PLoS Biology最新文献

{"title":"Better antibodies, better science.","authors":"Johan Duchêne","doi":"10.1371/journal.pbio.3004001","DOIUrl":"10.1371/journal.pbio.3004001","url":null,"abstract":"<p><p>Poorly validated antibodies generate misleading results and waste research resources. Two new studies in PLOS Biology quantify the ethical costs of this issue, examine why unvalidated antibodies are still used, and identify solutions to reduce their use.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004001"},"PeriodicalIF":7.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128981","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":"Inadequate antibody validation places substantial numbers of animal and human tissue samples at risk of waste.","authors":"Michael Biddle, Jemma Cooper, Katherine Blades, Dominic Ruddy, Eva M Krockow, Harvinder Virk","doi":"10.1371/journal.pbio.3003984","DOIUrl":"10.1371/journal.pbio.3003984","url":null,"abstract":"<p><p>Lack of antibody validation by researchers frequently misdirects biomedical research, yet the ethical consequences-particularly avoidable use of animal and human biological materials-remain unquantified. Using focus groups (n = 12), surveys (n = 107), and systematic analysis of 785 publications, we examined how researchers select and validate antibodies, and quantified the downstream ethical costs. Antibody selection is substantially influenced by social factors such as previous laboratory use and peer recommendations, while systematic evaluation of performance characteristics remains limited. From a dataset of 614 antibodies subjected to rigorous characterisation using knockout controls, 97 (15.8%) failed across all tested applications; we systematically searched for publications linked to these antibodies. Within the 760 publications (those where validation status could be confirmed), only 120 (15.8%) presented any validation evidence-despite 72.0% of surveyed researchers reporting having used at least one recommended validation method. The remaining 640 papers reported a minimum of 8,064 animal samples and 4,424 human tissue samples used with antibodies of demonstrated poor performance and without evidence of fitness for the specific experimental purpose; we describe these as samples at risk of waste. Reserving the term waste for samples used with reagents since withdrawn from sale, and therefore irreproducible, conservative extrapolation gives lower-bound, order-of-magnitude estimates of millions of animal and human tissue samples consumed globally. Researchers identified time, cost, and lack of supervisor support as primary barriers, whilst strongly supporting open data sharing, dedicated validation funding, and publisher requirements as solutions. These findings provide a first quantification of the ethical costs of inadequate antibody validation and highlight the need for coordinated stakeholder interventions to reduce avoidable biological sample waste in biomedical research.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003984"},"PeriodicalIF":7.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117234","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 binding-activated CRISPR/dCas13X imaging system enables precise RNA tracking in plants.","authors":"Jiayu Zhang, Yiran Tao, Yun Zhao, Miaomiao Lei, Yucheng Shen, Qicong Li, Chenxu Liu, Jiuyuan Bai","doi":"10.1371/journal.pbio.3004043","DOIUrl":"10.1371/journal.pbio.3004043","url":null,"abstract":"<p><p>Visualizing the spatiotemporal dynamics of native RNA molecules with single-transcript-level sensitivity in living plant cells remains a formidable challenge due to the high background noise caused by the unique cellular architecture of plants. Here, using transiently transformed Nicotiana benthamiana cells and stable Arabidopsis thaliana lines, we present a high-signal-to-noise RNA imaging platform that couples CRISPR-dCas13X with a binding-associated fluorescence stabilization strategy. We identified a novel plant-specific degron that selectively targets unbound probes for proteasomal degradation while preserving target-associated signal in a manner consistent with binding-dependent protection, enabling high-fidelity detection of endogenous mRNA puncta with minimal perturbation. Leveraging this platform, we characterized dynamics of FT mRNA trafficking in living plant cells, including plasmodesmata-targeting, cell-to-cell trafficking, and long-distance movement. Loss-of-function analysis further identified the established RNA-binding protein GRP7 as a factor that contributes to efficient FT mRNA transport. This work establishes a useful toolkit for investigating plant RNA biology and provides mechanistic insight into the systemic transport of florigenic signals.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004043"},"PeriodicalIF":7.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117214","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":"Actionable solutions to address antibody validation failures.","authors":"Katherine Blades, Michael Biddle, Robert Froud, Eva M Krockow, Harvinder Virk","doi":"10.1371/journal.pbio.3003981","DOIUrl":"10.1371/journal.pbio.3003981","url":null,"abstract":"<p><p>The experimental use of antibodies that have not been validated for context-specific use frequently misdirects biomedical research. Experimental results that derive from the use of inadequately validated antibodies are estimated to waste over $1 billion annually in the United States alone and to consume millions of animal and human biological samples in experiments whose conclusions may be unreliable. Community validation frameworks, reporting standards, and independent characterisation initiatives have made important progress, and multi-stakeholder coordination efforts are emerging. However, the research community lacks a formally developed, consensus-based action plan that specifies what each stakeholder group should do, by when, and with what priority. We conducted a modified Delphi study with international experts representing academic researchers, scientific publishers, research funders, antibody manufacturers, and institutional research leaders to develop actionable recommendations for improving antibody validation, selection, and reporting practices. Thirty-two participants rated 33 proposed actions on effectiveness and feasibility using 9-point scales, with consensus assessed using the RAND/UCLA Appropriateness Method. Over two rounds, the panel achieved consensus on 15 items as both effective and feasible for implementation by 2030. These spanned institutional actions (training in antibody validation, integration into research integrity frameworks, support for local expertise networks), funder actions (dedicated validation budgets, grant application requirements, endorsement of community reporting standards), publisher actions (complete antibody reporting packages, clear validation standards), manufacturer actions (assignment of unique identifiers at source), and cross-stakeholder coordination (a shared roadmap for improvement). An additional 15 items were rated as effective but with uncertain feasibility, reflecting a consistent pattern in which the panel agreed on the value of proposed interventions but expressed reservations about realistic implementation timelines. One item was rejected by the panel with concerns around effectiveness and feasibility. Participants described four interconnected barriers to progress: diffuse ownership of the problem across stakeholders; market dynamics that inadequately reward antibody quality; difficulty justifying investment when returns are distributed across the research system; and coordination challenges among actors with different incentive structures. These barriers are addressable through coordinated action, and the findings complement existing technical and data-sharing initiatives by providing the structured, expert-informed policy framework to help translate awareness of the problem into concrete practice and policy changes.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003981"},"PeriodicalIF":7.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117265","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":"Moral and perceptual conflict processing are implemented by distinct brain activation and functional connectivity patterns.","authors":"Ruida Zhu, Marcus Grueschow, Marius Moisa, Chao Liu, Christian C Ruff","doi":"10.1371/journal.pbio.3004025","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004025","url":null,"abstract":"<p><p>While humans resemble other primates in terms of motor and perceptual abilities, our behavior is uniquely characterized by morality-the ability to choose our actions based on specific ethical values. The evolutionary origins and neurobiological basis of moral behavior are debated intensely, with opposing proposals about whether moral decisions rely on domain-general decision-making neural circuitry (neural common currency hypothesis) or on unique neural processes that were shaped by evolutionary pressures associated with life in groups (social brain hypothesis). Here we examine the potential overlap between moral and perceptual decision-making, by combining functional magnetic resonance imaging with computational modeling of behavior in a novel task requiring human participants to make alternating moral and perceptual choices on identical stimuli. At the algorithmic level, we found that moral and perceptual choices were well fit by the same sequential sampling model, which allowed us to quantify and directly compare conflicts between the choice alternatives for both types of decision-making. At the implementational level, moral and perceptual choice conflicts were represented by distinct neural activity patterns; in fact, neural signals in some brain areas (e.g., temporoparietal junction) encoded the strength of the two types of conflict in opposite directions. Our findings suggest that while similar computational decision mechanisms underlie both moral and perceptual choices, their neural implementation is fundamentally different, supporting the social brain hypothesis.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004025"},"PeriodicalIF":7.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117242","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":"Uracil-driven ROS signaling and larval TrpA1-B neuron activation are required for priming the adult Drosophila gustatory response to bacteria.","authors":"Romane Milleville, Gérard Manière, Martine Berthelot-Grosjean, Olivier Lamotte, Yaël Grosjean, Julien Royet, Cyril Léopold Kurz","doi":"10.1371/journal.pbio.3004042","DOIUrl":"10.1371/journal.pbio.3004042","url":null,"abstract":"<p><p>Animals perceive their immediate environment through their sensory systems. While these systems rely on well-defined neuronal circuits and receptor proteins encoded by the genome, they can also be modulated by internal physiological conditions or exogenous factors. We have previously shown that the presence of certain pathogenic bacteria in the larval gut can alter the specificity of bacterial peptidoglycan recognition in the adults that emerge from these larvae. However, the nature of the bacterial signal and the host cells and molecules involved in receiving and transducing this signal remained unknown. Our results identify uracil as the bacterial metabolite responsible for this priming and demonstrate that the effect is mediated by Duox-dependent production of reactive oxygen species (ROS) in the larval gut. We further show that specific expression of TrpA1 isoforms in a Gr66a-expressing neuron of the larval terminal organ is required for the adult response. Together, these findings reveal uracil as the bacterial cue and the Duo/ROS signaling and TrpA1/Gr66a modules as key mediators linking larval gut microbial signals and host integration to subsequent sensory system modulation in the adult.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004042"},"PeriodicalIF":7.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116792","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":"Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism.","authors":"Dong Won Kim","doi":"10.1371/journal.pbio.3004014","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004014","url":null,"abstract":"<p><p>Neurodegenerative diseases often damage some neuronal populations while sparing closely related neighbors. But instead of asking why some neurons die, should we be asking why some survive? This Essay proposes that a neuron's capacity to sustain the gene-regulatory machinery that maintains its subtype identity helps set the stress threshold beyond which recovery fails. The initiating insult may be metabolic, proteostatic, inflammatory, or arise from the surrounding tissue, but it is the cell's capacity for maintenance that will determine where the tipping point lies: above a critical level, the identity program recovers, whereas below it, regulatory loss becomes self-sustaining. Such a framing could have implications for how neuronal vulnerability to neurodegeneration is understood.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004014"},"PeriodicalIF":7.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116764","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":"Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients.","authors":"Tao Pan, Xucui Zhuang, Ya Zhang, Jiyu Guo, Si Li, Can Zhang, Lili Han, Fuxia Li, Yueying Gao, Jinyang Yu, Yongsheng Li, Chaoyang Sun","doi":"10.1371/journal.pbio.3004029","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004029","url":null,"abstract":"<p><p>Genomic or transcriptomic sequencing guides the precision of cervical cancer (CC) diagnosis; however, the molecular profile of Asian patients remains poorly understood. We established a comprehensive multi-omics cohort comprising 112 tumor-normal adjacent tissue pairs from Chinese CC patients. Our integrated analysis revealed a mutational burden comparable to other populations, with three major mutational signatures primarily attributed to APOBEC-associated, age-associated, and DNA repair-associated biological categories. Multi-omics profiling elucidated the functional consequences of somatic mutations and copy number variations, identifying PIK3CA, EP300, and MPRIP as key driver events. We further uncovered both concordant and discordant activation patterns across cancer-related signaling pathways. Transcriptomic and proteomic analyses nominated cell cycle regulation, epithelial-mesenchymal transition, and LAMC2 as promising diagnostic and therapeutic targets. Comprehensive immune characterization enabled stratification of patients into three major immune phenotypes with varying microenvironmental profiles. This study provides valuable resources and novel insights into the molecular architecture of cervical cancer in the Chinese population, identifying potential biomarkers to guide precision detection and immunotherapy strategies.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004029"},"PeriodicalIF":7.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117303","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":"Targeting of conserved spike epitopes enables broad antibody neutralisation of diverse bat sarbecoviruses.","authors":"Ayush Upadhyay, Jeffrey Seow, Yilmaz Alguel, Joseph Newman, Nazia Thakur, Abigail L Hay, Jerry C H Tam, Andrea Nans, Richard J Orton, Dalan Bailey, Peter Cherepanov, Katie J Doores","doi":"10.1371/journal.pbio.3003882","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003882","url":null,"abstract":"<p><p>The continuing evolution of SARS-CoV-2 variants of concern, and the increasing spillover potential of sarbecoviruses into the human population presents an important and urgent need to discover cross-reactive monoclonal antibodies (mAbs) for future therapeutic use and identify conserved neutralising epitopes that can be used for rationale design of broadly protective sarbecovirus vaccines. Here we study the neutralising epitopes on WIV-1 Spike of three mAbs that confer broad sarbecovirus and SARS-CoV-2 variant neutralisation, including XEC, JN.1, and XFG. mAb V1WT_06 binds a highly conserved RBD site V epitope that is mediated by the heavy chain alone. V1WT_06 contact residues are highly conserved in circulating viruses suggesting that the epitope is evolutionarily and functionally constrained. mAbs V1WT_41 and VA14_26 bind overlapping RBD class 4 epitopes with differing angles of approach that impact on the degree of ACE2 competition. We show that neutralisation by these mAbs is maintained when virus entry is via Japanese horseshoe bat and Halcyon horseshoe bat ACE2s. These mAbs are ideal candidates for therapeutic antibody development and inform the rational design of pan-betacoronavirus vaccines.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003882"},"PeriodicalIF":7.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117268","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":"Breadth of ACE2 receptor usage predicts host range and antigenic relatedness across bat sarbecoviruses.","authors":"Nazia Thakur, Joseph Newman, Dongchun Ni, Jeffrey Seow, Abigail L Hay, Yeonjae Lee, Ayush Upadhyay, Babatunde E Ekundayo, John A Hammond, Thomas P Peacock, Kelvin Lau, Katie J Doores, Dalan Bailey","doi":"10.1371/journal.pbio.3003944","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003944","url":null,"abstract":"<p><p>Sarbecoviruses interact with their receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of Spike, the immunodominant target for neutralising antibodies. Understanding the interplay and correlation between ACE2-determined host range and antigenicity is vitally important for understanding the zoonotic potential of related bat sarbecoviruses. Using binding assays, pseudotype-entry assays and a diverse panel of mammalian ACE2 proteins, we examined the host range and related antigenicity of multiple bat coronaviruses. Broad bat ACE2 usage (a generalist phenotype) was most common in clade 1 sarbecoviruses, including SARS-CoV-2 and the BANAL isolates from Laos. In contrast, clade 3 (e.g., RhGB07) and 5 (e.g., Rc-o319) sarbecoviruses exhibited more restricted ACE2 usage (a specialist phenotype). A novel structure for RhGB07 Spike further helped to identify RBD residues associated with this receptor specialism. Interestingly, the generalist phenotypes were largely maintained with more diverse mammalian receptor libraries, including human, non-human primate, livestock, rodent ACE2 and potential intermediate reservoir hosts (e.g., civet, racoon dog, pangolin), while specialists, like RhGB07, exhibited wider phenotypic diversity. The impact of SARS-CoV-2's continued evolution in humans was also examined, identifying an expanding and/or shifting pattern of generalism for variants, especially Omicron and its sub-lineages. Furthermore, we compared and correlated these entry phenotypes with antigenicity using sera from SARS-CoV-2 convalescent individuals. Clade 1 viruses, phylogenetically related to SARS-CoV-2, were antigenically the most similar, with robust evidence for cross-neutralisation; however, there was still evidence for limited cross-neutralisation across the entire sub-genus. Finally, using monoclonal antibodies, derived from COVID-19 vaccinees with breakthrough infections, we pin-pointed the antibody epitope classes responsible for wider neutralisation. Our research indicates that generalist ACE2-using sarbecoviruses are phylogenetically and antigenically related to SARS-CoV-2.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003944"},"PeriodicalIF":7.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117307","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}