{"title":"Correction for Zhou et al., tRNA selectivity during ribosome-associated quality control regulates the critical sterility-inducing temperature in two-line hybrid rice.","authors":"","doi":"10.1073/pnas.2507697122","DOIUrl":"https://doi.org/10.1073/pnas.2507697122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"58 1","pages":"e2507697122"},"PeriodicalIF":11.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880197","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}
Ignacio Lopez-Gomez, Zhong Yi Wan, Leonardo Zepeda-Núñez, Tapio Schneider, John Anderson, Fei Sha
{"title":"Dynamical-generative downscaling of climate model ensembles","authors":"Ignacio Lopez-Gomez, Zhong Yi Wan, Leonardo Zepeda-Núñez, Tapio Schneider, John Anderson, Fei Sha","doi":"10.1073/pnas.2420288122","DOIUrl":"https://doi.org/10.1073/pnas.2420288122","url":null,"abstract":"Regional high-resolution climate projections are crucial for many applications, such as agriculture, hydrology, and natural hazard risk assessment. Dynamical downscaling, the state-of-the-art method to produce localized future climate information, involves running a regional climate model (RCM) driven by an Earth System Model (ESM), but it is too computationally expensive to apply to large climate projection ensembles. We propose an approach combining dynamical downscaling with generative AI to reduce the cost and improve the uncertainty estimates of downscaled climate projections. In our framework, an RCM dynamically downscales ESM output to an intermediate resolution, followed by a generative diffusion model that further refines the resolution to the target scale. This approach leverages the generalizability of physics-based models and the sampling efficiency of diffusion models, enabling the downscaling of large multimodel ensembles. We evaluate our method against dynamically downscaled climate projections from the Coupled Model Intercomparison Project 6 (CMIP6) ensemble. Our results demonstrate its ability to provide more accurate uncertainty bounds on future regional climate than alternatives such as dynamical downscaling of smaller ensembles, or traditional empirical statistical downscaling methods. We also show that dynamical-generative downscaling results in significantly lower errors than popular statistical downscaling techniques, and captures more accurately the spectra, tail dependence, and multivariate correlations of meteorological fields. These characteristics make the dynamical-generative framework a flexible, accurate, and efficient way to downscale large ensembles of climate projections, currently out of reach for pure dynamical downscaling.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"7 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875773","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":"Prevalence of simplex compression in adversarial deep neural networks","authors":"Yang Cao, Yanbo Chen, Weiwei Liu","doi":"10.1073/pnas.2421593122","DOIUrl":"https://doi.org/10.1073/pnas.2421593122","url":null,"abstract":"Neural collapse (NC) reveals that the last layer of the network can capture data representations, leading to similar outputs for examples within the same class, while outputs for examples from different classes form a simplex equiangular tight frame (ETF) structure. This phenomenon has garnered significant attention due to its implications on the intrinsic properties of neural networks. Interestingly, we observe a simplex compression phenomenon in NC, where the geometric size of the simplex ETF reduces under adversarial training, with the degree of compression increasing as the perturbation radius grows. We provide empirical evidence supporting the existence of simplex compression across a wide range of models and datasets. Furthermore, we establish a rigorous theoretical framework that explains our experimental observations, offering insights into NC under adversarial conditions.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"48 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875775","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":"Five-body recombination of identical bosons","authors":"Michael D. Higgins, Chris H. Greene","doi":"10.1073/pnas.2503390122","DOIUrl":"https://doi.org/10.1073/pnas.2503390122","url":null,"abstract":"This work treats resonant collisions between five identical ultracold bosons in the framework of the adiabatic hyperspherical representation. The five-body recombination rate coefficient is quantified using a semiclassical description in conjunction with an analysis of the lowest five-body hyperspherical adiabatic potential curves in a scattering length regime with no universal weakly bound tetramers, trimers, or dimers. A comparison is made between these results and the only existing experimental measurement of five-body loss in an ultracold gas of bosonic cesium atoms and with the lone theoretical estimation of the loss rate. The recombination rate for the process <jats:italic>B</jats:italic> + <jats:italic>B</jats:italic> + <jats:italic>B</jats:italic> + <jats:italic>B</jats:italic> + <jats:italic>B</jats:italic> → <jats:italic>B</jats:italic> <jats:sub>4</jats:sub> + <jats:italic>B</jats:italic> is also computed in a different regime of scattering lengths where there is one universal bound tetramer by implementing a few-channel quantum scattering calculation based on five-body hyperspherical potential curves and nonadiabatic couplings. Our calculations predict regions where five-body recombination can cause decay of the atom cloud in an ultracold gas that is even faster than 3-body and 4-body recombination, which can ideally be tested by using the current generation of box traps having nearly uniform density.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"35 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875776","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 Piacentino et al., Temporal changes in plasma membrane lipid content induce endocytosis to regulate developmental epithelial-to-mesenchymal transition.","authors":"","doi":"10.1073/pnas.2507940122","DOIUrl":"https://doi.org/10.1073/pnas.2507940122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"24 1","pages":"e2507940122"},"PeriodicalIF":11.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880198","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}
Julien B. Azimzadeh, Patricia M. Quiñones, John S. Oghalai, Anthony J. Ricci
{"title":"Infrared light stimulates the cochlea through a mechanical displacement detected and amplified by hair cells","authors":"Julien B. Azimzadeh, Patricia M. Quiñones, John S. Oghalai, Anthony J. Ricci","doi":"10.1073/pnas.2422076122","DOIUrl":"https://doi.org/10.1073/pnas.2422076122","url":null,"abstract":"Although cochlear implants (CI) are the standard of care for profound sensorineural hearing loss they are technically constrained by the tendency of electrical current to spread within the fluid-filled chambers of the cochlea. This limits the resolution of individual electrodes and patients’ perceptions of complex sounds. Infrared irradiation has been proposed as an alternative to electrical stimulation because it can elicit auditory responses while being spatially constrained, theoretically promising higher-fidelity hearing for the deaf. However, conflicting reports locate the site of infrared excitation at spiral ganglia neurons or hair cells. We use a combination of genetic, pharmacological, optical, and electrophysiological tools to determine the site of action of infrared irradiation. Infrared-evoked cochlear potentials are composed of two peaks: one driven by hair cells (the microphonic) and a second driven by spiral ganglion neurons (the neural response). Manipulations that prevented hair cell synaptic activity abolished the neural component, while manipulations blocking hair cell mechanotransduction abolished all responses, suggesting a mechanical component to the infrared response. Optical coherence tomography (OCT) confirmed that infrared irradiation creates a mechanical stimulus that is both amplified and detected by hair cells. Because infrared irradiation does not stimulate spiral ganglion neurons directly, it is unlikely to replace the electrical CI.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"7 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872460","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}
Emanuela Tumini, Ralf E. Wellinger, Emilia Herrera-Moyano, Patricia Navarro-Cansino, María García-Rubio, Daniel Salas-Lloret, Alejandro Losada, María J. Muñoz-Alonso, Hélène Gaillard, Rosa Luna, Andrés Aguilera
{"title":"Patulin and Xestoquinol are inhibitors of DNA topoisomerase 1","authors":"Emanuela Tumini, Ralf E. Wellinger, Emilia Herrera-Moyano, Patricia Navarro-Cansino, María García-Rubio, Daniel Salas-Lloret, Alejandro Losada, María J. Muñoz-Alonso, Hélène Gaillard, Rosa Luna, Andrés Aguilera","doi":"10.1073/pnas.2421167122","DOIUrl":"https://doi.org/10.1073/pnas.2421167122","url":null,"abstract":"DNA topoisomerase 1 (TOP1) is essential for transcription, replication, and repair. Its function relies on two catalytic steps, DNA breakage and rejoining. Inhibitors of the second step prevent DNA rejoining and lead to persistent DNA breaks, acting as topoisomerase poisons, used as anticancer drugs. However, reliable inhibitors of the first step are not available. Here, we provide genetic and molecular evidence supporting that Patulin and, to a lesser extent, Xestoquinol inhibit the first catalytic step of TOP1 in vitro, in yeast and in human cells. Particularly, Patulin prevents the accumulation of TOP1 cleavage complexes caused by the TOP1 poison camptothecin (CPT) in human cells. Moreover, Patulin pretreatment of human or yeast cells reduces DNA damage and the accumulation of DNA breaks upon CPT exposure. Consistent with the protective role of TOP1 against harmful R-loops, Patulin treatment increases R-loops and R-loop-associated cytotoxicity, mimicking the effect of TOP1 silencing. Altogether our findings indicate that Patulin and Xestoquinol are nonpoisoning inhibitors of TOP1, which should potentiate new research approaches in molecular biology and medicine.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"32 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872455","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}
Anna R. Girardeau, Grace E. Enochs, Julia B. Saltz
{"title":"Evolutionary feedbacks for Drosophila aggression revealed through experimental evolution","authors":"Anna R. Girardeau, Grace E. Enochs, Julia B. Saltz","doi":"10.1073/pnas.2419068122","DOIUrl":"https://doi.org/10.1073/pnas.2419068122","url":null,"abstract":"Evolutionary feedbacks occur when evolution in one generation alters the environment experienced by subsequent generations and are an expected result of indirect genetic effects (IGEs). Hypotheses abound for the role of evolutionary feedbacks in climate change, agriculture, community dynamics, population persistence, social interactions, the genetic basis of evolution, and more, but evolutionary feedbacks have rarely been directly measured experimentally, leaving open questions about how feedbacks influence evolution. Using experimental evolution, we manipulated the social environment in which aggression was expressed and selected in fruit fly ( <jats:italic>Drosophila melanogaster</jats:italic> ) populations to allow or limit feedbacks. We selected for increased male–male aggression while allowing either positive, negative, or no feedbacks, alongside unselected controls. We show that populations undergoing negative feedbacks had the weakest evolutionary changes in aggression, while populations undergoing positive evolutionary feedbacks evolved supernormal aggression. Further, the underlying social dynamics evolved only in the negative feedbacks treatment. Our results demonstrate that IGE-mediated evolutionary feedbacks can alter the rate and pattern of behavioral evolution.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"72 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872459","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}
Forson Gao, Fuzhou Ye, Martin Buck, Xiaodong Zhang
{"title":"Subunit specialization in AAA+ proteins and substrate unfolding during transcription complex remodeling","authors":"Forson Gao, Fuzhou Ye, Martin Buck, Xiaodong Zhang","doi":"10.1073/pnas.2425868122","DOIUrl":"https://doi.org/10.1073/pnas.2425868122","url":null,"abstract":"Bacterial RNA polymerase (RNAP) is a multisubunit enzyme that copies DNA into RNA in a process known as transcription. Bacteria use σ factors to recruit RNAP to promoter regions of genes that need to be transcribed, with 60% bacteria containing at least one specialized σ factor, σ <jats:sup>54</jats:sup> . σ <jats:sup>54</jats:sup> recruits RNAP to promoters of genes associated with stress responses and forms a stable closed complex that does not spontaneously isomerize to the open state where promoter DNA is melted out and competent for transcription. The σ <jats:sup>54</jats:sup> -mediated open complex formation requires specific AAA+ proteins ( <jats:underline>A</jats:underline> TPases <jats:underline>A</jats:underline> ssociated with diverse cellular <jats:underline>A</jats:underline> ctivities) known as bacterial enhancer-binding proteins (bEBPs). We have now obtained structures of new intermediate states of bEBP-bound complexes during transcription initiation, which elucidate the mechanism of DNA melting driven by ATPase activity of bEBPs and suggest a mechanistic model that couples the Adenosine triphosphate (ATP) hydrolysis cycle within the bEBP hexamer with σ <jats:sup>54</jats:sup> unfolding. Our data reveal that bEBP forms a nonplanar hexamer with the hydrolysis-ready subunit located at the furthest/highest point of the spiral hexamer relative to the RNAP. ATP hydrolysis induces conformational changes in bEBP that drives a vectoral transiting of the regulatory N terminus of σ <jats:sup>54</jats:sup> into the bEBP hexamer central pore causing the partial unfolding of σ <jats:sup>54</jats:sup> , while forming specific bEBP contacts with promoter DNA. Furthermore, our data suggest a mechanism of the bEBP AAA+ protein that is distinct from the hand-over-hand mechanism proposed for many other AAA+ proteins, highlighting the versatile mechanisms utilized by the large protein family.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"1 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872458","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":"Bounded dissipation law and profiles of turbulent velocity moments in wall flows","authors":"Xi Chen, Katepalli R. Sreenivasan","doi":"10.1073/pnas.2502265122","DOIUrl":"https://doi.org/10.1073/pnas.2502265122","url":null,"abstract":"Understanding the effects of solid boundaries on turbulent fluctuations remains a long-standing challenge. Available data on mean-square fluctuations in these flows show apparent contradiction with classical scaling. We had earlier proposed an alternative model based on the principle of bounded dissipation. Despite its putative success, a conclusive outcome requires much higher Reynolds numbers than are available at present, or can be expected to be available in the near future. However, the model can be validated satisfactorily even within the Reynolds number range already available by considering high-order moments and their distributions in the wall-normal direction. Expressions for high-order moments of streamwise velocity fluctuation <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mi>u</mml:mi> </mml:math> </jats:inline-formula> are derived in the form <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mrow> <mml:msup> <mml:mrow> <mml:mo stretchy=\"false\">⟨</mml:mo> <mml:msup> <mml:mi>u</mml:mi> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>2</mml:mn> <mml:mi>q</mml:mi> </mml:mrow> </mml:msup> <mml:mo stretchy=\"false\">⟩</mml:mo> </mml:mrow> <mml:mrow> <mml:mn>1</mml:mn> <mml:mo stretchy=\"false\">/</mml:mo> <mml:mi>q</mml:mi> </mml:mrow> </mml:msup> <mml:mo>=</mml:mo> <mml:msub> <mml:mi>α</mml:mi> <mml:mi>q</mml:mi> </mml:msub> <mml:mo>−</mml:mo> <mml:msub> <mml:mi>β</mml:mi> <mml:mi>q</mml:mi> </mml:msub> <mml:msup> <mml:mi>y</mml:mi> <mml:mrow> <mml:mrow/> <mml:mo>∗</mml:mo> <mml:mn>1</mml:mn> <mml:mo stretchy=\"false\">/</mml:mo> <mml:mn>4</mml:mn> </mml:mrow> </mml:msup> </mml:mrow> </mml:math> </jats:inline-formula> , where the superscript <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mo>+</mml:mo> </mml:math> </jats:inline-formula> indicates the wall unit normalization, and brackets stand for averages over time and the homogeneous plane normal to the wall, <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mi>q</mml:mi> </mml:math> </jats:inline-formula> is an integer, <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:msub> <mml:mi>α</mml:mi> <mml:mi>q</mml:mi> </mml:msub> </mml:math> </jats:inline-formula> and <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:msub> <mml:mi>β</mml:mi> <mml:mi>q</mml:mi> </mml:msub> </mml:math> </jats:inline-formula> are constants independent of the friction Reynolds number <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mrow> <mml:mi>R</mml:mi> <mml:msub> <mml:mi>e</mml:mi> <mml:mi>τ</mml:mi> </mml:msub> </mml:mrow> </mml:math> ","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"42 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872456","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}