Stress is not uniform in the Earth. Therefore, we must use natural experiments to measure the distribution of stresses and related quantities, rather than single values. For instance, dynamic triggering shows that faults are uniformly distributed over their loading cycles in Southern California. The probability that a fault ruptures across a barrier measures the in situ energy distribution. Fault roughness reflects the distribution of strength. These natural experiments produce observable distributions that are surprisingly consistent and suggest some degree of self-organization in the Earth’s crust. Once established, the functional form of the distributions can be used to track changes in response to earthquakes as well as to distinguish fundamentally different fault systems. Transient fault locking before stress release in laboratory experiments can be interpreted as a consequence of self-organization of fault stress. The robust self-organization of multiple variables in earthquake systems suggests that the most consequential mechanical outcome of earthquakes may be the redistribution of stress and the strain energy associated with it. The low friction on a fault during seismic slip as inferred by temperature measurements of the Tohoku earthquake is consistent with dissipation playing a secondary role to this redistribution process. Through stress redistribution and interaction, subduction zone faults tend to synchronize, perhaps due to their geometric simplicity, while the continental system of Southern California cannot synchronize, perhaps due to the complexity of the fault network. Earthquakes organize stress in the crust and produce a suite of well-defined, consistent distributions.
{"title":"How earthquakes organize stress","authors":"Emily E. Brodsky, Gaspard Farge","doi":"10.1073/pnas.2530754123","DOIUrl":"https://doi.org/10.1073/pnas.2530754123","url":null,"abstract":"Stress is not uniform in the Earth. Therefore, we must use natural experiments to measure the distribution of stresses and related quantities, rather than single values. For instance, dynamic triggering shows that faults are uniformly distributed over their loading cycles in Southern California. The probability that a fault ruptures across a barrier measures the in situ energy distribution. Fault roughness reflects the distribution of strength. These natural experiments produce observable distributions that are surprisingly consistent and suggest some degree of self-organization in the Earth’s crust. Once established, the functional form of the distributions can be used to track changes in response to earthquakes as well as to distinguish fundamentally different fault systems. Transient fault locking before stress release in laboratory experiments can be interpreted as a consequence of self-organization of fault stress. The robust self-organization of multiple variables in earthquake systems suggests that the most consequential mechanical outcome of earthquakes may be the redistribution of stress and the strain energy associated with it. The low friction on a fault during seismic slip as inferred by temperature measurements of the Tohoku earthquake is consistent with dissipation playing a secondary role to this redistribution process. Through stress redistribution and interaction, subduction zone faults tend to synchronize, perhaps due to their geometric simplicity, while the continental system of Southern California cannot synchronize, perhaps due to the complexity of the fault network. Earthquakes organize stress in the crust and produce a suite of well-defined, consistent distributions.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"30 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura German, Jesse Abrams, Cory L. Struthers, Sherry Pictou, C. Brock Woodson, Suneel Kumar, Tommy Cabe, Roger Merino, Elizabeth King
Conservation and environmental management are under increased scrutiny as the embeddedness of oppressive practices has gained wider societal and scholarly attention. As conservation and environmental practitioners and scholars grapple with foundational assumptions and practices of the field, there remains a pressing need to identify persistent problematic legacies and articulate a positive vision for conservation grounded in an ethic of justice. To help advance this conversation, we present a framework of four intersecting dimensions of oppression: 1) the physical or material manifestations of conservation and environmental management; 2) the knowledge practices and assumptions that inform and underpin conservation and environmental visions and decision-making; 3) the modes of governance associated with conservation and environmental practice; and 4) the forms of relational praxis implicitly and explicitly endorsed and/or imposed in conservation and other environmental arenas. We explain the framework through an analysis of the legacy of fortress conservation, then illustrate the framework’s wider application to diagnose ongoing elements of oppression in other environmental arenas (wildland fire, riverine flows). We then review prominent strategies and visions for moving forward for both nature and people to highlight both positive steps being taken and the utility of the framework in ensuring emergent environmental paradigms avoid the pitfalls of the past. Viewing each dimension of oppression as moveable levers to promote antioppressive conservation futures, we conclude with a set of questions to help conservation and environmental management scientists and practitioners identify where oppression might be manifest in their own work, and begin to embody antioppressive practices.
{"title":"Conservation and environmental management reimagined: Toward anti-oppressive futures","authors":"Laura German, Jesse Abrams, Cory L. Struthers, Sherry Pictou, C. Brock Woodson, Suneel Kumar, Tommy Cabe, Roger Merino, Elizabeth King","doi":"10.1073/pnas.2414948123","DOIUrl":"https://doi.org/10.1073/pnas.2414948123","url":null,"abstract":"Conservation and environmental management are under increased scrutiny as the embeddedness of oppressive practices has gained wider societal and scholarly attention. As conservation and environmental practitioners and scholars grapple with foundational assumptions and practices of the field, there remains a pressing need to identify persistent problematic legacies and articulate a positive vision for conservation grounded in an ethic of justice. To help advance this conversation, we present a framework of four intersecting dimensions of oppression: 1) the <jats:italic toggle=\"yes\">physical</jats:italic> or material manifestations of conservation and environmental management; 2) the <jats:italic toggle=\"yes\">knowledge</jats:italic> practices and assumptions that inform and underpin conservation and environmental visions and decision-making; 3) the modes of <jats:italic toggle=\"yes\">governance</jats:italic> associated with conservation and environmental practice; and 4) the forms of <jats:italic toggle=\"yes\">relational praxis</jats:italic> implicitly and explicitly endorsed and/or imposed in conservation and other environmental arenas. We explain the framework through an analysis of the legacy of fortress conservation, then illustrate the framework’s wider application to diagnose ongoing elements of oppression in other environmental arenas (wildland fire, riverine flows). We then review prominent strategies and visions for moving forward for both nature and people to highlight both positive steps being taken and the utility of the framework in ensuring emergent environmental paradigms avoid the pitfalls of the past. Viewing each dimension of oppression as moveable levers to promote antioppressive conservation futures, we conclude with a set of questions to help conservation and environmental management scientists and practitioners identify where oppression might be manifest in their own work, and begin to embody antioppressive practices.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"26 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Corentin Bisot, Loreto Oyarte Galvez, Félix Kahane, Marije van Son, Bianca Turcu, Rob Broekman, Kai-Kai Lin, Paco Bontenbal, Max Kerr Winter, Vasilis Kokkoris, Stuart A. West, Christophe Godin, E. Toby Kiers, Thomas S. Shimizu
Symbiotic nutrient exchange between arbuscular mycorrhizal (AM) fungi and their host plants varies widely depending on their physical, chemical, and biological environment. Yet dissecting this context dependency remains challenging because we lack methods for tracking nutrients such as carbon (C) and phosphorus (P). Here, we developed an approach to quantitatively estimate C and P fluxes in the AM symbiosis from comprehensive network morphology quantification, achieved by robotic imaging and machine learning based on roughly 100 million hyphal shape measurements. We found that rates of C transfer from the plant and P transfer from the fungus were, on average, related proportionally to one another. This ratio was nearly invariant across AM fungal strains despite contrasting growth phenotypes but was strongly affected by plant host genotype. Fungal phenotype distributions were bounded by a Pareto front with a shape favoring specialization in an exploration–exploitation trade-off. This means AM fungi can be fast range expanders or fast resource extractors, but not both. Manipulating the C/P exchange rate by swapping the plant host genotype shifted this Pareto front, indicating that the exchange rate constrains possible AM fungal growth strategies. We show by mathematical modeling how AM fungal growth at fixed exchange rate leads to qualitatively different symbiotic outcomes depending on fungal traits and nutrient availability.
{"title":"Carbon–phosphorus exchange rate constrains density–speed trade-off in arbuscular mycorrhizal fungal growth","authors":"Corentin Bisot, Loreto Oyarte Galvez, Félix Kahane, Marije van Son, Bianca Turcu, Rob Broekman, Kai-Kai Lin, Paco Bontenbal, Max Kerr Winter, Vasilis Kokkoris, Stuart A. West, Christophe Godin, E. Toby Kiers, Thomas S. Shimizu","doi":"10.1073/pnas.2512182123","DOIUrl":"https://doi.org/10.1073/pnas.2512182123","url":null,"abstract":"Symbiotic nutrient exchange between arbuscular mycorrhizal (AM) fungi and their host plants varies widely depending on their physical, chemical, and biological environment. Yet dissecting this context dependency remains challenging because we lack methods for tracking nutrients such as carbon (C) and phosphorus (P). Here, we developed an approach to quantitatively estimate C and P fluxes in the AM symbiosis from comprehensive network morphology quantification, achieved by robotic imaging and machine learning based on roughly 100 million hyphal shape measurements. We found that rates of C transfer from the plant and P transfer from the fungus were, on average, related proportionally to one another. This ratio was nearly invariant across AM fungal strains despite contrasting growth phenotypes but was strongly affected by plant host genotype. Fungal phenotype distributions were bounded by a Pareto front with a shape favoring specialization in an exploration–exploitation trade-off. This means AM fungi can be fast range expanders or fast resource extractors, but not both. Manipulating the C/P exchange rate by swapping the plant host genotype shifted this Pareto front, indicating that the exchange rate constrains possible AM fungal growth strategies. We show by mathematical modeling how AM fungal growth at fixed exchange rate leads to qualitatively different symbiotic outcomes depending on fungal traits and nutrient availability.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"57 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henry Alston, Mason Rouches, Arvind Murugan, Aleksandra M. Walczak, Thierry Mora
Biomolecular condensates form on timescales of seconds in cells upon environmental or compositional changes. Condensate formation is thus argued to act as a mechanism for sensing such changes and quickly initiating downstream processes, such as forming stress granules in response to heat stress and amplifying cyclic GMP-AMP synthase enzymatic activity upon detection of cytosolic DNA. Here, we study a dynamical model of droplet nucleation and growth to demonstrate how phase separation allows cells to discriminate small concentration differences on finite, biologically relevant timescales. We propose optimal sensing protocols, which use the sharp onset of phase separation. We show how, given experimentally measured rates, cells can achieve rapid and robust sensing of concentration differences of 1% on a timescale of minutes, offering an alternative to classical biochemical mechanisms.
{"title":"Theoretical limits for sensing through phase separation","authors":"Henry Alston, Mason Rouches, Arvind Murugan, Aleksandra M. Walczak, Thierry Mora","doi":"10.1073/pnas.2520040123","DOIUrl":"https://doi.org/10.1073/pnas.2520040123","url":null,"abstract":"Biomolecular condensates form on timescales of seconds in cells upon environmental or compositional changes. Condensate formation is thus argued to act as a mechanism for sensing such changes and quickly initiating downstream processes, such as forming stress granules in response to heat stress and amplifying cyclic GMP-AMP synthase enzymatic activity upon detection of cytosolic DNA. Here, we study a dynamical model of droplet nucleation and growth to demonstrate how phase separation allows cells to discriminate small concentration differences on finite, biologically relevant timescales. We propose optimal sensing protocols, which use the sharp onset of phase separation. We show how, given experimentally measured rates, cells can achieve rapid and robust sensing of concentration differences of <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mrow> <mml:mn>1</mml:mn> <mml:mo>%</mml:mo> </mml:mrow> </mml:math> </jats:inline-formula> on a timescale of minutes, offering an alternative to classical biochemical mechanisms.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"58 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anton Klimek, Benjamin A. Dalton, Lucas Tepper, Roland R. Netz
Proteins often exhibit subdiffusive configurational dynamics, the origins of which are still unresolved. We investigate the impact of non-Markovian friction and the free-energy landscape on the dynamics of fast-folding proteins in terms of the mean squared displacement (MSD) and the mean first-passage-time (MFPT) of the folding reaction coordinate. We find the friction memory kernel from published molecular dynamics simulations to be well-described by a hierarchical multiexponential function, which gives rise to subdiffusion in the MSD for times shorter than the longest memory time, while for longer times the confining free-energy landscape produces subdiffusion. Thus, for a wide range of times, friction memory effects in fast-folding proteins dominate the scaling behavior of the MSD compared to effects due to the folding free-energy landscape. As a consequence, Markovian models are insufficient to fully capture the folding dynamics, as quantified by the MSD and the MFPT, even when including coordinate-dependent friction. Our results demonstrate the importance of memory effects in protein folding and conformational dynamics and explicitly show that subdiffusion in fast-folding protein dynamics originates mainly from memory effects, not from the free-energy landscape and not from coordinate-dependent friction.
{"title":"Hierarchical friction memory leads to subdiffusive configurational dynamics of fast-folding proteins","authors":"Anton Klimek, Benjamin A. Dalton, Lucas Tepper, Roland R. Netz","doi":"10.1073/pnas.2516506123","DOIUrl":"https://doi.org/10.1073/pnas.2516506123","url":null,"abstract":"Proteins often exhibit subdiffusive configurational dynamics, the origins of which are still unresolved. We investigate the impact of non-Markovian friction and the free-energy landscape on the dynamics of fast-folding proteins in terms of the mean squared displacement (MSD) and the mean first-passage-time (MFPT) of the folding reaction coordinate. We find the friction memory kernel from published molecular dynamics simulations to be well-described by a hierarchical multiexponential function, which gives rise to subdiffusion in the MSD for times shorter than the longest memory time, while for longer times the confining free-energy landscape produces subdiffusion. Thus, for a wide range of times, friction memory effects in fast-folding proteins dominate the scaling behavior of the MSD compared to effects due to the folding free-energy landscape. As a consequence, Markovian models are insufficient to fully capture the folding dynamics, as quantified by the MSD and the MFPT, even when including coordinate-dependent friction. Our results demonstrate the importance of memory effects in protein folding and conformational dynamics and explicitly show that subdiffusion in fast-folding protein dynamics originates mainly from memory effects, not from the free-energy landscape and not from coordinate-dependent friction.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"91 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristyn Hayashi, Suganya Sekaran, Pelle Simpson, Christopher C. Ebmeier, Cole R. Michel, Natalie G. Ahn
Cell fates regulated by ERK respond to different thresholds of signaling strength. In mammalian cells, conditions that activate ERK to submaximal levels are sufficient to sustain proliferation, survival, and transformation, while stimuli that activate ERK to very high levels often lead to cell death or cell cycle arrest. But while this “Goldilocks effect” is well known, the mechanisms have never been fully explained. In particular, threshold responses have been shown at the level of transcription and cell state changes, but whether phosphorylation responses upstream of these events also respond to thresholds is unknown. Here, we used mass spectrometry-based phosphoproteomics to ask if molecular events in the ERK pathway respond to different thresholds of signaling strength, by quantifying changes in phosphorylation of pathway targets against the occupancy of the two activating phosphosites in ERK. The results show that most phosphorylation events track ERK activation faithfully, responding linearly with increasing 2P-ERK occupancy. But some sites respond nonlinearly, reaching maximal phosphorylation when 2P-ERK exceeds lower thresholds (10 to 40%), or increasing substantially after 2P-ERK exceeds higher thresholds (>60%). Low threshold sites are found on transcriptional repressors that facilitate proliferation when inactivated by ERK/ribosomal s6 kinase (RSK) phosphorylation. By contrast, high threshold sites are found on proteins that are recruited to double-stranded DNA breaks and mediate DNA repair. Measurement of phosphorylation occupancies also revealed unexpected differences between cell states not apparent from inhibitor fold-changes. Our findings demonstrate that signaling thresholds exist at the level of the phosphoproteome, providing potential mechanisms for regulating cellular responses to pathway strength.
{"title":"Variable thresholds for phosphorylation targets of the ERK signaling pathway","authors":"Kristyn Hayashi, Suganya Sekaran, Pelle Simpson, Christopher C. Ebmeier, Cole R. Michel, Natalie G. Ahn","doi":"10.1073/pnas.2517889123","DOIUrl":"https://doi.org/10.1073/pnas.2517889123","url":null,"abstract":"Cell fates regulated by ERK respond to different thresholds of signaling strength. In mammalian cells, conditions that activate ERK to submaximal levels are sufficient to sustain proliferation, survival, and transformation, while stimuli that activate ERK to very high levels often lead to cell death or cell cycle arrest. But while this “Goldilocks effect” is well known, the mechanisms have never been fully explained. In particular, threshold responses have been shown at the level of transcription and cell state changes, but whether phosphorylation responses upstream of these events also respond to thresholds is unknown. Here, we used mass spectrometry-based phosphoproteomics to ask if molecular events in the ERK pathway respond to different thresholds of signaling strength, by quantifying changes in phosphorylation of pathway targets against the occupancy of the two activating phosphosites in ERK. The results show that most phosphorylation events track ERK activation faithfully, responding linearly with increasing 2P-ERK occupancy. But some sites respond nonlinearly, reaching maximal phosphorylation when 2P-ERK exceeds lower thresholds (10 to 40%), or increasing substantially after 2P-ERK exceeds higher thresholds (>60%). Low threshold sites are found on transcriptional repressors that facilitate proliferation when inactivated by ERK/ribosomal s6 kinase (RSK) phosphorylation. By contrast, high threshold sites are found on proteins that are recruited to double-stranded DNA breaks and mediate DNA repair. Measurement of phosphorylation occupancies also revealed unexpected differences between cell states not apparent from inhibitor fold-changes. Our findings demonstrate that signaling thresholds exist at the level of the phosphoproteome, providing potential mechanisms for regulating cellular responses to pathway strength.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"303 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeffrey Granat, Sanxiong Liu, Luis Popoca, Ozgur Oksuz, Danny Reinberg
Polycomb Repressive Complex 2 (PRC2) facilitates the formation of facultative heterochromatin, instrumental to tissue specific gene expression. PRC2 catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3), which is targeted for chromatin compaction by PRC1. Importantly, PRC2-associated cofactors regulate its distinct activities, as in the case of MTF2 and JARID2 that direct PRC2 to specific chromatin nucleation sites based on preferred DNA-binding motifs. Here, we investigated EPOP whose role in regulating PRC2 was not well-defined. We find that both EPOP and MTF2 stimulate PRC2 histone methyltransferase (HMT) activity in vitro. Unlike MTF2, EPOP is ineffectual in PRC2 chromatin recruitment as evidenced by an EED-rescue system in vivo but promotes H3K27me3 deposition de novo in cooperation with MTF2 and JARID2. Binding assays using reconstituted dinucleosome substrates revealed that similar to MTF2, EPOP promotes PRC2 chromatin-binding activity in a distinct DNA-sequence-dependent manner (GCN-rich and GA-rich, respectively). Thus, EPOP and MTF2 in conjunction with JARID2 foster PRC2-mediated HMT activity at chromatin sites comprising cofactor-preferred DNA-binding sequences during the formation of H3K27me3-chromatin domains.
{"title":"EPOP and MTF2 activate PRC2 activity through DNA-sequence specificity","authors":"Jeffrey Granat, Sanxiong Liu, Luis Popoca, Ozgur Oksuz, Danny Reinberg","doi":"10.1073/pnas.2527303123","DOIUrl":"https://doi.org/10.1073/pnas.2527303123","url":null,"abstract":"Polycomb Repressive Complex 2 (PRC2) facilitates the formation of facultative heterochromatin, instrumental to tissue specific gene expression. PRC2 catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3), which is targeted for chromatin compaction by PRC1. Importantly, PRC2-associated cofactors regulate its distinct activities, as in the case of MTF2 and JARID2 that direct PRC2 to specific chromatin nucleation sites based on preferred DNA-binding motifs. Here, we investigated EPOP whose role in regulating PRC2 was not well-defined. We find that both EPOP and MTF2 stimulate PRC2 histone methyltransferase (HMT) activity in vitro. Unlike MTF2, EPOP is ineffectual in PRC2 chromatin recruitment as evidenced by an EED-rescue system in vivo but promotes H3K27me3 deposition de novo in cooperation with MTF2 and JARID2. Binding assays using reconstituted dinucleosome substrates revealed that similar to MTF2, EPOP promotes PRC2 chromatin-binding activity in a distinct DNA-sequence-dependent manner (GCN-rich and GA-rich, respectively). Thus, EPOP and MTF2 in conjunction with JARID2 foster PRC2-mediated HMT activity at chromatin sites comprising cofactor-preferred DNA-binding sequences during the formation of H3K27me3-chromatin domains.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"33 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Animals remain awake in unfamiliar environments to assess potential safety threats, a process involving changes in neuronal activity within sleep–wake regulatory brain regions. However, the specific circuits and neurotransmitters involved remain poorly understood. Here, we show that neurotensin (NTS) peptides in corticotropin-releasing factor (CRF) neurons of the lateral part of the interstitial nucleus of the posterior limb of the anterior commissure (IPACL) play a key role in maintaining wakefulness in response to environmental changes. Activation of IPACL CRF neurons increased wakefulness, whereas their inhibition or deletion of NTS reduced wakefulness in novel environments. These neurons are activated in response to exposure to a novel environment and project primarily to the substantia nigra pars reticulata (SNr) and release NTS, which modulates wakefulness. These findings suggest that NTS signaling from IPACL CRF neurons to the SNr is essential for sustaining wakefulness in unfamiliar or changing environments.
{"title":"Neurotensin in the extended amygdala maintains wakefulness in novel environments","authors":"Chi Jung Hung, Shuhei Ueda, Sheikh Mizanur Rahaman, Mikiyasu Yamamoto, Jiahui Li, Noriaki Fukatsu, Haruhiko Bito, Hiroshi Yamaguchi, Akihiro Yamanaka, Sayaka Takemoto-Kimura, Daisuke Ono","doi":"10.1073/pnas.2521268123","DOIUrl":"https://doi.org/10.1073/pnas.2521268123","url":null,"abstract":"Animals remain awake in unfamiliar environments to assess potential safety threats, a process involving changes in neuronal activity within sleep–wake regulatory brain regions. However, the specific circuits and neurotransmitters involved remain poorly understood. Here, we show that neurotensin (NTS) peptides in corticotropin-releasing factor (CRF) neurons of the lateral part of the interstitial nucleus of the posterior limb of the anterior commissure (IPACL) play a key role in maintaining wakefulness in response to environmental changes. Activation of IPACL <jats:sup>CRF</jats:sup> neurons increased wakefulness, whereas their inhibition or deletion of NTS reduced wakefulness in novel environments. These neurons are activated in response to exposure to a novel environment and project primarily to the substantia nigra pars reticulata (SNr) and release NTS, which modulates wakefulness. These findings suggest that NTS signaling from IPACL <jats:sup>CRF</jats:sup> neurons to the SNr is essential for sustaining wakefulness in unfamiliar or changing environments.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"47 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zihan Zheng, Cunyuan Jiang, Yangrui Chen, Matteo Baggioli, Jie Zhang
Active matter refers to a broad class of nonequilibrium systems where energy is continuously injected at the level of individual “particles.” These systems exhibit emergent collective behaviors that have no direct thermal-equilibrium counterpart. Their scale ranges from micrometer-sized swarms of bacteria to meter-scale human crowds. In recent years, the role of topology and self-propelled topological defects in active systems has garnered significant attention, particularly in polar and nematic active matter. Building on these ideas, we investigate emergent collective dynamics in apolar active granular fluids. Using isotropic granular vibrators as a model experimental system of apolar active Ornstein–Uhlenbeck particles in a dry environment, we uncover a distinctive three-stage time evolution arising from the intricate interplay between activity and inelastic interactions. By analyzing the statistics, spatial correlations, and dynamics of vortex-like topological defects in the displacement vector field, we demonstrate their ability to describe this intrinsic collective motion. Furthermore, associated to these topological defects, we reveal the onset of a turbulent-like inverse energy cascade, where kinetic energy transfers across different length scales over time. As the system evolves, the power scaling of the energy transfer increases with the duration of observation. Our findings show that topological concepts can be extended to the nonequilibrium dynamics of apolar active matter, revealing a direct link between microscopic topological processes and emergent large-scale behaviors in active granular fluids that lack both a well-defined direction of motion and an intrinsic axis of orientation at the particle scale.
{"title":"Topological signatures of collective dynamics and turbulent-like energy cascades in apolar active granular matter","authors":"Zihan Zheng, Cunyuan Jiang, Yangrui Chen, Matteo Baggioli, Jie Zhang","doi":"10.1073/pnas.2510873123","DOIUrl":"https://doi.org/10.1073/pnas.2510873123","url":null,"abstract":"Active matter refers to a broad class of nonequilibrium systems where energy is continuously injected at the level of individual “particles.” These systems exhibit emergent collective behaviors that have no direct thermal-equilibrium counterpart. Their scale ranges from micrometer-sized swarms of bacteria to meter-scale human crowds. In recent years, the role of topology and self-propelled topological defects in active systems has garnered significant attention, particularly in polar and nematic active matter. Building on these ideas, we investigate emergent collective dynamics in apolar active granular fluids. Using isotropic granular vibrators as a model experimental system of apolar active Ornstein–Uhlenbeck particles in a dry environment, we uncover a distinctive three-stage time evolution arising from the intricate interplay between activity and inelastic interactions. By analyzing the statistics, spatial correlations, and dynamics of vortex-like topological defects in the displacement vector field, we demonstrate their ability to describe this intrinsic collective motion. Furthermore, associated to these topological defects, we reveal the onset of a turbulent-like inverse energy cascade, where kinetic energy transfers across different length scales over time. As the system evolves, the power scaling of the energy transfer increases with the duration of observation. Our findings show that topological concepts can be extended to the nonequilibrium dynamics of apolar active matter, revealing a direct link between microscopic topological processes and emergent large-scale behaviors in active granular fluids that lack both a well-defined direction of motion and an intrinsic axis of orientation at the particle scale.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"303 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark D. Olchanyi, David R. Schreier, Jian Li, Chiara Maffei, Annabel Sorby-Adams, Hannah C. Kinney, Brian C. Healy, Holly J. Freeman, Jared Shless, Christophe Destrieux, Henry Tregidgo, Juan Eugenio Iglesias, Emery N. Brown, Brian L. Edlow
Brainstem white matter (WM) bundles are essential conduits for neural signals that modulate homeostasis and consciousness. Their architecture forms the anatomic basis for brainstem connectomics, subcortical circuit models, and deep brain navigation tools. However, their small size and complex morphology, compared to cerebral WM, makes mapping and segmentation challenging in neuroimaging. As a result, fundamental questions about brainstem modulation of human homeostasis and consciousness remain unanswered. We leverage diffusion MRI tractography to create BrainStem Bundle Tool (BSBT), which automatically segments eight WM bundles in the rostral brainstem. BSBT performs segmentation on a custom probabilistic fiber map using a convolutional neural network architecture tailored to detect small anatomic structures. We demonstrate BSBT’s robustness across diffusion MRI acquisition protocols with in vivo scans of healthy subjects and ex vivo scans of human brain specimens with corresponding histology. BSBT also detected distinct brainstem bundle alterations in patients with Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and traumatic brain injury through tract-based analysis and classification tasks. Finally, we provide proof-of-principle evidence for the prognostic utility of BSBT in a longitudinal analysis of traumatic coma recovery. BSBT creates opportunities for scalable mapping of brainstem WM bundles and investigation of their role in a broad spectrum of neurological disorders.
{"title":"Probabilistic mapping and automated segmentation of human brainstem white matter bundles","authors":"Mark D. Olchanyi, David R. Schreier, Jian Li, Chiara Maffei, Annabel Sorby-Adams, Hannah C. Kinney, Brian C. Healy, Holly J. Freeman, Jared Shless, Christophe Destrieux, Henry Tregidgo, Juan Eugenio Iglesias, Emery N. Brown, Brian L. Edlow","doi":"10.1073/pnas.2509321123","DOIUrl":"https://doi.org/10.1073/pnas.2509321123","url":null,"abstract":"Brainstem white matter (WM) bundles are essential conduits for neural signals that modulate homeostasis and consciousness. Their architecture forms the anatomic basis for brainstem connectomics, subcortical circuit models, and deep brain navigation tools. However, their small size and complex morphology, compared to cerebral WM, makes mapping and segmentation challenging in neuroimaging. As a result, fundamental questions about brainstem modulation of human homeostasis and consciousness remain unanswered. We leverage diffusion MRI tractography to create BrainStem Bundle Tool (BSBT), which automatically segments eight WM bundles in the rostral brainstem. BSBT performs segmentation on a custom probabilistic fiber map using a convolutional neural network architecture tailored to detect small anatomic structures. We demonstrate BSBT’s robustness across diffusion MRI acquisition protocols with in vivo scans of healthy subjects and ex vivo scans of human brain specimens with corresponding histology. BSBT also detected distinct brainstem bundle alterations in patients with Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and traumatic brain injury through tract-based analysis and classification tasks. Finally, we provide proof-of-principle evidence for the prognostic utility of BSBT in a longitudinal analysis of traumatic coma recovery. BSBT creates opportunities for scalable mapping of brainstem WM bundles and investigation of their role in a broad spectrum of neurological disorders.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"4 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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