PNAS nexus最新文献

{"title":"Mechanical cues guide the formation and patterning of 3D spheroids in fibrous environments.","authors":"Sharan Sharma, Atharva Agashe, Jennifer C Hill, Keya Ganguly, Puja Sharma, Tara D Richards, Weijian Huang, David J Kaczorowski, Pablo G Sanchez, Rakesh Kapania, Julie A Phillippi, Amrinder S Nain","doi":"10.1093/pnasnexus/pgaf263","DOIUrl":"10.1093/pnasnexus/pgaf263","url":null,"abstract":"<p><p>Multicellular spheroids have shown great promise in 3D biology. Many techniques exist to form spheroids, but how cells take mechanical advantage of native fibrous extracellular matrix (ECM) to form spheroids remains unknown. Here, we identify the role of fiber diameter, architecture, and cell contractility on spheroids' spontaneous formation and growth in ECM-mimicking fiber networks. We show that matrix deformability revealed through force measurements on aligned fiber networks promotes spheroid formation independent of fiber diameter. At the same time, larger-diameter crosshatched networks of low deformability abrogate spheroid formation. Thus, designing fiber networks of varying diameters and architectures allows spatial patterning of spheroids and monolayers simultaneously. Forces quantified during spheroid formation revealed the contractile role of Rho-associated protein kinase in spheroid formation and maintenance. Interestingly, we observed spheroid-spheroid and multiple spheroid mergers initiated by cell exchanges to form cellular bridges connecting the two spheroids. Unexpectedly, we found large pericyte spheroids contract rhythmically. Transcriptomic analysis revealed striking changes in cell-cell, cell-matrix, and mechanosensing gene expression profiles concordant with spheroid assembly on fiber networks. Overall, we ascertained that contractility and network deformability work together to spontaneously form and pattern 3D spheroids, potentially connecting in vivo matrix biology with developmental, disease, and regenerative biology.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 9","pages":"pgaf263"},"PeriodicalIF":3.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human nerve growth factor delivery to the retina: Quantitative methodology and mathematical modeling in preclinical settings.","authors":"Simone L Mattioli, Prashant Dogra, Francesco Longobardi, Grazia Casiello, Lucia Apparente, Nicola Detta, Rubina Novelli, Andrea Aramini, Franca Cattani, Maria I Antonangeli, Tiziana Romeo, Marcello Allegretti, Zhihui Wang, Cleide G Machado, Renata Pasqualini, Wadih Arap, Vittorio Cristini","doi":"10.1093/pnasnexus/pgaf250","DOIUrl":"10.1093/pnasnexus/pgaf250","url":null,"abstract":"<p><p>Nerve growth factor (NGF) plays a critical neuroprotective role in retinal health, supporting neuronal survival and regeneration. Recombinant human NGF (rhNGF) holds promise for treating retinal degenerative diseases such as glaucoma, retinitis pigmentosa, and optic neuropathies. However, efficient retinal delivery of rhNGF remains a major challenge due to anatomical barriers and rapid clearance from conventional routes. Here, we integrate in vivo experimentation with mathematical modeling to identify and validate optimized delivery strategies for rhNGF. By using stable isotope-labeled rhNGF, we quantified ocular biodistribution in rats and rabbits following topical eye drops, intravitreal (IVT) injections, and sustained-release formulations. Eye drop administration resulted in negligible retinal exposure (<0.04% of instilled dose), while IVT injection achieved ∼34% vitreous retention with sustained delivery to the retina and optic nerve over 60 days. A mechanistic compartmental model was developed and validated against the in vivo data to simulate route-specific drug transport and estimate delivery losses via a penalty factor ( <math><msub><mi>f</mi> <mi>B</mi></msub> </math> ). The model identified key parameters governing retinal exposure and guided the design of dose-release profiles to sustain therapeutic concentrations. Controlled-release platforms, such as bioadhesive tablets and gels, exhibited in vitro release rates (0.002-0.015 h⁻¹) aligned with model-predicted requirements for prolonged exposure. Together, these results highlight the importance of route-specific delivery design and demonstrate that combining isotope tracing with mechanistic modeling can quantitatively guide development of long-acting retinal therapeutics. This platform provides a translational framework for optimizing macromolecular drug delivery to the posterior eye.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf250"},"PeriodicalIF":3.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of water retention at carbohydrate-clay interfaces.","authors":"Sabrina E Kelch, Benjamin Barrios-Cerda, Yeonsoo Park, Eric Ferrage, Ludmilla Aristilde","doi":"10.1093/pnasnexus/pgaf259","DOIUrl":"10.1093/pnasnexus/pgaf259","url":null,"abstract":"<p><p>Clay minerals are well documented to facilitate the retention of water and organic matter in terrestrial soils, Martian regolith, and meteorites. Yet, the mechanisms underlying water trapping within these mineral-organic matter associations are poorly understood. Here, we investigate these mechanisms with montmorillonite, a smectite clay, populated with carbohydrates of different structures. By capturing relative proportion of bound versus freely exchangeable waters by mass spectrometry during thermogravimetric analysis, we observe up to a 2.3-fold increase in bound waters in samples with adsorbed carbohydrates. Temperature-dependent carbon loss from adsorbed ¹³C-labeled carbohydrate determines increase in carbohydrate trapping at low moisture. We determine that the amount of trapped organic carbon is correlated positively with the population of bound waters. Molecular dynamics simulations of a carbohydrate-populated clay nanopore identify different interfacial waters, involving direct single or multiple hydrogen bonds on the clay surface without or with simultaneous hydrogen bonding with adsorbed carbohydrates. Quantum mechanics-based computations highlight up to 5-fold greater binding energy for bound waters associated with adsorbed carbohydrates on the clay surface, compared to bound waters in the absence of carbohydrates. Thus, our experimental and theoretical results collectively reveal that interfacial waters bridging hydrated organic matter to the clay surface facilitate water trapping within mineral-organic associations.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf259"},"PeriodicalIF":3.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintaining diversity in structured populations.","authors":"David A Brewster, Jakub Svoboda, Dylan Roscow, Krishnendu Chatterjee, Josef Tkadlec, Martin A Nowak","doi":"10.1093/pnasnexus/pgaf252","DOIUrl":"10.1093/pnasnexus/pgaf252","url":null,"abstract":"<p><p>We examine population structures for their ability to maintain diversity in neutral evolution. We use the general framework of evolutionary graph theory and consider birth-death (bd) and death-birth (db) updating. The population is of size <i>N</i>. Initially all individuals represent different types. The basic question is: what is the time <math><msub><mi>T</mi> <mi>N</mi></msub> </math> until one type takes over the population? This time is known as consensus time in computer science and as total coalescent time in evolutionary biology. For the complete graph, it is known that <math><msub><mi>T</mi> <mi>N</mi></msub> </math> is quadratic in <i>N</i> for db and bd. For the cycle, we prove that <math><msub><mi>T</mi> <mi>N</mi></msub> </math> is cubic in <i>N</i> for db and bd. For the star, we prove that <math><msub><mi>T</mi> <mi>N</mi></msub> </math> is cubic for bd and quasilinear ( <math><mi>N</mi> <mi>log</mi> <mspace></mspace> <mi>N</mi></math> ) for db. For the double star, we show that <math><msub><mi>T</mi> <mi>N</mi></msub> </math> is quartic for bd. We derive upper and lower bounds for all undirected graphs for bd and db. We also show the Pareto front of graphs (of size <math><mi>N</mi> <mo>=</mo> <mn>8</mn></math> ) that maintain diversity the longest for bd and db. Further, we show that some graphs that quickly homogenize can maintain high levels of diversity longer than graphs that slowly homogenize. For directed graphs, we give simple contracting star-like structures that have superexponential time scales for maintaining diversity.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf252"},"PeriodicalIF":3.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Politricks: Teaching political tricks and discernment through active and passive tools.","authors":"Shaye-Ann M Hopkins, Rebecca M Rayburn-Reeves, Jan W Lindemans, Kathleen C O'Gorrman, Ian A Vandewalker, Caylin A Luebeck, Joseph J Sherlock","doi":"10.1093/pnasnexus/pgaf245","DOIUrl":"10.1093/pnasnexus/pgaf245","url":null,"abstract":"<p><p>In an age of information overload, misinformation poses a growing threat to democracy. Inoculation theory suggests that exposing individuals to manipulation techniques can help build resistance to misinformation and improve their ability to discern such content over time. However, little research has directly compared the effectiveness of active learning tools, such as gamified interventions, to passive learning methods, like informational guides, for enhancing the detection of misinformation within important public issues, such as elections and climate change. To address this gap, we designed two tools aimed at enhancing users' ability to recognize manipulation strategies used to disseminate misinformation: an interactive game (<i>Politricks</i>) and a passive learning-based guide, and compared the impact to a control condition (<i>Tetris</i>). Through two survey experiments (<i>N</i> = 1,035), we explored the effect on beliefs about election-related misinformation (study 1), and the transferability of these resources to climate change misinformation (study 2). Both learning tools significantly improved discernment and reduced engagement with manipulative content. While both interventions were almost equally effective, the tools had a stronger impact on election misinformation detection, compared to climate change misinformation. Notably, the <i>Politricks</i> game showed stronger discernment effects among individuals with lower initial discernment, particularly those with stronger beliefs in the inaccuracy of the 2020 election results and conservatives. These findings suggest that both active and passive tools can enhance discernment and resilience against misinformation. These results highlight the effectiveness of both active and passive learning tools across misinformation domains.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf245"},"PeriodicalIF":3.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global survey of secondary metabolism in <i>Aspergillus niger</i> via activation of specific transcription factors.","authors":"Cameron Semper, Thi Thanh My Pham, Shane Ram, Sylvester Palys, Gregory Evdokias, Jean-Paul Ouedraogo, Marie-Claude Moisan, Nicholas Geoffrion, Ian Reid, Marcos Di Falco, Zachary Bailey, Adrian Tsang, Isabelle Benoit-Gelber, Alexei Savchenko","doi":"10.1093/pnasnexus/pgaf249","DOIUrl":"10.1093/pnasnexus/pgaf249","url":null,"abstract":"<p><p>Genomics analysis confirmed the status of filamentous fungi as a rich source of novel secondary metabolites; however, the discovery of these compounds is hampered by the cryptic nature of their biosynthetic pathways under laboratory conditions. Consequently, despite substantial research effort over the past decades, much of the secondary metabolome remains uncharacterized in fungal organisms. Our manual curation of biosynthetic gene clusters (BGCs) in the <i>Aspergillus niger</i> NRRL3 genome revealed that only 13 of 86 BGCs have had their cognate secondary metabolite products confirmed or reliably inferred. We also identified 60 transcription factors (TFs) associated with cryptic BGCs. To further characterize <i>A. niger</i> secondary metabolism, we created a collection of strains each overexpressing a single BGC-associated TF. We analyzed the strain collection using a standardized pipeline where we monitored phenotypic changes and compound production using mass spectrometry. Strains showing evidence of secondary metabolism activation were selected for gene expression analysis. Our approach resulted in the production of multiple potentially novel secondary metabolites and linked a specific BGC to tensidol production in <i>A. niger</i>. More broadly, this study found evidence counter to the existing paradigm of BGC expression controlled by colocalized TFs, lending credence to the emerging picture of a complex regulatory network governing fungal secondary metabolism.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf249"},"PeriodicalIF":3.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restorative justice appeals trump retributive vigilance on social media.","authors":"Pengfei Zhao, Natalie N Bazarova, Inhwan Bae, Winice Hui, René F Kizilcec, Drew Margolin","doi":"10.1093/pnasnexus/pgaf255","DOIUrl":"10.1093/pnasnexus/pgaf255","url":null,"abstract":"<p><p>Human beings have a powerful urge to confront wrongdoing and reestablish justice. In online spaces, this typically takes the form of vigilante-like actions that shame or threaten wrongdoers. Though morally motivated, these retributive actions can draw disapproval, and even reciprocal shaming and threats, from others in the community, creating a toxic environment. This study investigates a prosocial alternative to retribution-restorative vigilance-aimed at reestablishing community values through moral appeals and encouraging apologies from offenders. We conducted two randomized experiments (<i>N</i> = 3,516 in total) on a simulated social media platform to examine how community members perceive and respond to different forms of vigilante interventions. Through observing actual user behaviors, our study demonstrates the effectiveness of restorative justice appeals in facilitating prosocial norms and achieving community goals. Specifically, the results reveal that while retribution is considered a legitimate response, restorative appeals are seen as a more effective way to achieve justice. Consequently, restorative responses elicit more supportive behaviors from the community, evidenced by increased upvotes and reduced downvotes/flags, as well as enhancing community members' satisfaction and future engagement intentions. However, in cases involving morally irredeemable offenders, the preference for restorative approaches over retribution diminishes. Our research sheds light on reasons why retribution is so common and directly informs interventions to promote restorative justice and foster more constructive and civil online communities.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 9","pages":"pgaf255"},"PeriodicalIF":3.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-interactome capture identifies SRSF3 as a key protein for herpesviral gene expression.","authors":"Carolin Vogt, Marco van Ham, Ruchira Bhowmik, Amir Argoetti, Daniel P Depledge, Lars Steinbrück, Jasper Götting, Carolina Henkel, Andrea Cuadra Granados, Yael Mandel-Gutfreund, Lothar Jänsch, Jens Bohne","doi":"10.1093/pnasnexus/pgaf225","DOIUrl":"10.1093/pnasnexus/pgaf225","url":null,"abstract":"<p><p>The primary mRNA sequence determines its secondary structure and the repertoire of interacting RNA-binding proteins (RBPs). The resulting mRNA ribonucleoprotein complex (mRNP) then influences all stages of the life of an mRNA. Here, we determined the mRNP composition of individual Kaposi sarcoma herpesviral (KSHV) mRNAs. Like all herpesviruses, KSHV switches between a latent and lytic stage of the viral life cycle. During reactivation from latency, the viral RNA regulator ORF57 ensures the translation of viral mRNAs by increasing their mRNA stability and nuclear export. We optimized an LNA/DNA mixmer RNA capture protocol for both transfection and viral infection settings. In combination with eCLIP, we confirmed that ORF57 directly binds to an AU-rich RNA motif, which may enable ORF57 to discriminate viral from cellular RNAs based on the nucleotide bias of KSHV lytic RNAs. In addition, we captured the RBPome of two ORF57-dependent viral transcripts and identified the host RNA processing factor SRSF3 as a key regulator of viral replication.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf225"},"PeriodicalIF":3.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topological protection in a Landau flat band at <i>v</i> = 7/11, a candidate filling factor for unconventional correlations.","authors":"Waseem Hussain, Haoyun Huang, Loren N Pfeiffer, Kenneth W West, Kirk W Baldwin, Gábor A Csáthy","doi":"10.1093/pnasnexus/pgaf254","DOIUrl":"10.1093/pnasnexus/pgaf254","url":null,"abstract":"<p><p>Strong interactions in Landau flat bands are known to stabilize correlated states that do not form in other types of flat bands. We report hallmarks of topological protection at the Landau level filling factor <math><mi>v</mi> <mo>=</mo> <mn>7</mn> <mo>/</mo> <mn>11</mn></math> in a 2D electron system. The <math><mi>v</mi> <mo>=</mo> <mn>7</mn> <mo>/</mo> <mn>11</mn></math> filling factor is the particle-hole conjugate of <math><mi>v</mi> <mo>=</mo> <mn>4</mn> <mo>/</mo> <mn>11</mn></math> , a filling factor intensely studied for the possibility of realizing unconventional electronic correlations. Our data establish a new instance for an unusual fractional quantum Hall state and opens up possibilities for the study of unconventional correlations in an enlarged parameter space. We report and discuss transport signatures developing at other filling factors of interest <math><mi>v</mi> <mo>=</mo> <mspace></mspace> <mn>11</mn> <mo>/</mo> <mn>17</mn> <mo>,</mo> <mspace></mspace> <mspace></mspace> <mn>5</mn> <mo>/</mo> <mn>8</mn> <mspace></mspace></math> , and <math><mspace></mspace> <mn>8</mn> <mo>/</mo> <mn>13</mn></math> , which however in our sample do not exhibit topological protection.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf254"},"PeriodicalIF":3.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Helicobacter pylori</i> base-excision restriction enzyme in stomach carcinogenesis.","authors":"Masaki Fukuyo, Noriko Takahashi, Katsuhiro Hanada, Ken Ishikawa, Česlovas Venclovas, Koji Yahara, Hideo Yonezawa, Takeshi Terabayashi, Yukako Katsura, Naoki Osada, Atsushi Kaneda, M Constanza Camargo, Charles S Rabkin, Ikuo Uchiyama, Takako Osaki, Ichizo Kobayashi","doi":"10.1093/pnasnexus/pgaf244","DOIUrl":"10.1093/pnasnexus/pgaf244","url":null,"abstract":"<p><p>Many recent lines of evidence from the human microbiome and other fields indicate bacterial involvement in various types of cancer. <i>Helicobacter pylori</i> has been recognized as the major cause of stomach cancer (gastric cancer), but the mechanism by which it destabilizes the human genome to cause cancer remains unclear. Our recent studies have identified a unique family of toxic restriction enzymes that excise a base (<b>A</b>: adenine) from their recognition sequence (5'-GT<b>A</b>C). At the resulting abasic sites (5'-GT<b>_</b>C), its inherent endonuclease activity or that of a separate endonuclease may yield atypical strand breaks that resist repair by ligation. Here, we present evidence demonstrating involvement of its <i>H. pylori</i> member, <i>Hp</i>PabI, in stomach carcinogenesis: (i) Association of intact <i>Hp</i>PabI gene with gastric cancer in the global <i>H. pylori</i> Genome Project and the open genomes; (ii) Frequent mutations at <b>A</b> in 5'-GT<b>A</b>C in the gastric cancer genomes as well as in <i>H. pylori</i> genomes; (iii) Its induction of chromosomal double-strand breaks in infected human cells and of mutagenesis in bacterial test systems. In addition, its unique regions that interact with DNA exhibit signs of diversifying selection. Our further analysis revealed similar oncogenic bacterium-restriction-enzyme pairs for other types of cancer. These results set another stage for cancer research and medicine around oncogenic restriction enzymes.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf244"},"PeriodicalIF":3.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}