Shu Kanno, Kenji Sugisaki, Hajime Nakamura, Hiroshi Yamauchi, Rei Sakuma, Takao Kobayashi, Qi Gao, Naoki Yamamoto
{"title":"Tensor-based quantum phase difference estimation for large-scale demonstration.","authors":"Shu Kanno, Kenji Sugisaki, Hajime Nakamura, Hiroshi Yamauchi, Rei Sakuma, Takao Kobayashi, Qi Gao, Naoki Yamamoto","doi":"10.1073/pnas.2425026122","DOIUrl":"10.1073/pnas.2425026122","url":null,"abstract":"<p><p>We develop an energy calculation algorithm leveraging quantum phase difference estimation (QPDE) scheme and a tensor-network-based unitary compression method in the preparation of superposition states and time-evolution gates. Alongside its efficient implementation, this algorithm reduces depolarization noise affections exponentially. We demonstrated energy gap calculations for one-dimensional Hubbard models on IBM superconducting devices using circuits up to 32-system (plus one-ancilla) qubits, a five-fold increase over previous Quantum phase estimation (QPE) demonstrations, at the 7242 controlled-Z gate level of standard transpilation, utilizing a Q-CTRL error suppression module. Additionally, we propose a technique toward molecular executions using spatial orbital localization and index sorting, verified linear polyene simulations up to 21 qubits. Since QPDE can handle the same objectives as QPE, our algorithm represents a leap forward in quantum computing on real devices.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 30","pages":"e2425026122"},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699277","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}
Johnny A Z Rockenbach, Guilherme P F Nader, Susumu Antoku, Gregg G Gundersen
{"title":"The kinesin KIF3AC recycles endocytosed integrin to polarize new adhesion formation toward the leading edge.","authors":"Johnny A Z Rockenbach, Guilherme P F Nader, Susumu Antoku, Gregg G Gundersen","doi":"10.1073/pnas.2513776122","DOIUrl":"10.1073/pnas.2513776122","url":null,"abstract":"<p><p>The recycling of integrin endocytosed during focal adhesion (FA) disassembly is critical for cell migration and contributes to the polarized formation of new FAs toward the leading edge. How this occurs is unclear. Here, we sought to identify the kinesin motor protein(s) that is involved in recycling endocytosed integrin back to the plasma membrane. We show that the kinesin-2 heterodimer, KIF3AC, and the Rab11 adaptor protein Rab coupling protein (RCP) are required for FA reformation after the disassembly of FAs in mouse and human fibroblasts. In the absence of KIF3AC, integrin does not return to the cell surface after FA disassembly and is found in the Rab11 endocytic recycling compartment. Biochemical pulldowns revealed that KIF3C associated with β1 integrin in an RCP-dependent fashion, but only after FA disassembly. KIF3AC knockdown inhibited cell migration, trafficking of RCP toward the leading edge, and polarized formation of FAs at the leading edge. These results show that KIF3AC promotes cell migration by recycling integrin so that it generates new FAs in a polarized fashion.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 30","pages":"e2513776122"},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699278","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}
Jane Frederick, Ranya K A Virk, I Chae Ye, Luay M Almassalha, Greta M Wodarcyk, David VanDerway, Ruyi Gong, Cody L Dunton, Tiffany Kuo, Karla I Medina, Margarita Loxas, Jared T Ahrendsen, Demirkan B Gursel, Paola Carrillo Gonzalez, Rikkert J Nap, Saira John, Vasundhara Agrawal, Nicholas M Anthony, John Carinato, Wing Shun Li, Rivaan Kakkaramadam, Surbhi Jain, Shohreh Shahabi, Guillermo A Ameer, Igal G Szleifer, Vadim Backman
{"title":"Leveraging chromatin packing domains to target chemoevasion in vivo.","authors":"Jane Frederick, Ranya K A Virk, I Chae Ye, Luay M Almassalha, Greta M Wodarcyk, David VanDerway, Ruyi Gong, Cody L Dunton, Tiffany Kuo, Karla I Medina, Margarita Loxas, Jared T Ahrendsen, Demirkan B Gursel, Paola Carrillo Gonzalez, Rikkert J Nap, Saira John, Vasundhara Agrawal, Nicholas M Anthony, John Carinato, Wing Shun Li, Rivaan Kakkaramadam, Surbhi Jain, Shohreh Shahabi, Guillermo A Ameer, Igal G Szleifer, Vadim Backman","doi":"10.1073/pnas.2425319122","DOIUrl":"https://doi.org/10.1073/pnas.2425319122","url":null,"abstract":"<p><p>Cancer cells exhibit a remarkable resilience to cytotoxic stress, often adapting through transcriptional changes linked to alterations in chromatin structure. In several types of cancer, these adaptations involve epigenetic modifications and restructuring of topologically associating domains. However, the underlying principles by which chromatin architecture facilitates such adaptability across different cancers remain poorly understood. To investigate the role of chromatin in this process, we developed a physics-based model that connects chromatin organization to cell fate decisions, such as survival following chemotherapy. Our model builds on the observation that chromatin forms packing domains, which influence transcriptional activity through macromolecular crowding. The model accurately predicts chemoevasion in vitro, suggesting that changes in packing domains affect the likelihood of survival. Consistent results across diverse cancer types indicate that the model captures fundamental principles of chromatin-mediated adaptation, independent of the specific cancer or chemotherapy mechanisms involved. Based on these insights, we hypothesized that compounds capable of modulating packing domains, termed Transcriptional Plasticity Regulators (TPRs), could prevent cellular adaptation to chemotherapy. We conducted a proof-of-concept compound screen using live-cell chromatin imaging to identify several TPRs that synergistically enhanced chemotherapy-induced cell death. The most effective TPR significantly improved therapeutic outcomes in a patient-derived xenograft model of ovarian cancer. These findings underscore the central role of chromatin in cellular adaptation to cytotoxic stress and present a framework for enhancing cancer therapies, with broad potential across multiple cancer types.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 30","pages":"e2425319122"},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691338","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}
Andrew Bender, Chong Zhao, Edward Vogel, Edward Awh, Bradley Voytek
{"title":"Differential representations of spatial location by aperiodic and alpha oscillatory activity in working memory.","authors":"Andrew Bender, Chong Zhao, Edward Vogel, Edward Awh, Bradley Voytek","doi":"10.1073/pnas.2506418122","DOIUrl":"10.1073/pnas.2506418122","url":null,"abstract":"<p><p>Decades of research have shown working memory (WM) relies on sustained prefrontal cortical activity and visual extrastriate activity, particularly in the alpha (8 to 12 Hz) frequency range. This alpha activity tracks the spatial location of WM items, even when spatial position is task-irrelevant and no stimulus is currently being presented. Traditional analyses of putative oscillations using bandpass filters, however, conflate oscillations with nonoscillatory aperiodic activity. Here, we reanalyzed seven human electroencephalography visual WM datasets to test the hypothesis that aperiodic activity, which is thought to reflect the relative contributions of excitatory and inhibitory drive-plays a distinct role in visual WM from true alpha oscillations. To do this, we developed a time-resolved spectral parameterization approach to disentangle oscillations from aperiodic activity during WM encoding and maintenance. Across all seven tasks, totaling 112 participants, we captured the representation of spatial location from total alpha power using inverted encoding models (IEMs), replicating traditional analyses. We then trained separate IEMs to estimate the strength of spatial location representation from aperiodic-adjusted alpha (reflecting just the oscillatory component) and aperiodic activity and find that IEM performance improves for aperiodic-adjusted alpha compared to total alpha power that blends the two signals. We also identify a distinct role for aperiodic activity, where IEM performance trained on aperiodic activity is highest during stimulus presentation, but not during the WM maintenance period. Our results emphasize the importance of controlling for aperiodic activity when studying neural oscillations while uncovering a functional role for aperiodic activity in encoding visual WM information.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 30","pages":"e2506418122"},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699265","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}
Evan C Fricke, Susan C Cook-Patton, Charles F Harvey, César Terrer
{"title":"Seed dispersal disruption limits tropical forest regrowth.","authors":"Evan C Fricke, Susan C Cook-Patton, Charles F Harvey, César Terrer","doi":"10.1073/pnas.2500951122","DOIUrl":"10.1073/pnas.2500951122","url":null,"abstract":"<p><p>Identifying linkages between biodiversity loss and climate change is required for understanding the scope of these interconnected challenges and developing approaches to address them. One crucial yet underexplored aspect is the influence of seed-dispersing animals on forest carbon storage. Here, we show that 81% of tropical trees rely on animals for seed dispersal and that disruption of this process, due to declines in animal diversity and movement, significantly hampers the carbon accumulation potential of regrowing tropical forests. Using a synthesis of animal biodiversity, movement, and seed dispersal data covering thousands of animal species, we developed an index of seed dispersal disruption and modeled its relationship to carbon accumulation observed across 3,026 tropical regrowth plots. Naturally regrowing areas with lowest seed dispersal disruption had aboveground carbon accumulation rates four times higher than those with most severe disruption. Across areas identified as locations suitable for reforestation, current levels of seed dispersal disruption yield a 57% average reduction in local carbon accumulation potential. Tropical regrowth forests currently represent the largest land-based carbon sink; ongoing animal biodiversity losses diminish their ability to recover naturally from disturbances and therefore threaten their climate mitigation potential. These results advance understanding of animal biodiversity's impact on carbon dynamics and emphasize the need to address biodiversity loss and climate change together.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 30","pages":"e2500951122"},"PeriodicalIF":9.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699276","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":"Mechanistic insights into the iron-sulfur cluster-dependent interaction of the autophagy receptor NCOA4 with the E3 ligase HERC2.","authors":"Haobo Liu,Liqiang Shen,Xinyu Gong,Xindi Zhou,Yichao Huang,Yuqian Zhou,Zhenpeng Guo,Hanbo Guo,Shichao Wang,Lifeng Pan","doi":"10.1073/pnas.2510269122","DOIUrl":"https://doi.org/10.1073/pnas.2510269122","url":null,"abstract":"NCOA4, a dedicated autophagy receptor for mediating selective autophagy of ferritin (ferritinophagy), plays a vital role in maintaining cellular iron homeostasis. The cellular abundance of NCOA4 is regulated by the E3 ligase HERC2 that can specifically target NCOA4 for proteasomal degradation under iron-replete conditions. However, the detailed molecular mechanism governing the iron-dependent recognition of NCOA4 by HERC2 remains elusive. Here, using multidisciplinary approaches, we systematically characterize the HERC2-binding domain (HBD) of NCOA4 and its interaction with HERC2. We uncover that NCOA4 HBD harbors a [2Fe-2S] cluster and can exist in two different states, the apo-form state and the [2Fe-2S] cluster-bound state. Moreover, we unravel that HERC2 can effectively recognize the [2Fe-2S] cluster-bound NCOA4 HBD through its Cullin-7-PARC-HERC2 (CPH) domain and iron-sulfur cluster-dependent NCOA4-binding domain (INBD) with a synergistic binding mode. The determined crystal structures of HERC2(2540-2700) and its complex with the [2Fe-2S] cluster-bound NCOA4 HBD together with relevant biochemical and cellular results not only elucidate how NCOA4 HBD specifically senses cellular iron level by binding a [2Fe-2S] cluster but also reveal the molecular basis underlying the specific interaction of HERC2 with the [2Fe-2S] cluster-bound NCOA4 HBD. In summary, our findings provide mechanistic insights into the iron-dependent turnover of NCOA4 by HERC2 and expand our understanding of the regulatory mechanism of NCOA4-mediated ferritinophagy.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"18 1","pages":"e2510269122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693173","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}
Sarah Soom,Stefan Urs Moning,Gregory M Cook,James P Lingford,Ashleigh Kropp,Sieu Tran,Rhys Grinter,Chris Greening,Christoph von Ballmoos
{"title":"ATP synthesis driven by atmospheric hydrogen concentrations.","authors":"Sarah Soom,Stefan Urs Moning,Gregory M Cook,James P Lingford,Ashleigh Kropp,Sieu Tran,Rhys Grinter,Chris Greening,Christoph von Ballmoos","doi":"10.1073/pnas.2506353122","DOIUrl":"https://doi.org/10.1073/pnas.2506353122","url":null,"abstract":"All cells require a continuous supply of the universal energy currency, adenosine triphosphate (ATP), to drive countless cellular reactions. The universally conserved F1Fo-ATP synthase regenerates ATP from ADP and Pi by harnessing a transmembrane electrochemical proton gradient (pmf). Bacteria have evolved diverse pmf-forming strategies using light, organic, and inorganic energy sources. Recently, we proposed that many bacteria survive using atmospheric trace gases to produce ATP when limited for other energy sources. However, direct evidence that atmospheric energy sources are sufficient to generate pmf or drive ATP synthesis is still lacking. Here, we show that the membrane-associated hydrogen:quinone oxidoreductase Huc from Mycobacterium smegmatis can enable ATP synthesis from air. Purified Huc couples H2 oxidation to the reduction of various ubiquinone and menaquinone analogues. We designed a minimal respiratory chain in which Huc interacts with liposomes containing the nonpumping, but pmf-generating, bd-I oxidase and F1Fo-ATP synthase from Escherichia coli. Our experiments show that passive hydrogen exchange from air to solution is sufficient for the electron transfer and pmf generation required to accumulate ATP. By combining continuous culture bioenergetics measurements with theoretical calculations, we show this process is sufficient for mycobacteria to sustain pmf and ATP synthesis (two ATP molecules per H2 oxidized) for maintenance energy requirements during nutrient starvation. These findings confirm that atmospheric energy sources can be dependable 'lifeline' substrates that enable continuous energy conservation during nutrient starvation. In addition, this work provides a unique tool for ATP production in synthetic applications, which unlike other approaches is traceless without by-product accumulation.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"75 1","pages":"e2506353122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693390","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}
Arianna Salazar-Miranda,Zhuangyuan Fan,Michael Baick,Keith N Hampton,Fabio Duarte,Becky P Y Loo,Edward Glaeser,Carlo Ratti
{"title":"Exploring the social life of urban spaces through AI.","authors":"Arianna Salazar-Miranda,Zhuangyuan Fan,Michael Baick,Keith N Hampton,Fabio Duarte,Becky P Y Loo,Edward Glaeser,Carlo Ratti","doi":"10.1073/pnas.2424662122","DOIUrl":"https://doi.org/10.1073/pnas.2424662122","url":null,"abstract":"We analyze changes in pedestrian behavior over a 30-y period in four urban public spaces located in New York, Boston, and Philadelphia. Building on William Whyte's observational work, which involved manual video analysis of pedestrian behaviors, we employ computer vision and deep learning techniques to examine video footage from 1979-80 and 2008-10. Our analysis measures changes in walking speed, lingering behavior, group sizes, and group formation. We find that the average walking speed has increased by 15%, while the time spent lingering in these spaces has halved across all locations. Although the percentage of pedestrians walking alone remained relatively stable (from 67% to 68%), the frequency of group encounters declined, indicating fewer interactions in public spaces. This shift suggests that urban residents are using streets as thoroughfares rather than as social spaces, which has important implications for the role of public spaces in fostering social engagement.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"20 1","pages":"e2424662122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693174","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":"Optimal kinetics for catalytic cycles from a single path-sampling simulation.","authors":"Peter G Bolhuis","doi":"10.1073/pnas.2500934122","DOIUrl":"https://doi.org/10.1073/pnas.2500934122","url":null,"abstract":"A catalyst's efficiency for accelerating a reaction rate is determined by its molecular structure and interactions with the substrate. While one can predict kinetics for a particular molecular model, tuning the (potentially many) model parameters to reach a desired or optimal kinetics for a catalytic cycle is usually considered computationally prohibitively expensive, especially in solvated systems. Here, we show for a simple model representing a minimal catalytic cycle that such optimization is possible using only one single (path-sampling) simulation, by applying a maximum caliber based path reweighting method. We compute the path ensemble for a single parameter setting of the molecular interactions and then expand the kinetic landscape around these parameters. We find that optimal catalytic turnover or efficiency is orders of magnitude improved and is achieved by relevant parameters that induce strain in the system. Thus, path-reweighting based optimization is not only capable of finding important ingredients that lead to desired kinetic rates but can also identify the mechanistic origins of the rate optimization at a fraction of the costs of a direct evaluation. We demonstrate the versatility of the methodology on a minimal model for kinase signaling. The approach promises efficient computational design of (complex) catalysts using realistic models.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"17 1","pages":"e2500934122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693388","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 Lin et al., BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly.","authors":"","doi":"10.1073/pnas.2517068122","DOIUrl":"https://doi.org/10.1073/pnas.2517068122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"706 1","pages":"e2517068122"},"PeriodicalIF":11.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693404","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}