Leif Karlstrom, Nathaniel Klema, Gordon E. Grant, Carol Finn, Pamela L. Sullivan, Sarah Cooley, Alex Simpson, Becky Fasth, Katharine Cashman, Ken Ferrier, Lyndsay Ball, Daniele McKay
Volcanic provinces are among the most active but least well understood landscapes on Earth. Here, we show that the central Cascade arc, USA, exhibits systematic spatial covariation of topography and hydrology that are linked to aging volcanic bedrock, suggesting systematic controls on landscape evolution. At the Cascade crest, a locus of Quaternary volcanism, water circulates deeply through the upper ∼ 1 km of crust but transitions to shallow and dominantly horizontal flow as rocks age away from the arc front. We argue that this spatial pattern reflects a temporal state shift in the deep Critical Zone. Chemical weathering at depth, surface particulate deposition, and tectonic forcing drive landscapes away from an initial state with minimal topographic dissection, large vertical hydraulic conductivity, abundant lakes, and muted hydrographs toward a state of deep fluvial dissection, small vertical hydraulic conductivity, few lakes, and flashy hydrographs. This state shift has major implications for regional water resources. Drill hole temperature profiles imply at least 81 km 3 of active groundwater currently stored at the Cascade Range crest, with discharge variability a strong function of bedrock age. Deeply circulating groundwater also impacts volcanism, and Holocene High Cascades eruptions reflect explosive magma–water interactions that increase regional volcanic hazard potential. We propose that a Critical Zone state shift drives volcanic landscape evolution in wet climates and represents a framework for understanding interconnected solid earth dynamics and climate in these terrains.
火山带是地球上最活跃但最不为人知的地貌之一。在这里，我们展示了美国卡斯卡特弧中部地形和水文的系统空间共变，这些共变与老化的火山基岩有关，表明地貌演变受到系统控制。卡斯卡特峰是第四纪火山活动的中心地带，水流在地壳上部 1 千米深处循环，但随着岩石老化远离弧前，水流过渡到浅层，并以水平流为主。我们认为，这种空间模式反映了深部临界区的时间状态转变。深部的化学风化作用、地表颗粒沉积以及构造作用促使地貌从地形剖面最小、垂直导水性大、湖泊丰富、水文图柔和的初始状态转变为深部河道剖面大、垂直导水性小、湖泊稀少、水文图急剧变化的状态。这种状态的转变对区域水资源具有重大影响。钻孔温度剖面图表明，目前至少有 81 km 3 的活跃地下水储存在喀斯喀特山脉顶峰，其排泄量的变化与基岩年龄密切相关。深层循环的地下水也会对火山活动产生影响，全新世的高卡斯卡特山脉火山爆发反映了岩浆与水之间的爆炸性相互作用，增加了区域火山灾害的可能性。我们提出，临界区状态的转变推动了湿润气候条件下火山地貌的演变，是理解这些地形中相互关联的固体地球动力学和气候的框架。
{"title":"State shifts in the deep Critical Zone drive landscape evolution in volcanic terrains","authors":"Leif Karlstrom, Nathaniel Klema, Gordon E. Grant, Carol Finn, Pamela L. Sullivan, Sarah Cooley, Alex Simpson, Becky Fasth, Katharine Cashman, Ken Ferrier, Lyndsay Ball, Daniele McKay","doi":"10.1073/pnas.2415155122","DOIUrl":"https://doi.org/10.1073/pnas.2415155122","url":null,"abstract":"Volcanic provinces are among the most active but least well understood landscapes on Earth. Here, we show that the central Cascade arc, USA, exhibits systematic spatial covariation of topography and hydrology that are linked to aging volcanic bedrock, suggesting systematic controls on landscape evolution. At the Cascade crest, a locus of Quaternary volcanism, water circulates deeply through the upper <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mo>∼</mml:mo> </mml:math> </jats:inline-formula> 1 km of crust but transitions to shallow and dominantly horizontal flow as rocks age away from the arc front. We argue that this spatial pattern reflects a temporal state shift in the deep Critical Zone. Chemical weathering at depth, surface particulate deposition, and tectonic forcing drive landscapes away from an initial state with minimal topographic dissection, large vertical hydraulic conductivity, abundant lakes, and muted hydrographs toward a state of deep fluvial dissection, small vertical hydraulic conductivity, few lakes, and flashy hydrographs. This state shift has major implications for regional water resources. Drill hole temperature profiles imply at least <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mn>81</mml:mn> </mml:math> </jats:inline-formula> km <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:msup> <mml:mrow/> <mml:mn>3</mml:mn> </mml:msup> </mml:math> </jats:inline-formula> of active groundwater currently stored at the Cascade Range crest, with discharge variability a strong function of bedrock age. Deeply circulating groundwater also impacts volcanism, and Holocene High Cascades eruptions reflect explosive magma–water interactions that increase regional volcanic hazard potential. We propose that a Critical Zone state shift drives volcanic landscape evolution in wet climates and represents a framework for understanding interconnected solid earth dynamics and climate in these terrains.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"205 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974861","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}
Emily E. Meyer, Marcelina Martynek, Sabine Kastner, Margaret S. Livingstone, Michael J. Arcaro
Human brain evolution is marked by a disproportionate expansion of cortical regions associated with advanced perceptual and cognitive functions. While this expansion is often attributed to the emergence of novel specialized brain areas, modifications to evolutionarily conserved cortical regions also have been linked to species-specific behaviors. Distinguishing between these two evolutionary outcomes has been limited by the ability to make direct comparisons between species. Here, we addressed this limitation by examining the expansion of the human visual cortex relative to macaques using a common functional architecture: retinotopy. Our findings revealed that human visual cortex expansion is primarily driven by increases in the surface area of a visual map architecture present in macaques rather than an increase in the number of individual areas. This expansion was not uniform, with higher-order areas, particularly in the parietal cortex, exhibiting the largest growth. Comparisons between neonate and adult humans revealed that these relative areal size differences were already established at birth. A meta-analysis of neuroimaging studies indicated that the most expanded areas are associated with advanced cognitive functions beyond visual processing. These results suggest that human perceptual and cognitive adaptations may be rooted in the expansion of evolutionarily conserved cortical architecture, with modifications even in the sensory cortex contributing to the broader cognitive functions characteristic of human behavior.
{"title":"Expansion of a conserved architecture drives the evolution of the primate visual cortex","authors":"Emily E. Meyer, Marcelina Martynek, Sabine Kastner, Margaret S. Livingstone, Michael J. Arcaro","doi":"10.1073/pnas.2421585122","DOIUrl":"https://doi.org/10.1073/pnas.2421585122","url":null,"abstract":"Human brain evolution is marked by a disproportionate expansion of cortical regions associated with advanced perceptual and cognitive functions. While this expansion is often attributed to the emergence of novel specialized brain areas, modifications to evolutionarily conserved cortical regions also have been linked to species-specific behaviors. Distinguishing between these two evolutionary outcomes has been limited by the ability to make direct comparisons between species. Here, we addressed this limitation by examining the expansion of the human visual cortex relative to macaques using a common functional architecture: retinotopy. Our findings revealed that human visual cortex expansion is primarily driven by increases in the surface area of a visual map architecture present in macaques rather than an increase in the number of individual areas. This expansion was not uniform, with higher-order areas, particularly in the parietal cortex, exhibiting the largest growth. Comparisons between neonate and adult humans revealed that these relative areal size differences were already established at birth. A meta-analysis of neuroimaging studies indicated that the most expanded areas are associated with advanced cognitive functions beyond visual processing. These results suggest that human perceptual and cognitive adaptations may be rooted in the expansion of evolutionarily conserved cortical architecture, with modifications even in the sensory cortex contributing to the broader cognitive functions characteristic of human behavior.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"42 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974857","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}
Rémi Gaillard, Philippe Peylin, Patricia Cadule, Vladislav Bastrikov, Frédérique Chéruy, Amélie Cuynet, Josefine Ghattas, Dan Zhu, Bertrand Guenet
The insulative properties of soil organic carbon (SOC) and surface organic layers (moss, lichens, litter) regulate surface–atmosphere energy exchanges in the Arctic through a coupling with soil temperatures. However, a physical description of this process is lacking in many climate models, potentially biasing their high-latitude climate predictions. Using a coupled surface–atmosphere model, we identified a strong feedback loop between soil insulation, surface air temperature, and snowfall. Without insulation, the latent heat needed for soil ice thawing leads to a late spring and summer cold bias in surface air temperature (above 2 °C) over Arctic regions. The integration of soil insulation eliminates this bias and significantly improves the simulation of permafrost dynamics. Our findings, including the potential consequences of large perturbations (e.g., fires), highlight the importance of combining soil water freezing with a physical representation of SOC and surface organic layer insulation in Earth system models, to improve Arctic climate predictions.
{"title":"Arctic soil carbon insulation averts large spring cooling from surface–atmosphere feedbacks","authors":"Rémi Gaillard, Philippe Peylin, Patricia Cadule, Vladislav Bastrikov, Frédérique Chéruy, Amélie Cuynet, Josefine Ghattas, Dan Zhu, Bertrand Guenet","doi":"10.1073/pnas.2410226122","DOIUrl":"https://doi.org/10.1073/pnas.2410226122","url":null,"abstract":"The insulative properties of soil organic carbon (SOC) and surface organic layers (moss, lichens, litter) regulate surface–atmosphere energy exchanges in the Arctic through a coupling with soil temperatures. However, a physical description of this process is lacking in many climate models, potentially biasing their high-latitude climate predictions. Using a coupled surface–atmosphere model, we identified a strong feedback loop between soil insulation, surface air temperature, and snowfall. Without insulation, the latent heat needed for soil ice thawing leads to a late spring and summer cold bias in surface air temperature (above 2 °C) over Arctic regions. The integration of soil insulation eliminates this bias and significantly improves the simulation of permafrost dynamics. Our findings, including the potential consequences of large perturbations (e.g., fires), highlight the importance of combining soil water freezing with a physical representation of SOC and surface organic layer insulation in Earth system models, to improve Arctic climate predictions.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"14 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974862","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}
Kameron B. Rodrigues, Ziming Weng, Zachary A. Graham, Kaleen Lavin, Jeremy McAdam, S. Craig Tuggle, Brandon Peoples, Regina Seay, Sufen Yang, Marcas M. Bamman, Timothy J. Broderick, Stephen B. Montgomery
Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear. To study these, 10 healthy individuals were randomized to a 12-wk exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD). Blood plasma was collected pre- and postexercise at weeks 0 and 12 and after 4 wk of detraining upon program completion. Whole-genome enzymatic methylation sequencing (EM-seq) with cell-type proportion deconvolution was applied to cfDNA obtained from the 50 plasma samples and paired to concentration measurements for 90 circulating cytokines. Acute exercise increased the release of cfDNA from neutrophils, dendritic cells (DCs), and macrophages proportional to exercise intensity. Exercise training reduced cfDNA released in HITT participants but not TRAD and from DCs and macrophages but not neutrophils. For most participants, training lowered mitochondrial cfDNA at rest, even after detraining. Using a sequencing analysis approach we developed, we concluded that rapid ETosis, a process of cell death where cells release DNA extracellular traps, was the likely source of cfDNA, demonstrated by enrichment of nuclear DNA. Further, several cytokines were induced by acute exercise, such as IL-6, IL-10, and IL-16, and training attenuated the induction of only IL-6 and IL-17F. Cytokine levels were not associated with cfDNA induction, suggesting that these cytokines are not the main cause of exercise-induced cfDNA. Overall, exercise intensity and training modulated cfDNA release and cytokine responses, contributing to the anti-inflammatory effects of regular exercise.
{"title":"Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans","authors":"Kameron B. Rodrigues, Ziming Weng, Zachary A. Graham, Kaleen Lavin, Jeremy McAdam, S. Craig Tuggle, Brandon Peoples, Regina Seay, Sufen Yang, Marcas M. Bamman, Timothy J. Broderick, Stephen B. Montgomery","doi":"10.1073/pnas.2406954122","DOIUrl":"https://doi.org/10.1073/pnas.2406954122","url":null,"abstract":"Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear. To study these, 10 healthy individuals were randomized to a 12-wk exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD). Blood plasma was collected pre- and postexercise at weeks 0 and 12 and after 4 wk of detraining upon program completion. Whole-genome enzymatic methylation sequencing (EM-seq) with cell-type proportion deconvolution was applied to cfDNA obtained from the 50 plasma samples and paired to concentration measurements for 90 circulating cytokines. Acute exercise increased the release of cfDNA from neutrophils, dendritic cells (DCs), and macrophages proportional to exercise intensity. Exercise training reduced cfDNA released in HITT participants but not TRAD and from DCs and macrophages but not neutrophils. For most participants, training lowered mitochondrial cfDNA at rest, even after detraining. Using a sequencing analysis approach we developed, we concluded that rapid ETosis, a process of cell death where cells release DNA extracellular traps, was the likely source of cfDNA, demonstrated by enrichment of nuclear DNA. Further, several cytokines were induced by acute exercise, such as IL-6, IL-10, and IL-16, and training attenuated the induction of only IL-6 and IL-17F. Cytokine levels were not associated with cfDNA induction, suggesting that these cytokines are not the main cause of exercise-induced cfDNA. Overall, exercise intensity and training modulated cfDNA release and cytokine responses, contributing to the anti-inflammatory effects of regular exercise.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"22 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974860","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}
Zhengqiang Hu, Fengling Zhang, Feng Wu, Li Li, Renjie Chen
Lithium-ion batteries (LIBs) have become advanced energy storage technologies; however, specific capacity remains limited by the active materials in cathodes. Here, we report Li–LiNO 3 batteries (LNBs) where LiNO 3 in electrolyte serves as both active materials and ion conductor at room temperature. LNBs operate on a highly reversible redox between NO 3− and NO 2− , which results in an impressive areal capacity of 19 mAh cm −2 at a plateau voltage of 1.75 V. Furthermore, the pouch cell exhibits stable cycling at a capacity of 100 mAh. This research underscores the potential of LNBs for high-capacity energy storage.
{"title":"A room temperature rechargeable Li–LiNO 3 battery with high capacity","authors":"Zhengqiang Hu, Fengling Zhang, Feng Wu, Li Li, Renjie Chen","doi":"10.1073/pnas.2416817122","DOIUrl":"https://doi.org/10.1073/pnas.2416817122","url":null,"abstract":"Lithium-ion batteries (LIBs) have become advanced energy storage technologies; however, specific capacity remains limited by the active materials in cathodes. Here, we report Li–LiNO <jats:sub>3</jats:sub> batteries (LNBs) where LiNO <jats:sub>3</jats:sub> in electrolyte serves as both active materials and ion conductor at room temperature. LNBs operate on a highly reversible redox between NO <jats:sub>3</jats:sub> <jats:sup>−</jats:sup> and NO <jats:sub>2</jats:sub> <jats:sup>−</jats:sup> , which results in an impressive areal capacity of 19 mAh cm <jats:sup>−2</jats:sup> at a plateau voltage of 1.75 V. Furthermore, the pouch cell exhibits stable cycling at a capacity of 100 mAh. This research underscores the potential of LNBs for high-capacity energy storage.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"1 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974856","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}
Victoria J. Sugrue, Melanie Prescott, Kelly A. Glendining, Donna M. Bond, Steve Horvath, Greg M. Anderson, Michael Garratt, Rebecca E. Campbell, Timothy A. Hore
Aging is a complex process characterized by biological decline and a wide range of molecular alterations to cells, including changes to DNA methylation. In this study, we used a male-specific epigenetic marker of aging to build an epigenetic predictor that measures long-term androgen exposure in sheep and mice (median absolute error of 4.3 and 1.4 mo, respectively). We term this predictor the androgen clock and show its “tick” is mediated by the androgen receptor and can be accelerated beyond that in normal male mice by supplementing females with dihydrotestosterone. Conversely, the removal of androgens by castration in sheep completely halted the androgen clock. In addition to potential applications in medicine and agriculture, we predict the androgen clock will prove a useful model to understand the mechanisms and processes of age-associated DNA methylation change because it can be precisely enhanced and halted using small molecule manipulation with few additional effects on the cell.
衰老是一个复杂的过程，其特点是生物衰退和细胞的各种分子改变，包括 DNA 甲基化的改变。在这项研究中，我们利用雄性特有的衰老表观遗传标记建立了一个表观遗传预测器，用于测量绵羊和小鼠长期暴露于雄激素的情况（绝对误差中位数分别为 4.3 个月和 1.4 个月）。我们将这一预测器称为雄激素时钟，并表明其 "滴答 "声是由雄激素受体介导的，而且通过向雌性小鼠补充双氢睾酮，可以加速其 "滴答 "声，使其超过正常雄性小鼠的 "滴答 "声。相反，通过阉割去除绵羊体内的雄激素，雄激素时钟就会完全停止。除了在医学和农业方面的潜在应用外，我们还预测雄激素钟将被证明是了解与年龄相关的 DNA 甲基化变化机制和过程的有用模型，因为它可以通过小分子操作精确地增强和停止，而对细胞的额外影响很小。
{"title":"The androgen clock is an epigenetic predictor of long-term male hormone exposure","authors":"Victoria J. Sugrue, Melanie Prescott, Kelly A. Glendining, Donna M. Bond, Steve Horvath, Greg M. Anderson, Michael Garratt, Rebecca E. Campbell, Timothy A. Hore","doi":"10.1073/pnas.2420087121","DOIUrl":"https://doi.org/10.1073/pnas.2420087121","url":null,"abstract":"Aging is a complex process characterized by biological decline and a wide range of molecular alterations to cells, including changes to DNA methylation. In this study, we used a male-specific epigenetic marker of aging to build an epigenetic predictor that measures long-term androgen exposure in sheep and mice (median absolute error of 4.3 and 1.4 mo, respectively). We term this predictor the androgen clock and show its “tick” is mediated by the androgen receptor and can be accelerated beyond that in normal male mice by supplementing females with dihydrotestosterone. Conversely, the removal of androgens by castration in sheep completely halted the androgen clock. In addition to potential applications in medicine and agriculture, we predict the androgen clock will prove a useful model to understand the mechanisms and processes of age-associated DNA methylation change because it can be precisely enhanced and halted using small molecule manipulation with few additional effects on the cell.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"49 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974854","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}
Understanding topological defects-controlled structural degradation of layered oxides—a key cathode material for high-performance lithium-ion batteries—plays a critical role in developing next-generation cathode materials. Here, by constructing a nanobattery in an electron microscope enabling atomic-scale monitoring of electrochemcial reactions, we captured the electrochemically driven atomistic dynamics and evolution of dislocations—a most important topological defect in material. We deciphered how dislocations nucleate, move, and annihilate within layered cathodes at the atomic scale. Specifically, we found two types of dislocation configurations, i.e., single dislocations and dislocation dipoles. Both pure dislocation glide/climb and mixed motions were captured, and the dislocation glide and climb velocities were first experimentally measured. Moreover, dislocation activity-mediated structural degradation such as crack nucleation, phase transformation, and lattice reorientation was unraveled. Our work provides deep insights into the atomistic dynamics of electrochemically driven dislocation activities in layered oxides.
{"title":"Resolving electrochemically triggered topological defect dynamics and structural degradation in layered oxides","authors":"Chunyang Wang, Rui Zhang, Ju Li, Huolin L. Xin","doi":"10.1073/pnas.2409494122","DOIUrl":"https://doi.org/10.1073/pnas.2409494122","url":null,"abstract":"Understanding topological defects-controlled structural degradation of layered oxides—a key cathode material for high-performance lithium-ion batteries—plays a critical role in developing next-generation cathode materials. Here, by constructing a nanobattery in an electron microscope enabling atomic-scale monitoring of electrochemcial reactions, we captured the electrochemically driven atomistic dynamics and evolution of dislocations—a most important topological defect in material. We deciphered how dislocations nucleate, move, and annihilate within layered cathodes at the atomic scale. Specifically, we found two types of dislocation configurations, i.e., single dislocations and dislocation dipoles. Both pure dislocation glide/climb and mixed motions were captured, and the dislocation glide and climb velocities were first experimentally measured. Moreover, dislocation activity-mediated structural degradation such as crack nucleation, phase transformation, and lattice reorientation was unraveled. Our work provides deep insights into the atomistic dynamics of electrochemically driven dislocation activities in layered oxides.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"51 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974858","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}
Mohammad K. Manik, Mengqi Pan, Le Xiao, Weixi Gu, Hyoyoung Kim, Sabrina Pospich, Andrew Hedger, Parimala R. Vajjhala, Morris Y. L. Lee, Xiaoqi Qian, Michael J. Landsberg, Thomas Ve, Jeffrey D. Nanson, Stefan Raunser, Katryn J. Stacey, Hao Wu, Bostjan Kobe
Innate immunity relies on Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns. The TIR (Toll/interleukin-1 receptor) domain-containing TLR adaptors TRIF (TIR domain–containing adaptor-inducing interferon-β) and TRAM (TRIF-related adaptor molecule) are essential for MyD88-independent TLR signaling. However, the structural basis of TRIF and TRAM TIR domain–based signaling remains unclear. Here, we present cryo-EM structures of filaments formed by TRIF and TRAM TIR domains at resolutions of 3.3 Å and 5.6 Å, respectively. Both structures reveal two-stranded parallel helical arrangements. Functional studies underscore the importance of intrastrand interactions, mediated by the BB-loop, and interstrand interactions in TLR4-mediated signaling. We also report the crystal structure of the monomeric TRAM TIR domain bearing the BB loop mutation C117H, which reveals conformational differences consistent with its inactivity. Our findings suggest a unified signaling mechanism by the TIR domains of the four signaling TLR adaptors MyD88, MAL, TRIF, and TRAM and reveal potential therapeutic targets for immunity-related disorders.
{"title":"Structural basis for TIR domain–mediated innate immune signaling by Toll-like receptor adaptors TRIF and TRAM","authors":"Mohammad K. Manik, Mengqi Pan, Le Xiao, Weixi Gu, Hyoyoung Kim, Sabrina Pospich, Andrew Hedger, Parimala R. Vajjhala, Morris Y. L. Lee, Xiaoqi Qian, Michael J. Landsberg, Thomas Ve, Jeffrey D. Nanson, Stefan Raunser, Katryn J. Stacey, Hao Wu, Bostjan Kobe","doi":"10.1073/pnas.2418988122","DOIUrl":"https://doi.org/10.1073/pnas.2418988122","url":null,"abstract":"Innate immunity relies on Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns. The TIR (Toll/interleukin-1 receptor) domain-containing TLR adaptors TRIF (TIR domain–containing adaptor-inducing interferon-β) and TRAM (TRIF-related adaptor molecule) are essential for MyD88-independent TLR signaling. However, the structural basis of TRIF and TRAM TIR domain–based signaling remains unclear. Here, we present cryo-EM structures of filaments formed by TRIF and TRAM TIR domains at resolutions of 3.3 Å and 5.6 Å, respectively. Both structures reveal two-stranded parallel helical arrangements. Functional studies underscore the importance of intrastrand interactions, mediated by the BB-loop, and interstrand interactions in TLR4-mediated signaling. We also report the crystal structure of the monomeric TRAM TIR domain bearing the BB loop mutation C117H, which reveals conformational differences consistent with its inactivity. Our findings suggest a unified signaling mechanism by the TIR domains of the four signaling TLR adaptors MyD88, MAL, TRIF, and TRAM and reveal potential therapeutic targets for immunity-related disorders.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"15 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940007","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}
Gege Qin, Xiying Shao, Xiaolong Liu, Jiachao Xu, Xiaojia Wang, Wenxi Wang, Lu Gao, Yuxin Liang, Lina Xie, Dan Su, Hongwei Yang, Wei Zhou, Xiaohong Fang
Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria–tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness. Here, we demonstrate that the quorum-sensing signaling molecule N-(3-oxo-dodecanoyl) homoserine lactone (3oc), a chemical compound released by Pseudomonas aeruginosa ( P. aeruginosa ), one tumor-resident bacteria with a relative high abundance in breast cancer, promotes breast cancer cell resistance to trastuzumab. Mechanically, 3oc directly leads to spontaneous dimerization of the transforming growth factor β (TGF-β) type II serine/threonine kinase receptor on the cell membrane in a ligand-independent manner. The 3oc-induced TGF-β signaling subsequently triggers ErbB2 phosphorylation and its downstream target activation, overcoming the inhibition effect of trastuzumab on ErbB2. With specific real-time qPCR, fluorescence in situ hybridization imaging, and liquid chromatography ionization tandem mass spectrometry analyses of clinical samples, we confirmed that P. aeruginosa and its signaling molecule 3oc exist in breast cancer tissues and there is a clinical correlation between P. aeruginosa colonization and trastuzumab resistance. This work expands the biological functions of intratumor bacteria in cancer treatment responsiveness and provides a unique perspective for overcoming trastuzumab resistance.
{"title":"A signaling molecule from intratumor bacteria promotes trastuzumab resistance in breast cancer cells","authors":"Gege Qin, Xiying Shao, Xiaolong Liu, Jiachao Xu, Xiaojia Wang, Wenxi Wang, Lu Gao, Yuxin Liang, Lina Xie, Dan Su, Hongwei Yang, Wei Zhou, Xiaohong Fang","doi":"10.1073/pnas.2421710122","DOIUrl":"https://doi.org/10.1073/pnas.2421710122","url":null,"abstract":"Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria–tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness. Here, we demonstrate that the quorum-sensing signaling molecule N-(3-oxo-dodecanoyl) homoserine lactone (3oc), a chemical compound released by <jats:italic>Pseudomonas aeruginosa</jats:italic> ( <jats:italic>P. aeruginosa</jats:italic> ), one tumor-resident bacteria with a relative high abundance in breast cancer, promotes breast cancer cell resistance to trastuzumab. Mechanically, 3oc directly leads to spontaneous dimerization of the transforming growth factor β (TGF-β) type II serine/threonine kinase receptor on the cell membrane in a ligand-independent manner. The 3oc-induced TGF-β signaling subsequently triggers ErbB2 phosphorylation and its downstream target activation, overcoming the inhibition effect of trastuzumab on ErbB2. With specific real-time qPCR, fluorescence in situ hybridization imaging, and liquid chromatography ionization tandem mass spectrometry analyses of clinical samples, we confirmed that <jats:italic>P. aeruginosa</jats:italic> and its signaling molecule 3oc exist in breast cancer tissues and there is a clinical correlation between <jats:italic>P. aeruginosa</jats:italic> colonization and trastuzumab resistance. This work expands the biological functions of intratumor bacteria in cancer treatment responsiveness and provides a unique perspective for overcoming trastuzumab resistance.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"15 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940008","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}
Yi Sun, Ruth A. Pumroy, Leena Mallik, Apala Chaudhuri, Chloe Wang, Daniel Hwang, Julia N. Danon, Kimia Dasteh Goli, Vera Y. Moiseenkova-Bell, Nikolaos G. Sgourakis
Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive. Here, we leverage a high-fidelity TAPBPR variant and conformationally stabilized MHC-I, to determine the solution structure of the human antigen editing complex bound to a peptide decoy by cryogenic electron microscopy (cryo-EM) at an average resolution of 3.0 Å. Antigen proofreading is mediated by transient interactions formed between the nascent peptide binding groove with the P2/P3 peptide anchors, where conserved MHC-I residues stabilize incoming peptides through backbone-focused contacts. Finally, using our high-fidelity chaperone, we demonstrate robust peptide exchange on the cell surface across multiple clinically relevant human MHC-I allomorphs. Our work has important ramifications for understanding the selection of immunogenic epitopes for T cell screening and vaccine design applications.
{"title":"CryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading","authors":"Yi Sun, Ruth A. Pumroy, Leena Mallik, Apala Chaudhuri, Chloe Wang, Daniel Hwang, Julia N. Danon, Kimia Dasteh Goli, Vera Y. Moiseenkova-Bell, Nikolaos G. Sgourakis","doi":"10.1073/pnas.2416992122","DOIUrl":"https://doi.org/10.1073/pnas.2416992122","url":null,"abstract":"Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive. Here, we leverage a high-fidelity TAPBPR variant and conformationally stabilized MHC-I, to determine the solution structure of the human antigen editing complex bound to a peptide decoy by cryogenic electron microscopy (cryo-EM) at an average resolution of 3.0 Å. Antigen proofreading is mediated by transient interactions formed between the nascent peptide binding groove with the P2/P3 peptide anchors, where conserved MHC-I residues stabilize incoming peptides through backbone-focused contacts. Finally, using our high-fidelity chaperone, we demonstrate robust peptide exchange on the cell surface across multiple clinically relevant human MHC-I allomorphs. Our work has important ramifications for understanding the selection of immunogenic epitopes for T cell screening and vaccine design applications.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"32 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940009","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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