Zhen Zhang, Ethan C. Quinn, Jacob K. Kenny, Alexandra Grigoropoulos, Jason S. DesVeaux, Tiffany Chen, Li Zhou, Ting Xu, Gregg T. Beckham, Eugene Y.-X. Chen
Commercial adhesives are petroleum-based thermoset networks or nonbiodegradable thermoplastic hot melts, making them ideal targets for replacement by biodegradable alternatives. Poly(3-hydroxybutyrate) (P3HB) is a biorenewable and biodegradable alternative to conventional plastics, but microbial P3HB, which has a stereoperfect stereomicrostructure, exhibits no adhesion. In this study, by elucidating the fundamental relationship between chemocatalytically engineered P3HB stereomicrostructures and adhesion properties, we found that biodegradable syndio-rich P3HB exhibits high adhesion strength and outperforms common commercial adhesives, whereas syndiotactic, isotactic, or iso-rich P3HB shows no measurable adhesion. The syndio-rich stereomicrostructure brings about desired thermomechanical and viscoelastic properties of P3HB that enable strong adhesion to a range of substrates tested, including aluminum, steel, glass, and wood, and its performance is insensitive to molar mass and reprocessing or reuse.
{"title":"Stereomicrostructure-regulated biodegradable adhesives","authors":"Zhen Zhang, Ethan C. Quinn, Jacob K. Kenny, Alexandra Grigoropoulos, Jason S. DesVeaux, Tiffany Chen, Li Zhou, Ting Xu, Gregg T. Beckham, Eugene Y.-X. Chen","doi":"10.1126/science.adr7175","DOIUrl":"https://doi.org/10.1126/science.adr7175","url":null,"abstract":"Commercial adhesives are petroleum-based thermoset networks or nonbiodegradable thermoplastic hot melts, making them ideal targets for replacement by biodegradable alternatives. Poly(3-hydroxybutyrate) (P3HB) is a biorenewable and biodegradable alternative to conventional plastics, but microbial P3HB, which has a stereoperfect stereomicrostructure, exhibits no adhesion. In this study, by elucidating the fundamental relationship between chemocatalytically engineered P3HB stereomicrostructures and adhesion properties, we found that biodegradable syndio-rich P3HB exhibits high adhesion strength and outperforms common commercial adhesives, whereas syndiotactic, isotactic, or iso-rich P3HB shows no measurable adhesion. The syndio-rich stereomicrostructure brings about desired thermomechanical and viscoelastic properties of P3HB that enable strong adhesion to a range of substrates tested, including aluminum, steel, glass, and wood, and its performance is insensitive to molar mass and reprocessing or reuse.","PeriodicalId":21678,"journal":{"name":"Science","volume":"7 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986998","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}
In the wake of the November 2024 US election, severalcommentators have suggested that the US Democratic Party abandon its commitment to so-called “identity politics,” which they identify as elitist, condescending, and divisive. They argue that rather than focusing on these “cultural” issues, progressives should prioritize economic concerns. Yet identity politics, at a fundamental level, is driven, and dominated, by economic concerns. Growing bodies of social science evidence make increasingly clear how identity politics—in terms of ensuring equal rights for minorities and women in the workplace and in the world and in terms of affirmative action to ensure equity of opportunity—is good economic policy. Opposition to identity politics is often built not by the culturally and ethnically diverse working class who benefit but by lower-ability economic elites who feel that their advantage is under threat. By making it harder for such entrenched elites to retain power, affirmative action may actually improve both the quality of individuals promoted in an ostensibly meritocratic system and overall economic outcomes.
{"title":"“Identity politics” is economic policy","authors":"Rohini Pande","doi":"10.1126/science.adu9409","DOIUrl":"https://doi.org/10.1126/science.adu9409","url":null,"abstract":"In the wake of the November 2024 US election, <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.nytimes.com/2024/11/09/opinion/democrats-identity-politics.html\">several</jats:ext-link> <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.youtube.com/watch?v=BtCK-dMb-F8\">commentators</jats:ext-link> have suggested that the US Democratic Party abandon its commitment to so-called “identity politics,” which they identify as elitist, condescending, and divisive. They argue that rather than focusing on these “cultural” issues, progressives should prioritize economic concerns. Yet identity politics, at a fundamental level, is driven, and dominated, by economic concerns. Growing bodies of social science evidence make increasingly clear how identity politics—in terms of ensuring equal rights for minorities and women in the workplace and in the world and in terms of affirmative action to ensure equity of opportunity—is good economic policy. Opposition to identity politics is often built not by the culturally and ethnically diverse working class who benefit but by lower-ability economic elites who feel that their advantage is under threat. By making it harder for such entrenched elites to retain power, affirmative action may actually improve both the quality of individuals promoted in an ostensibly meritocratic system and overall economic outcomes.","PeriodicalId":21678,"journal":{"name":"Science","volume":"5 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987061","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}
Just over 5 years ago, on New Year’s Eve 2019, the World Health Organization (WHO) became aware of the first cases of pneumonia of unknown etiology in Wuhan, China. A massive global infectious disease storm was already brewing—one that would shut down the world, with profound economic, social, and political impacts that still reverberate today. It’s understandable that governments and individuals may want to forget that the COVID-19 pandemic ever happened, but such collective amnesia prevents humanity from being ready for the next pandemic. The world did the same in the 1920s, eager to move on from the devastation of the 1918 influenza pandemic. A repeat of this behavior squanders opportunities right now to institutionalize and embed best practices for current and future threats.
{"title":"Don’t pretend COVID-19 didn’t happen","authors":"Maria D. Van Kerkhove","doi":"10.1126/science.adv8836","DOIUrl":"https://doi.org/10.1126/science.adv8836","url":null,"abstract":"Just over 5 years ago, on New Year’s Eve 2019, the World Health Organization (WHO) became aware of the first cases of pneumonia of unknown etiology in Wuhan, China. A massive global infectious disease storm was already brewing—one that would shut down the world, with profound economic, social, and political impacts that still reverberate today. It’s understandable that governments and individuals may want to forget that the COVID-19 pandemic ever happened, but such collective amnesia prevents humanity from being ready for the next pandemic. The world did the same in the 1920s, eager to move on from the devastation of the 1918 influenza pandemic. A repeat of this behavior squanders opportunities right now to institutionalize and embed best practices for current and future threats.","PeriodicalId":21678,"journal":{"name":"Science","volume":"131 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986993","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}
Marko Šestan, Bruno Raposo, Miguel Rendas, David Brea, Roksana Pirzgalska, Ana Rasteiro, Maria Aliseychik, Inês Godinho, Hélder Ribeiro, Tania Carvalho, Stephan Wueest, Daniel Konrad, Henrique Veiga-Fernandes
The immune system shapes body metabolism, while interactions between peripheral neurons and immune cells control tissue homeostasis and immunity. However, whether peripheral neuroimmune interactions orchestrate endocrine system functions remains unexplored. After fasting, mice lacking type 2 innate lymphoid cells (ILC2s) displayed disrupted glucose homeostasis, impaired pancreatic glucagon secretion, and inefficient hepatic gluconeogenesis. Additionally, intestinal ILC2s were found in the pancreas, which was dependent on their expression of the adrenergic beta 2 receptor. Targeted activation of catecholaminergic intestinal neurons promoted the accumulation of ILC2s in the pancreas. Our work provides evidence that immune cells can be regulated by neuronal signals in response to fasting, activating an inter-organ communication route that promotes pancreatic endocrine function and regulation of blood glucose levels.
{"title":"Neuronal-ILC2 interactions regulate pancreatic glucagon and glucose homeostasis","authors":"Marko Šestan, Bruno Raposo, Miguel Rendas, David Brea, Roksana Pirzgalska, Ana Rasteiro, Maria Aliseychik, Inês Godinho, Hélder Ribeiro, Tania Carvalho, Stephan Wueest, Daniel Konrad, Henrique Veiga-Fernandes","doi":"10.1126/science.adi3624","DOIUrl":"https://doi.org/10.1126/science.adi3624","url":null,"abstract":"The immune system shapes body metabolism, while interactions between peripheral neurons and immune cells control tissue homeostasis and immunity. However, whether peripheral neuroimmune interactions orchestrate endocrine system functions remains unexplored. After fasting, mice lacking type 2 innate lymphoid cells (ILC2s) displayed disrupted glucose homeostasis, impaired pancreatic glucagon secretion, and inefficient hepatic gluconeogenesis. Additionally, intestinal ILC2s were found in the pancreas, which was dependent on their expression of the adrenergic beta 2 receptor. Targeted activation of catecholaminergic intestinal neurons promoted the accumulation of ILC2s in the pancreas. Our work provides evidence that immune cells can be regulated by neuronal signals in response to fasting, activating an inter-organ communication route that promotes pancreatic endocrine function and regulation of blood glucose levels.","PeriodicalId":21678,"journal":{"name":"Science","volume":"54 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987060","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}
Liangzhi Chen, Philipp Brun, Pascal Buri, Simone Fatichi, Arthur Gessler, Michael James McCarthy, Francesca Pellicciotti, Benjamin Stocker, Dirk Nikolaus Karger
Persistent multiyear drought (MYD) events pose a growing threat to nature and humans in a changing climate. We identified and inventoried global MYDs by detecting spatiotemporally contiguous climatic anomalies, showing that MYDs have become drier, hotter, and led to increasingly diminished vegetation greenness. The global terrestrial land affected by MYDs has increased at a rate of 49,279 ± 14,771 square kilometers per year from 1980 to 2018. Temperate grasslands have exhibited the greatest declines in vegetation greenness during MYDs, whereas boreal and tropical forests have had comparably minor responses. With MYDs becoming more common, this global quantitative inventory of the occurrence, severity, trend, and impact of MYDs provides an important benchmark for facilitating more effective and collaborative preparedness toward mitigation of and adaptation to such extreme events.
{"title":"Global increase in the occurrence and impact of multiyear droughts","authors":"Liangzhi Chen, Philipp Brun, Pascal Buri, Simone Fatichi, Arthur Gessler, Michael James McCarthy, Francesca Pellicciotti, Benjamin Stocker, Dirk Nikolaus Karger","doi":"10.1126/science.ado4245","DOIUrl":"https://doi.org/10.1126/science.ado4245","url":null,"abstract":"Persistent multiyear drought (MYD) events pose a growing threat to nature and humans in a changing climate. We identified and inventoried global MYDs by detecting spatiotemporally contiguous climatic anomalies, showing that MYDs have become drier, hotter, and led to increasingly diminished vegetation greenness. The global terrestrial land affected by MYDs has increased at a rate of 49,279 ± 14,771 square kilometers per year from 1980 to 2018. Temperate grasslands have exhibited the greatest declines in vegetation greenness during MYDs, whereas boreal and tropical forests have had comparably minor responses. With MYDs becoming more common, this global quantitative inventory of the occurrence, severity, trend, and impact of MYDs provides an important benchmark for facilitating more effective and collaborative preparedness toward mitigation of and adaptation to such extreme events.","PeriodicalId":21678,"journal":{"name":"Science","volume":"94 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987066","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}
Madison I. Bardot, Cody W. Weyhrich, Zixiao Shi, Michael Traxler, Charlotte L. Stern, Jinlei Cui, David A. Muller, Matthew L. Becker, William R. Dichtel
Mechanical bonds arise between molecules that contain interlocked subunits, such as one macrocycle threaded through another. Within polymers, these linkages will confer distinctive mechanical properties and other emergent behaviors, but polymerizations that form mechanical bonds efficiently and use simple monomeric building blocks are rare. In this work, we introduce a solid-state polymerization in which one monomer infiltrates crystals of another to form a macrocycle and mechanical bond at each repeat unit of a two-dimensional (2D) polymer. This mechanically interlocked 2D polymer is formed as a layered solid that is readily exfoliated in common organic solvents, enabling spectroscopic characterization and atomic-resolution imaging using advanced electron microscopy techniques. The 2D mechanically interlocked polymer is easily prepared on multigram scales, which, along with its solution processibility, enables the facile fabrication of composite fibers with Ultem that exhibit enhanced stiffness and strength.
{"title":"Mechanically interlocked two-dimensional polymers","authors":"Madison I. Bardot, Cody W. Weyhrich, Zixiao Shi, Michael Traxler, Charlotte L. Stern, Jinlei Cui, David A. Muller, Matthew L. Becker, William R. Dichtel","doi":"10.1126/science.ads4968","DOIUrl":"https://doi.org/10.1126/science.ads4968","url":null,"abstract":"Mechanical bonds arise between molecules that contain interlocked subunits, such as one macrocycle threaded through another. Within polymers, these linkages will confer distinctive mechanical properties and other emergent behaviors, but polymerizations that form mechanical bonds efficiently and use simple monomeric building blocks are rare. In this work, we introduce a solid-state polymerization in which one monomer infiltrates crystals of another to form a macrocycle and mechanical bond at each repeat unit of a two-dimensional (2D) polymer. This mechanically interlocked 2D polymer is formed as a layered solid that is readily exfoliated in common organic solvents, enabling spectroscopic characterization and atomic-resolution imaging using advanced electron microscopy techniques. The 2D mechanically interlocked polymer is easily prepared on multigram scales, which, along with its solution processibility, enables the facile fabrication of composite fibers with Ultem that exhibit enhanced stiffness and strength.","PeriodicalId":21678,"journal":{"name":"Science","volume":"30 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986997","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}
Formamidinium lead triiodide (FAPbI 3 ) is considered the most promising composition for high-performing single-junction solar cells. However, nonalloyed α-FAPbI 3 is metastable with respect to the photoinactive δ-phase. We have developed a kinetic modulation strategy to fabricate high-quality and stable nonalloyed α-FAPbI 3 films, assisted by cogenetic volatile iodine intercalation and decalation. The intercalation of iodine facilitated the formation of corner-sharing Pb-I framework building blocks and reduced the kinetic barrier for α-FAPbI 3 formation, whereas the iodine decalation improved the final perovskite film quality in terms of composition purity and overall homogeneity. Solar cells based on this nonalloyed α-FAPbI 3 (free of other extrinsic composition ions) achieved a power conversion efficiency of >24%. The devices also exhibited excellent durability, retaining 99% of their original power conversion efficiency after operating for more than 1100 hours at 85° ± 5°C under illumination.
{"title":"Nonalloyed α-phase formamidinium lead triiodide solar cells through iodine intercalation","authors":"Yu Zhang, Yanrun Chen, Guilin Liu, Yuetong Wu, Zhenyu Guo, Rundong Fan, Kailin Li, Huifen Liu, Yepin Zhao, Tim Kodalle, Yihua Chen, Cheng Zhu, Yang Bai, Qi Chen, Huanping Zhou","doi":"10.1126/science.ads8968","DOIUrl":"https://doi.org/10.1126/science.ads8968","url":null,"abstract":"Formamidinium lead triiodide (FAPbI <jats:sub>3</jats:sub> ) is considered the most promising composition for high-performing single-junction solar cells. However, nonalloyed α-FAPbI <jats:sub>3</jats:sub> is metastable with respect to the photoinactive δ-phase. We have developed a kinetic modulation strategy to fabricate high-quality and stable nonalloyed α-FAPbI <jats:sub>3</jats:sub> films, assisted by cogenetic volatile iodine intercalation and decalation. The intercalation of iodine facilitated the formation of corner-sharing Pb-I framework building blocks and reduced the kinetic barrier for α-FAPbI <jats:sub>3</jats:sub> formation, whereas the iodine decalation improved the final perovskite film quality in terms of composition purity and overall homogeneity. Solar cells based on this nonalloyed α-FAPbI <jats:sub>3</jats:sub> (free of other extrinsic composition ions) achieved a power conversion efficiency of >24%. The devices also exhibited excellent durability, retaining 99% of their original power conversion efficiency after operating for more than 1100 hours at 85° ± 5°C under illumination.","PeriodicalId":21678,"journal":{"name":"Science","volume":"27 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986999","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}
Anqi Zhou, Annalise Kane, Sheng Wu, Kaibiao Wang, Michell Santiago, Yui Ishiguro, Kaori Yoneyama, Malathy Palayam, Nitzan Shabek, Xiaonan Xie, David C. Nelson, Yanran Li
Strigolactones (SLs) are methylbutenolide molecules derived from β-carotene through an intermediate carlactonoic acid (CLA). Canonical SLs act as signals to microbes and plants, whereas noncanonical SLs are primarily plant hormones. The cytochrome P450 CYP722C catalyzes a critical step, converting CLA to canonical SLs in most angiosperms. Using synthetic biology, we investigated the function of CYP722A , an evolutionary predecessor of CYP722C . CYP722A converts CLA into 16-hydroxy-CLA (16-OH-CLA), a noncanonical SL detected exclusively in the shoots of various flowering plants. 16-OH-CLA application restores control of shoot branching to SL-deficient mutants in Arabidopsis thaliana and is perceived by the SL signaling pathway. We hypothesize that biosynthesis of 16-OH-CLA by CYP722A was a metabolic stepping stone in the evolution of canonical SLs that mediate rhizospheric signaling in many flowering plants.
{"title":"Evolution of interorganismal strigolactone biosynthesis in seed plants","authors":"Anqi Zhou, Annalise Kane, Sheng Wu, Kaibiao Wang, Michell Santiago, Yui Ishiguro, Kaori Yoneyama, Malathy Palayam, Nitzan Shabek, Xiaonan Xie, David C. Nelson, Yanran Li","doi":"10.1126/science.adp0779","DOIUrl":"https://doi.org/10.1126/science.adp0779","url":null,"abstract":"Strigolactones (SLs) are methylbutenolide molecules derived from β-carotene through an intermediate carlactonoic acid (CLA). Canonical SLs act as signals to microbes and plants, whereas noncanonical SLs are primarily plant hormones. The cytochrome P450 CYP722C catalyzes a critical step, converting CLA to canonical SLs in most angiosperms. Using synthetic biology, we investigated the function of <jats:italic>CYP722A</jats:italic> , an evolutionary predecessor of <jats:italic>CYP722C</jats:italic> . CYP722A converts CLA into 16-hydroxy-CLA (16-OH-CLA), a noncanonical SL detected exclusively in the shoots of various flowering plants. 16-OH-CLA application restores control of shoot branching to SL-deficient mutants in <jats:italic>Arabidopsis thaliana</jats:italic> and is perceived by the SL signaling pathway. We hypothesize that biosynthesis of 16-OH-CLA by CYP722A was a metabolic stepping stone in the evolution of canonical SLs that mediate rhizospheric signaling in many flowering plants.","PeriodicalId":21678,"journal":{"name":"Science","volume":"23 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987063","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}
Thomas Hayes, Roshan Rao, Halil Akin, Nicholas J. Sofroniew, Deniz Oktay, Zeming Lin, Robert Verkuil, Vincent Q. Tran, Jonathan Deaton, Marius Wiggert, Rohil Badkundri, Irhum Shafkat, Jun Gong, Alexander Derry, Raul S. Molina, Neil Thomas, Yousuf A. Khan, Chetan Mishra, Carolyn Kim, Liam J. Bartie, Matthew Nemeth, Patrick D. Hsu, Tom Sercu, Salvatore Candido, Alexander Rives
More than three billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here we show that language models trained at scale on evolutionary data can generate functional proteins that are far away from known proteins. We present ESM3, a frontier multimodal generative language model that reasons over the sequence, structure, and function of proteins. ESM3 can follow complex prompts combining its modalities and is highly responsive to alignment to improve its fidelity. We have prompted ESM3 to generate fluorescent proteins. Among the generations that we synthesized, we found a bright fluorescent protein at a far distance (58% sequence identity) from known fluorescent proteins, which we estimate is equivalent to simulating five hundred million years of evolution.
{"title":"Simulating 500 million years of evolution with a language model","authors":"Thomas Hayes, Roshan Rao, Halil Akin, Nicholas J. Sofroniew, Deniz Oktay, Zeming Lin, Robert Verkuil, Vincent Q. Tran, Jonathan Deaton, Marius Wiggert, Rohil Badkundri, Irhum Shafkat, Jun Gong, Alexander Derry, Raul S. Molina, Neil Thomas, Yousuf A. Khan, Chetan Mishra, Carolyn Kim, Liam J. Bartie, Matthew Nemeth, Patrick D. Hsu, Tom Sercu, Salvatore Candido, Alexander Rives","doi":"10.1126/science.ads0018","DOIUrl":"https://doi.org/10.1126/science.ads0018","url":null,"abstract":"More than three billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here we show that language models trained at scale on evolutionary data can generate functional proteins that are far away from known proteins. We present ESM3, a frontier multimodal generative language model that reasons over the sequence, structure, and function of proteins. ESM3 can follow complex prompts combining its modalities and is highly responsive to alignment to improve its fidelity. We have prompted ESM3 to generate fluorescent proteins. Among the generations that we synthesized, we found a bright fluorescent protein at a far distance (58% sequence identity) from known fluorescent proteins, which we estimate is equivalent to simulating five hundred million years of evolution.","PeriodicalId":21678,"journal":{"name":"Science","volume":"75 3 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987068","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}
Luisina Ongaro, Xiang Zhou, Ying Wang, Hailey Schultz, Ziyue Zhou, Evan R. S. Buddle, Emilie Brûlé, Yeu-Farn Lin, Gauthier Schang, Adam Hagg, Roselyne Castonguay, Yewei Liu, Gloria H. Su, Nabil G. Seidah, Kevin C. Ray, Seth J. Karp, Ulrich Boehm, Frederique Ruf-Zamojski, Stuart C. Sealfon, Kelly L. Walton, Se-Jin Lee, Daniel J. Bernard
Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. In this work, we report a functional role for myostatin as an endocrine hormone that directly promotes pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function in mice. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor–β family, the activins. Our results both challenge activin’s eponymous role in FSH synthesis and establish an unexpected endocrine axis between skeletal muscle and the pituitary gland. Our data also suggest that efforts to antagonize myostatin to increase muscle mass may have unintended consequences on fertility.
{"title":"Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis","authors":"Luisina Ongaro, Xiang Zhou, Ying Wang, Hailey Schultz, Ziyue Zhou, Evan R. S. Buddle, Emilie Brûlé, Yeu-Farn Lin, Gauthier Schang, Adam Hagg, Roselyne Castonguay, Yewei Liu, Gloria H. Su, Nabil G. Seidah, Kevin C. Ray, Seth J. Karp, Ulrich Boehm, Frederique Ruf-Zamojski, Stuart C. Sealfon, Kelly L. Walton, Se-Jin Lee, Daniel J. Bernard","doi":"10.1126/science.adi4736","DOIUrl":"https://doi.org/10.1126/science.adi4736","url":null,"abstract":"Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. In this work, we report a functional role for myostatin as an endocrine hormone that directly promotes pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function in mice. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor–β family, the activins. Our results both challenge activin’s eponymous role in FSH synthesis and establish an unexpected endocrine axis between skeletal muscle and the pituitary gland. Our data also suggest that efforts to antagonize myostatin to increase muscle mass may have unintended consequences on fertility.","PeriodicalId":21678,"journal":{"name":"Science","volume":"4 1","pages":""},"PeriodicalIF":56.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987070","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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