PLoS BiologyPub Date : 2026-10-19eCollection Date: 2026-10-01DOI: 10.1371/journal.pbio.3004032
Shuji Wakatsuki, Toshiyuki Araki
{"title":"Oxidative signaling thresholds shape vulnerability in the central and peripheral nervous systems.","authors":"Shuji Wakatsuki, Toshiyuki Araki","doi":"10.1371/journal.pbio.3004032","DOIUrl":"10.1371/journal.pbio.3004032","url":null,"abstract":"<p><p>Neurodegeneration is frequently associated with oxidative stress, yet the mechanisms that convert reactive oxygen species (ROS) into irreversible degenerative signals remain incompletely understood. Neurons in the central and peripheral nervous systems often differ in their responses to injury, but these differences cannot be reduced to a simple contrast between weak and strong antioxidant capacity. This Essay proposes that neuronal vulnerability is shaped by multilayered signaling thresholds comprising ROS production, antioxidant and thiol buffering, redox-sensitive signal detection, molecular gating, and commitment to degeneration, survival, or repair. This framework may help explain selective neuronal vulnerability in neurodegenerative diseases and identify intervention points downstream of global ROS suppression.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004032"},"PeriodicalIF":7.2,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225274","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}
PLoS BiologyPub Date : 2026-10-16DOI: 10.1371/journal.pbio.3004060
Chang Ye, Yan-Yu Zang, Gui-Fang Duan, Jiang Chen, Dan Wu, Dan Wang, Changlin Li, Yun Xu, Tianjiao Xia, Xiaoping Gu, Yun Stone Shi
{"title":"The mechanosensitive channel TMEM63B contributes to noxious heat sensation in the dorsal root ganglia.","authors":"Chang Ye, Yan-Yu Zang, Gui-Fang Duan, Jiang Chen, Dan Wu, Dan Wang, Changlin Li, Yun Xu, Tianjiao Xia, Xiaoping Gu, Yun Stone Shi","doi":"10.1371/journal.pbio.3004060","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004060","url":null,"abstract":"<p><p>In mammals, heat sensation is primarily mediated by thermosensitive channels, particularly transient receptor potential (TRP) channels, in dorsal root ganglion (DRG) neurons. However, whether additional channels contribute to noxious heat detection remains unclear. Here, we investigated the role of the mechanosensitive cation channel TMEM63B in DRG neurons and unexpectedly discovered its involvement in noxious thermosensation rather than mechanosensation. TMEM63B was broadly expressed in DRG neurons, and its global knockout or DRG-specific conditional knockout markedly reduced heat sensitivity. Deletion of TMEM63B significantly attenuated heat-induced calcium responses and currents in DRG neurons and elevated the temperature threshold for action potential initiation. Recombinant TMEM63B exhibited moderate heat response in calcium imaging assays. Notably, in the presence of arachidonic acid, TMEM63B was strongly activated by heat, suggesting that its thermosensitivity is modulated by the membrane lipid environment. Together, these findings identify TMEM63B as a novel channel contributing to heat sensation and reveal a lipid-dependent modulation of its channel activity.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004060"},"PeriodicalIF":7.2,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208122","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}
PLoS BiologyPub Date : 2026-10-15DOI: 10.1371/journal.pbio.3004075
Ran Blekhman
{"title":"What is biology research for?","authors":"Ran Blekhman","doi":"10.1371/journal.pbio.3004075","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004075","url":null,"abstract":"<p><p>In the age of generative artificial intelligence (AI), the assumption that writing a paper requires doing science no longer holds true. Before deciding how to respond to the surge of AI-generated papers, the field needs to state what biology research is actually for.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004075"},"PeriodicalIF":7.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197422","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}
PLoS BiologyPub Date : 2026-10-15eCollection Date: 2026-10-01DOI: 10.1371/journal.pbio.3004010
Freddie King, Juan Carlos Lopez-Agudelo, Christopher Stephens, May Htet Aung, Tarhan Ibrahim, Enoch Lok Him Yuen, Ao Chen, Nick Eilmann, Saskia Jenkins, Cristina Vuolo, Yueh-Ning Swee, Wei-Jia Liu, Samuel Bruty, AmirAli Toghani, Chih-Horng Kuo, Erh-Min Lai, Jiorgos Kourelis, Lida Derevnina, Chih-Hang Wu, Tolga Bozkurt
{"title":"A broad-host-range Rhizobium rhizogenes strain enables transient expression across diverse crop species.","authors":"Freddie King, Juan Carlos Lopez-Agudelo, Christopher Stephens, May Htet Aung, Tarhan Ibrahim, Enoch Lok Him Yuen, Ao Chen, Nick Eilmann, Saskia Jenkins, Cristina Vuolo, Yueh-Ning Swee, Wei-Jia Liu, Samuel Bruty, AmirAli Toghani, Chih-Horng Kuo, Erh-Min Lai, Jiorgos Kourelis, Lida Derevnina, Chih-Hang Wu, Tolga Bozkurt","doi":"10.1371/journal.pbio.3004010","DOIUrl":"10.1371/journal.pbio.3004010","url":null,"abstract":"<p><p>Agrobacterium-mediated transient expression has revolutionised plant research, enabling numerous landmark discoveries across diverse areas of plant biology. Yet this powerful approach remains largely confined to solanaceous species, leaving most economically important crop families without a comparable rapid assay platform. Here, we show that an engineered Rhizobium rhizogenes strain, AS109, mediates efficient transient expression across diverse dicot species spanning multiple taxonomic families, consistently outperforming commonly used laboratory agrobacterial strains. Leveraging the broad host range of AS109, we establish a suite of functional assays in faba bean (Vicia faba), including protein localisation, RNA interference-mediated gene silencing, cell-surface elicitor recognition screens, nucleotide-binding leucine-rich repeat receptor (NLR) activation, and infection cell biology at the host-pathogen interface. We further demonstrate that both singleton NLRs and sensor-helper NLR pairs from Solanaceae retain effector recognition and cell death activity when transferred into faba bean, establishing a rapid platform for evaluating cross-family transferability of disease-resistance genes. AS109 thus provides an accessible and versatile chassis for functional genomics in non-model crops, bridging the widening gap between hypothesis generation and experimental validation across diverse plant species.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004010"},"PeriodicalIF":7.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197431","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}
PLoS BiologyPub Date : 2026-10-14DOI: 10.1371/journal.pbio.3004061
Xiao Peng Liu, Xiao Zhang, Chun Xia Cai, Miao Miao Qin, Xiang Kai Leng, Jia Hao Chen, Yi Fan Han, Jun Ying Xiao, Jia He Huang, Jiang Wei Wu
{"title":"Deficiency of placental GDF15 causes fetal growth restriction by inhibiting fetal hepatic STAT3-IGF2 axis.","authors":"Xiao Peng Liu, Xiao Zhang, Chun Xia Cai, Miao Miao Qin, Xiang Kai Leng, Jia Hao Chen, Yi Fan Han, Jun Ying Xiao, Jia He Huang, Jiang Wei Wu","doi":"10.1371/journal.pbio.3004061","DOIUrl":"10.1371/journal.pbio.3004061","url":null,"abstract":"<p><p>Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality, yet its underlying mechanism remains elusive. Here, we show that growth differentiation factor 15 (GDF15) levels are significantly reduced in the placenta and fetal circulation in mouse and pig FGR models and correlate positively with fetal weight. Placenta-specific GDF15 deficiency causes FGR, while placenta-specific Gdf15 mRNA delivery through targeted lipid nanoparticle (LNP) effectively alleviates FGR. Mechanistically, placental GDF15 is a major contributor to the fetal circulating GDF15 pool and enters the fetal compartment, where it activates the hepatic STAT3 signaling pathway to stimulate IGF2 production during pregnancy. Placental GDF15 deficiency decreases hepatic STAT3 phosphorylation and IGF2 levels in fetuses. Inhibition of STAT3 in primary mouse fetal hepatocytes blocks GDF15-induced IGF2 upregulation. Placenta-specific Gdf15 mRNA-LNP administration rescues the decreased hepatic p-STAT3 and IGF2 levels in FGR fetuses. Collectively, our findings identify a placenta-fetal liver metabolic axis where placental GDF15 promotes fetal growth by activating the fetal hepatic STAT3-IGF2 pathway, revealing a potential therapeutic target for FGR.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004061"},"PeriodicalIF":7.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185476","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}
PLoS BiologyPub Date : 2026-10-14DOI: 10.1371/journal.pbio.3004074
Shiying Liu, Shi-Yan Ng
{"title":"Cellular diversity in neural organoids is critical for neurodegenerative disease modeling.","authors":"Shiying Liu, Shi-Yan Ng","doi":"10.1371/journal.pbio.3004074","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004074","url":null,"abstract":"<p><p>Neuroinflammation and vascular dysfunction are hallmarks of most neurodegenerative diseases. For organoids intended to model neurodegeneration, immune, and vascular cells should therefore be considered fundamental components, rather than optional additions.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004074"},"PeriodicalIF":7.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185471","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}
PLoS BiologyPub Date : 2026-10-14eCollection Date: 2026-10-01DOI: 10.1371/journal.pbio.3004044
Hanyu Fu, Zhiqiu Liu, Jingwei Zhou, Luyao Zhang, Cai Liu, Dewei Tang, Shuangshuang Zhang, Anan Li, Dejuan Wang
{"title":"Oxytocin receptor signaling in the dorsal lateral septum is essential for social transmission of food preference in mice.","authors":"Hanyu Fu, Zhiqiu Liu, Jingwei Zhou, Luyao Zhang, Cai Liu, Dewei Tang, Shuangshuang Zhang, Anan Li, Dejuan Wang","doi":"10.1371/journal.pbio.3004044","DOIUrl":"10.1371/journal.pbio.3004044","url":null,"abstract":"<p><p>Social learning is a fundamental adaptive strategy that critically shapes decision-making and feeding behaviors. Through the social transmission of food preference (STFP), animals acquire information about food safety via social interactions, forming a food-odor memory that overrides innate preferences and guides subsequent food preferences. However, the neural mechanisms through which social cues durably influence feeding preferences remain unclear. Here, we identify the lateral septum (LS) as a key node in STFP. We show that LS neuronal activity increases following social learning and reliably distinguishes between socially cued and uncued foods. Chemogenetic inhibition of the dorsal LS (dLS), but not the ventral LS (vLS), abolishes STFP-driven food preference, revealing subregional specificity within the LS. Furthermore, oxytocin receptor (OXTR) signaling within the dLS is required for STFP in mice, where it enhances neuronal excitability through PLC pathway activation. Together, our results reveal a subregion-specific circuit mechanism through which the dLS integrates social information with feeding motivation, and highlight oxytocinergic modulation as a key mediator of socially guided food preferences.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004044"},"PeriodicalIF":7.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13667815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185488","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}
PLoS BiologyPub Date : 2026-10-14DOI: 10.1371/journal.pbio.3004059
James Matthew Ragle, Murugesan Pooranachithra, Guinevere E Ashley, Emma Cadena, Batia Blank, Katelyn Kang, Cincy Chen, Aditree R Bhowmick, Soraya H Mercado, Tabatha E Wells, John C Clancy, Andrew D Chisholm, Jordan D Ward
{"title":"A systematic fluorescently tagged protein toolkit for dissecting apical extracellular matrix patterning in C. elegans.","authors":"James Matthew Ragle, Murugesan Pooranachithra, Guinevere E Ashley, Emma Cadena, Batia Blank, Katelyn Kang, Cincy Chen, Aditree R Bhowmick, Soraya H Mercado, Tabatha E Wells, John C Clancy, Andrew D Chisholm, Jordan D Ward","doi":"10.1371/journal.pbio.3004059","DOIUrl":"https://doi.org/10.1371/journal.pbio.3004059","url":null,"abstract":"<p><p>Barrier epithelia are shielded from the external environment by their apical extracellular matrices (aECMs). The molecular complexity of aECMs has challenged understanding of their organization in vivo. To define the molecular architecture of a model aECM we generated a toolkit of 105 fluorescently tagged aECM components using gene editing in C. elegans, focusing on proteins secreted by the epidermis to form the collagen-rich cuticle. We developed efficient pipelines for modular protein tagging and rapid fluorophore swapping. Most tagged collagens were functional and exhibited exquisitely specific patterning across stages, cell types, and matrix substructures. We define multiple reference markers for key substructures including the little-understood cortical layer, as well as the helical crossed fiber arrays that function as a hydrostatic skeleton to maintain organismal shape. We further tagged 30 members of key aECM protein classes including proteases, protease inhibitors, and lipid transporters. Our standardized markers will allow dissection of the mechanistic basis of aECM spatiotemporal patterning in vivo.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3004059"},"PeriodicalIF":7.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185425","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}
PLoS BiologyPub Date : 2026-10-13eCollection Date: 2026-10-01DOI: 10.1371/journal.pbio.3003995
Mohammadjavad Meghrazi, Sarah P Otto
{"title":"Bridging energy and proteome allocation models allows prediction of the resource cost of traits across environments.","authors":"Mohammadjavad Meghrazi, Sarah P Otto","doi":"10.1371/journal.pbio.3003995","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003995","url":null,"abstract":"<p><p>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).</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003995"},"PeriodicalIF":7.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185469","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":"PrimeStack editors enable efficient and site-specific integration of large multigene cargos in plants.","authors":"Edith Sánchez, Khalid Sedeek, Haroon Butt, Magdy Mahfouz","doi":"10.1371/journal.pbio.3003778","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003778","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 10","pages":"e3003778"},"PeriodicalIF":7.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185428","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}