PLOS Biology: New Articles

Eye movements reflect capacity-dependent organization of working memory

2026-10-13T14:00:00Z

by Qiaoli Huang, Christian F. Doeller

Human cognition is capacity-limited, requiring strategies to actively structure information. Eye movements offer a natural mechanism for sequential sampling, but whether such sequences reflect memory organization is unknown. We developed a working-memory task where color-frequency pairings created a latent ordinal structure to optimally reduce memory load. Across two experiments, gaze patterns spontaneously aligned with this structure. Participants sampled items following this sequence during encoding and revisited them during maintenance. Critically, the expression of this structure depended on cognitive demand. In a 3-item task, high performers showed robust sequential sampling during encoding, whereas lower performers compensated with replay-like revisitation during maintenance. Under higher demand (4 items), encoding-based organization was disrupted, and structured revisitation emerged primarily during maintenance. These findings suggest that eye movements provide an overt expression of an internally generated organizational process that flexibly adapts to cognitive demands, revealing a behavioral analogue to neural replay when encoding resources are strained.

Interindividual vocal tract diversity influences the phonetic diversification of spoken languages

2026-10-13T14:00:00Z

by Steven Moran, Tiena Danner, Marcia S. Ponce de León, Christoph P. E. Zollikofer

Human vocal tracts, like other physical traits, exhibit extensive interindividual variation. However, little is known about how this variation translates into phonetic diversity between speakers, and ultimately, across languages. Here we develop a biocultural model of phonetic evolution, analogous to Russell Lande’s model of multivariate phenotypic evolution. We show that individual vocal tract morphologies and associated articulatory strategies leave consistent acoustic signatures, resulting in a characteristic pattern of phonetic variation within speaker groups that correlates with the pattern observed between groups. Recalling a central tenet of evolutionary biology—that within-group variation feeds between-group diversification—our findings suggest that phonologically similar vowel systems can attain phonetically diverse realizations according to a neutral-like evolutionary process. Our model serves as a null hypothesis for disentangling the biological versus cultural mechanisms underlying phonetic diversification, where deviations from the neutral expectation may indicate culturally mediated language change.

Bridging energy and proteome allocation models allows prediction of the resource cost of traits across environments

2026-10-13T14:00:00Z

by Mohammadjavad Meghrazi, Sarah P. Otto

Many traits divert resources from reproduction and are costly due to the physiological trade-offs organisms face. These traits might require the allocation of different resources, e.g., energy expenditure or production of macromolecules, and it is unclear how their costs can be compared given their different units. Moreover, the effect of environmental conditions and genetic background on the cost of traits is not well understood. Two different frameworks have been proposed to quantify the resource costs of traits, focusing on either energy allocation or proteome allocation. These frameworks implicitly assume energy provisioning or protein production limits growth, respectively, but the connection between the two limitations has been underexplored. To better connect these frameworks, we develop a framework that considers limitations in energy provisioning and macromolecule biosynthesis simultaneously to quantify and compare the cost of traits that require different resources. Using this model, we explore how environmental quality and genetic background affect the cost of traits. Notably, our model predicts that increasing food quality increases the cost of traits that require the production of new structures, while decreasing the cost of traits requiring energy expenditure. Moreover, our model makes novel predictions about the effect of degradation, recycling, and energetic demands for maintenance on the relationship between the macromolecular composition of the cells and growth rate (also known as bacterial growth laws).

PrimeStack editors enable efficient and site-specific integration of large multigene cargos in plants

2026-10-13T14:00:00Z

by Edith Sánchez, Khalid Sedeek, Haroon Butt, Magdy Mahfouz

Precise, site-specific integration of large DNA sequences into plant genomes is a long-standing goal of crop biotechnology and synthetic biology, yet remains constrained by random insertion, inefficient homologous recombination, and gene targeting. Here, we present PrimeStack, a DSB-independent platform that integrates PE with the unidirectional large serine integrase Bxb1, leveraging evolved variants for enhanced activity, to achieve the programmable insertion of multigene, multikilobase cargos at predefined genomic safe harbors (GSH) in rice (Oryza sativa). Optimized prime editors first install attP landing sites with high fidelity and heritability followed by Bxb1-mediated recombination that generates irreversible integration of genetic information. PrimeStack enabled targeted large-cargo integration in regenerated rice plants with efficiencies of up to 45%, as determined by junction-specific PCR analyses. No obvious morphological differences from WT plants were observed at 5 weeks after transfer to soil under the evaluated conditions. We validate its utility by achieving targeted insertion of a carotenoid cassette at an experimentally confirmed genomic safe harbor. PrimeStack delivers a modular, site-specific gene stacking platform that enables predictable, multigene trait pyramiding and pathway construction at GSH, thereby accelerating the development of improved and resilient crop varieties, as well as scalable plant-based biomanufacturing and a powerful chassis for synthetic biology.

An inositol receptor Itr4 coordinates carbon catabolite regulation and virulence in Cryptococcus neoformans

2026-10-13T14:00:00Z

by Yina Wang, Robert Tancer, Maggie Wear, Katrina M. Jackson, Yu Zhang, Kan Li, Jun Wang, Yong-Gui Gao, Kirsten Nielsen, Arturo Casadevall, Chaoyang Xue

Nutrient sensing and utilization are critical for microbes to adapt to their environment and evade predators. The encapsuled yeast Cryptococcus neoformans has a unique ability to sense and utilize the sugar inositol as both a signaling molecule and as a carbon source. This trait is advantageous not only in the natural environment but also to promote its pathogenesis, including invasion of the central nervous system. In this study, we have identified a novel inositol transporter-like receptor (transceptor) Itr4 that coordinates inositol and glucose metabolism by regulating inositol transporters (ITRs) and glucose sensor Hxs1. Itr4 binds inositol and regulates the function of other ITRs and its loss leads to a significant decrease in inositol uptake activity, resulting in a lack of mating, reduced capsule size, reduced blood–brain barrier (BBB) penetration, and virulence attenuation. Mutagenesis analysis of Itr4 protein identified an essential N-terminal tail and two amino acids, Q388 and Q389, as sites of functional importance. The ITR4^{Q388A, Q389A} allele showed a dominant phenotype with increased inositol uptake, enlarged capsule and significantly attenuated virulence. In summary, we identify a new C. neoformans inositol transceptor, Itr4, the first such example in eukaryotes, with novel regulatory roles in both inositol and glucose metabolism and fungal virulence.

Recombination shapes the dynamics of selective constraint in global populations of human gut bacteria

2026-10-12T14:00:00Z

by Zhiru Liu, Benjamin H. Good

The ratio of nonsynonymous to synonymous substitutions (dN/dS) encodes important information about the selection pressures acting on protein-coding genes. In bacterial populations, dN/dS often declines with the sequence divergence between strains, but the mechanisms responsible for this broad empirical trend are still debated. Existing models have primarily focused on de novo mutations, overlooking the older genetic variants that are continually introduced through horizontal gene transfer and recombination. Here we introduce a phenomenological model of dN/dS in recombining populations of bacteria, which allows us to disentangle the effects of recombination among pairs of closely related strains. We find that clonally inherited regions of the genome exhibit consistently higher dN/dS ratios, and that the accumulation of recombined segments can quantitatively explain the majority of the decline in dN/dS. We use these observations to re-examine models of purifying selection and adaptive reversion in human gut bacteria, and uncover evidence for widespread weak selection at a large fraction of protein-coding sites. Our findings show that horizontal gene transfer can be an important factor in shaping genome-wide patterns of selective constraint, and raise new questions about the effectiveness of natural selection in complex bacterial populations.

Does perturbed adaptive myelination contribute to cognitive dysfunction in Alzheimer’s disease?

2026-10-12T14:00:00Z

by Charles ffrench-Constant

The consequences of oligodendrocyte involvement in Alzheimer’s disease are poorly understood. Could a key role of gray-matter oligodendrocytes—activity-dependent adaptive myelination to sustain changes in activity—be perturbed, leading to cognitive loss? The consequences of oligodendrocyte involvement in Alzheimer’s disease are poorly understood. This Perspective suggests that activity-dependent adaptive myelination, a key role of grey-matter oligodendrocytes, could be perturbed, leading to cognitive loss.

The Cryptococcus neoformans titanide is a pathogenic cell type that arises from typical yeast cells in response to host conditions

2026-10-12T14:00:00Z

by Abigail M. Potton, Iana Kalinina, Gordon D. Brown, Maria Makarova, Sandra Catania, Dora E. Corzo-Leon, Elizabeth R. Ballou

Fungal morphogenesis is a major driver of disease outcome. For the opportunistic fungal pathogen Cryptococcus neoformans, extreme morphological heterogeneity within the lung environment drives dissemination, immune evasion, and drug resistance. One such cell type is the small, oval, titanide (2–4 µm). This poorly understood cell type is prevalent in lung histology as well as host-relevant in vitro conditions. In conditions that generate cellular heterogeneity, titanides comprise 4%–10% of cells 24 hours post-induction and by 72 hours are the dominant cell type. Despite their prevalence and the significance of cryptococcal morphogenesis for virulence, key questions pertaining to their origin, fate, and underlying biology remain unstudied. Using TEM, SEM, and fluorescence microscopy we demonstrate that titanides display distinct morphological features; they possess thin cell walls, single birth scars, and capsules, with reduced Pathogen-Associated Molecular Pattern exposure and altered distribution. These features distinguish titanides from previously described C. neoformans ‘small cells’ such as in vivo seed cells (6 µm, high cell-wall mannan content) and micro cells (round, <1 μm, with thick cell walls) among others. Using microfluidics, we reveal that titanides arise from yeast-like ‘typical’ mothers, highlighting the morphological plasticity of typical cells in host-relevant conditions. Upon birth, titanides have compact nuclei and do not immediately proliferate, but transfer to fresh media results in rapid swelling and cell division. Consistent with this, titanides are more resistant to some cell wall/membrane stressors and are an effective infectious propagule in a murine model. Together, these findings establish a definition and essential characterisation of the titanide cell type and provide new insight into a key player in C. neoformans cell biology and pathogenesis.

Implicit sensorimotor adaptation comprises distinct mechanisms for action selection and execution

2026-10-09T14:00:00Z

by Tianhe Wang, Tony Lam, Jordan A. Taylor, Richard B. Ivry

The sensorimotor system is continuously adjusted to minimize error. Current theories assume that this adaptation process entails the operation of multiple learning systems, with a key division between implicit and explicit components. Recent studies have revealed several inconsistencies regarding the characteristics and constraints of the implicit system, suggesting that the current framework is incomplete. Here, we propose that these conflicting findings can be understood by recognizing that there are multiple implicit subcomponents, each with distinct computational goals. One well-studied component is implicit recalibration, a process critical for action execution which uses sensory-prediction errors to automatically refine the sensorimotor map. In the current study, we describe a second, novel component, implicit aiming, a process which contributes to action selection to achieve specific goals. Through a series of studies using human participants, we find compelling evidence that those two implicit processes show a clear separation in their temporal stabilities and contextual modulations. These distinct properties correspond to different computational frameworks attributing learning dynamics to either contextual inference or cancellation of competing neural populations, respectively. Together, these findings suggest an alternative framework for sensorimotor adaptation based on the computational goals of the system rather than phenomenology.

FuChi is a cell cycle biosensor for tracking cell cycle dynamics during avian development

2026-10-09T14:00:00Z

by Zoe R. Sudderick, Tiernan Briggs, Shirooza Mubarak, Melinda Van Kerckvoorde, Ana R. Hernandez Rodriguez, Sudeepta K. Panda, Jon Riddell, Cameron Batho-Samblas, Lorna Taylor, Lynn McTeir, Dominique Meunier, Amy Findlay, Flossie S. Roberts, Anna Raper, Asako Sakaue-Sawano, Atsushi Miyawaki, Joe Rainger, Jeffrey J. Schoenebeck, Cornelis J. Weijer, Mike J. McGrew, Denis J. Headon, Megan G. Davey, Richard L. Mort, James D. Glover

The ability to monitor the proliferative status of live cells both in vitro and in vivo over time has revolutionised our understanding of development, growth and disease. This was first made possible by fluorescent ubiquitination-based cell cycle indicator (Fucci) technology, which distinguishes specific cell cycle phases through the reciprocal degradation of fluorescently tagged, truncated forms of human CDT1 and GMNN proteins. Fucci genetic systems have been successfully implemented in transgenic mice, zebrafish, and axolotls. To date, no viable, stably expressing Fucci line has been developed in an avian species. Although a range of continuously improving Fucci constructs have been developed in recent years, existing in vivo Fucci models remain limited because they rely on older reporter technology that fails to distinguish cells in S, G2, and M phases or to label cells in early G1. As a result, these models can be challenging to interpret and their utility for continuous cell tracking and precise analysis of cell-cycle dynamics is limited. Here, we introduce FuChi, a multicistronic Fucci-expressing chicken line incorporating a newly optimised reporter construct composed of an mCerulean-tagged histone H1.0 linker protein fused via a self-cleaving 2A peptide to the tandem Fucci(CA)2 cell cycle biosensor, with additional epitope tags included for detection in fixed tissues. We show that this system accurately discriminates and permits tracking of cells in G1, S, G2, and M phases both in vitro and in vivo, enabling faithful visualisation of cell cycle status in intact tissues and organs. Using FuChi embryos, we mapped proliferation dynamics across developing tissues, analysed cell cycle states of migrating cells, and performed live imaging of early embryos. These latter experiments revealed that transition from S phase may be a key morphogenetic event during gastrulation as mesendoderm cells egress from the primitive streak to form embryonic structures including the prechordal plate. Pairing this advanced reporter with the intrinsic experimental advantages of the chicken embryo positions FuChi as a premier in vivo system for studying cell-cycle kinetics in development, delivering clear technological improvements over current Fucci models. FuChi chickens provide a powerful new resource for studying embryonic development, organ growth, tissue homeostasis, disease processes, and infection responses.

A histidine-mediated supramolecular mechanism links temperature and pH activation of the sperm channel CatSper

2026-10-09T14:00:00Z

by Billy Zhao, Shweta Bhagwat, Juan Ferreira, Kiersten M. Ruff, Dilip K. Swain, Rohit V. Pappu, Celia M. Santi, Ziao Fu, Polina V. Lishko

The cation channel of sperm, CatSper, is a sperm-specific calcium channel essential for male fertility across metazoans. CatSper is activated by intracellular alkalinization, membrane depolarization, and elevated temperature, which together ensure maximal current generation. However, the structural mechanisms by which these physiological stimuli jointly regulate channel activation remain poorly understood, in part because CatSper is an unusually complex ~15-subunit assembly organized in zigzag supramolecular arrays along the sperm flagellum. Here, we combine comparative genomics across 47 species with AlphaFold3-based modeling and evolutionary sequence-structure analyses to investigate a mechanism underlying temperature and pH sensitivity of CatSper. Phylogenetic analysis shows that N-terminal length and histidine enrichment of the pore-forming subunit CatSper1 strongly correlate with species-specific fertilization temperatures, suggesting evolutionary adaptation of temperature and pH sensitivity. Structural modeling further revealed conserved surface-exposed histidine clusters that form predicted contact interfaces between adjacent CatSper assemblies, with this contact interface positioned near the dominant voltage-sensing module. Functional validation using electrophysiology and calcium imaging in mouse sperm shows that capacitation-associated partial removal of the CatSper1 N-terminus selectively impairs temperature-dependent activation. Together, these findings support a model in which temperature-dependent histidine deprotonation functionally couples neighboring CatSper complexes within the supramolecular assembly, thereby promoting synchronized channel activation.

The histone methyltransferase complex subunit RBBP5 serves as a central epigenetic regulator of proteostasis dynamics

2026-10-08T14:00:00Z

by Syeda Kubra, Michelle Sun, William Dion, Yu Bian, Ahmet Catak, Hannah Luong, Haokun Wang, Yinghong Pan, Jia-Jun Liu, Aishwarya Ponna, Lijun Liu, Ian Sipula, Jian-Hua Luo, Michael J. Jurczak, Silvia Liu, Bokai Zhu

Proteostasis is essential for cellular health, with its disruption contributing to aging, neurodegeneration, and metabolic disorders. While the upstream proteotoxic stress-sensing and protein-folding mechanisms in the ER and cytosol are well studied, the transcriptional regulation of proteostasis remains incompletely understood, particularly concerning the temporal epigenome dynamics, chromatin landscapes, and co-regulatory networks underlying dynamic proteostasis control. Traditionally, proteotoxic stress responses were viewed as acute reactions to noxious stimuli, but recent evidence shows that many proteostasis genes exhibit ~12-hour ultradian rhythms under physiological conditions, driven by an XBP1s-dependent oscillator independent of the canonical circadian clock and cell cycle. By mapping the chromatin landscape of the murine 12-hour oscillator, we identified RBBP5—an essential subunit of the COMPASS complex responsible for H3K4 trimethylation—as a pivotal epigenetic regulator of proteostasis dynamics. In contrast, histone acetyltransferases and H3K9 acetylation were dispensable for dynamic proteostasis gene expression. RBBP5 is not only indispensable for the 12-hour oscillator but also essential for the transcriptional regulation of diverse proteotoxic stresses response, by coactivating XBP1s and promoting H3K4me3 deposition at the promoters of proteostasis genes. As a result, loss of RBBP5 sensitizes cells to proteotoxic stress in part due to impaired autophagy. Proximity labeling of H3K4me3 further uncovered a dynamic chromatin-associated proteomic architecture, including components of COMPASS, the Integrator complex and SWI/SNF remodelers, that constitutes the transcriptional response to proteotoxic stress. Together, these findings establish RBBP5 as a central regulator of proteostasis dynamics, essential for maintaining cellular resilience.

Distinct millisecond-scale click-train patterns evoke discriminable behavioral and neural responses in humans and rats

2026-10-08T14:00:00Z

by Yuying Zhai, Peirun Song, Ana Belén Lao-Rodríguez, Xinyu Du, Haoxuan Xu, Hangting Ye, Xuehui Bao, Ishrat Mehmood, Nayaab Shahir Pandit, Cheng Chang, Zhouyou Dai, Zhiyi Tu, Pei Chen, Tingting Zhang, Lingling Zhang, Xuan Zhao, David Pérez-González, Manuel S. Malmierca, Xiongjie Yu

Natural sounds are shaped by both spectral content and temporal patterning. Here we ask whether click trains with the same mean inter-click interval, but different millisecond-scale temporal patterns evoke distinct behavioral and neural responses. Human listeners discriminated several such click-train patterns, and human EEG revealed context-dependent deviance-related responses. Awake rats showed analogous cortical response differences at the ECoG level. Along the IC–MGB–A1 pathway, unit recordings revealed weak oddball/context sensitivity in IC, intermediate sensitivity in MGB, and stronger stimulus-specific adaptation in A1. Reversible inactivation of the auditory cortex reduced MGB sensitivity, indicating a contribution of corticothalamic feedback. Further A1 layer analyses showed stronger effects in supragranular than deep cortical layers. Together, these results show that distinct click-train temporal patterns are differentially represented across the auditory system, with stronger sensitivity emerging in higher auditory structures.

Type III effectors of symbiotic Rhizobia include diverse predicted transcriptional and post-transcriptional modulators

2026-10-08T14:00:00Z

by Albin Teulet, Sebastian Schornack

Rhizobia are soil bacteria that establish nitrogen-fixing symbioses with legumes. While many rhizobia use a Type III Secretion System to deliver “Nodulation Outer Protein” (Nop) effectors, some uniquely use these proteins to initiate nodule organogenesis, bypassing classical signalling. The molecular functions of these effectors remain largely unknown due to extreme sequence divergence. Using AlphaFold2-mediated structural proteomics, we identified a modular architecture in rhizobial effectors composed of 22 distinct structural units. We reveal that many Nop effectors are cryptic transcriptional or post-transcriptional regulators, harbouring unrecognised nucleic acid–binding modules and RNA-dependent RNA polymerase domains. Crucially, these modules are conserved in specific plant pathogens, such as gall-inducing Pantoea, where our predicted structural units align with experimentally validated DNA-binding domains. Furthermore, we discovered the BPN (B3 and PUA-like nucleic acid binding) domain as a structural mimic of plant B3-domain transcription factors, pointing to a direct mechanism for hijacking legume development. Our findings strongly suggest that rhizobia employ a modular domain-fusion strategy to act as direct genetic modulators, uncovering a conserved mechanism used by both symbionts and pathogens to hijack host developmental programmes.

Better antibodies, better science

2026-10-07T14:00:00Z

by Johan Duchêne

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. Poorly validated antibodies generate misleading results and waste research resources. This Primer explores two new studies in PLOS Biology that quantify the ethical costs of this issue, examine why unvalidated antibodies are still used, and identify solutions to reduce their use.

A binding-activated CRISPR/dCas13X imaging system enables precise RNA tracking in plants

2026-10-06T14:00:00Z

by Jiayu Zhang, Yiran Tao, Yun Zhao, Miaomiao Lei, Yucheng Shen, Qicong Li, Chenxu Liu, Jiuyuan Bai

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.

Inadequate antibody validation places substantial numbers of animal and human tissue samples at risk of waste

2026-10-06T14:00:00Z

by Michael Biddle, Jemma Cooper, Katherine Blades, Dominic Ruddy, Eva M. Krockow, Harvinder Virk

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.

Actionable solutions to address antibody validation failures

2026-10-06T14:00:00Z

by Katherine Blades, Michael Biddle, Robert Froud, Eva M. Krockow, Harvinder Virk

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.

Uracil-driven ROS signaling and larval TrpA1-B neuron activation are required for priming the adult Drosophila gustatory response to bacteria

2026-10-05T14:00:00Z

by Romane Milleville, Gérard Manière, Martine Berthelot-Grosjean, Olivier Lamotte, Yaël Grosjean, Julien Royet, Cyril Léopold Kurz

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.

Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients

2026-10-05T14:00:00Z

by Tao Pan, Xucui Zhuang, Ya Zhang, Jiyu Guo, Si Li, Can Zhang, Lili Han, Fuxia Li, Yueying Gao, Jinyang Yu, Yongsheng Li, Chaoyang Sun

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.

Moral and perceptual conflict processing are implemented by distinct brain activation and functional connectivity patterns

2026-10-05T14:00:00Z

by Ruida Zhu, Marcus Grueschow, Marius Moisa, Chao Liu, Christian C. Ruff

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.

Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism

2026-10-05T14:00:00Z

by Dong Won Kim

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.

Breadth of ACE2 receptor usage predicts host range and antigenic relatedness across bat sarbecoviruses

2026-10-01T14:00:00Z

by 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

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.

Targeting of conserved spike epitopes enables broad antibody neutralisation of diverse bat sarbecoviruses

2026-10-01T14:00:00Z

by 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

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.

Adaptive introgression between two Drosophila species enhances heat tolerance despite barriers to gene flow

2026-09-30T14:00:00Z

by Noora Poikela, Rhonda R. Snook, Jonna Kulmuni, Michael G. Ritchie

As global temperatures rise and heat waves become more frequent, populations must adapt rapidly to avoid local extinctions. Adaptive introgression allows species to quickly acquire adaptive genetic material from close relatives. However, certain genomic regions, containing barrier loci, may resist introgression. We experimentally tested whether strong heat stress selection can overcome such barriers and facilitate the transfer of adaptive alleles to improve heat tolerance. We also examined whether chromosomal inversions, which can tightly link adaptive and barrier loci through reduced recombination, promote or prevent introgression. We conducted a hybridize, evolve, and re-sequence experiment by crossing the heat-sensitive D. flavomontana with the more heat-tolerant D. montana, exposing heat-selection lines to transient heat for three generations while maintaining control lines. We also mapped long-term barriers to gene flow between natural populations using a demographically explicit genome scan. The heat-selection lines exhibited approximately twice the introgression and higher male fertility under heat stress compared to control lines and the heat-sensitive parental D. flavomontana. This introgression was primarily located in colinear autosomal regions and correlated with improved heat tolerance. Some introgression occurred also in inverted autosomal regions in the heat-selection lines but not in the control lines. The X chromosome, with three overlapping inversions, resisted introgression in both heat-selection and control lines, thereby maintaining a strong species barrier. Finally, genetic barriers in the control lines significantly overlapped with long-term barriers, but this overlap was less pronounced in the heat-selection lines. Our study demonstrates that strong selection can lead to adaptive introgression despite long-standing genetic barriers. These findings highlight that introgression can serve as a rapid source of adaptive genetic material under stressful thermal conditions, potentially mitigating climate-induced population extinctions.

Nightjars trade off cruising speed efficiency for hovering capabilities and link upstroke thrust production with restricted wing folding

2026-09-30T14:00:00Z

by L. Christoffer Johansson, Gabriel Norevik, Sonja Friman, Anders Hedenström

The European nightjar (Caprimulgus europaeus) is a long-distance migrant that also uses slow, hovering, flight as part of its feeding ecology. This reflects complex tradeoffs in aerodynamic mechanisms and makes studies of their flight performance, in relation to their wing shape, particularly interesting. Here we reveal, using wake visualization and aerodynamic measurements of nightjars flying in a wind tunnel, a unique double tip vortex phenomenon at cruising speeds. This correlates with reduced span efficiency at these flight speeds, suggesting relatively high costs of generating lift. Our interpretation is that the nightjar’s broad, slotted wing tip shape promotes lift during slow flight while incurring reduced aerodynamic efficiency at faster speeds. In addition, we found outer wing upstroke thrust generation during cruising flight—a characteristic previously attributed to bats and hummingbirds—in nightjars. This challenges an existing paradigm that considers an active upstroke to primarily add weight support in birds. Our kinematic analysis suggests this phenomenon may stem from constraints on wing folding during the upstroke, something that may apply generally to flapping flight. Our results highlight the tradeoffs seen in animals engaged in multiple costly behaviors with different aerodynamics optimization criteria based on ecological demands and offer potential solutions applicable in bioinspired engineering.

Intrinsic timescale develops hierarchically from sensorimotor to association cortex in youth and stabilizes in adulthood

2026-09-29T14:00:00Z

by Golia Shafiei, Joëlle Bagautdinova, Valerie J. Sydnor, Dani S. Bassett, Deanna M. Barch, Matthew Cieslak, Yong Fan, Elizabeth Flook, Alexandre R. Franco, Gregory Kiar, Audrey C. Luo, Michael P. Milham, Linden Parkes, Taylor Salo, Leah H. Somerville, Tien T. Tong, Russell T. Shinohara, Theodore D. Satterthwaite

Intrinsic timescale is a commonly used measure of spontaneous neural dynamics that quantifies the temporal window of processing of neuronal populations. Intrinsic timescale displays a hierarchical cortical organization across multiple species and imaging modalities, with shorter timescales in sensorimotor cortex compared to association cortex. However, less is known about how intrinsic timescale evolves during human brain development and whether its cortical maturation patterns generalize to independent developmental samples. Here we estimate the intrinsic timescale in two independent cross-sectional datasets of youth (HCPD: n = 565; HBN: n = 729; age range 8–22 years) and investigate its neurodevelopmental patterns. We find that developmental patterns in the intrinsic timescale follow a hierarchical pattern that recapitulates an axis spanning sensorimotor to association cortices (S–A axis). Our analysis of an independent healthy young adult dataset (HCPYA: n = 973, age range 22–37 years) underscores the specificity of these developmental findings, suggesting that the intrinsic timescale develops along the S–A axis in youth and stabilizes in adulthood. Together, these results reveal convergence between major axes of cortical organization and development, highlighting intrinsic timescale as a principled marker of hierarchical brain maturation in youth.

Correction: Correction: Data-driven analyses of motor impairments in animal models of neurological disorders

2026-09-29T14:00:00Z

by The PLOS Biology Staff

A trade-off between fungal biofilm formation and persistence in the host

2026-09-29T14:00:00Z

by Shannon Esher Righi

Fungal biofilm formation has long been considered an important virulence trait. A new study on Candida parapsilosis outbreak isolates in PLOS Biology challenges this, finding that low biofilm-producing strains are better adapted for immune evasion and survival. Fungal biofilm formation has long been considered an important virulence trait. A new study on Candida parapsilosis outbreak isolates in PLOS Biology challenges this, finding that low biofilm-producing strains are better adapted for immune evasion and survival.

Intestinal lipid metabolism controls molecular and behavioral immunity through NHR-68 and gut–brain signaling in Caenorhabditis elegans

2026-09-29T14:00:00Z

by Jie Ren, Yu Sang, Young-Mo Kim, Ernesto S. Nakayasu, Alejandro Aballay

Animals must allocate limited energetic resources across competing defense programs in response to infection. Here, we show that the conserved nuclear hormone receptor NHR-68 integrates fatty acid metabolism with the neural control of molecular and behavioral immunity in Caenorhabditis elegans. Acting in parallel with NHR-10, NHR-68 controls genes involved in polyunsaturated fatty acid (PUFA) metabolism. Loss of NHR-68 disrupts linoleic acid (LA) homeostasis, impairing pathogen avoidance behavior. Supplementation with LA restores avoidance, and fat-3 inhibition, which elevates LA, enhances pathogen avoidance, whereas loss of LA synthesis by fat-2 inhibition diminishes this behavior, indicating that LA promotes behavioral immunity. We further show that NHR-68 acts in the intestine to regulate linoleic acid homeostasis, and that changes in intestinal lipid metabolism influence an AWC-dependent pathogen-avoidance circuit through intestine-to-neuron communication. NHR-68 suppresses activation of the PMK-1/p38 MAPK and DAF-16/FOXO pathways, which mediate molecular immune responses. These findings identify a gut-brain transcriptional circuit that connects intestinal lipid metabolism to neural and immune outputs, revealing a mechanism by which the metabolic state coordinates behavioral and molecular defenses to optimize host protection.