Communications Biology最新文献

{"title":"Conserved heavy/light contacts and germline preferences revealed by a large-scale analysis of natively paired human antibody sequences and structural data.","authors":"Pawel Dudzic, Dawid Chomicz, Weronika Bielska, Igor Jaszczyszyn, Michał Zieliński, Bartosz Janusz, Sonia Wróbel, Marguerite-Marie Le Pannérer, Andrew Philips, Prabakaran Ponraj, Sandeep Kumar, Konrad Krawczyk","doi":"10.1038/s42003-025-08388-y","DOIUrl":"10.1038/s42003-025-08388-y","url":null,"abstract":"<p><p>Understanding the pairing preferences and structural interactions between antibody heavy and light chains can enhance our ability to design more effective and specific therapeutic antibodies. Insights from natural antibody repertoires and conserved contact sites help reduce autoreactivity and improve drug safety and efficacy. Current databases represent only a limited portion of the estimated diversity of unique paired antibody molecules. To address this, we introduce PairedAbNGS, a novel database with paired heavy/light antibody chains. To our knowledge, this is the largest resource for paired natural antibody sequences with 58 bioprojects and over 14 million assembled productive sequences. Using this dataset, we investigated heavy and light chain variable (V) gene pairing preferences and found significant biases beyond gene usage frequencies, possibly due to receptor editing favoring less autoreactive combinations. Analyzing the available antibody structures from the Protein Data Bank, we studied conserved contact residues between heavy and light chains, particularly interactions between the CDR3 region of one chain and the FWR2 region of the opposite chain. Examination of amino acid pairs at key contact sites revealed significant deviations of amino acids distributions compared to random pairings, in the heavy chain's CDR3 region contacting the opposite chain, indicating specific interactions might be crucial for proper chain pairing. This observation is further reinforced by preferential IGHV-IGLJ and IGLV-IGHJ pairing preferences. We hope that both our resources and the findings would contribute to improving the engineering of biological drugs. We make the database accessible at https://naturalantibody.com/paired-ab-ngs as a valuable tool for biological and machine-learning applications.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1110"},"PeriodicalIF":5.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717664","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}

{"title":"Serine clamp of Clostridium perfringens binary toxin BECb (CPILEb)-pore confers cytotoxicity and enterotoxicity.","authors":"Toru Yoshida, Chie Monma, Yuki Ninomiya, Sotaro Takiguchi, Shoko Fujita, Yuto Uchida, Noriaki Sakoda, Vladimir A Karginov, Jun-Ichi Kishikawa, Tomohito Yamada, Ryuji Kawano, Hideaki Tsuge","doi":"10.1038/s42003-025-08519-5","DOIUrl":"10.1038/s42003-025-08519-5","url":null,"abstract":"<p><p>BEC (CPILE) is a virulence factor of the pathogen, Clostridium perfringens, which has caused foodborne outbreaks in Japan. BEC is a binary toxin that comprises the enzymatic A-component (BECa) and the B-component (BECb); the latter forms a membrane pore to translocate the A-component into target cells. Although BEC differs from other binary toxins in that the B-component alone shows enterotoxic activity, the reason for this remains unclear. We focus on the narrowest region of BECb-pore formed by not phenylalanine residues conserved in other binary toxins including iota toxin B-component (Ib) but serine residues. Comparisons between BECb and BECb (S405F) where the serine residue forming the narrowest region is substituted to the phenylalanine residue reveal that the serine residue is responsible for both cytotoxicity and enterotoxic activity. Though attempts to prepare the BECb-pore were unsuccessful, we reveal the cryo-EM structure of Ib (F454S) where the phenylalanine residue forming the narrowest region is substituted to the serine residue as a surrogate of BECb. Furthermore, Ib (F454S) increases current conductance to nine times that of Ib due to the larger pore diameter and the hydrophilic nature. These results suggest that BECb functions as a pore-forming toxin and as a translocation channel for BECa.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1102"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717698","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}

{"title":"Publisher Correction: IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8.","authors":"Linjie Wang, Jingyun Zhang, Shijuan Qiu, Ruizhen Huang, Yuge Wang, Yuting Wang, Mingyu Li, Qingqing Ye, Sibo Zhang, Zhenhua Qi, Lan Cao, Guohao Li, Yajie An, Denghui Xie, Wenli Mi, Huaqiao Wang, Tao Luo, Jingdun Xie, Junting Huang","doi":"10.1038/s42003-025-08552-4","DOIUrl":"10.1038/s42003-025-08552-4","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1103"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717696","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}

{"title":"A systematic benchmark of integrative strategies for microbiome-metabolome data.","authors":"Loïc Mangnier, Antoine Bodein, Margaux Mariaz, Alban Mathieu, Marie-Pier Scott-Boyer, Neerja Vashist, Matthew S Bramble, Arnaud Droit","doi":"10.1038/s42003-025-08515-9","DOIUrl":"10.1038/s42003-025-08515-9","url":null,"abstract":"<p><p>The rapid advancement of high-throughput sequencing technologies has enabled the integration of various omic layers into computational frameworks. Among these, metagenomics and metabolomics are increasingly studied for their roles in complex diseases. However, no standard currently exists for jointly integrating microbiome and metabolome datasets within statistical models. We benchmarked nineteen integrative methods to disentangle the relationships between microorganisms and metabolites. These methods address key research goals, including global associations, data summarization, individual associations, and feature selection. Through realistic simulations, we identified the best-performing methods and validated them on real gut microbiome datasets, revealing complementary biological processes across the two omic layers. Practical guidelines are provided for specific scientific questions and data types. This work establishes a foundation for research standards in metagenomics-metabolomics integration and supports future methodological developments, while also providing guidance for designing optimal analytical strategies tailored to specific integration questions.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1100"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706601","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}

{"title":"Pericyte-mediated regulation of angiogenesis during cutaneous wound healing in adult zebrafish.","authors":"Tomohiro Ishii, Shinya Yuge, Koji Ando, Weibin Zhou, Shigetomo Fukuhara","doi":"10.1038/s42003-025-08517-7","DOIUrl":"10.1038/s42003-025-08517-7","url":null,"abstract":"<p><p>Pericytes are mural cells that wrap small caliber vessels, playing a crucial role in stabilizing vascular structure. Upon induction of angiogenesis, pericytes were thought to detach from the vessel wall, thereby facilitating the sprouting of endothelial cells (ECs). However, the precise roles of pericytes in regulating angiogenesis still remain elusive. Here, we demonstrate, by performing live-imaging of adult zebrafish, that pericytes actively regulate angiogenesis during wound healing. We generated a zebrafish line which enables the conditional ablation of mural cells, including pericytes, and analyzed cutaneous wound angiogenesis. Loss of pericytes significantly increased the number of sprouting events of ECs and promoted their proliferation, resulting in the formation of dense and disorganized blood vessel networks. Furthermore, in the absence of pericytes, the injured vessels showed abnormal vessel elongation, thereby generating ectopic vascular networks. These results suggest that pericytes play an active role for generating functional blood vessels during wound angiogenesis.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1101"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717695","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}

{"title":"Fear perception as a function of hemisphere- and time-specific dynamics in the medial temporal lobes.","authors":"Enya M Weidner, Lea Marie Reisch, Malena Mielke, Christian G Bien, Johanna Kissler","doi":"10.1038/s42003-025-08542-6","DOIUrl":"10.1038/s42003-025-08542-6","url":null,"abstract":"<p><p>The medial temporal lobes (mTL) are thought to enhance visual processing of fearful faces, yet the underlying mechanisms remain underspecified. To fill this gap, we recorded and compared event-related potentials (ERPs) and stimulus-induced gamma-band activity (GBA) from 36 patients with left- or right-hemispheric antero-medial temporal lobe resections including the amygdala (lTLR/rTLR) and 18 healthy controls. Only rTLR patients were found to lack fear-neutral differentiation in early P1 amplitudes (~100 ms) and exhibited heightened GBA for neutral faces over ipsi-resectional occipito-temporal areas (95-300 ms). lTLR patients showed strongest emotion differentiation in ERP components beyond the P1. Therefore, the right mTL, potentially particularly the amygdala, appears to support rapid attentional shifts toward fear and to coordinate fear-neutral differentiation in GBA. Conversely, the left mTL seems to down-regulate fear responses. These results reveal complementary, lateralized, and time-specific roles of the medial temporal lobes in fear processing, thereby refining models of emotional vision.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1105"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717694","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}

{"title":"Biallelic BRCA2 variants induce premature ovarian insufficiency by impaired meiotic homologous recombination.","authors":"Xinyi Wu, Qian Zhang, Chang Li, Shuning Zhuang, Hongyuan Liu, Xue Jiao, Shidou Zhao, Yingying Qin, Ting Guo","doi":"10.1038/s42003-025-08426-9","DOIUrl":"10.1038/s42003-025-08426-9","url":null,"abstract":"<p><p>The DNA damage response plays a pivotal role in ovarian aging. Breast cancer susceptibility gene 2 (BRCA2), which participates in homologous recombination (HR), is a key regulator of natural menopause. Rare BRCA2 variants have been identified in patients with premature ovarian insufficiency (POI). However, the underlying molecular mechanisms are not well understood. Using a viable mouse model, Brca2^{c.68-1G>C/c.4384-4394del}, carrying compound heterozygous variants mirroring the ones identified in a POI pedigree, we illustrated the essential role of BRCA2 in primordial follicle pool establishment. Germline deficiency of BRCA2 did not affect primordial germ cell (PGC) proliferation but impaired the recruitment of RAD51 and DMC1 to programmed DNA double-strand breaks (DSBs) during meiotic HR, causing postnatal oocyte depletion. Moreover, Brca2^{c.68-1G>C/c.4384-4394del} mice presented increased tumor susceptibility. These findings confirmed the pathogenicity of BRCA2 biallelic variants in POI, revealing the dual impact on germ cell development and somatic cancer risk, underscoring the necessity of tumor surveillance in POI patients with BRCA2 mutations.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1104"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717663","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}

{"title":"Correcting errors in PCR-derived libraries for rare allele detection by reconstructing parental and daughter strand information.","authors":"Hyeonseob Lim, Soyeong Jun, Taehoon Kim, Ji Hyun Lee, Duhee Bang","doi":"10.1038/s42003-025-08537-3","DOIUrl":"10.1038/s42003-025-08537-3","url":null,"abstract":"<p><p>Molecular barcoding methods enable high-sensitivity detection of circulating tumor DNA that is rarely present in liquid biopsy samples. Many methods involve ligation of molecular barcodes to DNA prior to hybridization capture, enabling recovery of starting molecules. Development of polymerase chain reaction (PCR)-based methods could facilitate more cost- and labor- effective detection; however, tracking molecular identity can be difficult, as new barcodes overwrite old barcodes in each cycle. Here, we present a sensitive genotyping method based on a peer-to-peer network-derived identifier for error reduction in amplicon sequencing (SPIDER-seq) and enable molecular identity tracking with PCR-derived libraries using overwritten barcodes. SPIDER-seq detected mutations at frequences as low as 0.125% after only two consecutive general PCR cycles and systematically analyzed the error pattern in the peer-to-peer network. Our method could facilitate the rapid detection of mutations associated with various cancers.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1098"},"PeriodicalIF":5.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706602","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}

{"title":"Pseudomonadal itaconate degradation gene cluster encodes enzymes for methylsuccinate utilization.","authors":"Lena Gonner, Eric A Cassens, Simone König, Ivan A Berg","doi":"10.1038/s42003-025-08538-2","DOIUrl":"10.1038/s42003-025-08538-2","url":null,"abstract":"<p><p>Branched-chain C₅-dicarboxylic acids (e.g., citramalate, mesaconate or methylsuccinate) and their CoA-esters are important intermediates in bacterial metabolism, while itaconate is an antimicrobial agent, a potent immunomodulator and a growth substrate for many bacteria. The itaconate degradation pathway consists of three reactions catalyzed by itaconate CoA transferase, itaconyl-CoA hydratase and (S)-citramalyl-CoA lyase encoded in a cluster, which in saprophytic bacteria contains two additional genes for a putative acyl-CoA dehydrogenase and a protein of the MmgE/PrpD family. Here, we heterologously produced the corresponding proteins from Cupriavidus necator and Pseudomonas aeruginosa and showed that they catalyze the (RS)-methylsuccinyl-C4-CoA dehydrogenase and an (S)-(R)-methylsuccinate isomerase reaction, respectively. Together with itaconate CoA transferase, which is highly active with (R)-methylsuccinate but has low activity with (S)-methylsuccinate, these enzymes allow the utilization of both stereoisomers of methylsuccinate. Our bioinformatic analysis revealed that 1.6% of the sequenced prokaryotes (mainly Betaproteobacteria) possess an identified methylsuccinate isomerase. Analysis of the conserved amino acids of methylsuccinate isomerase and other MmgE/PrpD proteins suggests that they share a common catalytic mechanism via the formation of an enolate intermediate. The presence of specific methylsuccinate utilization genes in the itaconate degradation cluster, which is widespread in saprophytic bacteria, suggests the importance of methylsuccinate in the environment.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1099"},"PeriodicalIF":5.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706603","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}

{"title":"Agxt2l-mediated glycerophospholipid metabolism in trophocytes explains Apis mellifera queen's higher oviposition over A. cerana.","authors":"Luxia Pan, Zilong Wang, Shiqing Zhong, Tianyu Xu, Weixuan Chen, Fuping Cheng, Zhijiang Zeng","doi":"10.1038/s42003-025-08526-6","DOIUrl":"10.1038/s42003-025-08526-6","url":null,"abstract":"<p><p>Apis mellifera and Apis cerana are two important honey bee species widely kept and studied. But their queens differ greatly in egg-laying capacity. To determine the mechanisms of this difference, we compare gene expression, chromatin accessibility and spatial localization of differential genes in the ovaries of the two species in virgin queens and laying queens using ATAC-seq, RNA-Seq, homologous gene alignment and spatial transcriptome. The results reconfirm that the egg-laying capability of A. mellifera queens is significantly higher than that of A. cerana queens. The chromatin accessibility and nutrient cells ratio of A. mellifera queens are higher than those of A. cerana queens. Further investigations reveal that agxt2l (LOC408817) is significantly over-expressed in the ovaries of A. mellifera queens compared to A. cerana queens and is crucial for ovary development. Moreover, agxt2l can increase the phospholipid content in ovarian nutrient cells through the glycerophospholipid metabolism pathway to promote embryo formation and is regulated by brc-z1 (LOC552255). These findings suggest that the brc-z1-agxt2l signal pathway causes increased egg-laying in the queens of A. mellifera compared to the queens of A. cerana by accelerating lipid synthesis due to heightened glycerophospholipid metabolism.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1091"},"PeriodicalIF":5.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689109","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}