PLoS Biology最新文献

{"title":"Environmental uncertainty shapes human effort learning.","authors":"Rong Bi, Jan Grohn, Patricia L Lockwood, Miriam C Klein-Flügge, Lilian Weber","doi":"10.1371/journal.pbio.3003791","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003791","url":null,"abstract":"<p><p>Humans show remarkable flexibility in adapting their behaviour to constantly changing environments. This flexibility relies on the ability to regulate motivation in response to changing motivational demands. Typically, the amount of effort required to achieve a certain goal is not precisely signalled by the environment but needs to be learnt from experience. By contrast, prior work examining motivated choices has usually directly instructed effort requirements. It therefore remains unclear how healthy individuals estimate and flexibly regulate effort and how they might achieve this in dynamically changing environments. In the current study, we examine how effort learning is shaped by different types of environmental uncertainty when motivational requirements are not explicitly instructed. Analogous to tasks in the reward learning domain, we designed a novel effort learning task that systematically manipulated two key sources of uncertainty: volatility and noise. Participants were asked to exert effort by squeezing hand-held dynamometers. We characterised effort learning across different stages of the effort production process (e.g., initiation of effort production, effort expectation, error-driven adjustment), which allowed us to capture the dynamics underlying effort estimation and regulation over time. Our findings reveal that humans are able to learn effort requirements by integrating both effort priors and sensorimotor feedback. We further show that effort learning is modulated by environmental statistics, with slower force initiation, weaker priors, slower learning, and faster within-trial force adjustments in high noise environments, but slower learning and slower within-trial force adjustments in high volatility environments. In summary, when effort information is not instructed, different sources of uncertainty about an action's required effort are integrated into participants' internal priors to flexibly guide effort exertion. Our work may provide a useful framework for understanding motivational disorders where abnormal effort learning and estimation may underlie the reduced willingness to exert effort for reward.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003791"},"PeriodicalIF":7.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted sequencing enhances detection of pangolin trafficking hotspots and dynamics of both domestic and global trade markets.","authors":"Sean P Heighton, Jérôme Murienne, Mukesh Thakur, Alain Didier Missoup, Wirdateti Wirdateti, Chabi Sylvestre Djagoun, Sery Bi Gonedelé, Gabriel Ngua Ayecaba, Brice Roxan Momboua, Flobert Njiokou, Anne-Lise Chaber, Helen C Nash, Barbora Černá Bolfíková, Sylvain Dufour, Guy T Gembu, Ayodeji Olayemi, Jordi Salmona, Amaia Iribar, Yves Cuenot, Philippe Gaubert","doi":"10.1371/journal.pbio.3003762","DOIUrl":"10.1371/journal.pbio.3003762","url":null,"abstract":"<p><p>Pangolins have become emblematic of the global wildlife trade crisis due to intense trafficking for consumption and traditional medicine. Coupled with habitat loss, the illicit trade in pangolins has severely threatened wild populations. Genetic identification of distinct pangolin populations is an imperative step toward guiding effective and informed conservation management. These populations can serve as a reference for assigning seized individuals to their geographic origins, and thus tracing trafficking networks. However, pangolin population genetics studies have been hindered by limited sampling of geo-referenced individuals, largely due to the species' elusive nature. To address this, we developed a tailored gene-capture approach targeting 671 loci totaling 627 kb with high evolutionary and adaptive value across all eight pangolin species. We optimized the approach for low-quality DNA, including samples from museum collections and wildlife trade, such as bushmeat and scale seizures. We reassessed range-wide population delineations for the three most traded species, the white-bellied (Phataginus tricuspis), Sunda (Manis javanica), and Chinese (M. pentadactyla) pangolins, highlighting the need for biogeographically consistent lineage nomenclature and spatially aware analyses to support coherent conservation planning. The unprecedented geo-referenced DNA database for the three species yielded snapshot insights into pangolin trafficking hotspots and trade dynamics of both domestic markets and global trade seizures, the former providing novel insights into bushmeat trade. Domestic trade reflects local and occasional cross-border sourcing, averaging 454 km across the three species, while international trafficking seizures in mostly scales point to broader, regional procurement. However, common sourcing regions between the two trade market types indicate their interconnectivity, suggesting that local trade may contribute to international trade supply. Our study identified significant international trade hotspots for the white-bellied, Sunda, and Chinese pangolins, centered around southwestern Cameroon, southwestern Borneo Island, and Myanmar, respectively. Addressing geo-referenced sampling gaps and increasing local-to-global seizure data over time may offer deeper spatiotemporal insights into pangolin trade dynamics. Our study design may serve as a replicable model for enabling authorities and practitioners to implement intelligence-driven, geographically targeted interventions, by identifying the key regions most implicated in pangolin trafficking.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003762"},"PeriodicalIF":7.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844868","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":"The KMT2F histone methyltransferase interacts with the RNA polymerase I machinery to promote ribosomal RNA transcription.","authors":"Kaisar Ahmad Lone, Amit Mahendra Karole, Geethanjali Ravindran, Shweta Tyagi","doi":"10.1371/journal.pbio.3003785","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003785","url":null,"abstract":"<p><p>Trimethylation of histone 3 lysine 4 (H3K4me3) is a mark of active transcription, and its regulatory role in RNA polymerase II-mediated transcription has been well-studied. However, if and how this mark regulates RNA polymerase I (RNA Pol I) is not known. Here, we used customized genome assemblies for rDNA to demonstrate that KMT2A and KMT2F bind to entire rDNA loci. The binding of these enzymes was mirrored by the binding of H3K4me2 and H3K4me3 marks. Using biochemical assays, we demonstrate the interaction of KMT2-specific subunits with RNA Pol I transcriptional machinery. Our findings reveal KMT2F as the primary KMT depositing the H3K4me3 on rDNA. Loss of H3K4me3 adversely affects the epigenetic landscape and leads to repression of the rDNA locus. Mechanistically, using mammalian cells as a model system, we demonstrate that KMT2F promotes the formation of the pre-initiation complex by RNA Pol I. Our findings highlight the thus far undiscovered role of H3K4me3 in the transcriptional initiation of rDNA genes.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003785"},"PeriodicalIF":7.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: An international consensus on core reproducibility items in research.","authors":"","doi":"10.1371/journal.pbio.3003792","DOIUrl":"10.1371/journal.pbio.3003792","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pbio.3003726.].</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003792"},"PeriodicalIF":7.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844716","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":"Structured water molecules drive activation and G protein selectivity in the GPR174 receptor.","authors":"Ying-Jun Dong, Kun Xi, Ya-Zhi Zhang, Jian-Heng Xue, Dan-Dan Shen, Shao-Kun Zang, Ruozhu Zhao, Hai Qi, Chunyou Mao, Wei-Wei Wang, Yan Zhang","doi":"10.1371/journal.pbio.3003447","DOIUrl":"10.1371/journal.pbio.3003447","url":null,"abstract":"<p><p>G protein-coupled receptor 174 (GPR174), a key modulator of autoimmune responses, maintains immune homeostasis through distinct G protein signaling pathways, particularly Gs and Gi. Although the structural mechanism of lysophosphatidylserine (LysoPS)-activated GPR174 in the Gs pathway has been characterized, how hydration-mediated interactions influence GPR174 activation and signaling selectivity remains unclear. Here, we determined high-resolution cryo-electron microscopy (cryo-EM) structures of LysoPS-activated human GPR174 bound to Gs (2.0 Å) and Gi (3.4 Å), revealing a continuous hydration-mediated signal transduction network that bridges the sodium-binding pocket, the NPxxY and DRY motifs, and the G protein-binding interface. This network stabilizes the active-state conformation of GPR174 and dynamically reshapes the intracellular cavity, thereby enabling differential engagement of Gs and Gi. Molecular dynamics simulations and functional assays demonstrated that the hydration network is essential for receptor activation and selectively modulates G protein coupling. To evaluate its conservation, we performed sequence alignments and structural analyses across class A GPCRs, defining three hydration cavities: the conserved water cavity (CWC), the junctional water cavity (JWC), and the extended water cavity (EWC), whose hydration is determined by residue properties at position 5.58. Together, our study reveals a hydration-driven molecular mechanism that underlies the activation of GPR174 and its dual G protein selectivity. These findings advance the understanding of hydration-mediated signaling in GPR174 and provide a framework for investigating water-mediated regulation across class A GPCRs.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003447"},"PeriodicalIF":7.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844924","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":"Ultrasound neuromodulation reveals distinct roles of the dorsal anterior cingulate cortex and anterior insula in learning.","authors":"Nomiki Koutsoumpari, Johannes Algermissen, Siti Nurbaya Yaakub, Hanneke Em den Ouden, Nadege Bault, Elsa Fouragnan","doi":"10.1371/journal.pbio.3003767","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003767","url":null,"abstract":"<p><p>Pavlovian biases reflect how evolutionarily hard-wired tendencies-automatic approach toward reward cues and withdrawal from threat cues-can interfere with flexible, goal-directed action. Such biases arise through three mechanisms: (a) anticipated rewards energize action while anticipated punishments suppress it (response bias), (b) agents learn differently from actions than from inactions (learning bias), and (c) reward/punishment cues themselves drive repetitive behavior, independent of outcomes (perseveration bias). The neural origin of these biases is unclear. Past evidence suggests dorsal anterior cingulate cortex (dACC) and anterior insula (aIns) as part of a \"reset network\" that rapidly responds to salient information and might contribute to these biases. We used transcranial ultrasonic stimulation (TUS) in 29 healthy participants to interfere with neural activity in these regions and test their causal role in a within-subject, counter-balanced design across three sessions (sham, TUS-dACC, TUS-aIns). Computational modeling revealed a functional differentiation of both regions in Pavlovian biases: while TUS to either region did not affect the response bias, TUS to the aIns decreased people's learning bias, while TUS to dACC increased participants' perseveration bias. Although the dACC and aIns are part of the same network and often co-activate during decision-making tasks, TUS interference reveals their distinct roles: the dACC mediates cue-dependent persistence while the aIns is critical for inferring whether outcomes are self-caused.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003767"},"PeriodicalIF":7.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844906","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":"Cryptococcus neoformans adapts to host CO2 concentrations via metabolic and stress-response remodeling.","authors":"Laura C Ristow, Emma E Blackburn, Andrew J Jezewski, Xiaorong Lin, Damian J Krysan","doi":"10.1371/journal.pbio.3003561","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003561","url":null,"abstract":"<p><p>Cryptococcus neoformans is an environmental pathogen that remodels its cellular physiology to survive within mammals and, in susceptible hosts, cause life-threatening meningoencephalitis. Of the many distinctions between the external environment and mammalian tissues, CO2 concentration in the host is two orders of magnitude higher than in the environment and represents a critical stress for C. neoformans. C. neoformans strains that do not replicate at host CO2 concentrations are less virulent in mouse models of infection, further supporting CO2 tolerance as a virulence trait. To further understand the genetic determinants of C. neoformans CO2 tolerance, we performed a near genome-wide screen for deletion mutants with altered CO2 fitness using a competitive growth assay. A total of 301 of 4,692 deletion mutants showed altered CO2 tolerance (245 reduced fitness; 56 increased fitness) demonstrating the global effect of host CO2 on C. neoformans physiology. Based on this data set as well as a metabolomic analysis of C. neoformans adaptation to host CO2, we show that remodeling of central carbon metabolism, oxidative stress buffering, and membrane homeostasis represent an integrated response to CO2 stress that is mediated in part by the TOR-Ypk1 signaling axis. We propose that CO2-induced capsule formation leads to reduced cellular glucose which, in turn, triggers remodeling of central carbon metabolism toward utilization of alternative carbon sources and increased mitochondrial respiration/reactive oxygen generation. Thus, these data provide a near genome-wide profile of the genetic determinants of C. neoformans CO2 tolerance as well as a model for how this important environmental human fungal pathogen alters its physiology to proliferate in the host.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003561"},"PeriodicalIF":7.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surveillance on California dairy farms reveals multiple possible sources of H5N1 influenza virus transmission.","authors":"A J Campbell, Meredith Shephard, Abigail P Paulos, Matthew D Pauly, Michelle N Vu, Chloe Stenkamp-Strahm, Kaitlyn Bushfield, Betsy Hunter-Binns, Orlando Sablon, Emily E Bendall, William J Fitzimmons, Kayla Brizuela, Grace E Quirk, Nirmal Kumar, Brian McCluskey, Nishit Shetty, Linsey C Marr, Jenna J Guthmiller, Jefferson J S Santos, Scott E Hensley, Edith S Marshall, Kevin Abernathy, Adam S Lauring, Blaine T Melody, Marlene K Wolfe, Jason Lombard, Seema S Lakdawala","doi":"10.1371/journal.pbio.3003761","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003761","url":null,"abstract":"<p><p>Transmission routes of highly pathogenic H5N1 between cows or to humans remain unclear due to limited data from affected dairy farms. We performed air, farm wastewater, and milk sampling on 14 H5N1-positive dairy farms across two different California regions. Infectious virus was detected in the air in milking parlors and in wastewater streams, while viral RNA was found in exhaled breath of cows. Sequence analysis of infectious H5N1 virus from air and wastewater samples on one farm revealed viral variants relevant for potential human susceptibility. Longitudinal analysis of milk from the individual quarters of cows revealed a high prevalence of subclinical H5N1-positive cows. Additionally, a heterogeneous distribution of infected quarters that maintained a consistent pattern over time was observed, inconsistent with shared milking equipment serving as the sole transmission mode. The presence of subclinically infected cows was further supported by detection of antibodies in the milk of animals that exhibited no clinical signs during the H5N1 outbreak on one farm. Our data highlight additional sources and potential modes of H5N1 transmission on dairy farms.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003761"},"PeriodicalIF":7.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844943","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":"Past and present goals are represented concurrently during visual search.","authors":"Damian Koevoet, Dirk Van Moorselaar, Edward Awh, Stefan Van der Stigchel","doi":"10.1371/journal.pbio.3003779","DOIUrl":"10.1371/journal.pbio.3003779","url":null,"abstract":"<p><p>Visual selection is often conceptualized as emerging from goal-, stimulus- and history-driven processes within spatial priority maps. Although extensive work detailed the interplay between goal- and stimulus-driven selection, it is largely unknown how goal- and history-driven processes jointly drive selection. While persistent neural firing likely underlies goal-driven selection, it is generally assumed that activity-silent mechanisms effectuate history-driven selection. Due to these different underlying neural mechanisms, simultaneously tracking goal- and history-driven influences neurally has proven difficult. We here employed EEG decoding techniques to simultaneously track and compare goal- and history-driven influences on search. We first established a history-driven signal: Neural decoding closely tracked the target location from the preceding trial. We further demonstrated simultaneous, distinct neural representations of the current and preceding target locations. Strikingly, even when participants attended an upcoming target location before search could commence, prior target locations were reactivated. Our results show that past experiences are reactivated in an inflexible fashion, and do so even when prior targets are completely task-irrelevant. Together, we demonstrate that goal- and history-driven selection are neurally distinct, and reveal that both influences are represented in parallel.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003779"},"PeriodicalIF":7.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An anatomical and connectivity atlas of the tree shrew brain to bridge rodent and primate neuroanatomy.","authors":"Xiaojia Zhu, Rui Bi, Haotian Yan, Qiyu Wang, Lin Li, Hongli Li, Long-Bao Lv, Cirong Liu, Yong-Gang Yao","doi":"10.1371/journal.pbio.3003773","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003773","url":null,"abstract":"<p><p>The tree shrew (Tupaia belangeri), phylogenetically proximal to primates, serves as a critical model for evolutionary neurobiology and disease mechanisms. High-resolution MRI provides a unique opportunity to refine its neuroanatomical architecture and facilitate cross-species comparisons. Here, we present a comprehensive, ultra-high-resolution (9.4T) MRI atlas of the tree shrew brain, integrating structural and diffusion imaging to resolve fine-scale anatomical features and whole-brain connectivity gradients. Our comparative analysis characterizes the tree shrew as a distinct evolutionary mosaic: the cerebellum exhibits pronounced volumetric expansion and connectivity gradients recapitulating those of primates, whereas the hippocampus retains rodent-like architectural scaling yet preserves evolutionarily conserved longitudinal functional axes. Moving beyond these regional adaptations, we uncovered a universal organizational principle: geometry-gradient coupling (GGC)-the fundamental constraint of brain shape on functional organization. By systematically linking geometric eigenmodes to connectivity gradients across diverse species (from mice to humans), we demonstrate that despite dramatic morphological divergence, the spatial alignment between brain geometry and functional organization remains evolutionarily invariant. Collectively, these results establish the tree shrew as a pivotal phylogenetic bridge and provide a neuroanatomical benchmark for deciphering the interplay between structural diversity and universal biophysical constraints.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 5","pages":"e3003773"},"PeriodicalIF":7.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844691","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}