综合性期刊最新文献

{"title":"When AI rejects your grant proposal: algorithms are helping to make funding decisions","authors":"","doi":"10.1038/d41586-025-02852-9","DOIUrl":"https://doi.org/10.1038/d41586-025-02852-9","url":null,"abstract":"A Spanish foundation using an artificial-intelligence tool to screen grant applications says it makes the peer-review process more efficient, but other researchers say it’s a breakdown in trust.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"57 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995813","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":"Cotranslational protein folding through non-native structural intermediates","authors":"Siyu Wang,&nbsp;Amir Bitran,&nbsp;Ekaterina Samatova,&nbsp;Eugene I. Shakhnovich,&nbsp;Marina V. Rodnina","doi":"10.1126/sciadv.ady2211","DOIUrl":"10.1126/sciadv.ady2211","url":null,"abstract":"<div >Cotranslational protein folding follows a distinct pathway shaped by the vectorial emergence of the peptide and spatial constraints of the ribosome exit tunnel. Variations in translation rhythm can cause misfolding linked to disease; however, predicting cotranslational folding pathways remains challenging. Here, we computationally predict and experimentally validate a vectorial hierarchy of folding resolved at the atomistic level, where early intermediates are stabilized through non-native hydrophobic interactions before rearranging into the native-like fold. Disrupting these interactions destabilizes intermediates and impairs folding. The chaperone trigger factor alters the cotranslational folding pathway by keeping the nascent peptide dynamic until the full domain emerges. Our results highlight an unexpected role of surface-exposed residues in protein folding on the ribosome and provide tools to improve folding prediction and protein design.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady2211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999167","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}

{"title":"Synaptic imbalance and increased inhibition impair motor function in SMA","authors":"Emily V. Fletcher,&nbsp;Joshua I. Chalif,&nbsp;Travis M. Rotterman,&nbsp;John G. Pagiazitis,&nbsp;Meaghan Van Alstyne,&nbsp;Nandhini Sivakumar,&nbsp;Danny Florez-Paz,&nbsp;Joseph E. Rabinowitz,&nbsp;Livio Pellizzoni,&nbsp;Francisco J. Alvarez,&nbsp;George Z. Mentis","doi":"10.1126/sciadv.adt4126","DOIUrl":"10.1126/sciadv.adt4126","url":null,"abstract":"<div >Movement is executed through balanced excitation-inhibition in spinal motor circuits. Short-term perturbations in one type of neurotransmission are homeostatically counteracted by the opposing type, but prolonged excitation-inhibition imbalance causes dysfunction at both single neuron and circuit levels. However, whether dysfunction in one or both types of neurotransmission leads to pathogenicity in neurodegenerative diseases characterized by select synaptic deficits is not known. Here, we used functional, morphological, and viral-mediated approaches to uncover the pathogenic contribution of unbalanced excitation-inhibition in a mouse model of spinal muscular atrophy (SMA). We show that vulnerable SMA motor circuits fail to respond homeostatically to reduced excitation and instead increase inhibition. This imposes an excessive burden on motor neurons and further restricts their recruitment. Reducing inhibition genetically or pharmacologically improves neuronal function and motor behavior in SMA mice. Thus, the disruption of excitation-inhibition homeostasis is a major maladaptive mechanism that diminishes the capacity of premotor commands to recruit motor neurons and elicit muscle contractions in SMA.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt4126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999179","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}

{"title":"Chiral spin constrained assemblies for polarized optical mapping","authors":"Mingjiang Zhang,&nbsp;Shanshan Zhao,&nbsp;Jintong Li,&nbsp;Zeyi Li,&nbsp;Junjie Cai,&nbsp;Yajie Zhou,&nbsp;Qi Guo,&nbsp;Wenting Gao,&nbsp;Zhi Tong,&nbsp;Yaxin Wang,&nbsp;Guangen Li,&nbsp;Xueru Guo,&nbsp;Anqi Li,&nbsp;Jing Lin,&nbsp;Taotao Zhuang","doi":"10.1126/sciadv.ady1001","DOIUrl":"10.1126/sciadv.ady1001","url":null,"abstract":"<div >Optical-enabled identification and interaction provide an integral link between the digital and physical realms. However, nowadays optic-encodings, predominantly reliant on light’s intensity and wavelength, are hindered by environmental light interference and limited information capacity. The introduction of unusual polarization states, such as circular polarization—which is absent from ordinary surroundings—holds promise for higher-dimensional interaction. Here, we propose a circularly polarized optical mapper capable of generating high-entropy, noise-resistant keys, serving as a physical interface for unique interaction process between parties. To materialize this mapper, we developed an automated, in situ synthesis platform that facilitates the self-acting fabrication of robust, solid-state, chiral optical spin constrained assemblies. Our mappers, formed by randomized arrays of discrete assemblies, demonstrate near-theoretical performance in uniformity (0.4917), uniqueness (0.4968), and reliability (0.9355). By emitting high-dimensional spin-polarized light, our mappers enable both far-field readout and near-field authentication, with resistance to stray light interference, offering promising applications in the internet of things, augmented reality, and beyond.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ady1001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999157","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}

{"title":"PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity","authors":"Shen Yang,&nbsp;Eugenio Santelli,&nbsp;Carlos G. Gonzalez,&nbsp;Wade T. Johnson,&nbsp;Irene V. Choi,&nbsp;Chuling Zhuang,&nbsp;Myungja Ro,&nbsp;Leigh-Ana M. Rossitto,&nbsp;I-Shing Yu,&nbsp;Shu-Wha Lin,&nbsp;Yuan Zhan,&nbsp;Qinwei Chen,&nbsp;Jonathan D. Yoshihara,&nbsp;Daniel J. Wallace,&nbsp;Caroline A. Jefferies,&nbsp;Michifumi Yamashita,&nbsp;David J. Gonzalez,&nbsp;Richard I. Ainsworth,&nbsp;Nisarg J. Shah,&nbsp;Stephanie M. Stanford,&nbsp;Nunzio Bottini","doi":"10.1126/sciadv.adw2568","DOIUrl":"10.1126/sciadv.adw2568","url":null,"abstract":"<div >Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a gene strongly associated with lupus and other autoimmune diseases. PTPN22 regulates T cell receptor (TCR) signaling through dephosphorylation of the kinases lymphocyte-specific protein tyrosine kinase (LCK) and zeta-chain–associated protein kinase 70 (ZAP70). The regulation of PTPN22 remains poorly understood. Here, we identify PTPN22 Ser⁴⁴⁹ as a protein kinase A phosphorylation site, which is triggered by TCR engagement and is hyperphosphorylated in lupus peripheral blood cells. PTPN22 Ser⁴⁴⁹ phosphorylation selectively lowered the affinity of PTPN22 for ZAP70 versus LCK but also indirectly suppressed inhibitory LCK Tyr¹⁹² phosphorylation through a ZAP70-CD45 signaling axis. The resulting dephosphorylation of LCK Tyr¹⁹² not only enhanced TCR signaling but also modulated pathway activation downstream the TCR. In vivo loss of PTPN22 Ser⁴⁴⁹ phosphorylation reduced T cell responses and suppressed experimental lupus nephritis. These results suggest that PTPN22 Ser⁴⁴⁹ phosphorylation promotes a CD45-mediated retrograde ZAP70-LCK feedback loop that enhances T cell responses and promotes autoimmunity.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw2568","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999164","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}

{"title":"Joint models reveal human subcortical underpinnings of choice and learning behavior","authors":"Steven Miletić, Niek Stevenson, Pierre-Louis Bazin, Anneke Alkemade, Scott J. S. Isherwood, Anne C. Trutti, Desmond H. Y. Tse, Asta K. Håberg, Birte U. Forstmann","doi":"10.1073/pnas.2502269122","DOIUrl":"https://doi.org/10.1073/pnas.2502269122","url":null,"abstract":"Decision making and learning processes together enable adaptive strategic behavior. Animal studies demonstrated the importance of subcortical regions in these cognitive processes, but the human subcortical contributions remain poorly characterized. Here, we study choice and learning processes in the human subcortex, using a tailored ultra-high field 7T functional MRI protocol combined with joint models. Joint models provide unbiased estimates of brain–behavior relations by simultaneously including behavioral and neural data at the participant and group level. Results demonstrate relations between subcortical regions and the adjustment of decision urgency. Value-related blood-oxygenation level dependent (BOLD) differences were found with opposite BOLD polarity in different parts of the striatum. Multiple subcortical regions showed BOLD signatures of reward prediction error processing, but contrary to expectations, these did not include the dopaminergic midbrain. Combined, this study characterizes the human subcortical contributions to choice and learning, and demonstrates the feasibility and value of joint modeling in facilitating our understanding of brain–behavior relationships.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"20 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002986","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":"Chromatin‐associated condensates as an inspiration for the system architecture of future DNA computers","authors":"Lennart Hilbert, Aaron Gadzekpo, Simon Lo Vecchio, Mona Wellhäusser, Xenia Tschurikow, Roshan Prizak, Barbara Becker, Sandra Burghart, Ewa Anna Oprzeska‐Zingrebe","doi":"10.1111/nyas.15415","DOIUrl":"https://doi.org/10.1111/nyas.15415","url":null,"abstract":"The genome stores and processes approximately 1.5 gigabytes of encoded information. In this article, we propose that the eukaryotic genome and its adaptable three‐dimensional packing in the form of chromatin offer a valuable template for the system architecture of DNA‐based digital computers. We examine embryonic and stem cells, which exhibit distinct chromatin‐associated condensates enriched in transcription machinery. These dynamic biomolecular condensates facilitate the spatial association of genes, genomic control elements, and molecular machinery responsible for reading the genomic code. Drawing a compelling analogy to the von Neumann computer architecture—which integrates storage, processing, and memory in most electronic computers—we reflect on how the operational principles of these condensates could inspire the design of a similar architecture for future DNA computers. In particular, we describe how one could recreate such an architecture by exploiting the process of surface condensation, which underlies the formation of chromatin‐associated condensates. We conclude by reviewing our initial steps of constructing synthetic DNA nanostructures that follow the same operational principles and enable programmable surface condensation. Finally, we outline how computational methods from accelerated materials design could further advance the development of DNA computer system architectures.","PeriodicalId":8250,"journal":{"name":"Annals of the New York Academy of Sciences","volume":"14 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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":"The role of the North American continent in strengthening the Asian summer monsoon","authors":"Linlin Chen,&nbsp;Paul J. Valdes,&nbsp;Alexander Farnsworth","doi":"10.1126/sciadv.adu8589","DOIUrl":"10.1126/sciadv.adu8589","url":null,"abstract":"<div >Most studies on modern Asian monsoon formation focus on mechanisms arising within the Afro-Eurasian continent, while fewer compare the effects from remote continents. Here, we explore this question using a coupled climate model. We show that the existence of the North American continent is critical for the intensity of the Asian summer monsoon. The mechanism involves North America acting as an additional heating center, resulting in the strengthening and extension of oceanic advection toward the monsoon region. This is achieved via the Rodwell-Hoskins mechanism that strengthens the North Pacific subtropical high and through a widespread Northern Hemisphere heating that shifts the Hadly circulation subsidence center poleward. This teleconnection is independent of the presence of the Tibetan Plateau, and its impact on East Asian summer precipitation is found to be smaller but comparable to that of Tibet. The individual role of other continents outside Afro-Eurasia is found to be less important.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu8589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999185","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}

{"title":"Friedel oscillations and chiral superconductivity in monolayer NbSe2","authors":"Julian Siegl, Anton Bleibaum, Wen Wan, Marcin Kurpas, John Schliemann, Miguel M. Ugeda, Magdalena Marganska, Milena Grifoni","doi":"10.1038/s41467-025-63319-z","DOIUrl":"https://doi.org/10.1038/s41467-025-63319-z","url":null,"abstract":"<p>The nature of the dominant pairing mechanism in some two-dimensional transition metal dichalcogenides is still debated. Focusing on monolayer 1H-NbSe₂, we show that superconductivity can be induced by the Coulomb interaction when accounting for screening effects on the trigonal lattice with multiple orbitals. Using ab initio based tight-binding parametrizations for the relevant low-energy <i>d</i>-bands, we evaluate the screened interaction microscopically. In the direct space, we find pronounced Friedel oscillations, a key to the Kohn-Luttinger mechanism for superconductivity. The momentum-resolved gap equations predict at the critical temperature <i>T</i>_c two degenerate solutions of <span>({E}^{{prime} })</span> symmetry, signalling the unconventional nature of the pairing. Their complex linear combination, i.e., a chiral gap with <i>p</i>-like symmetry, provides the ground state of the model. Our prediction of a fully gapped chiral phase well below <i>T</i>_c is in good agreement with the spectral function extracted from tunnelling spectroscopy measurements.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"12 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995160","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":"Aplf/Dna2 variants drive chromosomal fission and accelerate speciation in zokors","authors":"Na Wan,&nbsp;Qijiao Duan,&nbsp;Zhenyuan Cai,&nbsp;Zhanwu Zhu,&nbsp;JingOu Wang,&nbsp;Yonghui Tian,&nbsp;Wei Shen,&nbsp;Bowen Li,&nbsp;Zhuoran Kuang,&nbsp;Xiaolong Liang,&nbsp;Sanyuan Liu,&nbsp;Xuan An,&nbsp;Xiaojie Yang,&nbsp;Xi Liu,&nbsp;Leyan Mao,&nbsp;Jiaqi Chen,&nbsp;Yinjia Wang,&nbsp;Zhilong Feng,&nbsp;Wenwen Liu,&nbsp;Yueting Bu,&nbsp;Eviatar Nevo,&nbsp;Riccardo Papa,&nbsp;Axel Meyer,&nbsp;Jianquan Liu,&nbsp;Kexin Li","doi":"10.1126/sciadv.adt2282","DOIUrl":"10.1126/sciadv.adt2282","url":null,"abstract":"<div >Chromosomal fissions and fusions are common, yet the molecular mechanisms and implications in speciation remain poorly understood. Here, we confirm a fission event in one zokor species through multiple-omics and functional analyses. We traced this event to a mutation in a splicing enhancer of the DNA repair gene <i>Aplf</i> in the fission-bearing species, which caused exon skipping and produced a truncated protein that disrupted DNA repair. An intronic deletion in <i>Dna2</i>, known to facilitate neo-telomere formation when knocked out, reduced gene activity. These variants collectively drove chromosomal fission in this zokor species. The newly formed chromosome became fixed due to carrying essential genes and strong selective pressure. While geographic isolation likely initiated the divergence of this species and the sister one, the fission event and associated decline at the chromosome level in gene flow probably exacerbated the speciation process. Our work elucidates the genetic basis of chromosomal fission and underscores its role in speciation dynamics.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 36","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt2282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999168","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}