综合性期刊最新文献

{"title":"A genetically encoded nanobody sensor reveals conformational diversity in β-arrestins orchestrated by distinct seven transmembrane receptors.","authors":"Parishmita Sarma, Vendula Nagy Marková, Annu Dalal, Sudha Mishra, Nashrah Zaidi, Divyanshu Tiwari, Manish K Yadav, Nabarun Roy, Gargi Mahajan, Paul Miclea, Josef Lazar, Arun K Shukla","doi":"10.1073/pnas.2507384122","DOIUrl":"10.1073/pnas.2507384122","url":null,"abstract":"<p><p>Agonist-induced interaction of G protein-coupled receptors (GPCRs) with β-arrestins (βarrs) is a critical mechanism that regulates the spatiotemporal pattern of receptor localization and signaling. While the underlying mechanism governing GPCR-βarr interaction is primarily conserved and involves receptor activation and phosphorylation, there are several examples of receptor-specific fine-tuning of βarr-mediated functional outcomes. Considering the key contribution of conformational plasticity of βarrs in driving receptor-specific functional responses, it is important to develop novel sensors capable of reporting distinct βarr conformations in cellular context. Here, we design an intrabody version of a βarr-recognizing nanobody (nanobody32), referred to as intrabody32 (Ib32), in NanoLuc enzyme complementation assay format and measure its ability to recognize βarr1 and 2 in live cells upon activation of a broad set of GPCRs. Ib32 robustly recognizes activated βarr1 and 2 in the plasma membrane and endosomes, and effectively mirrors βarr recruitment profile upon stimulation of selected GPCRs. We also design an Ib32 sensor for polarization microscopy with a change in linear dichroism as readout and demonstrate its utility for monitoring βarr activation upon stimulation of selected GPCRs by natural and biased agonists. Taken together with a previously described sensor of βarr1 activation, Ib32 underscores the inherent flexibility encoded in βarrs and conformational diversity imparted by different GPCRs, which is further corroborated using an orthogonal limited proteolysis assay. Our study presents Ib32 as a sensor of βarr activation and highlights the structural diversity of βarrs, which likely allows their ability to interact with, and regulate, a large repertoire of GPCRs.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2507384122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024030","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":"Structure of a polymorphic repeat at the <i>CACNA1C</i> schizophrenia locus.","authors":"Raquel Moya, Xiaohan Wang, Richard W Tsien, Matthew T Maurano","doi":"10.1073/pnas.2415650122","DOIUrl":"10.1073/pnas.2415650122","url":null,"abstract":"<p><p>Genetic variation within intron 3 of the <i>CACNA1C</i> calcium channel gene is associated with schizophrenia and other neuropsychiatric disorders, but analysis of the causal variants and their effect is complicated by a nearby variable-number tandem repeat (VNTR). Here, we explored the structure and population variability of the <i>CACNA1C</i> intron 3 VNTR using 155 long-read genome assemblies from 78 diverse individuals. Based on sequence differences among repeat units, we clustered individual sequences into 7 VNTR structural alleles called Types. Three Types were related through large duplications, but the other Types diverged much earlier such that only 12 repeat units at the 5' end of the VNTR were shared across most Types. The most diverged Types were rare and present only in individuals with African ancestry, but a multiallelic structural polymorphism was present across populations at different frequencies, consistent with expansion of the VNTR preceding the emergence of early hominins. We demonstrated that this polymorphism was in complete linkage disequilibrium with fine-mapped schizophrenia variants from genome-wide association studies (GWAS) and that this risk haplotype was associated with decreased <i>CACNA1C</i> gene expression in the brain. Our work suggests that sequence variation within a human-specific VNTR affects gene expression and provides a detailed characterization of new alleles at a flagship neuropsychiatric GWAS locus.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2415650122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034251","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":"Giant mobility of surface-trapped ionic charges following liquid tribocharging.","authors":"Zouhir Benrahla, Tristan Saide, Louis Burnaz, Emilie Verneuil, Simon Gravelle, Jean Comtet","doi":"10.1073/pnas.2505841122","DOIUrl":"https://doi.org/10.1073/pnas.2505841122","url":null,"abstract":"<p><p>The sliding motion of aqueous droplets on hydrophobic surfaces leads to charge separation at the trailing edge, with implications from triple-line friction to hydrovoltaic energy generation. Charges deposited on the solid surface have been attributed to ions or electrons ripped off from the liquid drop. However, the dynamics and exact physicochemical nature of these surface-trapped charges remains poorly explored. Here, we take advantage of a scanning-based electrostatic mapping technique, to directly quantify the spatiotemporal dynamics of surface deposited charges in the wake of droplets sliding on hydrophobic surfaces. We confirm the ionic nature of these interfacially trapped charges, and evidence that they undergo very fast bidimensional diffusive transport, gliding with low friction at the solid/gas interface. We interpret our observations in the framework of molecular dynamics simulation of hydrated ions adsorbed on solid surfaces, revealing a peculiar transport mechanism limited by purely interfacial friction of the ionic solvation shell with the solid surface. By uncovering the unexpected dynamics of these ionic puddles-a distinct state of interfacial ionic matter-our findings have general implications for molecular-scale ionic transport, electrified matter, and wetting dynamics at interfaces.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2505841122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024065","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 for Rad54- and Hed1-mediated regulation of Rad51 during the transition from mitotic to meiotic recombination.","authors":"Yeonoh Shin, Michael T Petassi, Aidan M Jessop, Stefan Y Kim, Razvan Matei, Katherine Morse, Vivek B Raina, Upasana Roy, Eric C Greene","doi":"10.1073/pnas.2510007122","DOIUrl":"10.1073/pnas.2510007122","url":null,"abstract":"<p><p>Rad51 catalyzes the DNA pairing reactions that take place during homologous recombination (HR), and HR must be tightly regulated to ensure physiologically appropriate outcomes. Rad54 is an ATP-dependent DNA motor protein that stimulates Rad51 activity during mitosis. In meiosis Rad51 is downregulated by the protein Hed1, which blocks Rad54 binding to Rad51, and allows Dmc1 to function as the active recombinase. We currently have a poor understanding of the regulatory interplay between Rad54, Hed1, Rad51, and Dmc1. Here, we identify a conserved Rad51 interaction motif within Rad54, and we solve a CryoEM structure of this motif bound to Rad51. We also identify a distinct Rad51 interaction motif within Hed1 and solve its structure bound to Rad51. These structures explain how Rad54 engages Rad51 to promote recombination between sister chromatids during mitosis and how Rad51 is downregulated by Hed1 upon entry into meiosis such that its meiosis-specific homolog Dmc1 can promote recombination between homologous chromosomes.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2510007122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034276","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 coherence of US cities.","authors":"Simone Daniotti, Matté Hartog, Frank Neffke","doi":"10.1073/pnas.2501504122","DOIUrl":"https://doi.org/10.1073/pnas.2501504122","url":null,"abstract":"<p><p>Diversified economies are critical for cities to sustain their growth and development, but they are also costly because diversification often requires expanding a city's capability base. We analyze how cities manage this trade-off by measuring the coherence of the economic activities they support, defined as the technological distance between randomly sampled productive units in a city. We use this framework to study how the US urban system developed over almost two centuries, from 1850 to today. To do so, we rely on historical census data, covering over 600M individual records to describe the economic activities of cities between 1850 and 1940, as well as 8 million patent records and detailed occupational and industrial profiles of cities for more recent decades. Despite massive shifts in the economic geography of the United States over this 170-y period, average coherence in its urban system remains unchanged. Moreover, across different time periods, datasets, and relatedness measures, coherence falls with city size at the exact same rate, pointing to constraints to diversification that are governed by a city's size in universal ways.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2501504122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055710","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":"Relationship dynamics and behavioral adaptations in the control of the 2022 mpox epidemic.","authors":"Ulrik Hvid, Lone Simonsen, Morten Frisch, Kim Sneppen","doi":"10.1073/pnas.2502861122","DOIUrl":"https://doi.org/10.1073/pnas.2502861122","url":null,"abstract":"<p><p>We analyzed the patterns of transmission in the 2022 clade IIb mpox epidemic as it unfolded in the European population of men who have sex with men (MSM). We developed an agent-based model that simulates sexual pair formation, incorporating both brief and longer-term sexual relationships. The model implements survey data on the sexual behavior of MSM and accounts for the highly heterogeneous nature of the sexual contact network within this community. When simulating the mpox epidemic, the model reproduces the reported numbers of sexual partners of mpox-infected individuals. We find that infection-derived immunity had little impact on ending the European outbreak. Instead, we suggest that the marked decrease in serial interval observed across the epidemic reflects a substantial increase in self-isolating behavior among infected persons and that this is sufficient to explain the early control of the epidemic. Our work highlights the critical interplay between relationship dynamics and adaptive behaviors in shaping mpox epidemic patterns and achieving control in 2022. Despite continued propagation of clade IIb mpox, the European MSM population remains protected by immunity, primarily vaccine-induced.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2502861122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034240","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":"Conflicting roles of cell geometry, microtubule deflection, and orientation-dependent dynamic instability in cortical array organization.","authors":"Tim Y Y Tian, Geoffrey O Wasteneys, Colin B Macdonald, Eric N Cytrynbaum","doi":"10.1073/pnas.2426171122","DOIUrl":"https://doi.org/10.1073/pnas.2426171122","url":null,"abstract":"<p><p>The self-organization of cortical microtubule (MT) arrays within plant cells is an emergent phenomenon with important consequences for the synthesis of the cell wall, cell shape, and subsequently the structure of plants. Mathematical modeling and experiments have elucidated the underlying processes involved. There has been recent interest in the influence of geometric cues on array orientation, be it direct (cell shape) or indirect (tension in the membrane). However, the mechanical influence of membrane curvature on these elastic filaments has largely been ignored. A previous model was proposed to describe how the anchoring process may control the deflection of individual MTs seeking to minimize bending on a cylindrical cell. We incorporate this process into a model of interacting MTs and find the cell curvature influence to be significant: the array favors orientations parallel to the direction of elongation rather than the expected transverse direction. Even without elasticity, the geometry of large cells hinders robust MT organization. These results suggest the necessity of additional processes to overcome these factors. We propose an orientation-dependent catastrophe rate, hypothetically caused by cellulose microfibrils impeding MT polymerization. We find a combination of anchoring and impedance to be sufficient to generate transverse arrays despite the geometric influences.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 37","pages":"e2426171122"},"PeriodicalIF":9.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055712","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":"Operando interlayer expansion of multiscale curved graphene for volumetrically-efficient supercapacitors","authors":"Petar Jovanović, Meysam Sharifzadeh Mirshekarloo, Phillip Aitchison, Mahdokht Shaibani, Mainak Majumder","doi":"10.1038/s41467-025-63485-0","DOIUrl":"https://doi.org/10.1038/s41467-025-63485-0","url":null,"abstract":"<p>Supercapacitors deliver high power but are limited in compact applications by low volumetric energy and power densities. Two-dimensional materials like graphene, despite their high packing density, are hindered by poor ion transport kinetics. A rapid thermal annealing step generates unusually curved turbostratic graphene crystallites, integrated and interwoven within disordered domains in micron-size particles to yield multiscale graphene. Ion insertion into the interlayers enables precise pore-ion matching and partial charge transfer, enabling a high Brunauer-Emmett-Teller surface area-normalized capacitance of 85 µF/cm². Here, we show that multiscale graphene exhibits rapid ion transport dynamics within the curved crystallites and disordered domains. When the thin electrodes are assembled into symmetric pouch cell devices, they deliver a stack-level volumetric energy density of 99.5 Wh/L in ionic liquid electrolytes and 49.2 Wh/L in organic electrolyte with a high power density of 69.2 kW/L at 9.6 Wh/L.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"78 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059751","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 retrospective cohort study of valproate and infertility in men with epilepsy or bipolar disorder using international health data","authors":"Gashirai K. Mbizvo, Susan E. Duncan, Lewis Nancarrow, Tessa Sagarino, Lance V. Watkins, Michael T. Mbizvo, Gregory Y. H. Lip, Anthony G. Marson","doi":"10.1038/s41467-025-63469-0","DOIUrl":"https://doi.org/10.1038/s41467-025-63469-0","url":null,"abstract":"<p>Valproate is highly effective at treating epilepsy and bipolar disorder. It faces prescribing restrictions in men due to concerns it causes testicular dysfunction and infertility. These mostly stem from animal models – the human evidence is limited and conflicting. We report the largest ever retrospective cohort study of infertility in men with epilepsy or bipolar disorder, using real-world healthcare data from TriNetX. 91,917 of the men are exposed to valproate, and 535,803 unexposed. Cohorts are propensity score matched for a comprehensive set of baseline covariates, and survival analysis is undertaken using Cox-proportional hazards models. No significant difference is seen between valproate-exposed and unexposed men across lifetime risks of infertility, testicular hypofunction, testicular atrophy, and a composite of low sperm concentration, motility, vitality, normal forms, and semen volume (<i>p</i> &gt; 0.05). Our findings do not support an association between valproate and infertility in men with epilepsy or bipolar disorder in real-world settings.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"26 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059752","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":"Weird ‘time crystals’ are made visible at last","authors":"","doi":"10.1038/d41586-025-02939-3","DOIUrl":"https://doi.org/10.1038/d41586-025-02939-3","url":null,"abstract":"Time crystals, a state of matter once thought physically impossible, could soon be on a banknote.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"24 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059596","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}