综合性期刊最新文献

{"title":"Ice gliding diatoms establish record-low temperature limits for motility in a eukaryotic cell.","authors":"Qing Zhang, Hope T Leng, Hongquan Li, Kevin R Arrigo, Manu Prakash","doi":"10.1073/pnas.2423725122","DOIUrl":"10.1073/pnas.2423725122","url":null,"abstract":"<p><p>Despite periods of permanent darkness and extensive ice coverage in polar environments, photosynthetic ice diatoms display a remarkable capability of living inside the ice matrix. How these organisms navigate such hostile conditions with limited light and extreme cold remains unknown. Using a custom subzero temperature microscope during an Arctic expedition, we present the finding of motility at record-low temperatures in a Eukaryotic cell. By characterizing the gliding motility of several ice diatom species, collected from ice cores in the Chukchi Sea, we record that they retain motility at temperatures as low as [Formula: see text]15 ^°C. Remarkably, ice diatoms can glide on ice substrates, a capability absent in temperate diatoms of the same genus. This unique ability arises from adaptations in extracellular mucilage that allow ice diatoms to adhere to ice, essential for gliding. Even on glass substrates where both cell types retain motility at freezing temperatures, ice diatoms move an order of magnitude faster, with their optimal motility shifting toward colder temperatures. Combining field and laboratory experiments with thermo-hydrodynamic modeling, we reveal adaptive strategies that enable gliding motility in cold environments. These strategies involve increasing internal energy efficiency with minimal changes in heat capacity and activation enthalpy, and reducing external dissipation by minimizing the temperature sensitivity of mucilage viscosity. The finding of diatoms' ice gliding motility opens new routes for understanding their survival within a harsh ecological niche and their migratory responses to environmental changes. Our work highlights the robust adaptability of ice diatoms in one of Earth's most extreme settings.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2423725122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024108","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":"Stress-induced organismal death is genetically regulated by the mTOR-Zeste-Phae1 axis.","authors":"Takashi Matsumura, Masasuke Ryuda, Hitoshi Matsumoto, Takumi Kamiyama, Kyoko Jinnai, Shu Kondo, Akira Nakamura, Yoichi Hayakawa, Ryusuke Niwa","doi":"10.1073/pnas.2427014122","DOIUrl":"10.1073/pnas.2427014122","url":null,"abstract":"<p><p>All organisms are exposed to various stressors, which can sometimes lead to organismal death, depending on their intensity. While stress-induced organismal death has been observed in many species, the underlying mechanisms remain unclear. In this study, we investigated the molecular mechanisms of stress-induced organismal death in the fruit fly <i>Drosophila melanogaster</i>. We identified a chymotrypsin-like serine protease <i>Phaedra1</i> (<i>Phae1</i>) as a death mediator in <i>D. melanogaster</i> larvae. <i>Phae1</i> expression was up-regulated by lethal heat stress (40 °C) but not nonlethal heat stress (38 °C or lower). The most prominent induction of <i>Phae1</i> occurred in the central nervous system (CNS). We found neuro-specific knockdown of <i>Phae1</i> increased survival and reduced neuronal caspase activity following exposure to lethal heat stress, suggesting that the transcriptional upregulation of <i>Phae1</i> in the CNS is essential for stress-induced organismal death. We next found via bioinformatic and biochemical analyses that the transcription factor Zeste (Z) bound the <i>Phae1</i> enhancer region and that <i>z</i> loss-of-function impaired <i>Phae1</i> induction in the CNS, increasing survival following lethal heat stress. In addition, we found via chemical screening that rapamycin, a chemical inhibitor of mechanistic target of rapamycin (mTOR), suppressed <i>Phae1</i> expression. Neuro-specific knockdown of <i>mTor</i> reduced the protein levels of both Phae1 and Z, leading to an increase in survival following lethal heat stress. Together, these results indicate that heat stress-induced organismal death in <i>D. melanogaster</i> larvae is regulated by a genetically encoded transcriptional signaling pathway involving the mTOR-Z-Phae1 axis.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2427014122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024192","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":"Climate warming is expanding dengue burden in the Americas and Asia.","authors":"Marissa L Childs, Kelsey Lyberger, Mallory J Harris, Marshall Burke, Erin A Mordecai","doi":"10.1073/pnas.2512350122","DOIUrl":"10.1073/pnas.2512350122","url":null,"abstract":"<p><p>Climate change is expected to pose significant threats to public health, particularly vector-borne diseases. Despite dramatic recent increases in dengue that many anecdotally connect with climate change, the effect of anthropogenic climate change on dengue remains poorly quantified. To assess this link, we assembled local-level data on dengue across 21 countries in Asia and the Americas. We found a nonlinear relationship between temperature and dengue incidence with the largest impact of warming at lower temperatures, peak incidence at 27.8°C, and a decline at higher temperatures. Using this inferred temperature response, we estimate 18% (95% CI: 11 to 27%) of historical dengue incidence on average across our study countries is attributable to anthropogenic warming. Future warming could further increase incidence by 49% (95% CI: 16 to 136%) to 76% (95% CI: 27 to 239%) by midcentury for low or high emissions scenarios, respectively, with cooler regions projected to double in incidence due to warming while other currently hot regions experience little impact or even small declines. Under the highest emissions scenario, we estimate that 262 million people are currently living in places in these 21 countries where dengue incidence is expected to more than double due to climate change by midcentury. These insights highlight the major impacts of anthropogenic warming on dengue burden across most of its endemic range, providing a foundation for public health planning and the development of strategies to mitigate future risks due to climate change.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2512350122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024103","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":"The RecBC complex protects single-stranded DNA gaps during lesion bypass.","authors":"Gaëlle Philippin, Pauline Dupaigne, Élodie Chrabaszcz, Maialen Iturralde, Mauro Modesti, Eric Le Cam, Vincent Pagès, Luisa Laureti","doi":"10.1073/pnas.2503839122","DOIUrl":"https://doi.org/10.1073/pnas.2503839122","url":null,"abstract":"<p><p>Following encounter with an unrepaired DNA lesion, replication is halted and can restart downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA) gap. To complete replication, this ssDNA gap is filled in by one of the two lesion tolerance pathways: the error-prone Translesion Synthesis (TLS) or the error-free Homology Directed Gap Repair (HDGR). In the present work, we evidence a role for the RecBC complex distinct from its canonical function in homologous recombination at DNA double strand breaks. We show that upon lesion encounter RecBC (independently of its catalytic activity and of the RecD subunit) is required to protect the nascent DNA in order to promote efficient lesion bypass. In the absence of RecBC, our data indicate that the nuclease ExoI can access and degrade the nascent DNA, affecting both TLS and HDGR mechanisms. We show that the recruitment of RecBC becomes particularly important at strong blocking lesions, when postreplicative ssDNA gaps persist and are covered by the ssDNA binding proteins. This protective role of RecBC is reminiscent of the role of BRCA2 in protecting the nascent DNA in human cells, highlighting once again the evolutionary conservation of DNA replication mechanisms across all living organisms.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2503839122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034223","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":"DNA polymerase α-primase can function as a translesion DNA polymerase.","authors":"Ryan Mayle, Roxana Georgescu, Michael E O'Donnell","doi":"10.1073/pnas.2517556122","DOIUrl":"https://doi.org/10.1073/pnas.2517556122","url":null,"abstract":"<p><p>Replication of cellular chromosomes requires a primase to generate short RNA primers to initiate genomic replication. While bacterial and archaeal primase generate short RNA primers, the eukaryotic primase, Polα-primase, contains both RNA primase and DNA polymerase (Pol) subunits that function together to form a >20 base hybrid RNA-DNA primer. Interestingly, the DNA Pol1 subunit of Polα lacks a 3'-5' proofreading exonuclease, contrary to the high-fidelity normally associated with DNA replication. However, Polδ and Polε synthesize the majority of the eukaryotic genome, and both contain 3'-5' exonuclease activity for high fidelity. Nonetheless, even the small amount of DNA produced by Pol1 in each of the many RNA/DNA primers during chromosome replication adds up to tens of millions of nucleotides in a human genome. Thus, it has been a longstanding question why Pol1 lacks a proofreading exonuclease. We show here that Polα is uniquely capable of traversing common oxidized or hydrolyzed template nucleotides and propose that Polα evolved to bypass these common template lesions when they are encountered during chromosome replication. Additionally, we show a unique ability of replication factor C (RFC) to stimulate Polδ lesion bypass, independent of its sliding clamp. This suggests that there may be a coordination between Polδ and RFC that does not involve RFC loading of PCNA.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2517556122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034285","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":"The <i>Arabidopsis</i> TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins.","authors":"Adam M Bayless, Lijiang Song, Mitchell Sorbello, Sam C Ogden, Tyler S Todd, Alice Flint, Natsumi Maruta, Jedidiah Tulu, Mikhail Drenichev, Vardis Ntoukakis, Thomas Ve, Mehdi Mobli, Li Wan, Qingli Liu, Jeffery L Dangl, Bostjan Kobe, Murray Grant, Marc T Nishimura","doi":"10.1073/pnas.2505893122","DOIUrl":"https://doi.org/10.1073/pnas.2505893122","url":null,"abstract":"<p><p>The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions in immune and cell death responses across the Tree of Life. TIR domains encoded by plants and prokaryotes function as enzymes to produce diverse small molecule immune signals. Plant genomes can encode hundreds of TIR-domain containing proteins-many of which confer important agricultural disease resistance as TIR-NLR (nucleotide-binding, leucine-rich repeat) immune receptors. Despite their importance, how natural variation influences TIR enzymatic output and immunity-associated cell death is largely unexplored. We assayed a complete collection of the TIR domains of <i>Arabidopsis thaliana</i> Col-0 (the \"AtTIRome\") to explore variation in TIR metabolite production and cell death signaling. Roughly half of the AtTIRome triggered cell death in transient assays. Artificial TIR proteins designed based on consensus sequences of the AtTIRome's cell death phenotypic classes revealed polymorphisms controlling variation in TIR cell death elicitation and metabolite production. Structure-function analyses of artificial TIRs revealed that natural variation in the \"BB-loop\", a flexible region overlying the catalytic pocket, determines differences in function across <i>Arabidopsis</i> TIR-containing proteins. We further demonstrate that artificial TIRs are functional on an NLR chassis and that BB-loop variation can tune the activity of a natural TIR-NLR protein. These findings shed light on the diversity of TIR outputs and reveal methods to design and engineer TIR-based immune receptors.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2505893122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055715","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":"Critical exponents of the spin-glass transition in a field at zero temperature.","authors":"Maria Chiara Angelini, Saverio Palazzi, Giorgio Parisi, Tommaso Rizzo","doi":"10.1073/pnas.2511882122","DOIUrl":"https://doi.org/10.1073/pnas.2511882122","url":null,"abstract":"<p><p>We analyze the spin-glass transition in a field in finite dimension [Formula: see text] below the upper critical dimension directly at zero temperature using a recently introduced perturbative loop expansion around the Bethe lattice solution. The expansion is generated by the so-called [Formula: see text]-layer construction, and it has [Formula: see text] as the associated small parameter. Computing analytically and numerically these nonstandard diagrams at first order in the [Formula: see text] expansion, we construct an [Formula: see text]-expansion around the upper critical dimension [Formula: see text], with [Formula: see text]. Following standard field theoretical methods, we can write a [Formula: see text] function, finding a new zero-temperature fixed-point associated with the spin-glass transition in a field in dimensions [Formula: see text]. We are also able to compute, at first order in the [Formula: see text]-expansion, the three independent critical exponents characterizing the transition, plus the correction-to-scaling exponent.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2511882122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034229","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 cross-tolerance to metals in yeast.","authors":"Anna L Bazzicalupo, Penelope C Kahn, Eully Ao, Joel Campbell, Sarah P Otto","doi":"10.1073/pnas.2505337122","DOIUrl":"https://doi.org/10.1073/pnas.2505337122","url":null,"abstract":"<p><p>Organisms often face multiple selective pressures simultaneously (e.g., mine tailings with multiple heavy metal contaminants), yet we know little about when adaptation to one stressor provides cross-tolerance or cross-intolerance to other stressors. To explore the potential for cross-tolerance, we adapted <i>Saccharomyces cerevisiae</i> to high concentrations of six single metals in a short-term evolutionary rescue experiment. We then measured cross-tolerance of each metal-adapted line to the other five metals. We tested three predictors for the degree of cross-tolerance, based on similarity in 1) the physiochemical properties of each metal pair, 2) the overlap in genes known to impact tolerance to both metals, and 3) their co-occurrence in the environment. None of these predictors explained significant variation in cross-tolerance. Instead, the strongest predictor was the metal in which adaptation occurred: Cobalt-adapted lines performed well in most metals (generalists) while manganese-adapted lines typically performed poorly (specialists). To determine the genetic basis, we sequenced the genomes of 109 metal-adapted lines. Broader cross-tolerance characterized lines bearing mutations affecting phosphorus metabolism, with three genes related to phosphate metabolism bearing several independent mutations (<i>PHO84</i>, <i>SIW14</i>, <i>VTC4</i>). Thus, while a genome-wide analysis failed to predict cross-tolerance, a subset of genes facilitated growth in multiple metals. We also observed two \"mutator\" lines (both in manganese) and report evidence that cadmium, cobalt, and manganese altered the mutation spectrum. While it is challenging to predict how evolutionary adaptation to one stressor will impact tolerance to other stresses, our work helps reveal the environments and pathways that contribute to cross-tolerance among metals.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2505337122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034305","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":"Measuring multisubunit mechanics of geometrically programmed colloidal assemblies via cryo-EM multi-body refinement.","authors":"Thomas E Videbæk, Daichi Hayakawa, Michael F Hagan, Gregory M Grason, Seth Fraden, W Benjamin Rogers","doi":"10.1073/pnas.2500716122","DOIUrl":"https://doi.org/10.1073/pnas.2500716122","url":null,"abstract":"<p><p>Programmable self-assembly has recently enabled the creation of complex structures through precise control of the interparticle interactions and the particle geometries. Targeting ever more structurally complex, dynamic, and functional assemblies necessitates going beyond the design of the structure itself, to the measurement and control of the local flexibility of the intersubunit connections and its impact on the collective mechanics of the entire assembly. In this study, we demonstrate a method to infer the mechanical properties of multisubunit assemblies using cryogenic electron microscopy (cryo-EM) and RELION's multi-body refinement. Specifically, we analyze the fluctuations of pairs of DNA-origami subunits that self-assemble into tubules. By measuring the fluctuations of dimers using cryo-EM, we extract mechanical properties such as the bending modulus and interparticle spring constant. These properties are then applied to elastic models to predict assembly outcomes, which align well with experimental observations. This approach not only provides a deeper understanding of nanoparticle mechanics but also opens pathways to refining subunit designs to achieve precise assembly behavior. This methodology could have broader applications in the study of nanomaterials, including protein assemblies, where understanding the interplay of mechanical properties and subunit geometry is essential for controlling complex self-assembled structures.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2500716122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024054","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":"Modeling human retinal ganglion cell axonal outgrowth, development, and pathology using pluripotent stem cell-based microfluidic platforms.","authors":"Cátia Gomes, Kang-Chieh Huang, Sailee S Lavekar, Jade Harkin, Carson G Prosser, Yue Fang, Claire Kalem, Adrian Oblak, Chi Zhang, Jason S Meyer","doi":"10.1073/pnas.2423682122","DOIUrl":"10.1073/pnas.2423682122","url":null,"abstract":"<p><p>Retinal ganglion cells (RGCs) are highly compartmentalized neurons whose long axons serve as the sole connection between the eye and the brain. In both injury and disease, RGC degeneration occurs in a similarly compartmentalized manner, with distinct molecular and cellular responses in the axonal and somatodendritic regions. The goal of this study was to establish a microfluidic-based platform to investigate RGC compartmentalization in both health and disease states. Human pluripotent stem cell (hPSC)-derived RGCs were seeded into microfluidic devices that allow physical separation of axons from the somatodendritic compartment, enabling precise study of each region. Initial experiments characterized axonal outgrowth and the specific segregation of axons and dendrites. We then examined compartment-specific phenotypes in RGCs carrying the OPTN(E50K) glaucoma mutation compared to isogenic controls, including differences in axonal growth and axonal transport efficiency, with OPTN-mutant RGCs showing reduced axon length and slower transport, hallmarks of neurodegeneration. Axonal RNA-seq analyses revealed transcriptomic alterations related to disease states, including specific transcriptomic changes along OPTN axons. To assess glial influences on axonal health, we developed models with astrocytes localized specifically to the proximal axonal compartment and modulated their disease states to simulate pathological conditions. Importantly, the induction of diseased astrocytes solely along proximal axons triggered compartment-specific neurodegenerative changes in RGCs. Collectively, this platform represents a successful recapitulation of the spatially distinct features of hPSC-derived RGCs under both healthy and disease conditions, offering a physiologically relevant, human-specific in vitro system to study neuronal development, axon-glia interactions, and mechanisms underlying neurodegeneration.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2423682122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024176","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}