{"title":"Misguided negative adaptation narratives are hurting the poor","authors":"E. L. F. Schipper, A. Mukherji","doi":"10.1126/science.adq7821","DOIUrl":"10.1126/science.adq7821","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6722","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.adq7821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606594","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}
Lauren N. Woodie, Lily C. Melink, Mohit Midha, Alan M. de Araújo, Caroline E. Geisler, Ahren J. Alberto, Brianna M. Krusen, Delaine M. Zundell, Guillaume de Lartigue, Matthew R. Hayes, Mitchell A. Lazar
Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.
{"title":"Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake","authors":"Lauren N. Woodie, Lily C. Melink, Mohit Midha, Alan M. de Araújo, Caroline E. Geisler, Ahren J. Alberto, Brianna M. Krusen, Delaine M. Zundell, Guillaume de Lartigue, Matthew R. Hayes, Mitchell A. Lazar","doi":"10.1126/science.adn2786","DOIUrl":"10.1126/science.adn2786","url":null,"abstract":"<div >Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6722","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594625","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}
{"title":"Untangling bias: Racial and phenotypic bias in neuroimaging methods must be addressed","authors":"Jasmine Kwasa","doi":"10.1126/science.ads7375","DOIUrl":"10.1126/science.ads7375","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6722","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.ads7375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606607","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}
Given the negative fitness effects that pathogens impose on their hosts, the benefits of resistance should be universal. However, there is marked variation across plant species in the number of nucleotide-binding leucine-rich repeat receptors, which form a cornerstone of defense. The growth–defense trade-off hypothesis predicts costs associated with defense investment to generate variation in these traits. Our analysis comparing features of the intracellular immune-receptor repertoires with trait data of 187 species shows that in wild plants, the size of the molecular defense repertoire correlates negatively with growth. By contrast, we do not find evidence for a growth–defense trade-off in agricultural plants. Our cross-species approach highlights the central role of defense investment in shaping ecological trait variation and its sensitivity to domestication.
{"title":"A trade-off between investment in molecular defense repertoires and growth in plants","authors":"Michael Giolai, Anna-Liisa Laine","doi":"10.1126/science.adn2779","DOIUrl":"10.1126/science.adn2779","url":null,"abstract":"<div >Given the negative fitness effects that pathogens impose on their hosts, the benefits of resistance should be universal. However, there is marked variation across plant species in the number of nucleotide-binding leucine-rich repeat receptors, which form a cornerstone of defense. The growth–defense trade-off hypothesis predicts costs associated with defense investment to generate variation in these traits. Our analysis comparing features of the intracellular immune-receptor repertoires with trait data of 187 species shows that in wild plants, the size of the molecular defense repertoire correlates negatively with growth. By contrast, we do not find evidence for a growth–defense trade-off in agricultural plants. Our cross-species approach highlights the central role of defense investment in shaping ecological trait variation and its sensitivity to domestication.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6722","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594929","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}
Timing mechanisms have evolved across all kingdoms of life to anticipate daily changes in the light environment and to optimize opportunities for nutrition. In mammals, the central circadian clock in the hypothalamic suprachiasmatic nucleus synchronizes to external light. However, other cells, tissues, and organs in the body have their own circadian clocks. For example, the liver has a molecular clock that can be entrained by feeding-fasting cycles. Desynchrony between the lightentrained suprachiasmatic nucleus and the food-entrained liver carries adverse health consequences, including increased risk of cardiometabolic diseases or type 2 diabetes; yet, how these clocks become misaligned remains unknown. On page 673 of this issue, Woodie et al. (1) report a neural link from the liver to the brain that conveys the misalignment signal to drive changes in eating behavior, body weight maintenance, and energy metabolism. This reveals a potential therapeutic target to mitigate the metabolic impact of circadian disruption.
肝迷走神经介导昼夜节律紊乱对小鼠食物摄入量的影响。
{"title":"Rhythmic liver drives feeding behavior","authors":"Noelia Martinez-Sanchez, David Ray","doi":"10.1126/science.adt0743","DOIUrl":"10.1126/science.adt0743","url":null,"abstract":"<div >Timing mechanisms have evolved across all kingdoms of life to anticipate daily changes in the light environment and to optimize opportunities for nutrition. In mammals, the central circadian clock in the hypothalamic suprachiasmatic nucleus synchronizes to external light. However, other cells, tissues, and organs in the body have their own circadian clocks. For example, the liver has a molecular clock that can be entrained by feeding-fasting cycles. Desynchrony between the lightentrained suprachiasmatic nucleus and the food-entrained liver carries adverse health consequences, including increased risk of cardiometabolic diseases or type 2 diabetes; yet, how these clocks become misaligned remains unknown. On page 673 of this issue, Woodie <i>et al</i>. (<i>1</i>) report a neural link from the liver to the brain that conveys the misalignment signal to drive changes in eating behavior, body weight maintenance, and energy metabolism. This reveals a potential therapeutic target to mitigate the metabolic impact of circadian disruption.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6722","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606605","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}
Andy M. Lau, Nicola Bordin, Shaun M. Kandathil, Ian Sillitoe, Vaishali P. Waman, Jude Wells, Christine A. Orengo, David T. Jones
The AlphaFold Protein Structure Database (AFDB) contains more than 214 million predicted protein structures composed of domains, which are independently folding units found in multiple structural and functional contexts. Identifying domains can enable many functional and evolutionary analyses but has remained challenging because of the sheer scale of the data. Using deep learning methods, we have detected and classified every domain in the AFDB, producing The Encyclopedia of Domains. We detected nearly 365 million domains, over 100 million more than can be found by sequence methods, covering more than 1 million taxa. Reassuringly, 77% of the nonredundant domains are similar to known superfamilies, greatly expanding representation of their domain space. We uncovered more than 10,000 new structural interactions between superfamilies and thousands of new folds across the fold space continuum.
{"title":"Exploring structural diversity across the protein universe with The Encyclopedia of Domains","authors":"Andy M. Lau, Nicola Bordin, Shaun M. Kandathil, Ian Sillitoe, Vaishali P. Waman, Jude Wells, Christine A. Orengo, David T. Jones","doi":"10.1126/science.adq4946","DOIUrl":"10.1126/science.adq4946","url":null,"abstract":"<div >The AlphaFold Protein Structure Database (AFDB) contains more than 214 million predicted protein structures composed of domains, which are independently folding units found in multiple structural and functional contexts. Identifying domains can enable many functional and evolutionary analyses but has remained challenging because of the sheer scale of the data. Using deep learning methods, we have detected and classified every domain in the AFDB, producing The Encyclopedia of Domains. We detected nearly 365 million domains, over 100 million more than can be found by sequence methods, covering more than 1 million taxa. Reassuringly, 77% of the nonredundant domains are similar to known superfamilies, greatly expanding representation of their domain space. We uncovered more than 10,000 new structural interactions between superfamilies and thousands of new folds across the fold space continuum.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6721","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556142","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 : 2024-11-01Epub Date: 2024-10-31DOI: 10.1126/science.adu2100
Kai Kupferschmidt
Misinformation research has exploded. But scientists are still grappling with fundamental challenges.
误报研究呈爆炸式增长。但科学家们仍在努力应对根本性的挑战。
{"title":"A field's dilemmas.","authors":"Kai Kupferschmidt","doi":"10.1126/science.adu2100","DOIUrl":"10.1126/science.adu2100","url":null,"abstract":"<p><p>Misinformation research has exploded. But scientists are still grappling with fundamental challenges.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6721","pages":"478-482"},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558697","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 : 2024-11-01Epub Date: 2024-10-31DOI: 10.1126/science.adu2102
Kai Kupferschmidt
At the Center for an Informed Public, Kate Starbird tracks falsehoods and counters them in real time.
凯特-斯塔伯德（Kate Starbird）在 "知情公众中心"（Center for an Informed Public）实时跟踪和反驳虚假信息。
{"title":"The rumor clinic.","authors":"Kai Kupferschmidt","doi":"10.1126/science.adu2102","DOIUrl":"10.1126/science.adu2102","url":null,"abstract":"<p><p>At the Center for an Informed Public, Kate Starbird tracks falsehoods and counters them in real time.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6721","pages":"486-489"},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558718","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}
Luca McDermott, Zach G. Walters, Sarah A. French, Allison M. Clark, Jiaming Ding, Andrew V. Kelleghan, K. N. Houk, Neil K. Garg
The π-bonds in unsaturated organic molecules are typically associated with having well-defined geometries that are conserved across diverse structural contexts. Nonetheless, these geometries can be distorted, leading to heightened reactivity of the π-bond. Although π-bond–containing compounds with bent geometries are well utilized in synthetic chemistry, the corresponding leveraging of π-bond–containing compounds that display twisting or pyramidalization remains underdeveloped. We report a study of perhaps the most notorious class of geometrically distorted molecules that contain π-bonds: anti-Bredt olefins (ABOs). ABOs have been known since 1924, and conventional wisdom maintains that ABOs are difficult or impossible to access. We provide a solution to this long-standing problem. Our study also highlights the strategic manipulation of compounds that display considerable distortion arising from the presence of geometrically constrained π-bonds.
{"title":"A solution to the anti-Bredt olefin synthesis problem","authors":"Luca McDermott, Zach G. Walters, Sarah A. French, Allison M. Clark, Jiaming Ding, Andrew V. Kelleghan, K. N. Houk, Neil K. Garg","doi":"10.1126/science.adq3519","DOIUrl":"10.1126/science.adq3519","url":null,"abstract":"<div >The π-bonds in unsaturated organic molecules are typically associated with having well-defined geometries that are conserved across diverse structural contexts. Nonetheless, these geometries can be distorted, leading to heightened reactivity of the π-bond. Although π-bond–containing compounds with bent geometries are well utilized in synthetic chemistry, the corresponding leveraging of π-bond–containing compounds that display twisting or pyramidalization remains underdeveloped. We report a study of perhaps the most notorious class of geometrically distorted molecules that contain π-bonds: anti-Bredt olefins (ABOs). ABOs have been known since 1924, and conventional wisdom maintains that ABOs are difficult or impossible to access. We provide a solution to this long-standing problem. Our study also highlights the strategic manipulation of compounds that display considerable distortion arising from the presence of geometrically constrained π-bonds.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6721","pages":""},"PeriodicalIF":44.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556144","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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