Pub Date : 2025-02-07Epub Date: 2025-02-06DOI: 10.1126/science.adw4662
Ian S Osborne, Madeleine Seale, Corinne Simonti, Peter Stern, Yevgeniya Nusinovich, Annalisa M VanHook, Hannah M Isles, Sarah H Ross, Di Jiang, Caroline Ash, Sacha Vignieri, Marc S Lavine, Melissa L Norton
Highlights from the Science family of journals.
{"title":"In Science Journals.","authors":"Ian S Osborne, Madeleine Seale, Corinne Simonti, Peter Stern, Yevgeniya Nusinovich, Annalisa M VanHook, Hannah M Isles, Sarah H Ross, Di Jiang, Caroline Ash, Sacha Vignieri, Marc S Lavine, Melissa L Norton","doi":"10.1126/science.adw4662","DOIUrl":"https://doi.org/10.1126/science.adw4662","url":null,"abstract":"<p><p>Highlights from the <i>Science</i> family of journals.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":"622-624"},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365097","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 : 2025-02-07Epub Date: 2025-02-06DOI: 10.1126/science.adr7939
Jennifer Spence, John Holdren, Fran Ulmer
Rapid Arctic change requires multifaceted approaches with Arctic peoples at the forefront.
{"title":"Arctic research cooperation in a turbulent world.","authors":"Jennifer Spence, John Holdren, Fran Ulmer","doi":"10.1126/science.adr7939","DOIUrl":"https://doi.org/10.1126/science.adr7939","url":null,"abstract":"<p><p>Rapid Arctic change requires multifaceted approaches with Arctic peoples at the forefront.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":"598-600"},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365962","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 : 2025-02-07Epub Date: 2025-02-06DOI: 10.1126/science.adw4664
Martin Enserink
Bangladesh is leading the fight against this ancient scourge, and vaccine researcher Firdausi Qadri is on the front lines.
{"title":"In the cradle of cholera.","authors":"Martin Enserink","doi":"10.1126/science.adw4664","DOIUrl":"https://doi.org/10.1126/science.adw4664","url":null,"abstract":"<p><p>Bangladesh is leading the fight against this ancient scourge, and vaccine researcher Firdausi Qadri is on the front lines.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":"572-577"},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365461","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 : 2025-02-07Epub Date: 2025-02-06DOI: 10.1126/science.adv2328
Robert W Moon, Ellen S C Bushell
Functional genomics in malaria unlocks comparative biology across the family tree.
{"title":"Not just monkey business.","authors":"Robert W Moon, Ellen S C Bushell","doi":"10.1126/science.adv2328","DOIUrl":"https://doi.org/10.1126/science.adv2328","url":null,"abstract":"<p><p>Functional genomics in malaria unlocks comparative biology across the family tree.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":"582-583"},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365761","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}
Hongbo Liu, Amin Abedini, Eunji Ha, Ziyuan Ma, Xin Sheng, Bernhard Dumoulin, Chengxiang Qiu, Tamas Aranyi, Shen Li, Nicole Dittrich, Hua-Chang Chen, Ran Tao, Der-Cherng Tarng, Feng-Jen Hsieh, Shih-Ann Chen, Shun-Fa Yang, Mei-Yueh Lee, Pui-Yan Kwok, Jer-Yuarn Wu, Chien-Hsiun Chen, Atlas Khan, Nita A. Limdi, Wei-Qi Wei, Theresa L. Walunas, Elizabeth W. Karlson, Eimear E. Kenny, Yuan Luo, Leah Kottyan, John J. Connolly, Gail P. Jarvik, Chunhua Weng, Ning Shang, Joanne B. Cole, Josep M. Mercader, Ravi Mandla, Timothy D. Majarian, Jose C. Florez, Mary E. Haas, Luca A. Lotta, Regeneron Genetics Center, GHS-RGC DiscovEHR Collaboration, Theodore G. Drivas, Penn Medicine BioBank, Ha My T. Vy, Girish N. Nadkarni, Laura K. Wiley, Melissa P. Wilson, Christopher R. Gignoux, Humaira Rasheed, Laurent F. Thomas, Bjørn Olav Åsvold, Ben M. Brumpton, Stein I. Hallan, Kristian Hveem, Jie Zheng, Jacklyn N. Hellwege, Matthew Zawistowski, Sebastian Zöllner, Nora Franceschini, Hailong Hu, Jianfu Zhou, Krzysztof Kiryluk, Marylyn D. Ritchie, Matthew Palmer, Todd L. Edwards, Benjamin F. Voight, Adriana M. Hung, Katalin Susztak
Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the “Kidney Disease Genetic Scorecard” for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.
{"title":"Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants","authors":"Hongbo Liu, Amin Abedini, Eunji Ha, Ziyuan Ma, Xin Sheng, Bernhard Dumoulin, Chengxiang Qiu, Tamas Aranyi, Shen Li, Nicole Dittrich, Hua-Chang Chen, Ran Tao, Der-Cherng Tarng, Feng-Jen Hsieh, Shih-Ann Chen, Shun-Fa Yang, Mei-Yueh Lee, Pui-Yan Kwok, Jer-Yuarn Wu, Chien-Hsiun Chen, Atlas Khan, Nita A. Limdi, Wei-Qi Wei, Theresa L. Walunas, Elizabeth W. Karlson, Eimear E. Kenny, Yuan Luo, Leah Kottyan, John J. Connolly, Gail P. Jarvik, Chunhua Weng, Ning Shang, Joanne B. Cole, Josep M. Mercader, Ravi Mandla, Timothy D. Majarian, Jose C. Florez, Mary E. Haas, Luca A. Lotta, Regeneron Genetics Center, GHS-RGC DiscovEHR Collaboration, Theodore G. Drivas, Penn Medicine BioBank, Ha My T. Vy, Girish N. Nadkarni, Laura K. Wiley, Melissa P. Wilson, Christopher R. Gignoux, Humaira Rasheed, Laurent F. Thomas, Bjørn Olav Åsvold, Ben M. Brumpton, Stein I. Hallan, Kristian Hveem, Jie Zheng, Jacklyn N. Hellwege, Matthew Zawistowski, Sebastian Zöllner, Nora Franceschini, Hailong Hu, Jianfu Zhou, Krzysztof Kiryluk, Marylyn D. Ritchie, Matthew Palmer, Todd L. Edwards, Benjamin F. Voight, Adriana M. Hung, Katalin Susztak","doi":"","DOIUrl":"","url":null,"abstract":"<div >Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the “Kidney Disease Genetic Scorecard” for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253912","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}
Brendan Elsworth, Sida Ye, Sheena Dass, Jacob A. Tennessen, Qudseen Sultana, Basil T. Thommen, Aditya S. Paul, Usheer Kanjee, Christof Grüring, Marcelo U. Ferreira, Marc-Jan Gubbels, Kourosh Zarringhalam, Manoj T. Duraisingh
Measures to combat the parasites that cause malaria have become compromised because of reliance on a small arsenal of drugs and emerging drug resistance. We conducted a transposon mutagenesis screen in the primate malaria parasite Plasmodium knowlesi, producing the most complete classification of gene essentiality in any Plasmodium spp. to date, with the resolution to define truncatable genes. We found conservation in the druggable genome between Plasmodium spp. and divergences in mitochondrial metabolism. Perturbation analyses with the frontline antimalarial artemisinin revealed modulators that both increase and decrease drug susceptibility. Our findings aid prioritization of drug and vaccine targets for the Plasmodium vivax clade and reveal mechanisms of resistance that can inform therapeutic development.
{"title":"The essential genome of Plasmodium knowlesi reveals determinants of antimalarial susceptibility","authors":"Brendan Elsworth, Sida Ye, Sheena Dass, Jacob A. Tennessen, Qudseen Sultana, Basil T. Thommen, Aditya S. Paul, Usheer Kanjee, Christof Grüring, Marcelo U. Ferreira, Marc-Jan Gubbels, Kourosh Zarringhalam, Manoj T. Duraisingh","doi":"","DOIUrl":"","url":null,"abstract":"<div >Measures to combat the parasites that cause malaria have become compromised because of reliance on a small arsenal of drugs and emerging drug resistance. We conducted a transposon mutagenesis screen in the primate malaria parasite <i>Plasmodium knowlesi</i>, producing the most complete classification of gene essentiality in any <i>Plasmodium</i> spp. to date, with the resolution to define truncatable genes. We found conservation in the druggable genome between <i>Plasmodium</i> spp. and divergences in mitochondrial metabolism. Perturbation analyses with the frontline antimalarial artemisinin revealed modulators that both increase and decrease drug susceptibility. Our findings aid prioritization of drug and vaccine targets for the <i>Plasmodium vivax</i> clade and reveal mechanisms of resistance that can inform therapeutic development.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.adq6241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253927","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}
Jenna Oberstaller, Shulin Xu, Deboki Naskar, Min Zhang, Chengqi Wang, Justin Gibbons, Camilla Valente Pires, Matthew Mayho, Thomas D. Otto, Julian C. Rayner, John H. Adams
Malaria parasites are highly divergent from model eukaryotes. Large-scale genome engineering methods effective in model organisms are frequently inapplicable, and systematic studies of gene function are few. We generated more than 175,000 transposon insertions in the Plasmodium knowlesi genome, averaging an insertion every 138 base pairs, and used this “supersaturation” mutagenesis to score essentiality for 98% of genes. The density of mutations allowed mapping of putative essential domains within genes, providing a completely new level of genome annotation for any Plasmodium species. Although gene essentiality was largely conserved across P. knowlesi, Plasmodium falciparum, and rodent malaria model Plasmodium berghei, a large number of shared genes are differentially essential, revealing species-specific adaptations. Our results indicated that Plasmodium essential gene evolution was conditionally linked to adaptive rewiring of metabolic networks for different hosts.
{"title":"Supersaturation mutagenesis reveals adaptive rewiring of essential genes among malaria parasites","authors":"Jenna Oberstaller, Shulin Xu, Deboki Naskar, Min Zhang, Chengqi Wang, Justin Gibbons, Camilla Valente Pires, Matthew Mayho, Thomas D. Otto, Julian C. Rayner, John H. Adams","doi":"","DOIUrl":"","url":null,"abstract":"<div >Malaria parasites are highly divergent from model eukaryotes. Large-scale genome engineering methods effective in model organisms are frequently inapplicable, and systematic studies of gene function are few. We generated more than 175,000 transposon insertions in the <i>Plasmodium knowlesi</i> genome, averaging an insertion every 138 base pairs, and used this “supersaturation” mutagenesis to score essentiality for 98% of genes. The density of mutations allowed mapping of putative essential domains within genes, providing a completely new level of genome annotation for any <i>Plasmodium</i> species. Although gene essentiality was largely conserved across <i>P. knowlesi</i>, <i>Plasmodium falciparum</i>, and rodent malaria model <i>Plasmodium berghei</i>, a large number of shared genes are differentially essential, revealing species-specific adaptations. Our results indicated that <i>Plasmodium</i> essential gene evolution was conditionally linked to adaptive rewiring of metabolic networks for different hosts.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":""},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/science.adq7347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253931","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}
Pub Date : 2025-02-07Epub Date: 2025-02-06DOI: 10.1126/science.adt7848
Madeline Davey, James E M Watson
{"title":"Australia's inadequate marine protection.","authors":"Madeline Davey, James E M Watson","doi":"10.1126/science.adt7848","DOIUrl":"https://doi.org/10.1126/science.adt7848","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":"586-587"},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364838","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 : 2025-02-07Epub Date: 2025-02-06DOI: 10.1126/science.adv2318
Andrew Whiten, Mason Youngblood
The complex songs of humpback whales conform to fundamental laws of language.
{"title":"Convergent evolution in whale and human vocal cultures.","authors":"Andrew Whiten, Mason Youngblood","doi":"10.1126/science.adv2318","DOIUrl":"https://doi.org/10.1126/science.adv2318","url":null,"abstract":"<p><p>The complex songs of humpback whales conform to fundamental laws of language.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6734","pages":"581-582"},"PeriodicalIF":44.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364841","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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