Pub Date : 2026-02-11DOI: 10.1038/s41586-026-10239-7
Simone Gallarati, Erin M. Bucci, Abigail G. Doyle, Matthew S. Sigman
Identifying a catalyst class to optimize the enantioselectivity of a new reaction, either involving a different combination of known substrate types or an entirely unfamiliar class of compounds, is a formidable challenge. Statistical models trained on a reported set of reactions can help predict out-of-sample transformations1–5 but often face two challenges: (1) only sparse data are available i.e., limited information on catalyst–substrate interactions, and (2) simple stereoelectronic parameters may fail to describe mechanistically complex transformations.6,7 Here we report a descriptor generation strategy that accounts for changes in the enantiodetermining step with catalyst or substrate identity, allowing us to model reactions involving distinct ligand and substrate types. As validating case studies, we collected data on enantioselective nickel-catalyzed C(sp3)-couplings8 and trained statistical models with features extracted from the transition states and intermediates proposed to be involved in asymmetric induction. These models allow for the optimization of poorly performing examples reported in a substrate scope and are applicable to unseen ligands and reaction partners. This approach offers the opportunity to streamline catalyst and reaction development, quantitatively transferring knowledge learned on sparse data to novel chemical spaces.
{"title":"Transferable enantioselectivity models from sparse data","authors":"Simone Gallarati, Erin M. Bucci, Abigail G. Doyle, Matthew S. Sigman","doi":"10.1038/s41586-026-10239-7","DOIUrl":"https://doi.org/10.1038/s41586-026-10239-7","url":null,"abstract":"Identifying a catalyst class to optimize the enantioselectivity of a new reaction, either involving a different combination of known substrate types or an entirely unfamiliar class of compounds, is a formidable challenge. Statistical models trained on a reported set of reactions can help predict out-of-sample transformations1–5 but often face two challenges: (1) only sparse data are available i.e., limited information on catalyst–substrate interactions, and (2) simple stereoelectronic parameters may fail to describe mechanistically complex transformations.6,7 Here we report a descriptor generation strategy that accounts for changes in the enantiodetermining step with catalyst or substrate identity, allowing us to model reactions involving distinct ligand and substrate types. As validating case studies, we collected data on enantioselective nickel-catalyzed C(sp3)-couplings8 and trained statistical models with features extracted from the transition states and intermediates proposed to be involved in asymmetric induction. These models allow for the optimization of poorly performing examples reported in a substrate scope and are applicable to unseen ligands and reaction partners. This approach offers the opportunity to streamline catalyst and reaction development, quantitatively transferring knowledge learned on sparse data to novel chemical spaces.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"69 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152346","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}
Pub Date : 2026-02-11DOI: 10.1038/s41586-025-10096-w
Sofia Skromne Carrasco, Guillaume Viejo, Adrien Peyrache
Spatial orientation enables animals to navigate their environment by rapidly mapping the external world and remembering key locations1. In mammals, the head-direction (HD) system is an essential component of the navigation system of the brain2. Although the tuning of neurons in other areas of this system is unstable—evidenced, for example, by the change in the spatial tuning of hippocampal place cells3 across days4,5,6,7,8,9,10,11—the stability of the neuronal code that underlies the sense of direction remains unclear. Here, by longitudinally tracking the activity of the same HD cells in the post-subiculum of freely moving mice, we show stability and plasticity at two levels. Although the population structure remained highly conserved across environments and over time, subtle shifts in population coherence encoded environment identity. In addition, the HD system established a distinct, environment-specific alignment between its internal representation and external landmarks, which persisted for weeks, even after a single exposure. These findings suggest that the HD system forms long-lasting orientation memories that are anchored to specific environments.
{"title":"Months-long stability of the head-direction system","authors":"Sofia Skromne Carrasco, Guillaume Viejo, Adrien Peyrache","doi":"10.1038/s41586-025-10096-w","DOIUrl":"https://doi.org/10.1038/s41586-025-10096-w","url":null,"abstract":"Spatial orientation enables animals to navigate their environment by rapidly mapping the external world and remembering key locations1. In mammals, the head-direction (HD) system is an essential component of the navigation system of the brain2. Although the tuning of neurons in other areas of this system is unstable—evidenced, for example, by the change in the spatial tuning of hippocampal place cells3 across days4,5,6,7,8,9,10,11—the stability of the neuronal code that underlies the sense of direction remains unclear. Here, by longitudinally tracking the activity of the same HD cells in the post-subiculum of freely moving mice, we show stability and plasticity at two levels. Although the population structure remained highly conserved across environments and over time, subtle shifts in population coherence encoded environment identity. In addition, the HD system established a distinct, environment-specific alignment between its internal representation and external landmarks, which persisted for weeks, even after a single exposure. These findings suggest that the HD system forms long-lasting orientation memories that are anchored to specific environments.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"91 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152348","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}
Pub Date : 2026-02-10DOI: 10.1038/d41586-026-00390-6
Amanda Heidt
Documents that lay out a research group’s ethos and practical guidelines are becoming increasingly popular in the academic community. Documents that lay out a research group’s ethos and practical guidelines are becoming increasingly popular in the academic community.
{"title":"Lab morale got you down? Try a handbook","authors":"Amanda Heidt","doi":"10.1038/d41586-026-00390-6","DOIUrl":"10.1038/d41586-026-00390-6","url":null,"abstract":"Documents that lay out a research group’s ethos and practical guidelines are becoming increasingly popular in the academic community. Documents that lay out a research group’s ethos and practical guidelines are becoming increasingly popular in the academic community.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"650 8101","pages":"512-513"},"PeriodicalIF":48.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://media.nature.com/original/magazine-assets/d41586-026-00390-6/d41586-026-00390-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}