2026-09-18
Mona Nazemi, Bian Yanes, Eric Vancauwenberghe, Ifeoluwa Oyelade, Heather Walker, Elena Rainero
by Mona Nazemi, Bian Yanes, Eric Vancauwenberghe, Ifeoluwa Oyelade, Heather Walker, Elena Rainero Invasive breast and pancreatic cancer cells thrive within a collagen I-rich, poorly perfused extracellular matrix (ECM) network, necessitating robust metabolic adaptation to endure nutrient deficiency, such as glucose starvation. Here we demonstrate that collagen I is critical for the survival and growth of breast and pancreatic cancer cells. Mechanistically, collagen I promotes α2 β1 integrin-dependent S6 phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) and drives the membrane localisation of the (LAT1)−4F2hc amino acid transporter. This process ensures a sustained intracellular essential amino acid supply, further fuelling mTORC1 signalling and limiting autophagy. This collagen I-driven pathway is essential for cancer cell survival, as inhibiting the activity of α2 β1 integrin or the LAT1-4F2hc transporter significantly reduces cell growth and invasion in both 2D and 3D models. Finally, the clinical relevance of these transporters is underscored by the significant upregulation of LAT1-4F2hc expression in basal-like breast and pancreatic cancer patients, correlating with poor prognosis and drug resistance. Collectively, our findings highlight that targeting the LAT1−4F2hc transporter might represent a highly promising therapeutic strategy to limit cancer cell growth and invasion in highly fibrotic and nutrient-deprived tumours.
DOI: 10.1371/journal.pbio.30035552026-09-18
Tal Gordon, Tom Levy, Chester Jiamu Yu, Benyamin Rosental, Lauren Lubeck, Lucia Manni, Irving L. Weissman, Ayelet Voskoboynik
by Tal Gordon, Tom Levy, Chester Jiamu Yu, Benyamin Rosental, Lauren Lubeck, Lucia Manni, Irving L. Weissman, Ayelet Voskoboynik Many tissues harbor quiescent stem cells that activate after injury, yet how local signals regulate this transition is not well understood. The solitary ascidian Ciona robusta provides a unique model, as bottom body fragments regenerate while upper fragments fail to do so. By comparing these regenerative and non-regenerative contexts, we reveal striking differences in transcriptional dynamics and signaling environments. Combining flow cytometry, scRNA-seq, transplantation, and fate mapping, we identified a candidate stem cell population with robust proliferative and differentiation potential following transplantation. However, regenerative capacity does not simply reflect stem cell abundance, but instead depends on region-specific signaling cues. Local expression of metabolic, immune and differentiation-related factors further underscores the importance of spatially distinct environments in shaping outcomes. Our findings show how a shared injury response is associated with divergent regenerative outcomes, highlighting principles that may inform strategies to enhance tissue repair in other systems.
DOI: 10.1371/journal.pbio.30040002026-09-16
Audam Chhun, Andrew Quinn, Alicia I. Pérez-Lorente, Théodora Steiner, Florian Zoppi, Thi Huong Giang Nguyen, Philipp Engel, Yolanda Schaerli
by Audam Chhun, Andrew Quinn, Alicia I. Pérez-Lorente, Théodora Steiner, Florian Zoppi, Thi Huong Giang Nguyen, Philipp Engel, Yolanda Schaerli The honeybee gut microbiota plays a key role in shaping host health and susceptibility to disease. Yet, the nutrient environment it experiences within the gut remains poorly characterized. In particular, little is known about the spatial distribution of nutrients across the microbial community, as resolving such fine gradients in vivo has been technically challenging. Here, we engineer the native honeybee symbiont Snodgrassella alvi as a living biosensor to quantify the bioavailability of the dietary sugar arabinose within the gut. By expanding the genetic toolkit for S. alvi through chromosomal integration of high-burden genes and a suite of low-strength promoters, we achieve stable multi-gene expression without compromising host colonization. The resulting biosensor generates a specific, dose-dependent fluorescent response to arabinose in the living host, enabling visualization of sugar gradients across gut-associated bacterial biofilms at micron-scale resolution. Upon co-colonization with distinct Gilliamella species that differ in arabinose metabolism, the biosensor reported differential in vivo arabinose consumption, directly validating species-specific metabolic specialization within the host. Feeding bees with pollen further uncovered pronounced radial heterogeneity in the distribution of pollen-derived arabinose. These findings demonstrate how diet composition and microbial specialization generate fine-scale microenvironments within the gut. More broadly, this work establishes S. alvi as a genetically tractable platform for in situ biosensing, opening new avenues for dissecting metabolic interactions and nutrient distribution within living hosts.
DOI: 10.1371/journal.pbio.30039972026-09-16
Jinxia Wang, Yuying Huo, Rui Zhao, Yan Pan, Jianqiang Wu, Han Wang, Xiangyu Li
by Jinxia Wang, Yuying Huo, Rui Zhao, Yan Pan, Jianqiang Wu, Han Wang, Xiangyu Li Recent advances in spatial multi-omics technologies have opened new avenues for characterizing tissue architecture and function in situ, by simultaneously providing multimodal and complementary information—such as spatially resolved transcriptomic, epigenomic, and proteomic features. Current computational approaches face substantial challenges, such as effective integration of multi-omics molecular information with spatial information and corresponding high-resolution histology images. To address this challenge, we proposed SpaMOAL (Spatially Multi-Omics graph contrAstive Learning), a graph-based contrastive learning approach for spatial domain identification. SpaMOAL learns clustering-friendly representations from spatial multi-omics data by integrating spatial coordinates, histological image features, and molecular profiles, enabling accurate delineation of spatial tissue domains. Benchmarking across multiple recent paired spatial multi-omics datasets from mouse and human demonstrated that SpaMOAL consistently outperforms existing methods. By enabling accurate spatial domain delineation, SpaMOAL provides a powerful framework for interpreting tissue organization and cellular microenvironments.
DOI: 10.1371/journal.pbio.30036902026-09-16
Anna B. Adelstein, Naama Aviram
by Anna B. Adelstein, Naama Aviram Most bacterial immune systems raise an alarm when they sense a phage. A new study in PLOS Biology shows how type II Panoptes reverses this logic by maintaining a quiet signal and sensing infection through its sudden disappearance. Most bacterial immune systems raise an alarm when they sense a phage. A new study in PLOS Biology shows how type II Panoptes reverses this logic by maintaining a quiet signal and sensing infection through its sudden disappearance
DOI: 10.1371/journal.pbio.30039782026-09-15
Jonathan Einterz Owen, Cheyanne Lynn Bemis, Qingyi Wang, Ambarish C. Varadan, Jacob W. Vander Velden, Laura Andačić, Olus Uyar, Mansi Gupta, Christopher D. Scharer, Laurent Chatel-Chaix, Pietro Scaturro, Mehul S. Suthar, Christopher J. Neufeldt
by Jonathan Einterz Owen, Cheyanne Lynn Bemis, Qingyi Wang, Ambarish C. Varadan, Jacob W. Vander Velden, Laura Andačić, Olus Uyar, Mansi Gupta, Christopher D. Scharer, Laurent Chatel-Chaix, Pietro Scaturro, Mehul S. Suthar, Christopher J. Neufeldt Flaviviruses (genus Orthoflavivirus ) are arthropod-borne viruses which cause approximately 400 million annual global infections in humans. Flavivirus infection requires cellular machinery to facilitate replication and spread. All known flaviviruses replicate in association with the host endoplasmic reticulum (ER), where genome replication is confined within virus-induced ER invaginations called viral replication organelles (vROs). Despite the central role of these structures during flavivirus infection, the mechanisms underlying vRO biogenesis remain undefined—particularly the membrane rearrangements required for their formation. In this work, we report a conserved role for a cellular ER remodeling protein, atlastin-2 (ATL2), in the organization of vROs within infected cells. Using confocal and electron microscopy, we show that ATL2 depletion leads to a reduction in vRO spatial distribution in flavivirus-infected cells. Changes in vRO distribution corresponded with a decrease in virus production and robust induction of innate immune responses. We also demonstrate that ATL2 accumulates in areas of vRO formation during flavivirus infection. Critically, mutational analysis showed that a tethering-competent but fusion-defective ATL2 mutant was sufficient to rescue DENV and ZIKV replication in ATL2-knockout cells. Finally, targeting of ATL2 activity using synthetic peptides significantly reduced DENV replication in both immortalized and human primary cells, suggesting a possible avenue for targeting host ER functions to limit flavivirus replication. Taken together, these results show that membrane tethering plays a critical and conserved role in flavivirus infection, functioning to organize membranes for vRO biogenesis and limit cellular immune activation. Importantly, we provide evidence that ATL2-mediated membrane organization can be targeted to inhibit viral replication.
DOI: 10.1371/journal.pbio.30035562026-09-15
Felipe Valença-Pereira, Bryan Johnson, James DeGregori, Mercedes Rincon
by Felipe Valença-Pereira, Bryan Johnson, James DeGregori, Mercedes Rincon Chronic infections are associated with cancer incidence and progression in human epidemiological data, but less is known about how such infections might promote cancer progression. Recent data implicate acute infection with common respiratory viruses, such as influenza and SARS-CoV-2, in cancer progression, providing evidence that infection-driven inflammation can promote tumor expansion and dissemination in experimental systems. The resulting acute inflammatory cascade and dynamic immune cell reprogramming can rapidly remodel the tissue microenvironment to favor cancer cell survival, growth, and evasion of immune elimination. However, acute infections can also elicit anti-tumor immune responses. Defining how infections differentially skew immune programs to promote or restrain cancer progression will therefore be essential for developing future strategies to target this disease.
DOI: 10.1371/journal.pbio.30039622026-09-15
Sabine Grüschow, Peter Wotherspoon, Emma Hilton-Balfe, Shirley Graham, Malcolm F. White
by Sabine Grüschow, Peter Wotherspoon, Emma Hilton-Balfe, Shirley Graham, Malcolm F. White Cyclic nucleotide second messengers are used in all domains of life to amplify viral infection signals and activate cellular defences. In prokaryotes, CBASS (cyclic nucleotide-based antiphage signalling system) and type III CRISPR-Cas systems generate a range of cyclic nucleotides which bind and allosterically activate effector proteins to mount an anti-viral response. Viruses have evolved counter measures to antagonise these signalling pathways in the form of cyclic nucleotide sponges and phosphodiesterases that sequester or degrade these molecules to subvert immunity. Recently, the Panoptes system was shown to function as a guard against these viral tactics. The type I Panoptes polymerase, mCpol, generates cyclic dinucleotides as decoy molecules that, when sequestered by phage proteins, results in the activation of the membrane-permeabilising effector 2TMβ to halt the phage infection cycle. Here, we investigate the type II Panoptes system, demonstrating that it generates cyclic tri-adenylate (cA 3 ) to maintain a CRISPR-associated Rossmann fold-transmembrane (CARF-TM) effector in an inactive, dimeric state. When cA 3 is sequestered or degraded, the CARF protein undergoes conformational changes. In vivo, the absence of cA 3 results in membrane disruption and growth arrest. Type II Panoptes provides defence against phages that express the cA 3 -degrading enzyme Acb1; phage escapers introduce mutations into the acb1 gene to avoid triggering the Panoptes system. These findings expand our understanding of the guard systems that constitute a fascinating component of the bacterial immune system.
DOI: 10.1371/journal.pbio.30039342026-09-15
Chuanying Niu, Xiaohan Huang, Qihong Yan, Banghui Liu, Xijie Gao, Yidong Song, Jingjing Wang, Longyu Wang, Zimu Li, Huiran Zheng, Ping He, Xiaodong Huang, Hang Yuan, Binqian Zou, Yuedong Yang, Fandi Wu, Yicheng Yao, Gul Habib, Xinwen Chen, Ling Chen, Jun He, Jianhua Yao, Jincun Zhao, Xiaoli Xiong
by Chuanying Niu, Xiaohan Huang, Qihong Yan, Banghui Liu, Xijie Gao, Yidong Song, Jingjing Wang, Longyu Wang, Zimu Li, Huiran Zheng, Ping He, Xiaodong Huang, Hang Yuan, Binqian Zou, Yuedong Yang, Fandi Wu, Yicheng Yao, Gul Habib, Xinwen Chen, Ling Chen, Jun He, Jianhua Yao, Jincun Zhao, Xiaoli Xiong R1-32-like public antibodies, characterized by shared IGHV1-69/IGLV1-40 usage, are elicited in more than 50% of individuals with COVID-19 and have been implicated in driving recurrent mutations at L452 SARS2 and F490 SARS2 within their convergent epitope in the SARS-CoV-2 spike receptor-binding domain. These mutations effectively mediate escape from non-affinity-matured R1-32-like antibodies with germline-like sequences. Here, we characterize four affinity-matured human R1-32-like antibodies, C092, C807, BD56-104, and BD56-597, that tolerate L452 SARS2 and F490 SARS2 mutations. We show that this tolerance arises from residues introduced by somatic hypermutation at convergent positions across multiple CDR loops and surrounding regions, thereby creating additional contacts that reinforce epitope binding. An unusual N354 SARS2 glycosylation site, which emerged in BA.2.86 and became fixed in its descendants, is linked to escape from affinity-matured R1-32-like antibodies, implying ongoing selection by this public antibody class. Using an AI model trained on extensive neutralization data, we further identified ZL525, an ultrapotent human R1-32-like antibody with pan-SARS-CoV-2 variant activity, including against the highly evasive KP.3 variant carrying the N354 SARS2 glycosylation, and broad sarbecovirus cross-reactivity extending to SARS-CoV-1. Together, these findings show how affinity maturation enables public antibodies to adapt to viral antigenic drift, reveal their role in shaping SARS-CoV-2 antigenic evolution, and demonstrate the potential of AI-empowered strategies for discovering broadly neutralizing antibodies.
DOI: 10.1371/journal.pbio.30039962026-09-11
Chih-Ying Su
by Chih-Ying Su Mosquitoes use CO2 as a critical cue to sense if humans are nearby. A new study in PLOS Biology reveals that CO2-sensing neurons in mosquitoes can amplify each other’s signals, creating a neural echo chamber that may explain the remarkable sensitivity of mosquitoes to human presence. Mosquitoes use carbon dioxide as a critical cue to sense if humans are nearby. This Primer explores a new study in PLOS Biology that reveals that carbon dioxide-sensing neurons in mosquitoes can amplify each other’s signals, creating a neural echo chamber that may explain the remarkablesensitivity of mosquitoes to human presence.
DOI: 10.1371/journal.pbio.30039582026-09-10
Jialu Bao, Wesley Alford, Avinash Khandelwal, Laurel Walsh, George Lantz, Santiago Poncio, Laia Serratosa Capdevila, Yervand Azatian, Brian DePasquale, David G. C. Hildebrand, Meg A. Younger, Wei-Chung Allen Lee
by Jialu Bao, Wesley Alford, Avinash Khandelwal, Laurel Walsh, George Lantz, Santiago Poncio, Laia Serratosa Capdevila, Yervand Azatian, Brian DePasquale, David G. C. Hildebrand, Meg A. Younger, Wei-Chung Allen Lee The mosquito Aedes aegypti ’s human host-seeking behavior depends on the integration of multiple sensory cues. One of these cues, carbon dioxide (CO 2 ), gates odorant and heat pathways and activates host-seeking behavior. The neuronal circuits underlying processing of CO 2 information remain unclear. We used automated serial-section transmission electron microscopy (EM) to image and reconstruct the circuitry of the glomeruli that are innervated by the Ae. aegypti maxillary palp, including the glomerulus that responds to CO 2 . Notably, CO 2 -sensitive olfactory sensory neurons (OSNs) make high levels of recurrent synaptic connections with one another, while making a low density of feedforward synapses. At some of these contacts between CO 2 OSNs, we observe ribbon-like presynaptic structures, which may further enhance recurrent signaling. We compared both feedforward and recurrent connectivity with all olfactory glomeruli in Drosophila melanogaster, and we found more recurrent connections between the Ae. aegypti CO 2 -responsive OSNs than in any D. melanogaster glomeruli. We developed a computational circuit model that demonstrates recurrent synapses are necessary for robust CO 2 detection under normal physiological conditions. Together, elevated levels of recurrent connectivity and ribbon-like structures may amplify sensory information detected by CO 2 -sensitive OSNs to support mosquito activation and sensitization by CO 2 , even in the presence of high levels of other odorants in the environment. We propose that this circuit organization supports the salience of CO 2 as a mosquito host cue.
DOI: 10.1371/journal.pbio.30039592026-09-09
Ruoke Zhao, Mingyang Li, Yuqi Zhang, Ruike Chen, Chenglin Ning, Zhiyong Zhao, Zhihan Yan, Meihao Wang, Dan Wu
by Ruoke Zhao, Mingyang Li, Yuqi Zhang, Ruike Chen, Chenglin Ning, Zhiyong Zhao, Zhihan Yan, Meihao Wang, Dan Wu Brain anatomical architecture supports its functional activity and complex cognitive processes. However, how the structure–function (SF) relationship establishes and develops during early life, as well as its underlying mechanisms, remain largely unclear. To address these questions, we leveraged multimodal MRI data from two large-scale public databases, the developing Human Connectome Project (dHCP) and the Baby Connectome Project (BCP), to characterize the spatiotemporal dynamics of SF coupling from the perinatal period to toddlerhood. Our results revealed that SF coupling at birth exhibited a spatial variation along the sensorimotor-association cortical axis. During the perinatal period (26–44 postmenstrual weeks), SF coupling strengthened drastically and followed three distinct developmental trajectories across the cortex, with sensorimotor and visual areas showing the fastest growth and the earliest plateau. After birth, SF coupling shifted toward a weakening pattern across the cortex during infancy and toddlerhood (1–28 months). These developmental changes of SF coupling were more strongly associated with the maturation of functional connectivity, which first converged toward the local structural architecture prenatally and then diverged postnatally through the expansion of global inter-modular pathways. Furthermore, SF coupling at birth, the developmental transition point, exhibited a significant association with individual differences in cognition and language outcomes at 18 months of age. Collectively, these findings offer valuable insights into the organizational principles underlying structural and functional network development during early life as well as the complex evolving relationship between them.
DOI: 10.1371/journal.pbio.30039272026-09-08
Meixi Lin, Sneha Chakraborty, Carlos Eduardo G. Amorim, Sergio F. Nigenda-Morales, Annabel C. Beichman, Paulina G. Nuñez-Valencia, Jonathan C. Mah, Jacqueline A. Robinson, Christopher C. Kyriazis, Christian D. Huber, Andrew E. Webb, Sarah D. Kocher, Frederick I. Archer, Andrés Moreno-Estrada, Robert K. Wayne, Kirk E. Lohmueller
by Meixi Lin, Sneha Chakraborty, Carlos Eduardo G. Amorim, Sergio F. Nigenda-Morales, Annabel C. Beichman, Paulina G. Nuñez-Valencia, Jonathan C. Mah, Jacqueline A. Robinson, Christopher C. Kyriazis, Christian D. Huber, Andrew E. Webb, Sarah D. Kocher, Frederick I. Archer, Andrés Moreno-Estrada, Robert K. Wayne, Kirk E. Lohmueller The distribution of fitness effects (DFE) describes the selection coefficients of newly arising mutations and fundamentally influences population genetic processes. However, the extent and mechanisms of differences in the DFE for non-synonymous mutations have not been systematically investigated across species with divergent phylogenetic histories and ecologies. Here, we inferred the DFE in natural populations of 11 animal (sub)species, including humans, mice, fin whales, vaquitas, wolves, collared flycatchers, pied flycatchers, halictid bees, Drosophila , and mosquitoes. We found that mammals have a higher proportion of strongly deleterious mutations (defined as s≤−0.01; 22% to 47% in mammals; 0.0% to 5.4% in insects and birds) and a lower proportion of weakly deleterious mutations than insects and birds. Further, the DFE co-varies with phylogeny, such that the mean mutation effects are more similar in closely related species (Pagel’s λ = 0.84, P = 0.01). Next, we investigated whether various summary statistics of the DFE were related to variation in life-history traits across these organisms. We found some support for genome size, body mass, and long-term effective population size being correlated with the DFE. Overall, our findings are consistent with predictions derived independently from the Fisher’s Geometric Model (FGM), which defines organismal complexity as the number of phenotypes under selection. FGM predicts that mutations are more deleterious in complex organisms, while strongly deleterious mutations occur more frequently in smaller populations. Our study demonstrates strong phylogenetic signal in the evolution of a fundamental population genetics parameter, and proposes that, through mechanisms of epistasis, long-term population size and organismal complexity could be underlying variation in the DFE across animals.
DOI: 10.1371/journal.pbio.30039762026-09-08
Kate Harline, Brendan Lane, Maura J. Zimmermann, Antoine Fruleux, Gabriella Mosca, Sören Strauss, Nik Tavakolian, James W. Satterlee, Chun-Biu Li, Abhyudai Singh, Arezki Boudaoud, Richard S. Smith, Adrienne H. K. Roeder
by Kate Harline, Brendan Lane, Maura J. Zimmermann, Antoine Fruleux, Gabriella Mosca, Sören Strauss, Nik Tavakolian, James W. Satterlee, Chun-Biu Li, Abhyudai Singh, Arezki Boudaoud, Richard S. Smith, Adrienne H. K. Roeder The growth and division of cells in plant leaves is highly dynamic in time and space, even though cells cannot move relative to their neighbors. Thus, organ shape must emerge from carefully coordinated growth, especially in leaves that remain relatively flat as they grow. Here we explored the phenotype of the jagged and wavy ( jaw-D ) mutant in Arabidopsis thaliana , in which the leaves do not remain flat. It has previously been shown that the jaw-D mutant phenotype is caused by the overexpression of miR319 , which represses TCP transcription factors, thus delaying maturation of the leaf. We analyzed cell dynamics in wild type and jaw-D by performing time-lapse live imaging of developing leaves. We found that the progression of maturation from the tip of the leaf downward was delayed in jaw-D relative to wild type based on several markers of maturation, in agreement with the role of TCP transcription factors in promoting maturation. We further found that these changes in maturation were accompanied by differences in the coordination of growth across the leaf, particularly across the mediolateral axis, causing growth conflicts that prevent the leaf from remaining flat. Modeling revealed that curvature develops when growth is uneven across the leaf in the direction perpendicular to the direction of growth. Although leaf flatness is often framed as a problem that requires the local synchronization of growth on the abaxial versus adaxial sides (bottom versus top) of the leaf, our results based on the jaw-D phenotype suggest that wild-type plants also need to coordinate growth more globally across the leaf blade to maintain flatness.
DOI: 10.1371/journal.pbio.30039932026-09-08
Maureen A. McGargill, Beiyun C. Liu, Michael S. Kuhns, Daniel Mucida, Isabella Rauch, Lauren B. Rodda, Meghan A. Koch, Hugo Gonzalez Velozo, Ken Cadwell, Tanya S. Freedman, Tiffany C. Scharschmidt, Richard Sever, Jose Ordovas-Montanes, Sara Suliman, Andrew Oberst, Brooke Runnette, Matthew F. Krummel
by Maureen A. McGargill, Beiyun C. Liu, Michael S. Kuhns, Daniel Mucida, Isabella Rauch, Lauren B. Rodda, Meghan A. Koch, Hugo Gonzalez Velozo, Ken Cadwell, Tanya S. Freedman, Tiffany C. Scharschmidt, Richard Sever, Jose Ordovas-Montanes, Sara Suliman, Andrew Oberst, Brooke Runnette, Matthew F. Krummel Peer review serves as the cornerstone of scientific quality control. Yet, the current journal-centric system is hindered by long timelines, high publication costs, inconsistent review quality, systemic biases, and editorial gatekeeping. Notably, the system relies on misaligned measures of impact that are tethered to journal branding and conflate scientific rigor ( Quality ) with perceived significance ( Impact ). Here, we report findings from the Discovery Stack Pilot Study, which tested a scientist-designed, journal-independent peer review model. The Discovery Stack model integrates in-line reviewer comments to promote constructive feedback and separately evaluates scientific Quality and Impact using defined criteria. To examine feasibility and effectiveness, manuscripts were reviewed in parallel with traditional journal review. A total of 162 reviews were completed, and survey data from 86 participants were analyzed. The results showed that reviewers effectively evaluated Quality and Impact as separate dimensions, with Quality scores being more consistent across reviewers than Impact scores. Participants strongly supported the core elements of the Discovery Stack model and expressed enthusiasm for its broader adoption to enhance transparency, efficiency, and value in peer review. Future studies will explore integrating this model into a digital platform for reviewing and curating scientific discoveries to improve the production and dissemination of high-quality research.
DOI: 10.1371/journal.pbio.30039862026-09-08
Karen Filbee-Dexter, Albert Pessarrodona, Kira A. Krumhansl, Thomas Wernberg
by Karen Filbee-Dexter, Albert Pessarrodona, Kira A. Krumhansl, Thomas Wernberg The prevailing narrative of seaweed carbon as a possible climate change mitigation solution overlooks the central challenge that climate change itself is adversely impacting seaweed forests worldwide, potentially shifting these ecosystems from carbon sinks to carbon sources. In this Essay, we show that climate-induced seaweed forest loss is eroding their carbon sink capacity three to four orders of magnitude (1,000–10,000×) faster than it can currently be restored or recovered through active interventions. We consider that this stark disparity calls for a fundamental shift in seaweed carbon research away from a focus on future sequestration gains and toward explicitly assessing the risk of carbon emissions from climate-driven ecosystem loss.
DOI: 10.1371/journal.pbio.30039492026-09-03
Jie Ran, Changfeng Wei, Yang Yang, Yufei Zhang, Guizhi Guo, Nan Ma, Long Yin, Hongjun Fan, Jingrui Li, Heng Guo, Renshuai Zhang, Runa Wang, Dengwen Li, Min Liu
by Jie Ran, Changfeng Wei, Yang Yang, Yufei Zhang, Guizhi Guo, Nan Ma, Long Yin, Hongjun Fan, Jingrui Li, Heng Guo, Renshuai Zhang, Runa Wang, Dengwen Li, Min Liu Primary cilia are essential microtubule-based sensory organelles, and their dysfunction has been increasingly linked to metabolic stress. However, the underlying molecular mechanisms remain poorly understood. Herein, we reveal that ciliary defects in retinal photoreceptors and renal tubules exacerbate tissue damage during the progression of diabetic complications. Under hyperglycemic stress, protein arginine methyltransferase 1 (PRMT1) and histone deacetylase 6 (HDAC6) are significantly upregulated in both retinal and renal tissues. Genetic ablation of either enzyme effectively preserves ciliary architecture and restores organ function in diabetic mice. Mechanistically, PRMT1 localizes to the basal body, where it interacts with and methylates HDAC6 at arginine 16, consequently enhancing HDAC6 stability. In turn, HDAC6 mediates the deacetylation of PRMT1 at lysine 128, which elevates PRMT1 protein levels. This mutual modification crosstalk establishes a pathological positive feedback loop that stabilizes a pro-disassembly complex at the basal body, thereby potentiating ciliary impairment and expediting the progression of diabetic complications. Pharmacological inhibition of the PRMT1-HDAC6 loop significantly attenuates the pathological features of both diabetic retinopathy and nephropathy. Collectively, our findings uncover a reciprocal regulatory mechanism mediated by deacetylation and arginine methylation that drives cilium disassembly under hyperglycemic stress, providing promising therapeutic targets for the treatment of metabolic ciliopathies.
DOI: 10.1371/journal.pbio.30039752026-09-02
Lucas Jeay-Bizot, Raniyah Chishti, Uri Maoz, Aaron Schurger
by Lucas Jeay-Bizot, Raniyah Chishti, Uri Maoz, Aaron Schurger Respiratory processes are increasingly implicated in shaping neural activity and behavior. Recent studies have reported a coupling between respiratory phase and the cortical readiness potential (RP), suggesting that breathing may modulate the neural processes preceding voluntary action. Here, using electroencephalography recordings in humans, we re-examine this claim using the original dataset and a new independent dataset, as well as in simulated data with no coupling. We show that the reported association arises from a confound: both RP amplitude and respiratory phase are coupled to movement onset. The original analysis does not control for this dependency, leading to a spurious effect that is also observed in simulated data. When trials are instead grouped by respiratory phase at the time of movement, thereby controlling for this confound, the apparent coupling disappears. Across datasets, Bayesian analyses provide evidence for the absence of an effect under natural breathing conditions. These findings indicate that respiratory phase does not directly modulate RP amplitude during spontaneous behavior. More broadly, they reveal a shortcoming of phase-amplitude coupling analyses applied to epoched data with slowly varying signals, and highlight the importance of controlling for shared dependencies when interpreting physiological–neural relationships.
DOI: 10.1371/journal.pbio.30039822026-09-02
Audrey J. Sederberg
by Audrey J. Sederberg The brain’s functional connectivity dynamics have been explained by a critically tuned model, but such models miss occasional reconfigurations. A new PLOS Biology study shows that modulatory control near a critical point can account for these rare events. The brain’s functional connectivity dynamics have been explained by a critically tuned model, but such models miss occasional reconfigurations. This Primer discusses new PLOS Biology study showing that modulatory control near a critical point can account for these rare events.
DOI: 10.1371/journal.pbio.30039502026-09-01
Yu Pang, Dongsheng Zhou, Ziwen Peng, Wanting Liu, Ruojie Huang, Carol A. Seger, Qi Chen
by Yu Pang, Dongsheng Zhou, Ziwen Peng, Wanting Liu, Ruojie Huang, Carol A. Seger, Qi Chen Obsessive‑compulsive disorder (OCD) is characterized by an insight‑action dissociation, in which people with OCD recognize that their behavior is irrational but still struggle to inhibit habitual responses. This dissociation may be related to abnormally strong motivational biases, reflected in excessive tendencies to approach reward and avoid punishment. We employed a motivational Go/NoGo learning task, combined with computational modeling and electroencephalography (EEG), to investigate how 36 people with OCD and 37 healthy controls (HC) regulate maladaptive biases during motivated action. People with OCD showed stronger Pavlovian bias and lower learning rates. Similar to HC, people with OCD also showed increased midfrontal theta power related to conflict detection and to the generation of a control demand to increase the weighting of instrumental action values during choice, suggesting that they were able to detect the mismatch between their behavior and task goals. However, in OCD, conflict‑related theta enhancement overlapped with the response window, indicating that control signals emerged or arrived too late to effectively influence choice. Midfrontal‑motor theta phase synchrony provided the strongest model evidence for the modulation of maladaptive biases in OCD, yet this pathway showed no significant conflict‑related enhancement and failed to effectively modulate motivational biases under conflict. Taken together, these findings suggest a neural mechanism underlying the insight‑action dissociation in OCD and identify midfrontal‑motor theta phase synchrony as a potential treatment target.
DOI: 10.1371/journal.pbio.30039792026-09-01
Brandon Reyes-Chavez, Joshua D. Kerkaert, Lori B. Huberman
by Brandon Reyes-Chavez, Joshua D. Kerkaert, Lori B. Huberman Cells must sense and respond to nutrients to survive. To efficiently grow in mixed carbon environments, microbes repress genes necessary to utilize carbon sources that require substantial resources to catabolize when a simpler carbon source, such as glucose, is present. This process is known as carbon catabolite repression. Canonically, in fungi, nutrient sensing transcriptional networks are composed of carbon source-specific transcription factors that activate carbon source utilization genes and carbon catabolite repression regulators, which broadly repress all nonpreferred carbon source utilization genes when a preferred carbohydrate is present. In contrast to this model, we identified a transcription factor (Cbr1) in the basidiomycete yeast Rhodotorula ( Rhodosporidium ) toruloides that specifically inhibits glucose-mediated repression of disaccharide and proline utilization, presenting a mechanism of tailored carbon catabolite repression regulation that combats a negative feedback loop formed when glucose is released during disaccharide utilization. Cbr1 is also required for cellobiose, gentiobiose, carboxylic acid, and fucose utilization. Using transcriptomic and molecular analyses, we demonstrated that catabolism of these carbon sources is not metabolically linked, but genes necessary for their utilization are coactivated by Cbr1 in response to each of the carbon sources. This coactivation suggests R. toruloides may encounter these carbon sources together, potentially during complex interactions among microbes in nature. Coregulation of nutrient-specific gene activation and carbon catabolite repression by a transcription factor establishes a previously uncharacterized mechanism for building nutrient sensing transcriptional networks in fungi. Characterizing diverse nutrient sensing regulatory mechanisms is critical for understanding resource acquisition during fungal pathogenesis, where carbon catabolite repression is important for virulence and drug tolerance, and metabolically engineering fungi for green biotechnology.
DOI: 10.1371/journal.pbio.30039832026-09-01
Thomas Mock, Gust Bilcke, Eliott Flaum, Shunan Fu, Lilian Hoch, Kevin Moog, Nadine Rijsdijk, Elizabeth C. Ruck, Ian W. Bishop, Carole Duchene, Reuben Gilbertson, Amanda Hopes, Christopher Johns, Francesco Manfellotto, Wade R. Roberts, Nigel Belshaw, Udita Chandola, Peter Chaerle, Olga Chepurnova, Daan Deleu, Sofie D’hondt, Federica Di Costanzo, Omaya Dudin, Serena Flori, Trupti Gaikwad, Agnes Groisillier, Andrea Hall, Pengyu Ji, Louis J. Lavier-Aydat, William H. Lewis, Samuel Menicot, Eveline Pinseel, Eléonore Pottier, Krisztina Sarkozi, Arianna Smerilli, Jan Strauss, Sander Thierens, Andrew Toseland, Yousef Touhami, Robert Utting, Michiel Van Bel, Cock van Oosterhout, Yue Wu, Feng Yang, Erika Allhusen, John J. Bolton, Chris Bowler, Thorsten Brinkhoff, Anja Poehlein, Tim Brovarone, Nansheng Chen, Greg Clark, Matthew D. Clark, Dario Copetti, Zongmei Cui, Beini Deng, Jianbo Jian, Uwe John, Anne D. Jungblut, JiHeon Kang, Jon Bent Kristoffersen, JunMo Lee, Shuya Liu, David G. Mann, Linda Medlin, Vincent Moulton, Jelena Radojicic, Shinya Sato, Rosa Trobajo, Klara Wolf, Norico Yamada, Naihao Ye, Libin Zhang, Yunyun Zhuang, Gautam Dey, Valeria Di Dato, Katherine Helliwell, Marianne Jaubert, Peter G. Kroth, Marina Montresor, Giovanna Romano, Tatiana A. Rynearson, Jayson Talag, Klaus U. Valentin, Flora Vincent, Ross F. Waller, Glen Wheeler, Andrew J. Alverson, Kerrie Barry, LoriBeth Boston, Angela Falciatore, Maria Immacolata Ferrante, Jie Guo, Jane Grimwood, Richard Hayes, Andrei Herdean, Jerry Jenkins, Min Kim, Wiebe HCF Kooistra, Alan Kuo, Anna Lipzen, Nicole Poulsen, Jeremy Schmutz, Leïla Tirichine, Klaas Vandepoele, Frédéric Verret, Wim Vyverman, Igor V. Grigoriev
by Thomas Mock, Gust Bilcke, Eliott Flaum, Shunan Fu, Lilian Hoch, Kevin Moog, Nadine Rijsdijk, Elizabeth C. Ruck, Ian W. Bishop, Carole Duchene, Reuben Gilbertson, Amanda Hopes, Christopher Johns, Francesco Manfellotto, Wade R. Roberts, Nigel Belshaw, Udita Chandola, Peter Chaerle, Olga Chepurnova, Daan Deleu, Sofie D’hondt, Federica Di Costanzo, Omaya Dudin, Serena Flori, Trupti Gaikwad, Agnes Groisillier, Andrea Hall, Pengyu Ji, Louis J. Lavier-Aydat, William H. Lewis, Samuel Menicot, Eveline Pinseel, Eléonore Pottier, Krisztina Sarkozi, Arianna Smerilli, Jan Strauss, Sander Thierens, Andrew Toseland, Yousef Touhami, Robert Utting, Michiel Van Bel, Cock van Oosterhout, Yue Wu, Feng Yang, Erika Allhusen, John J. Bolton, Chris Bowler, Thorsten Brinkhoff, Anja Poehlein, Tim Brovarone, Nansheng Chen, Greg Clark, Matthew D. Clark, Dario Copetti, Zongmei Cui, Beini Deng, Jianbo Jian, Uwe John, Anne D. Jungblut, JiHeon Kang, Jon Bent Kristoffersen, JunMo Lee, Shuya Liu, David G. Mann, Linda Medlin, Vincent Moulton, Jelena Radojicic, Shinya Sato, Rosa Trobajo, Klara Wolf, Norico Yamada, Naihao Ye, Libin Zhang, Yunyun Zhuang, Gautam Dey, Valeria Di Dato, Katherine Helliwell, Marianne Jaubert, Peter G. Kroth, Marina Montresor, Giovanna Romano, Tatiana A. Rynearson, Jayson Talag, Klaus U. Valentin, Flora Vincent, Ross F. Waller, Glen Wheeler, Andrew J. Alverson, Kerrie Barry, LoriBeth Boston, Angela Falciatore, Maria Immacolata Ferrante, Jie Guo, Jane Grimwood, Richard Hayes, Andrei Herdean, Jerry Jenkins, Min Kim, Wiebe HCF Kooistra, Alan Kuo, Anna Lipzen, Nicole Poulsen, Jeremy Schmutz, Leïla Tirichine, Klaas Vandepoele, Frédéric Verret, Wim Vyverman, Igor V. Grigoriev One hundred diatom species have been selected for genome and transcriptome sequencing. The 100 Diatom Genomes Project aims to provide a scalable framework for understanding diatom biodiversity, ecology and evolution, and for investigating their use in biotechnology. This Community Page presents the 100 Diatom Genomes Project, which aims to sequence the genomes and transcriptomes of 100 diatom species across major lineages, life forms and ecological strategies. This resource will provide a scalable framework for understanding diatom biodiversity, ecology and evolution, and for investigating their use in biotechnology.
DOI: 10.1371/journal.pbio.30039472026-09-01
Farnaz Daneshnia, Deepika Gunasekaran, Sean Bergin, Lisa Lombardi, Austin M. Perry, Liuyang Cai, Louise A. Walker, Tibor Nemeth, Süleyha Hilmioglu-Polat, Letal I. Salzberg, Arefeh Ebadati, Tobias Köhler, Gabriel Braune, João N. de Almeida, Giuseppina Caggiano, Julianne V. Kus, Pegah Mosharaf Ghahfarokhy, Julieta Munoz, Daniel J. Floyd, Diego Fuentes-Palacios, Samuel M. Gonçalves, Relber A. Gonçales, Mostafa Salehi, Jigar V. Desai, Agostinho Carvalho, Shenglin Mei, Carol A. Munro, Alex Hopke, Toni Gabaldón, Attila Gacser, Oliver Kurzai, Geraldine Butler, David S. Perlin, Wenjie Fang, Clarissa J. Nobile, Michael K. Mansour, Amir Arastehfar
by Farnaz Daneshnia, Deepika Gunasekaran, Sean Bergin, Lisa Lombardi, Austin M. Perry, Liuyang Cai, Louise A. Walker, Tibor Nemeth, Süleyha Hilmioglu-Polat, Letal I. Salzberg, Arefeh Ebadati, Tobias Köhler, Gabriel Braune, João N. de Almeida, Giuseppina Caggiano, Julianne V. Kus, Pegah Mosharaf Ghahfarokhy, Julieta Munoz, Daniel J. Floyd, Diego Fuentes-Palacios, Samuel M. Gonçalves, Relber A. Gonçales, Mostafa Salehi, Jigar V. Desai, Agostinho Carvalho, Shenglin Mei, Carol A. Munro, Alex Hopke, Toni Gabaldón, Attila Gacser, Oliver Kurzai, Geraldine Butler, David S. Perlin, Wenjie Fang, Clarissa J. Nobile, Michael K. Mansour, Amir Arastehfar Candida parapsilosis is a major human fungal pathogen, with recent global outbreaks driven by fluconazole-resistant (FLCR-Cp) isolates that are difficult to eradicate and associated with poor clinical outcomes. However, the microbial traits enabling persistence of these outbreak lineages remain poorly defined. Here, we show that FLCR-Cp isolates responsible for prolonged, multi-country outbreaks consistently exhibit a striking low-biofilm-producing (LBP) phenotype. Contrary to the prevailing view that robust biofilm formation promotes persistence, LBP strains displayed enhanced stress tolerance, increased cell wall masking, and reduced immune recognition. These traits conferred resistance to neutrophil and macrophage killing and enhanced survival in immune cell-rich organs during systemic infection. Genome-wide transcriptomic profiling revealed extensive metabolic and regulatory rewiring in LBP strains. Whole-genome sequencing (WGS) of a global isolate collection further demonstrated that the LBP phenotype has emerged independently multiple times, supporting convergent evolution under host selection. Functional genomic analyses suggest that biofilm attenuation arises through multigenic changes, and disruption of key biofilm-associated transcriptional regulators enhanced fitness during immune interactions. Together, our findings overturn the assumption that robust biofilm formation drives outbreak persistence and instead identify biofilm attenuation as an adaptive tradeoff that promotes immune evasion and long-term survival. These results redefine our understanding of C. parapsilosis adaptation during healthcare-associated outbreaks and shift attention toward host-driven evolutionary processes than environmental persistence alone.
DOI: 10.1371/journal.pbio.30039732026-09-01
Anagh Pathak, Demian Battaglia
by Anagh Pathak, Demian Battaglia Ongoing brain activity displays rich temporal variability associated with efficient cognition, with functional connectivity (FC) continually reconfiguring over time. The resulting functional connectivity dynamics (FCD) specifically show complex, fat-tailed statistics that alternate between persistent epochs and faster reconfiguration transients. While nonlinear whole-brain models tuned nearby a critical point have reproduced some aspects of FCD, they fall short of capturing its full temporal complexity. We propose that slow fluctuations in arousal offer a biologically plausible mechanism for exploring critical regimes in large-scale brain dynamics and thus enrich FCD. Using a connectome-based model of coupled cortical populations, we identified phase boundaries where system dynamics transition between regimes of faster or slower FCD. We then phenomenologically incorporated arousal changes, modeling them as stochastic fluctuations in key parameters such as cortical excitability, input gain, and noise amplitude. This explicitly time-dependent formulation enables the system to roam dynamically across regime boundaries, flexibly tuning its distance from critical transition lines and producing intermittent transitions that mirror the stochastic evolution observed in empirical FCD. Fitting these models to human resting-state fMRI and performing model comparison, we find that arousal-driven models more accurately reproduce the distinctive quantitative features of FCD, with the greatest improvements coming from the previously poorly accounted fat-tailed portions of the distributions. Together, these results suggest that arousal fluctuations—likely mediated by changes in neuromodulatory tone—shape the brain’s attractor landscape over time, expanding the repertoire of accessible functional network states and providing a mechanistic basis for the complexity of spontaneous functional dynamics.
DOI: 10.1371/journal.pbio.30039162026-08-31
Lex J. Gómez, Robyn L. Mildren, Faisal Karmali, Kathleen E. Cullen
by Lex J. Gómez, Robyn L. Mildren, Faisal Karmali, Kathleen E. Cullen Visual motion is known to influence perceptions of tilt, verticality, and translation, suggesting that optic flow is combined with vestibular cues to estimate orientation relative to gravity. The cerebellar nodulus and ventral uvula (NU) are a prime candidate to perform this computation because this region uniquely receives convergent semicircular canal, otolith, and proprioceptive inputs, and in non-primate species full-field visual motion robustly modulates NU activity. Here, we tested whether visual roll motion, known to bias perceived orientation relative to gravity, alters the internal gravity-referenced transformation used by NU neurons to encode vestibular self-motion. To test this, we recorded single-unit activity from NU Purkinje cells in rhesus macaques during whole-body translations in darkness, either without visual stimulation or after prolonged full-field optokinetic roll motion. We hypothesized that visual motion simulating head tilt would bias the NU’s internal gravity estimate, leading to altered translation-evoked responses. Contrary to this prediction, visual motion had no effect on either baseline firing rates or vestibular responses. Moreover, a computational model predicting visually induced shifts in neural tuning was not supported by the data. These results show that visual roll motion, although known to influence perceived orientation, does not bias gravity-referenced vestibular coding in the primate NU. This specialization may preserve a fast, body-anchored gravity estimate for postural and reflexive motor control, delegating visual–vestibular integration for perception to downstream circuits.
DOI: 10.1371/journal.pbio.30039722026-08-31
Theophane Piette, Chundra Cathcart, Chiara Barbieri, Keesha Martin Ming, Didier Grandjean, Balthasar Bickel, Eloïse Déaux, Anne-Lise Giraud
by Theophane Piette, Chundra Cathcart, Chiara Barbieri, Keesha Martin Ming, Didier Grandjean, Balthasar Bickel, Eloïse Déaux, Anne-Lise Giraud
DOI: 10.1371/journal.pbio.30039802026-08-31
Shelby E. Andersen, Joshua M. Kirsch, Navtej Singh, Stephen R. Garrett, John C. Whitney, Jay R. Hesselberth, Breck A. Duerkop
by Shelby E. Andersen, Joshua M. Kirsch, Navtej Singh, Stephen R. Garrett, John C. Whitney, Jay R. Hesselberth, Breck A. Duerkop Renewed interest in phage therapy has highlighted a need to understand how bacteria subvert phage infection through antiphage defense systems. Traditionally, strategies to identify antiphage defense systems lack throughput or have limitations for bacterial species where antiphage defense systems are understudied. Herein, we developed a bioinformatic pipeline that uses a small serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that small serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our bioinformatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage domains and reinforce prokaryotic Schlafen proteins as a new class of antiphage defense. Our work shows that small serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.
DOI: 10.1371/journal.pbio.30039912026-08-28
Zhemin Zhang, William D. Gregor, Muslum Ilgu, Yue Yin, Philip A. Klenotic, Qijing Zhang, Edward W. Yu
by Zhemin Zhang, William D. Gregor, Muslum Ilgu, Yue Yin, Philip A. Klenotic, Qijing Zhang, Edward W. Yu Bacterial outer membrane proteins (OMPs) are critical players in host–pathogen interactions and environmental adaptation. Here we describe the newly developed “Gradient Enrichment of Native Targets from Lipid Environments” (GENTLE) methodology and use this approach to elucidate the structures of Campylobacter jejuni OMPs directly from native, detergent-solubilized crude membranes. We identify and solve high-resolution cryo-EM structures of PorA, OMP50, and Cj0034c from C. jejuni membranes, all of which are required for Campylobacter invasion, adhesion, and initiation of host infection. Notably, our results provide the first structural information of OMP50, revealing a two-domain architecture constructed with an all β-stranded transmembrane domain and an all α-helical periplasmic domain. This structure depicts that all tyrosine residues, many of which are expected to be critical for phosphorylation and host–pathogen interaction, are localized to the outer membrane of C. jejuni . Our studies also led to the first structure of the full-length Cj0034c protein, which assembles as a nonamer with each protomer containing a single-spanning transmembrane helix and a large periplasmic domain. The nine protomers stack side-by-side to form a channel that spans the entire lipid bilayer. However, whether Cj0034c spans the outer membrane (OM) or inner membrane (IM) of C. jejuni must await further experimental studies. In addition, we observed that the surface-exposed extracellular loop L4 of PorA is very flexible, which may be critical for the virulence of this porin. Collectively, this work provides novel structural information for functionally important OMPs and sheds light on how they assemble in native bacterial membranes. These findings further demonstrate that it is possible to obtain high-resolution structural information for targeted membrane proteins from crude native membranes without their overexpression and purification.
DOI: 10.1371/journal.pbio.30039612026-08-28
Rémi Tuffet, Emma Acacia, Charles Coluzzi, Xavier Charpentier, Thomas Koffel, Samuel Venner
by Rémi Tuffet, Emma Acacia, Charles Coluzzi, Xavier Charpentier, Thomas Koffel, Samuel Venner Bacterial genomes are remarkably dynamic, shaped by horizontal gene transfer. Plasmids are key actors in this process, fueling rapid bacterial adaptation to stresses such as antibiotics. Yet, plasmids follow evolutionary trajectories of their own, defying traditional genetic frameworks. Beyond the co-evolution of traits directly involved in plasmid-host relationships, it is now essential to draw from ecological theory to understand plasmid assemblages. By viewing plasmids as ecological entities competing for a shared resource, the bacterial host, we show that their distribution within bacterial genomes mirrors the structure of ecological communities. Our minimal stochastic model, inspired by community ecology, reveals that plasmid diversity arises from the combined action of niche differentiation and neutral processes. These results challenge deterministic views of genome organization, highlighting the central role of stochasticity and drift. This work establishes a theoretical bridge between microbial genomics and ecology, offering a new framework to understand—and potentially control—the evolution of bacterial genomes.
DOI: 10.1371/journal.pbio.30039182026-08-28
Joanna Clarke, on behalf of the PLOS Biology Staff Editors
by Joanna Clarke, on behalf of the PLOS Biology Staff Editors Despite recent progress in clinical research into Women’s Health, basic research is still lagging behind. Until we understand the fundamental physiology of women across the life span, we cannot expect to bring about meaningful change. Despite recent progress in clinical research into Women’s Health, basic research is still lagging behind. This Editorial calls for a renewed focus on basic physiology research into both sexes to close the gap.
DOI: 10.1371/journal.pbio.3003990