综合性期刊最新文献

{"title":"A general framework for interpretable neural learning based on local information-theoretic goal functions.","authors":"Abdullah Makkeh, Marcel Graetz, Andreas C Schneider, David A Ehrlich, Viola Priesemann, Michael Wibral","doi":"10.1073/pnas.2408125122","DOIUrl":"https://doi.org/10.1073/pnas.2408125122","url":null,"abstract":"<p><p>Despite the impressive performance of biological and artificial networks, an intuitive understanding of how their local learning dynamics contribute to network-level task solutions remains a challenge to this date. Efforts to bring learning to a more local scale indeed lead to valuable insights, however, a general constructive approach to describe local learning goals that is both interpretable and adaptable across diverse tasks is still missing. We have previously formulated a local information processing goal that is highly adaptable and interpretable for a model neuron with compartmental structure. Building on recent advances in Partial Information Decomposition (PID), we here derive a corresponding parametric local learning rule, which allows us to introduce \"infomorphic\" neural networks. We demonstrate the versatility of these networks to perform tasks from supervised, unsupervised, and memory learning. By leveraging the interpretable nature of the PID framework, infomorphic networks represent a valuable tool to advance our understanding of the intricate structure of local learning.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2408125122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557607","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":"Adeno-associated viruses for efficient gene expression in the axolotl nervous system.","authors":"Katharina Lust, Elly M Tanaka","doi":"10.1073/pnas.2421373122","DOIUrl":"https://doi.org/10.1073/pnas.2421373122","url":null,"abstract":"<p><p>Axolotls are amphibian models for studying nervous system evolution, development, and regeneration. Tools to visualize and manipulate cells of the axolotl nervous system with high-efficiency, spatial and temporal precision are therefore greatly required. Recombinant adeno-associated viruses (AAVs) are frequently used for in vivo gene transfer of the nervous system but virus-mediated gene delivery to the axolotl nervous system has not yet been described. Here, we demonstrate the use of AAVs for efficient gene transfer within the axolotl brain, the spinal cord, and the retina. We show that serotypes AAV8, AAV9, and AAVPHP.eB are suitable viral vectors to infect both excitatory and inhibitory neuronal populations of the axolotl brain. We further use AAV9 to trace retrograde and anterograde projections between the retina and the brain and identify a cell population projecting from the brain to the retina. Together, our work establishes AAVs as a powerful tool to interrogate neuronal organization in the axolotl.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2421373122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557645","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":"Correction for Qin et al., A signaling molecule from intratumor bacteria promotes trastuzumab resistance in breast cancer cells.","authors":"","doi":"10.1073/pnas.2502214122","DOIUrl":"https://doi.org/10.1073/pnas.2502214122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2502214122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524199","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":"Phased ERK responsiveness and developmental robustness regulate teleost skin morphogenesis.","authors":"Nitya Ramkumar, Christian Richardson, Makinnon O'Brien, Faraz Ahmed Butt, Jieun Park, Anna T Chao, Michel Bagnat, Kenneth D Poss, Stefano Di Talia","doi":"10.1073/pnas.2410430122","DOIUrl":"https://doi.org/10.1073/pnas.2410430122","url":null,"abstract":"<p><p>Elongation of the vertebrate embryonic axis necessitates rapid expansion of the epidermis to accommodate the growth of underlying tissues. Here, we generated a toolkit to visualize and quantify signaling in entire cell populations of the periderm, the outermost layer of the epidermis, in live developing zebrafish. We find that oriented cell divisions facilitate growth of the early periderm during axial elongation rather than cell addition from the basal layer. Activity levels of Extracellular signal-regulated kinase (ERK), a downstream effector of the MAPK pathway, gauged by a live biosensor, predict cell cycle entry, and optogenetic ERK activation regulates cell cycling dynamics. As development proceeds, rates of peridermal cell proliferation decrease, and ERK activity becomes more pulsatile and functionally transitions to promote hypertrophic cell growth. Targeted genetic blockade of cell division generates animals with oversized periderm cells, yet, unexpectedly, development to adulthood is not impaired. Our findings reveal stage-dependent differential responsiveness to ERK signaling and marked developmental robustness in growing teleost skin.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2410430122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557794","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":"Correction for Patel et al., Aspirin binds to PPARα to stimulate hippocampal plasticity and protect memory.","authors":"","doi":"10.1073/pnas.2502115122","DOIUrl":"https://doi.org/10.1073/pnas.2502115122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2502115122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468870","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":"Structural basis of SARS-CoV-2 polymerase inhibition by nonnucleoside inhibitor HeE1-2Tyr.","authors":"Florian Kabinger, Valerie Doze, Jana Schmitzová, Michael Lidschreiber, Christian Dienemann, Patrick Cramer","doi":"10.1073/pnas.2419854122","DOIUrl":"https://doi.org/10.1073/pnas.2419854122","url":null,"abstract":"<p><p>Targeting the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with small molecules is a promising therapeutic strategy against COVID-19, but potent and safe inhibitors are lacking. HeE1-2Tyr, a nonnucleoside inhibitor of Dengue virus RdRp, was also shown to inhibit SARS-CoV-2 RdRp in vitro and to have antiviral activity in cells, but the underlying mechanism remains unclear. Here, we elucidate the molecular mechanism of HeE1-2Tyr-mediated SARS-CoV-2 RdRp inhibition. Biochemical assays confirm that HeE1-2Tyr inhibits RdRp with an IC₅₀ of 5 µM and show that it competes with RNA binding to RdRp in vitro. Structural analysis using cryo-EM reveals that a stack of three HeE1-2Tyr molecules binds to the RNA binding site of RdRp. The identification of the conserved HeE1-2Tyr binding site and its intriguing inhibition mechanism of three stacked molecules that outcompete RNA may facilitate further development of pan-corona nonnucleoside inhibitors.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2419854122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542860","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":"Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways.","authors":"Monika Evdokimova, Shuchen Feng, Allen Caobi, Fernando R Moreira, Dakota Jones, Konstantinos-Dionysios Alysandratos, Ena S Tully, Darrell N Kotton, David F Boyd, Bridget S Banach, Robert N Kirchdoerfer, Mohsan Saeed, Susan C Baker","doi":"10.1073/pnas.2419620122","DOIUrl":"https://doi.org/10.1073/pnas.2419620122","url":null,"abstract":"<p><p>Identifying conserved mechanisms used by viruses to delay host innate responses can reveal potential targets for antiviral therapeutics. Here, we investigated coronavirus nonstructural protein 15 (nsp15), which encodes a highly conserved endoribonuclease (EndoU). EndoU functions as an immune antagonist by limiting the accumulation of viral replication intermediates that would otherwise be sensed by the host. Despite being a promising antiviral target, it has been difficult to develop small-molecule inhibitors that target the EndoU active site. We generated nsp15 mutants of the coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mouse hepatitis virus (MHV)-A59 and identified conserved residues within the amino-terminal domain that are required for EndoU activity. Loss of EndoU activity caused the activation of host sensors, which limited viral replication in interferon-responsive cells and attenuated disease in MHV-infected mice. Using transcriptional profiling, we found that MHV EndoU mutant viruses upregulate multiple host sensors, including Z-form nucleic acid-binding protein 1 (ZBP1). We found that nsp15 mutants induced early, robust ZBP1-mediated necroptosis. EndoU mutant viruses also induced ZBP1-independent apoptosis and pyroptosis pathways, causing early, robust cell death that limits virus replication and pathogenesis. Overall, we document the importance of the amino-terminal domain for EndoU function. We also highlight the importance of nsp15/EndoU activity for evading host sensors, delaying cell death, and promoting pathogenesis.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2419620122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543164","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":"Effects of binding partners on thermal reversion rates of photoswitchable molecules.","authors":"P Maximilian M Reed, Jaewan Jang, Ryan M Woloschuk, Jakeb Reis, Jacques I C Hille, Maruti Uppalapati, G Andrew Woolley","doi":"10.1073/pnas.2414748122","DOIUrl":"https://doi.org/10.1073/pnas.2414748122","url":null,"abstract":"<p><p>The binding of photoswitchable molecules to partners forms the basis of many naturally occurring light-dependent signaling pathways and various photopharmacological and optogenetic tools. A critical parameter affecting the function of these molecules is the thermal half-life of the light state. Reports in the literature indicate that, in some cases, a binding partner can significantly influence the thermal half-life, while in other cases it has no effect. Here, we present a unifying framework for quantitatively analyzing the effects of binding partners on thermal reversion rates. We focus on photoswitchable protein/binder interactions involving LOV domains, photoactive yellow protein, and CBCR GAF domains with partners that bind either the light or the dark state of the photoswitchable domain. We show that the effect of a binding partner depends on the extent to which the transition state for reversion resembles the dark state or the light state. We quantify this resemblance with a ϕ_switching value, where ϕ_switching = 1 if the conformation of the part of the photoswitchable molecule that interacts with the binding partner closely resembles its dark state conformation and ϕ_switching = 0 if it resembles its light state. In addition to providing information on the transition state for switching, this analysis can guide the design of photoswitchable systems that retain useful thermal half-lives in practice. The analysis also provides a basis for the use of simple kinetic measurements to determine effective changes in affinity even in complex milieu.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2414748122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543166","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":"A WRKY transcription factor confers broad-spectrum resistance to biotic stresses and yield stability in rice.","authors":"Daoming Liu, Jun He, Qi Li, Xiao Zhang, Yongsheng Wang, Quanguang Sun, Wenhui Wang, Menglong Zhang, Yunlong Wang, Haosen Xu, Liang Fang, Ling Jiang, Shijia Liu, Liangming Chen, Yunlu Tian, Xi Liu, Ruyi Wang, Zhengguang Zhang, Mawsheng Chern, Xiaoou Dong, Haiyang Wang, Yuqiang Liu, Pamela C Ronald, Jianmin Wan","doi":"10.1073/pnas.2411164122","DOIUrl":"https://doi.org/10.1073/pnas.2411164122","url":null,"abstract":"<p><p>Plants are subject to attack by diverse pests and pathogens. Few genes conferring broad-spectrum resistance to both insects and pathogens have been identified. Because of the growth-defense tradeoff, it is often challenging to balance biotic stress resistance and yield for crops. Here, we report that <i>OsWRKY36</i> suppresses the resistance to insects and pathogens via transcriptional repression of <i>Phenylalanine Ammonia Lyases</i> (<i>PALs</i>), a key enzyme in phenylpropanoid pathway in rice. Knocking out <i>OsWRKY36</i> causes elevated lignin biosynthesis and increased sclerenchyma thickness of leaf sheath, leading to enhanced resistance to multiple pests and pathogens. Additionally, loss of <i>OsWRKY36</i> also derepresses the transcription of <i>Ideal Plant Architecture 1</i> (<i>IPA1</i>) and <i>MONOCULM2</i> (<i>MOC2</i>), resulting in increased spikelet number per panicle and tiller number. These findings provide mechanistic insights into biotic stress tolerance in rice and offer a promising strategy to breed rice cultivars with broad-spectrum resistance to insects and pathogens while maintaining stable yield.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2411164122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557638","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":"Monitoring chalcogenide ions-guided in situ transform active sites of tailored bismuth electrocatalysts for CO₂ reduction to formate.","authors":"Zheng Chen, Yi Xiao, Xianji Qiao, Honghui Ou, Chi-Feng Lee, Hsiao-Tsu Wang, Yu-Cheng Shao, Lili Han","doi":"10.1073/pnas.2420922122","DOIUrl":"https://doi.org/10.1073/pnas.2420922122","url":null,"abstract":"<p><p>Although bismuth catalysts enable accelerated electrochemical CO₂-to-formate conversion, the intrinsic active sites and forming mechanisms under operating conditions remain elusive. Herein, we prepared Bi₂O₂NCN, Bi₂O₃, and Bi₂O₂S as precatalysts. Among them, Bi₂O₂NCN-derived catalyst possesses optimum performance of electrochemical CO₂-to-formate, exhibiting an upsurge of Faradaic efficiency to 98.3% at -0.6 V vs. reversible hydrogen electrodes. In-situ infrared and electrochemical impedance spectra trace and interpret the superior performance. Multimodal structural analyses utilizing quasi-in-situ X-ray diffraction, in-situ X-ray absorption near edge structure and in-situ Raman spectra provide powerful support to monitoring the catalysts' in-situ transforms to metallic Bi, identifying the formation of the active sites influenced by the chalcogenide ions-guided: Carbodiimide promotes to form of the dominant Bi(003) facet exposure, which distinguishes from sulfide- and oxide-preferred dominant Bi(012) facets exposure. Concurrently, theoretical insights garnered from multiscale/multilevel computational analyses harmoniously corroborate the experimental findings. These findings show the pivotal role of chalcogenide in tailoring bismuth electrocatalysts for selective CO₂ reduction to formate, illuminating the significance of controlling structural chemistry in designing catalysts toward high-efficiency renewable energy conversion.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2420922122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557776","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}