SciencePub Date : 2026-05-07DOI: 10.1126/science.aea1676
Junna Wang, Brunno F. Oliveira, Frances C. Moore, Daniel J. Kozar, Yongshuo Fu, Xiaoli Dong
{"title":"Climate-induced range shifts support local plant diversity but don’t reduce extinction risk","authors":"Junna Wang, Brunno F. Oliveira, Frances C. Moore, Daniel J. Kozar, Yongshuo Fu, Xiaoli Dong","doi":"10.1126/science.aea1676","DOIUrl":"10.1126/science.aea1676","url":null,"abstract":"<div >Climate change is driving widespread plant range shifts, yet their consequences for extinction and biodiversity remain unclear as realistic range shift dynamics have rarely been incorporated into global-scale biodiversity models. We integrate species-specific range shift velocities into species distribution models to project distributions of 67,664 plant species (18% of all global flora) by 2081 to 2100. Across emissions scenarios, 7 to 16% of species are projected to lose >90% of their range, placing them at high risk of extinction. These losses are driven primarily by climate-induced habitat loss, rather than dispersal limitation. Although range shifts offer little relief from global extinctions, they are projected to increase local plant richness across 28% of Earth’s land. Facilitating range shifts may thus sustain local richness but not reduce global extinctions.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827816","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.aec6396
Ashwin N Skelly, Harry B Gristick, Hui Li, Edem Gavor, Andrew J Connell, Edward F Kreider, Lorie Marchitto, Michael P Hogarty, Maddy L Newby, Joel D Allen, Weimin Liu, Anthony P West, Kasirajan Ayyanathan, Mary S Campion, Kaitlyn Winters, Colette G Gordon, Rebecca A Osbaldeston, Macy J Akeley, Emily Lewis, Yingying Li, Ajay Singh, Kendra Cruickshank, Younghoon Park, Chengyan Zhao, Xuduo Li, Khaled Amereh, Elizabeth Van Itallie, John W Carey, Amie Albertus, Andrew T DeLaitsch, Jennifer R Keeffe, Melinda G Lituchy, Agnes A Walsh, Daniel J Morris, Rumi Habib, Frederic Bibollet-Ruche, Nitesh Mishra, Gabriel Avillion, Nicholas S Koranda, Samantha J Plante, Christian L Martella, Jinery Lora, Eric J D Wang, Mark G Lewis, Malcolm A Martin, Michel C Nussenzweig, Michael S Seaman, Darrell J Irvine, Kevin J Wiehe, Barton F Haynes, Kshitij Wagh, Bette Korber, Raiees Andrabi, Max Crispin, Drew Weissman, Pamela J Bjorkman, Beatrice H Hahn, George M Shaw
{"title":"Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design.","authors":"Ashwin N Skelly, Harry B Gristick, Hui Li, Edem Gavor, Andrew J Connell, Edward F Kreider, Lorie Marchitto, Michael P Hogarty, Maddy L Newby, Joel D Allen, Weimin Liu, Anthony P West, Kasirajan Ayyanathan, Mary S Campion, Kaitlyn Winters, Colette G Gordon, Rebecca A Osbaldeston, Macy J Akeley, Emily Lewis, Yingying Li, Ajay Singh, Kendra Cruickshank, Younghoon Park, Chengyan Zhao, Xuduo Li, Khaled Amereh, Elizabeth Van Itallie, John W Carey, Amie Albertus, Andrew T DeLaitsch, Jennifer R Keeffe, Melinda G Lituchy, Agnes A Walsh, Daniel J Morris, Rumi Habib, Frederic Bibollet-Ruche, Nitesh Mishra, Gabriel Avillion, Nicholas S Koranda, Samantha J Plante, Christian L Martella, Jinery Lora, Eric J D Wang, Mark G Lewis, Malcolm A Martin, Michel C Nussenzweig, Michael S Seaman, Darrell J Irvine, Kevin J Wiehe, Barton F Haynes, Kshitij Wagh, Bette Korber, Raiees Andrabi, Max Crispin, Drew Weissman, Pamela J Bjorkman, Beatrice H Hahn, George M Shaw","doi":"10.1126/science.aec6396","DOIUrl":"10.1126/science.aec6396","url":null,"abstract":"<p><p>A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":" ","pages":"eaec6396"},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842153","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.aei6157
Jennie Erin Smith
{"title":"How 'spikes' in the epileptic brain are harmful-and might be tamed.","authors":"Jennie Erin Smith","doi":"10.1126/science.aei6157","DOIUrl":"https://doi.org/10.1126/science.aei6157","url":null,"abstract":"<p><p>Abnormal electrical bursts hijack neurons involved in cognition and can be predicted up to 1 second in advance, new study finds.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":"571"},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842164","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.aeh1396
Rebecca Buller, Joelle N. Pelletier
{"title":"Building an oral peptide drug","authors":"Rebecca Buller, Joelle N. Pelletier","doi":"10.1126/science.aeh1396","DOIUrl":"10.1126/science.aeh1396","url":null,"abstract":"<div >Biologics are nature-inspired pharmaceutical compounds for treating diseases such as cancer, chronic autoimmune disorders, and high-cholesterol conditions. They are often based on proteins in which amino acids are linked by amide bonds that undergo rapid degradation by digestive enzymes if taken orally. Biologics are therefore primarily administered through intravenous injection. Orally available alternatives can improve patients’ quality of life and adherence to health management. Peptide-based drugs can be chemically modified to withstand degradation and are simpler alternatives to biologics. However, their synthesis often involves many steps and is inefficient (<i>1</i>). On page 643 of this issue, Klapars <i>et al</i>. (<i>2</i>) report a kilogram-scale synthesis of enlicitide, a peptide drug for lowering low-density cholesterol that is in a Phase 3 clinical trial for atherosclerotic cardiovascular disease (<i>3</i>, <i>4</i>). This new synthesis route leverages engineered enzymes and crystallization of key intermediates, substantially cutting down the number of reaction steps while improving yield.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827813","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.ady8732
Haochuan Cui, Yiling Lin, Lingfei Wu, James A. Evans
{"title":"Aging and the narrowing of scientific innovation","authors":"Haochuan Cui, Yiling Lin, Lingfei Wu, James A. Evans","doi":"10.1126/science.ady8732","DOIUrl":"10.1126/science.ady8732","url":null,"abstract":"<div >Scientific careers today are marked by growing polarization: A small number of scientists now remain active and influential for longer than ever (<i>1</i>), whereas many others pass through research as temporary workers (<i>2</i>). Lengthened training periods, the elimination of mandatory retirement, and funding systems that reward experience have concentrated resources among senior scientists (<i>3</i>, <i>4</i>). As science becomes increasingly dependent on its aging core, a central question arises: How does academic age influence creativity? The answer has long divided scholars. Analyzing more than 12.5 million scientists who published between 1960 and 2020, we find that novelty—the linking of previously unconnected ideas—increases with academic age, whereas disruption—the replacement of established ideas with new ones—declines. These and other findings invite reflection on potential implications for policy, such as funding, tenure, and promotion systems; immigration and mobility; workforce development; and incentives for (and barriers to) collaboration and innovation.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827817","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.aea2097
Narayana R. Aluru, Seth B. Darling, Jeffrey W. Elam, Oleg Gang, Alberto Salleo, Zuzanna Siwy, A. Alec Talin, Aleksandr Noy
{"title":"Knowledge gaps for neuromorphic ionic computing","authors":"Narayana R. Aluru, Seth B. Darling, Jeffrey W. Elam, Oleg Gang, Alberto Salleo, Zuzanna Siwy, A. Alec Talin, Aleksandr Noy","doi":"10.1126/science.aea2097","DOIUrl":"10.1126/science.aea2097","url":null,"abstract":"<div >Neuromorphic ionic computing is inspired by the brain’s use of ions for ultralow-energy computation—its massive parallelism, adaptability, and learning capabilities. This emerging paradigm can overcome limitations of conventional silicon-based computing by enabling colocated memory and processing, multicarrier information streams, and massive three-dimensional connectivity. However, substantial knowledge gaps remain in understanding and engineering ionic transport, energy dissipation, materials design, and scalable device architectures. This Review explores these critical challenges across seven key domains, highlighting the need for new theoretical approaches, materials, device concepts, and fabrication strategies. We argue that advancing ionic neuromorphic systems requires an interdisciplinary approach, integrating insights from biology and neuroscience, nanofluidics, materials science, and systems engineering to enable a new class of energy-efficient, robust, and reconfigurable computing technologies.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827818","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.aec8514
James D Pearce, Sara E Simmonds, Gita Mahmoudabadi, Lakshmi Krishnan, Giovanni Palla, Ana-Maria Istrate, Alexander Tarashansky, Benjamin Nelson, Omar Valenzuela, Donghui Li, Stephen R Quake, Theofanis Karaletsos
{"title":"TranscriptFormer: A generative cell atlas across 1.5 billion years of evolution.","authors":"James D Pearce, Sara E Simmonds, Gita Mahmoudabadi, Lakshmi Krishnan, Giovanni Palla, Ana-Maria Istrate, Alexander Tarashansky, Benjamin Nelson, Omar Valenzuela, Donghui Li, Stephen R Quake, Theofanis Karaletsos","doi":"10.1126/science.aec8514","DOIUrl":"https://doi.org/10.1126/science.aec8514","url":null,"abstract":"<p><p>Single-cell transcriptomics is revolutionizing our understanding of cellular diversity, yet comparing transcriptional programs across the tree of life remains challenging. We developed TranscriptFormer, a family of generative foundation models trained on up to 112 million cells spanning 1.53 billion years of evolution across 12 species. We demonstrate state-of-the-art performance on cell type classification, even for species separated over 685 million years of evolution, and zero-shot disease state identification in human cells. Developmental trajectories, phylogenetic relationships and cellular hierarchies emerge naturally in TranscriptFormer's representations without any explicit training on these annotations. This work establishes a powerful framework for quantitative single-cell analysis and comparative cellular biology, thus demonstrating that universal principles of cellular organization can be learned and predicted across the tree of life.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":" ","pages":"eaec8514"},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842227","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.aeh2866
Rosa A. Scherson, Federico Luebert
{"title":"The future of plant extinction","authors":"Rosa A. Scherson, Federico Luebert","doi":"10.1126/science.aeh2866","DOIUrl":"10.1126/science.aeh2866","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827803","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.ady3237
Mingqi Liu, Binhao Wang, Sezim E. Guvercin, Zhen Li, Teng Wang, Chuanjin Liu, Lingyun Ji, Sylvain Barbot
{"title":"Dynamic segmentation of the Sagaing fault","authors":"Mingqi Liu, Binhao Wang, Sezim E. Guvercin, Zhen Li, Teng Wang, Chuanjin Liu, Lingyun Ji, Sylvain Barbot","doi":"10.1126/science.ady3237","DOIUrl":"10.1126/science.ady3237","url":null,"abstract":"<div >The structurally simple Sagaing fault, which ruptured during the 2025 moment magnitude 7.7 Mandalay earthquake, exhibits clear dynamic segmentation despite lacking major geometric complexities. Using physics-based seismic cycle simulations, we tested the hypothesis that dynamic segmentation on the Sagaing fault is influenced by a northward increase in long-term slip rates from 18 to 28 millimeter/year. Models incorporating geodetically constrained long-term slip rates reproduced the rupture extent of historical earthquakes and the geodetically inferred slip distribution of the 2025 mainshock. Slip rate contrasts of 10 to 20% between adjacent segments generate sufficient heterogeneous stress accumulation to initiate dynamic segmentation, regulating earthquake recurrence patterns and maximum magnitudes across the fault system. These results highlight the value of integrating geodetic, geological, and seismological observations to improve seismic hazard assessment.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827805","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}
SciencePub Date : 2026-05-07DOI: 10.1126/science.adv3301
Katie E. Copley, Jocelyn C. Mauna, Helen L. Danielson, Qizan Chen, Busra Ozguney, Marilyn Ngo, Longxin Xie, Ashleigh Smirnov, Matt Davis, Leland Mayne, Miriam Linsenmeier, Jack D. Rubien, Cristian A. Bergmann, Bede Portz, Bo Lim Lee, Hana M. Odeh, Longsheng Lai, Yi-Wei Chang, Martina Hallegger, Jernej Ule, Piera Pasinelli, Yan Poon, Jeetain Mittal, Nicolas L. Fawzi, Ben E. Black, Christopher J. Donnelly, Brigid K. Jensen, James Shorter
{"title":"Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration","authors":"Katie E. Copley, Jocelyn C. Mauna, Helen L. Danielson, Qizan Chen, Busra Ozguney, Marilyn Ngo, Longxin Xie, Ashleigh Smirnov, Matt Davis, Leland Mayne, Miriam Linsenmeier, Jack D. Rubien, Cristian A. Bergmann, Bede Portz, Bo Lim Lee, Hana M. Odeh, Longsheng Lai, Yi-Wei Chang, Martina Hallegger, Jernej Ule, Piera Pasinelli, Yan Poon, Jeetain Mittal, Nicolas L. Fawzi, Ben E. Black, Christopher J. Donnelly, Brigid K. Jensen, James Shorter","doi":"10.1126/science.adv3301","DOIUrl":"10.1126/science.adv3301","url":null,"abstract":"<div >Aberrant aggregation of the prion-like RNA binding protein TDP-43 drives several fatal neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS). In this work, we define how short, specific RNAs solubilize TDP-43. These short RNAs engage and stabilize the TDP-43 RNA recognition motifs, which allosterically destabilizes a conserved helical region in the prion-like domain, thereby promoting aggregation-resistant conformers. Sequence-space mining identified short RNA chaperones with enhanced activity against TDP-43 and disease-linked variants. Enhanced short RNA chaperones mitigated aberrant TDP-43 phenotypes in optogenetic models and in ALS patient–derived and control motor neurons. In mice with cytoplasmic TDP-43 aggregation and motor neuron loss, an enhanced short RNA chaperone reduced pathological aggregation, restored TDP-43 function, and conferred neuroprotection. These results define a mechanistic and therapeutic framework for RNA-based strategies to counter TDP-43 proteinopathies.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"392 6798","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147827824","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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