRab GTPases involved in fast synaptic vesicle recycling. LC/A1 traffics on fast synaptic vesicles to the intracellular plasma membrane to cleave SNAP-25. Our data suggest, like Heavy Chain host cell entry and LC catalysis, LC intracellular trafficking to target host substrates can contribute to bacterial toxin potency.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1383"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191355","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

Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast. Rapalink-1揭示了裂变酵母中TOR依赖基因和基于agmatinergic轴的代谢反馈调节TOR活性和寿命。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-29 DOI: 10.1038/s42003-025-08731-3

Juhi Kumar, Kristal Ng, Charalampos Rallis

{"title":"Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast.","authors":"Juhi Kumar, Kristal Ng, Charalampos Rallis","doi":"10.1038/s42003-025-08731-3","DOIUrl":"10.1038/s42003-025-08731-3","url":null,"abstract":"The Target of Rapamycin, TOR, is a conserved signalling pathway with characterised chemical inhibitors such as rapamycin and torin1. Bi-steric third-generation inhibitors, such as rapalink-1 have been developed, however, their effects on organismal gene expression and lifespan have not been characterised. Here, we demonstrate that rapalink-1 affects fission yeast spatial and temporal growth and prolongs chronological lifespan with a distinct TORC1 selectivity profile. Endosome and vesicle-mediated transport and homeostasis processes related to autophagy render cells resistant to rapalink-1. Our study reveals TOR-regulated genes with unknown roles in ageing, including all fission yeast agmatinases, the enzymes that convert agmatine to putrescine and urea. Through genome-wide screens, we identify sensitive and resistant mutants to agmatine and putrescine. Genetic interactome assays for the agmatinase agm1 and further cell and molecular analyses demonstrate that impairing the agmatinergic branch of arginine catabolism results in TOR activity levels that are beneficial for growth but detrimental for chronological ageing. Our study reveals the anti-ageing action of agmatinases within a metabolic circuit that regulates TOR activity, protein translation levels and lifespan.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1364"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191360","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

Isoleucyl-tRNA synthetase depletion reveals vulnerabilities in Mycobacterium abscessus and Mycobacterium marinum. 异亮基trna合成酶缺失揭示了脓肿分枝杆菌和海洋分枝杆菌的脆弱性。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-29 DOI: 10.1038/s42003-025-08841-y

Dan Luo, Weile Xie, Chuan Wang, Yicheng Sun, Lu Zhang, Lan Qian, Jianming Zhang, Guanghui Dang, Siguo Liu, Zhe Wang

{"title":"Isoleucyl-tRNA synthetase depletion reveals vulnerabilities in Mycobacterium abscessus and Mycobacterium marinum.","authors":"Dan Luo, Weile Xie, Chuan Wang, Yicheng Sun, Lu Zhang, Lan Qian, Jianming Zhang, Guanghui Dang, Siguo Liu, Zhe Wang","doi":"10.1038/s42003-025-08841-y","DOIUrl":"10.1038/s42003-025-08841-y","url":null,"abstract":"Mycobacterium abscessus and Mycobacterium marinum are nontuberculous mycobacteria that pose significant challenges due to their high drug resistance and persistence in hostile host environments. Aminoacyl-tRNA synthetases, such as isoleucyl-tRNA synthetase (IleRS), are crucial for protein synthesis and represent promising targets for antimicrobial development. This study investigates the role of IleRS in mycobacterial growth, metabolism, and pathogenesis using conditional gene silencing combined with microbiological, metabolomic, and transcriptomic analyses. Our findings indicate that IleRS is essential for mycobacterial growth and survival during infection. Depletion of IleRS disrupts branched-chain amino acid and pantothenate biosynthesis, leading to metabolic vulnerabilities and impaired persistence in macrophages and in mouse infection models. Based on our metabolic findings, we tested drug susceptibility and found that depletion of IleRS enhances sensitivity to pyrazinamide, highlighting a synergistic effect that could improve tuberculosis treatment. Furthermore, global gene set enrichment analysis reveals that IleRS knockdown might promote bacterial clearance by upregulating cholesterol metabolism and lysosome organization processes in macrophages. These results establish IleRS as a potential therapeutic target, offering new insights into reducing drug resistance and enhancing current treatment regimens for mycobacterial infections, including tuberculosis.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1379"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191284","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

RhoA allosterically activates phospholipase Cε via its EF hands. RhoA通过其EF手变构激活磷脂酶Cε。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08742-0

Vaani Ohri, Kadidia Samassekou, Kaushik Muralidharan, Elisabeth E Garland-Kuntz, Isaac J Fisher, William C Hogan, Bailey M Davis, Angeline M Lyon

{"title":"RhoA allosterically activates phospholipase Cε via its EF hands.","authors":"Vaani Ohri, Kadidia Samassekou, Kaushik Muralidharan, Elisabeth E Garland-Kuntz, Isaac J Fisher, William C Hogan, Bailey M Davis, Angeline M Lyon","doi":"10.1038/s42003-025-08742-0","DOIUrl":"10.1038/s42003-025-08742-0","url":null,"abstract":"Phospholipase Cε (PLCε) cleaves phosphatidylinositol lipids to increase intracellular Ca2+ and activate protein kinase C (PKC) in response to stimulation of cell surface receptors. PLCε is activated via direct binding of small GTPases at the cytoplasmic leaflets of cellular membranes. In the cardiovascular system, the RhoA GTPase regulates PLCε to initiate a pathway that protects against ischemia/reperfusion injuries, but the underlying molecular mechanism is not known. We present here the cryo-electron microscopy (cryo-EM) reconstruction of RhoA bound to PLCε, showing that the G protein binds a unique insertion within the PLCε EF hands. Deletion of or mutations to this PLCε insertion decrease RhoA-dependent activation without impacting its regulation by other G proteins. Together, our data support a model wherein RhoA binding to PLCε allosterically activates the lipase and increases its interactions with the membrane, resulting in maximum activity and cardiomyocyte survival.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1368"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173982","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

Systems-level exploitation of OxyR regulon unravels a potential antibacterial target in Pseudomonas aeruginosa. 系统级开发的OxyR调控揭示了铜绿假单胞菌潜在的抗菌靶点。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08770-w

Kaiyu Cui, Zhiyu Fu, Ruiling Sun, Qiuyun You, Fei Wang, Xuan Sun, Yong Tan, Yuwen Xia, Ping Wang, Qing Wei, Dao Wang, Weifeng Yang

引用次数: 0

IL6ST participates in the development of adolescent idiopathic scoliosis by regulating bone marrow mesenchymal stem cells. IL6ST通过调节骨髓间充质干细胞参与青少年特发性脊柱侧凸的发展。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08746-w

Zhuo-Tao Liang, Hao Tang, Jiong Li, Jia-Ke Li, Rong Rong, Zhong-Jing Jiang, Meng-Jun Li, Ming-Xing Tang, Hong-Qi Zhang

{"title":"IL6ST participates in the development of adolescent idiopathic scoliosis by regulating bone marrow mesenchymal stem cells.","authors":"Zhuo-Tao Liang, Hao Tang, Jiong Li, Jia-Ke Li, Rong Rong, Zhong-Jing Jiang, Meng-Jun Li, Ming-Xing Tang, Hong-Qi Zhang","doi":"10.1038/s42003-025-08746-w","DOIUrl":"10.1038/s42003-025-08746-w","url":null,"abstract":"Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity that primarily affects adolescents, and its pathogenesis remains elusive. Several studies have indicated that AIS may be associated with low bone mineral density, and bone marrow mesenchymal stem cells (BMSCs) are known to play a crucial role in bone metabolism. Through high-throughput sequencing of the BMSC transcriptome, we identified 1919 differentially expressed genes and pinpointed IL6ST as a key gene influencing osteogenic differentiation in AIS. Mechanistic experiments revealed that IL6ST regulates the osteogenic differentiation of BMSCs by activating the JAK/STAT3/RANKL/OPG pathway. Moreover, knockout of IL6ST expression significantly increased the malformation rate in zebrafish models. We further explored upstream regulators of IL6ST. Using high-throughput sequencing and bioinformatics analysis, we identified CircSCAF8 as a potential upstream regulatory circRNA of IL6ST. Collectively, these findings suggest that IL6ST may be a pivotal gene in the development of AIS, deepening our understanding of its pathogenesis.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1369"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174047","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

Brain insulin receptor gene network shapes risk for metabolic disease after early-life stress in women. 大脑胰岛素受体基因网络影响女性早期生活压力后代谢疾病的风险。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08750-0

Angela Marcela Jaramillo-Ospina, Guillaume Elgbeili, Sachin Patel, Irina Pokhvisneva, Patricia Pelufo Silveira

{"title":"Brain insulin receptor gene network shapes risk for metabolic disease after early-life stress in women.","authors":"Angela Marcela Jaramillo-Ospina, Guillaume Elgbeili, Sachin Patel, Irina Pokhvisneva, Patricia Pelufo Silveira","doi":"10.1038/s42003-025-08750-0","DOIUrl":"10.1038/s42003-025-08750-0","url":null,"abstract":"Stress happening during critical periods of development shapes individual physiology and increases the risk for obesity, inflammatory, and metabolic disturbances throughout life. However, there are individual differences and not everyone exposed to stress or adversity early during development develops chronic adult disease. Insulin regulates peripheral glucose metabolism, acts as a neuromodulator in the brain, and is possibly implicated in individual differences in response to early adversity. Expression-based polygenic scores (ePRS) reflect variations in the expression of a tissue-specific gene co-expression network. We have previously shown that brain-based insulin receptor ePRS (ePRS-IR) can identify risk for metabolic and frailty outcomes in older adults. Here, we show that the mesocorticolimbic ePRS-IR moderates the association between early adversity and increased visceral adipose tissue as well as metabolic syndrome in a large sample of adult women (UK Biobank). These findings suggest that variations in the function of the brain insulin receptor network influence the susceptibility to the long-term effects of adversity, highlighting a target system for prevention and novel treatments.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1372"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173974","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