综合性期刊最新文献

{"title":"Reply to Ye: Parallel progress in funder practices and expansion of academic incentives to support engaged research.","authors":"Angela T Bednarek, Ben Miyamoto","doi":"10.1073/pnas.2500539122","DOIUrl":"https://doi.org/10.1073/pnas.2500539122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2500539122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524215","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":"Environmental justice beyond race: Skin tone and exposure to air pollution.","authors":"Sandra Aguilar-Gomez, Juan Camilo Cardenas, Ricardo Salas Diaz","doi":"10.1073/pnas.2407064122","DOIUrl":"https://doi.org/10.1073/pnas.2407064122","url":null,"abstract":"<p><p>Recent research, focused mostly on the United States and Western Europe, shows that marginalized communities often face greater environmental degradation. However, the ethnoracial categories used in these studies may not fully capture environmental inequality in the Global South. Moving beyond conventional ethnoracial variables, this study presents findings exploring the link between skin tone and fine particulate matter (PM_2.5) exposure in Colombia. By matching household geolocations from a large-scale longitudinal survey with satellite-based PM_2.5 estimates, we find that skin tone predicts both initial pollution exposure levels and their changes over time. Although average exposure levels remained stable during our study period, the environmental justice (EJ) landscape in Colombia contemporaneously underwent a complete transformation. In 2010, lighter-skinned individuals faced higher PM_2.5 exposure, but darker-skinned individuals experienced steeper increases in the following years. By 2016, the EJ gap had reversed, with people with the darkest skin tones exposed to PM_2.5 levels nearly one SD higher than those faced by people with the lightest skin tones. These patterns remain robust when controlling for a comprehensive set of theoretically relevant covariates, including ethnoracial self-identification and income. Disproportionate exposure to pollution from fires partially explains the observed disparities. Decomposition analysis shows that this variable, local collective action, and economic marginalization account for a sizeable share of the EJ gap. However, one-third of the gap remains unexplained by observable characteristics. With climate change intensifying fire incidence, the disproportionate disease burdens that vulnerable groups face might deepen unless policy measures are taken to reverse this trend.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2407064122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543167","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 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":"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":"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":"Bacterial estrogenesis without oxygen: Wood-Ljungdahl pathway likely contributed to the emergence of estrogens in the biosphere.","authors":"Po-Hsiang Wang, Tien-Yu Wu, Yi-Lung Chen, Ronnie G Gicana, Tzong-Huei Lee, Mei-Jou Chen, Tsun-Hsien Hsiao, Mei-Yeh Jade Lu, Yi-Li Lai, Tzi-Yuan Wang, Jeng-Yi Li, Yin-Ru Chiang","doi":"10.1073/pnas.2422930122","DOIUrl":"https://doi.org/10.1073/pnas.2422930122","url":null,"abstract":"<p><p>Androgen and estrogen, key sex hormones, were long thought to be exclusively produced by vertebrates. The O₂-dependent aromatase that converts androgen to estrogen (estrogenesis) has never been identified in any prokaryotes. Here, we report the finding of anaerobic estrogenesis in a Peptococcaceae bacterium (<i>Phosphitispora</i> sp. strain TUW77) isolated from the gut of the great blue-spotted mudskipper (<i>Boleophthalmus pectinirostris</i>). This strain exhibits testosterone fermentation pathways, transforming testosterone into estrogens and androstanediol under anaerobic conditions. Physiological experiments revealed that strain TUW77 grows exclusively on testosterone, utilizing the androgenic C-19 methyl group as both the carbon source and electron donor. The genomic analysis identified three copies of a polycistronic gene cluster, <i>abeABC</i> (anaerobic bacterial estrogenesis), encoding components of a classic cobalamin-dependent methyltransferase system. These genes, highly expressed under testosterone-fed conditions, show up to 57% protein identity to the characterized EmtAB from denitrifying <i>Denitratisoma</i> spp., known for methylating estrogen into androgen (the reverse reaction). Tiered transcriptomic and proteomic analyses suggest that the removed C-19 methyl group is completely oxidized to CO₂ via the oxidative Wood-Ljungdahl pathway (WLP), while the reducing equivalents (NADH) fully reduce remaining testosterone to androstanediol. Consistently, the addition of anthraquinone-2,6-disulfonate, an extracellular electron acceptor, to testosterone-fed TUW77 cultures enabled complete testosterone conversion into estrogen without androstanediol accumulation (anaerobic testosterone oxidation). This finding of aromatase-independent estrogenesis in anaerobic bacteria suggests that the ancient WLP may have contributed to the emergence of estrogens in the early biosphere.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2422930122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573659","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":"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":"Evolution of the <i>JULGI-SMXL4/5</i> module for phloem development in angiosperms.","authors":"Chanyoung Park, Hyun Seob Cho, Yookyung Lim, Chung Hyun Cho, Hoyoung Nam, Sangkyu Choi, Hojun Lim, Young-Dong Kim, Hwan Su Yoon, Hyunwoo Cho, Ildoo Hwang","doi":"10.1073/pnas.2416674122","DOIUrl":"https://doi.org/10.1073/pnas.2416674122","url":null,"abstract":"<p><p>Bifacial cambium, which produces xylem and phloem, and monopodial architecture, characterized by apical dominance and lateral branching from axillary buds, are key developmental features of seed plants, consisting of angiosperms and gymnosperms. These allow seed plants to adapt to diverse environments by optimizing resource allocation and structural integrity. In seed plants, <i>SUPPRESSOR OF MAX2-LIKE</i> (<i>SMXL</i>) family members function in phloem development and strigolactone-induced inhibition of axillary bud outgrowth. Although strigolactone signaling regulates most <i>SMXL</i> family members, the only known regulator of <i>SMXL4</i> and <i>SMXL5</i> is the RNA-binding protein JULGI. We demonstrate that in angiosperms, by directly regulating <i>SMXL4/5</i> expression, JULGI uncouples SMXL4/5 activity from strigolactone signaling. <i>JULGI</i> and ancestral <i>SMXL</i>s from seedless vascular plants or <i>SMXL4/5</i> from seed plants are coexpressed in the phloem tissues of vascular plants, from lycophytes to angiosperms. Core angiosperm <i>SMXL4/5</i> mRNAs contain a G-rich element in the 5' untranslated region (UTR) that serves as a target sequence for JULGI to negatively regulate <i>SMXL4/5</i> expression. Heterologous expression of <i>JULGI</i>s from various angiosperms rescued the <i>Arabidopsis jul1 jul2</i> mutant. Expressing <i>SMXL4/5</i>s from seed plants and ancestral <i>SMXL</i>s rescued <i>Arabidopsis smxl4 smxl5</i>. Angiosperm SMXL4/5s lack an RGKT motif for proteasomal degradation. Indeed, treatment with the synthetic strigolactone analog <i>rac</i>-GR24 induced proteasomal degradation of SMXL from ferns and SMXL5a from gymnosperms, but not SMXL4/5 from angiosperms. These findings suggest that in ancestral angiosperms, the 5' UTR of <i>SMXL4/5</i> gained G-rich elements, creating a regulatory module with <i>JULGI</i> that allows the phloem development pathway to act independently of strigolactone signaling.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 10","pages":"e2416674122"},"PeriodicalIF":9.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573662","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}