PLoS Biology最新文献

{"title":"Correction: Why PLoS Became a Publisher.","authors":"","doi":"10.1371/journal.pbio.3003714","DOIUrl":"10.1371/journal.pbio.3003714","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pbio.0000036.].</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003714"},"PeriodicalIF":7.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475925","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":"Fine-tuning ERK activity enables proliferation-differentiation balance during lineage specification of human embryonic stem cells.","authors":"Chenyang Ma, Weikang Meng, Jinghan Huang, Wanling Zheng, Xiao Xu, Tao Cheng, Zhengyi Li, Yang Liu, Hao Shen, Feng He, Alessandro Esposito, Pengfei Xu, Ashok Venkitaraman, Jun Ma, Heng Xu, Hongqing Liang","doi":"10.1371/journal.pbio.3003711","DOIUrl":"10.1371/journal.pbio.3003711","url":null,"abstract":"<p><p>ERK is a key signaling mediator controlling both proliferation and lineage specification during embryo development. How ERK choreographs differentiation and proliferation to achieve balanced developmental outcomes in lineages with variable ERK activities remains unclear. To investigate this, we established multiplex quantitative live-cell imaging to track human pluripotent stem cell differentiation into mesendoderm (ME), a lineage specified by gastrulation morphogens and dependent on high ERK activity. We found that distinct morphogen combinations generate varying ERK activity levels, which correlate with heterogeneous ME fate choices despite relatively uniform cell cycle dynamics. To dissect how heterogenous ERK levels directly modulate and coordinate ME differentiation and proliferation, we engineered a synthetic spectrum of titrated ERK activities. Our results showed that ERK fine-tunes ME differentiation potential and cell division speed under nonoverlapping activity ranges, enabling quantitative control of ME fate specification without major effect on cell cycle progression. Mechanistically, this uncoupling stems from differential transcriptional and translational sensitivities of ME-specifying genes versus cell cycle genes to ERK input. Together, our findings reveal how a single signaling pathway quantitatively balances differentiation and proliferation during lineage commitment and embryogenesis.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003711"},"PeriodicalIF":7.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13012617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475936","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":"Comparative embryogenesis of two salp species reveals rogue development and evolutionary divergence from sessile tunicates.","authors":"Marie Lebel, Alexandre Alié, Patrick Lemaire, Stefano Tiozzo","doi":"10.1371/journal.pbio.3003636","DOIUrl":"10.1371/journal.pbio.3003636","url":null,"abstract":"<p><p>Tunicates are the closest living relatives of vertebrates. Recent phylogenies place the little-studied, free-swimming thaliaceans-including salps-within sessile ascidians, highlighting a remarkable ecological transition. Historical reports hinted at a parallel developmental shift. Salp embryogenesis diverges from that of ascidians and involves unique maternal cells called calymmocytes. Here, we provide foundational resources for two distantly related salp species, Salpa fusiformis and Thalia democratica. Using advanced microscopy, we generated developmental staging tables showing that while embryogenesis is stereotyped within species, it differs in cleavage patterns and blastomere positioning between them. We traced the origins of calymmocytes and confirmed their conserved role in separating blastomere clusters that form adult tissues. Apoptosis contributes to the progressive elimination of maternal calymmocytes. Finally, we show that calymmocytes express embryonic developmental regulators, suggesting co-option of an embryonic gene program. These findings provide an advanced framework for studying embryogenesis evolution in a previously underexplored chordate lineage.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003636"},"PeriodicalIF":7.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475702","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 Rpd3 histone deacetylase is a critical regulator of temperature-mediated morphogenesis and virulence in the human fungal pathogen Histoplasma.","authors":"Nebat Ali, Mark Voorhies, Rosa A Rodriguez, Anita Sil","doi":"10.1371/journal.pbio.3003341","DOIUrl":"10.1371/journal.pbio.3003341","url":null,"abstract":"<p><p>Adaptive responses to environmental stimuli are integral to the survival and virulence of microbial pathogens. The thermally dimorphic human fungal pathogen Histoplasma senses temperature to transition between a mold form in soil and a pathogenic yeast in mammalian hosts. The contributions of chromatin-modifying enzymes to the ability of Histoplasma to appropriately respond to temperature have never been explored. Through chemical inhibition and genetics, we determined that the class I histone deacetylase (HDAC) RPD3 is required for normal Histoplasma yeast morphology at 37 °C. Rpd3 regulated the expression of key morphology-specific genes, including critical virulence factors and transcription factors (TFs), was required for normal DNA-binding activity of yeast-promoting TFs, and influenced histone acetylation levels at the loci of putative pro-filamentation TFs. Furthermore, Rpd3 was required for virulence in a macrophage model of infection. Taken together, Rpd3 is a critical regulatory component that both activates the pathogenesis program and represses the filamentation program to enable thermal dimorphism in Histoplasma. This work uncovers the crucial role that chromatin regulation plays in temperature response of this ubiquitous pathogen.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003341"},"PeriodicalIF":7.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475917","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":"Systematic identification of Salmonella T6SS effectors uncovers diverse new families and lipid-targeting activities.","authors":"Gianlucca G Nicastro, Stephanie Sibinelli-Sousa, Julia T Hespanhol, Thomas W C Santos, Joseph P Munoz, Rosangela S Santos, Blanca M Perez-Sepulveda, Sayuri Miyamoto, L Aravind, Robson F de Souza, Ethel Bayer-Santos","doi":"10.1371/journal.pbio.3003680","DOIUrl":"10.1371/journal.pbio.3003680","url":null,"abstract":"<p><p>Bacterial warfare is a widespread phenomenon in which bacteria deploy toxins to inhibit or kill competitors. These toxins disrupt essential cellular processes, and their diversification is driven by an evolutionary arms race involving toxin and immunity gene acquisition. Here, we used in-silico approaches to analyze genomes from the 10k Salmonella Project and identify effectors secreted via the Type VI Secretion System (T6SS). We uncovered 128 candidates distributed across diverse Salmonella serovars and other bacterial species. Among them, Tox-Act1 was selected for in-depth characterization. Tox-Act1 contains a permuted NlpC/P60 papain-like catalytic core typical of lipid-targeting enzymes. Evolutionary analysis revealed its relationship with acyltransferases. Biochemical assays and lipidomics of intoxicated cells showed that Tox-Act1 acts as a phospholipase, cleaving phosphatidylglycerol and phosphatidylethanolamine. We further demonstrate that Tox-Act1 is secreted in a T6SS-dependent manner and provides a competitive advantage during mouse gut colonization. This study broadens our understanding of toxin domain diversity and provides the first direct characterization of a lipid-targeting NlpC/P60 toxin domain.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003680"},"PeriodicalIF":7.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475893","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":"Engineered romidepsin biosynthetic pathways in Escherichia coli Nissle 1917 improve the efficacy of bacteria-mediated cancer therapy.","authors":"Chenghao Ma, Geng Li, Tao Sun, Ximi Tang, Tong Qiu, Jingwen Song, Hailong Wang, Youming Zhang, Tianyu Jiang","doi":"10.1371/journal.pbio.3003657","DOIUrl":"10.1371/journal.pbio.3003657","url":null,"abstract":"<p><p>The probiotic strain Escherichia coli Nissle 1917 (EcN), a potential member of tumor-targeting bacteria, shows great promise for cancer treatment. By leveraging engineered EcN, we can design a bacteria-assisted, tumor-targeted therapy for the biosynthesis and targeted delivery of small-molecule anticancer agents. In this study, we aimed to use EcN as a base for synthesizing Romidepsin (FK228), an FDA-approved drug originally made by Chromobacterium violaceum No. 96. Through gene cluster reconstruction, promoter optimization, and genome modification, we created FK228-producing strains to boost anticancer efficacy. The engineered strain achieved a maximum in vitro yield of 1.5 mg/L. In 4T1 tumor-bearing BALB/c mouse xenograft models, six recombinant strains outperformed the wild-type EcN. Proteome showed that inflammatory response induced by EcN combined with intratumoral FK228 production improved treatment results. Also, targeted synthesis reduced FK228's cardiotoxicity and mortality. Engineered EcN enables drug biosynthesis and precise delivery, offering powerful anticancer activity.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003657"},"PeriodicalIF":7.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475945","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":"Eye movements reflect memory-related theta activity in the human brain.","authors":"Humza N Zubair, Matthias Stangl, Uros Topalovic, Cory Inman, Martin Seeber, Sonja Hiller, Vikram R Rao, Casey H Halpern, Dawn Eliashiv, Itzhak Fried, Nanthia Suthana","doi":"10.1371/journal.pbio.3003695","DOIUrl":"10.1371/journal.pbio.3003695","url":null,"abstract":"<p><p>Numerous studies across species emphasize the importance of theta oscillations within medial temporal lobe (MTL) regions, such as the hippocampus, in relation to memory. In rodents, physical movement strongly influences theta activity, while this relationship remains more ambiguous in primates. This disparity could stem from the increased reliance on visual search in primates during navigation. To explore this, we analyzed intracranial electroencephalographic (iEEG) activity from the human MTL recorded simultaneously with body and eye movements during ambulatory navigation. We found that MTL theta power was significantly higher during periods when saccadic eye movements were taking place, and this effect was observed only during periods with overt memory demands. The largest increases occurred during saccades with more variable and exploratory gaze patterns, on trials with better memory performance, and during the early planning period of each route. The modulation was also amplified near environmental boundaries, spatial features known to anchor memory representations and guide navigation. During memory-guided navigation, theta power further tended to increase during both locomotion and stationary periods, consistent with broad engagement during active information gathering. In addition to these memory-specific effects, theta aligned its phase to saccade onset during both memory-guided and visually-guided navigation, suggesting that eye movements impose a consistent temporal structure on ongoing MTL activity. Together, these findings reveal that memory-related theta dynamics in the human MTL are tightly coupled to exploratory visual search and prospective planning during memory-guided navigation, revealing a mechanism by which saccades may help organize mnemonic computations in naturalistic settings.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003695"},"PeriodicalIF":7.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468606","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":"Non-peptide dysbiosis metabolites reprogram a peptide quorum-sensing receptor to induce sustained predation in beneficial streptococci.","authors":"Guillaume Cerckel, Denis Dereinne, Laura Ledesma-García, Vincent Meuric, Benoît Desguin, Johann Mignolet, Patrice Soumillion, Pascal Hols","doi":"10.1371/journal.pbio.3003718","DOIUrl":"10.1371/journal.pbio.3003718","url":null,"abstract":"<p><p>Cytoplasmic receptors of the RRNPPA superfamily mediate peptide-based quorum sensing in Gram-positive bacteria and are thought to be activated exclusively by short, unmodified pheromones. Here, we show that the RRNPPA regulator ComR in the human commensal Streptococcus salivarius can also be activated by a distinct class of non-peptide metabolites. A screen of ~200 organic compounds identified hydroxyphenylacetic acid (HPAA)-a microbial dysbiosis-associated catabolite-as a potent activator of ComR. Using biochemical and genetic approaches, we demonstrate that HPAA and related aromatic carboxylic acids bind the canonical pheromone pocket and induce sustained expression of predatory bacteriocins, while bypassing the competence program triggered by the native peptide signal (XIP). We further show that the oral pathogen Porphyromonas gingivalis produces physiologically relevant amounts of (H)PAA, enabling metabolite-driven activation of predation in S. salivarius. These findings reveal an unexpected capacity of RRNPPA receptors to sense both peptide and metabolite cues, uncovering a chemical mode of interspecies communication that links dysbiosis to predatory behavior in the oral microbiome.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003718"},"PeriodicalIF":7.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147460705","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":"Behavioral engagement facilitates auditory neuron responses beyond their receptive fields.","authors":"Chenggang Chen, Evan D Remington, Xiaoqin Wang","doi":"10.1371/journal.pbio.3003707","DOIUrl":"10.1371/journal.pbio.3003707","url":null,"abstract":"<p><p>In the auditory cortex, neural responses to stimuli inside receptive fields (RFs) can be further facilitated by behavioral demands, such as attending to a spatial location. It is less clear how off-RF stimuli modulate neural responses and contribute to behavioral tasks. Our recent study revealed a particular form of location-specific facilitation evoked by repeated stimulation from an off-RF location, suggesting behavioral modulation of spatial RFs. To further explore this question, we trained marmosets to attend to sound locations that were either inside or outside the RFs of auditory cortical neurons. The majority of neurons showed increased firing rates at target locations inside their RFs. Interestingly, this increase also occurred outside the RFs, sometimes exceeding the responses at the RF center during passive listening. This task-related off-RF facilitation was much more common in the caudal area than in the rostral area and the primary auditory cortex. A normalization model reproduced the off-RF facilitation using widespread suppression. The model's prediction was confirmed by experimental observations of widespread reductions in firing rate and hyperpolarized membrane potentials for off-RF stimuli. These results suggest that behavioral task demands recruit a broader range of neurons than those that are responsive to a target sound in the passive state.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003707"},"PeriodicalIF":7.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13012619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147460719","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":"Thalamic reticular neurons provide cell type-specific modulation of sound processing in the auditory thalamus.","authors":"Solymar Rolón-Martínez, Austin J Mendoza, Christopher F Angeloni, Nathan W Vogler, Audrey C Drotos, Mark Aizenberg, Ruoyi Chen, Kaylie Vu, Julie S Haas, Maria N Geffen","doi":"10.1371/journal.pbio.3003693","DOIUrl":"10.1371/journal.pbio.3003693","url":null,"abstract":"<p><p>Inhibition plays an important role in controlling the flow and processing of auditory information throughout the central auditory pathway, yet how inhibitory circuits shape auditory processing in the medial geniculate body (MGB), the key region in the auditory thalamus, is poorly understood. The MGB gates the flow of auditory information to the auditory cortex, and it is inhibited largely by the thalamic reticular nucleus (TRN). The TRN contains two major classes of inhibitory neurons: parvalbumin (PVTRN)-positive and somatostatin (SSTTRN)-positive neurons. PV and SST neurons have been shown to play differential roles in controlling sound responses in auditory cortex. In the somatosensory and visual subregions of the TRN, PVTRN and SSTTRN neurons exhibit anatomical and functional differences. However, it remains unknown whether and how PVTRN and SSTTRN neurons differ in their anatomical projections from the TRN to the auditory thalamus, and whether and how they differentially modulate activity in the MGB. Here, we investigated virally labeled projections of PVTRN or SSTTRN neurons, and recorded neuronal responses in the MGB of awake, head-fixed mice while presenting sound stimuli and selectivity suppressing PVTRN or SSTTRN neurons on a subset of trials. We find that PVTRN and SSTTRN neurons exhibit differential projection patterns within the auditory thalamus: PVTRN neurons predominantly project to ventral MGB, whereas SSTTRN neurons project to the dorso-medial regions of MGB. Optogenetic inactivation of PVTRN neurons bidirectionally modulated sound-evoked activity in MGB, increasing firing in 29% of MGB neurons, while suppressing firing in 41%. In contrast, inactivating SSTTRN neurons largely suppressed tone-evoked activity in MGB neurons. Cell type-specific computational models identified candidate circuit mechanisms for generating the differential effects of TRN inactivation on MGB sound responses. These distinct inhibitory pathways within the auditory thalamus reveal cell type-specific organization of thalamic inhibition in auditory computation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 3","pages":"e3003693"},"PeriodicalIF":7.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445756","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}