Alex Reinhart, Ben Markey, Michael Laudenbach, Kachatad Pantusen, Ronald Yurko, Gordon Weinberg, David West Brown
{"title":"Do LLMs write like humans? Variation in grammatical and rhetorical styles","authors":"Alex Reinhart, Ben Markey, Michael Laudenbach, Kachatad Pantusen, Ronald Yurko, Gordon Weinberg, David West Brown","doi":"10.1073/pnas.2422455122","DOIUrl":"https://doi.org/10.1073/pnas.2422455122","url":null,"abstract":"Large language models (LLMs) are capable of writing grammatical text that follows instructions, answers questions, and solves problems. As they have advanced, it has become difficult to distinguish their output from human-written text. While past research has found some differences in features such as word choice and punctuation and developed classifiers to detect LLM output, none has studied the rhetorical styles of LLMs. Using several variants of Llama 3 and GPT-4o, we construct two parallel corpora of human- and LLM-written texts from common prompts. Using Douglas Biber’s set of lexical, grammatical, and rhetorical features, we identify systematic differences between LLMs and humans and between different LLMs. These differences persist when moving from smaller models to larger ones and are larger for instruction-tuned models than base models. This observation of differences demonstrates that despite their advanced abilities, LLMs struggle to match human stylistic variation. Attention to more advanced linguistic features can hence detect patterns in their behavior not previously recognized.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"13 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443256","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}
Omid Saleh Ziabari, Fangzhou Liu, Kevin D. Deem, Xiaomi Liu, Akhil Kholwadwala, Jennifer A. Brisson
{"title":"Gene duplication captures morph-specific promoter usage in the evolution of aphid wing dimorphisms","authors":"Omid Saleh Ziabari, Fangzhou Liu, Kevin D. Deem, Xiaomi Liu, Akhil Kholwadwala, Jennifer A. Brisson","doi":"10.1073/pnas.2420893122","DOIUrl":"https://doi.org/10.1073/pnas.2420893122","url":null,"abstract":"Understanding how morphology evolves requires identifying the types of mutations that contribute to changes in development. We integrated comparative genomics and transcriptomics to reconstruct the evolution and regulation of <jats:italic>follistatin</jats:italic> paralogs in relation to the evolution of aphid winged and wingless morphs. We find that different pea aphid <jats:italic>follistatin</jats:italic> duplicates play an essential molecular role in both the male and female wing dimorphisms, linking the genetic and environmental control of morph determination in each sex, respectively. We also find that an ancestral <jats:italic>follistatin</jats:italic> gene likely had multiple promoters and that the <jats:italic>follistatin</jats:italic> duplicates that evolved wingless-specific expression retained only the ancestral wingless-specific promoter. Our work provides a roadmap for how alternative promoter usage and subsequent gene duplication can enable the evolution of animal form.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"14 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443288","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}
Delai Huang, Emaan H. Kapadia, Yipeng Liang, Leah P. Shriver, Shengkun Dai, Gary J. Patti, Bruno M. Humbel, Vincent Laudet, David M. Parichy
{"title":"Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish","authors":"Delai Huang, Emaan H. Kapadia, Yipeng Liang, Leah P. Shriver, Shengkun Dai, Gary J. Patti, Bruno M. Humbel, Vincent Laudet, David M. Parichy","doi":"10.1073/pnas.2424180122","DOIUrl":"https://doi.org/10.1073/pnas.2424180122","url":null,"abstract":"The often-distinctive pigment patterns of vertebrates are varied in form and function and depend on several types of pigment cells derived from embryonic neural crest or latent stem cells of neural crest origin. These cells and the patterns they produce have been useful for uncovering features of differentiation and morphogenesis that underlie adult phenotypes, and they offer opportunities to discover how patterns and the cell types themselves have diversified. In zebrafish, a body pattern of stripes arises by self-organizing interactions among three types of pigment cells. Yet these fish also exhibit white ornamentation on their fins that depends on the transdifferentiation of black melanophores to white cells, “melanoleucophores.” To identify mechanisms underlying this conversion we used ultrastructural, transcriptomic, mutational, and other approaches. We show that melanophore–melanoleucophore transition depends on regional BMP signals transduced through noncanonical receptors (Rgmb-Neo1a-Lrig2) as well as BMP-dependent signaling by Agouti genes, <jats:italic>asip1</jats:italic> and <jats:italic>asip2b</jats:italic> . These signals lead to expression of transcription factor genes including <jats:italic>foxd3</jats:italic> and <jats:italic>runx3</jats:italic> that are necessary to induce loss of melanin, curtail new melanin production, and deploy a pathway for accumulating guanine crystals that, together, confer a white phenotype. These analyses uncover an important role for positional information in specifying ornamentation in zebrafish and show how tissue environmental cues and an altered gene regulatory program have allowed terminal addition of a distinct phenotype to a preexisting cell type.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"13 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443289","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":"Decoding resistance in the age of T6SS warfare.","authors":"Nicholas J Shikuma","doi":"10.1073/pnas.2500342122","DOIUrl":"https://doi.org/10.1073/pnas.2500342122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"e2500342122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391543","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":"In This Issue.","authors":"","doi":"10.1073/iti0725122","DOIUrl":"https://doi.org/10.1073/iti0725122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"eiti0725122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441686","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":"Superfluid weight cross-over and critical temperature enhancement in singular flat bands.","authors":"Guodong Jiang, Päivi Törmä, Yafis Barlas","doi":"10.1073/pnas.2416726122","DOIUrl":"https://doi.org/10.1073/pnas.2416726122","url":null,"abstract":"<p><p>Nonanalytic Bloch eigenstates at isolated band degeneracy points exhibit singular behavior in the quantum metric. Here, a description of superfluid weight for zero-energy flat bands in proximity to other high-energy bands is presented, where they together form a singular band gap system. When the singular band gap closes, the geometric and conventional contributions to the superfluid weight as a function of the superconducting gap exhibit different cross-over behaviors. The scaling behavior of superfluid weight with the band gap is studied in detail, and the effect on the Berezinskii-Kosterlitz-Thouless transition temperature is explored. It is found that tuning the singular band gap provides a unique mechanism for enhancing the supercurrent and critical temperature of two-dimensional superconductors.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"e2416726122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417050","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}
Hyung Soon Kim, Seung Ah Jee, Ariandokht Einisadr, Yeojin Seo, Hyo Gyeong Seo, Byeong Seong Jang, Hee Hwan Park, Won-Suk Chung, Byung Gon Kim
{"title":"Detrimental influence of Arginase-1 in infiltrating macrophages on poststroke functional recovery and inflammatory milieu.","authors":"Hyung Soon Kim, Seung Ah Jee, Ariandokht Einisadr, Yeojin Seo, Hyo Gyeong Seo, Byeong Seong Jang, Hee Hwan Park, Won-Suk Chung, Byung Gon Kim","doi":"10.1073/pnas.2413484122","DOIUrl":"https://doi.org/10.1073/pnas.2413484122","url":null,"abstract":"<p><p>Poststroke inflammation critically influences functional outcomes following ischemic stroke. Arginase-1 (Arg1) is considered a marker for anti-inflammatory macrophages, associated with the resolution of inflammation and promotion of tissue repair in various pathological conditions. However, its specific role in poststroke recovery remains to be elucidated. This study investigates the functional impact of Arg1 expressed in macrophages on poststroke recovery and inflammatory milieu. We observed a time-dependent increase in Arg1 expression, peaking at 7 d after photothrombotic stroke in mice. Cellular mapping analysis revealed that Arg1 was predominantly expressed in LysM-positive infiltrating macrophages. Using a conditional knockout (cKO) mouse model, we examined the role of Arg1 expressed in infiltrating macrophages. Contrary to its presumed beneficial effects, Arg1 cKO in LysM-positive macrophages significantly improved skilled forelimb motor function recovery after stroke. Mechanistically, Arg1 cKO attenuated fibrotic scar formation, enhanced peri-infarct remyelination, and increased synaptic density while reducing microglial synaptic elimination in the peri-infarct cortex. Gene expression analysis of fluorescence-activated single cell sorting (FACS)-sorted CD45<sup>low</sup> microglia revealed decreased transforming growth factor-β (TGF-β) signaling and proinflammatory cytokine activity in peri-infarct microglia from Arg1 cKO animals. In vitro coculture experiments demonstrated that Arg1 activity in macrophages modulates microglial synaptic phagocytosis, providing evidence for macrophage-microglia interaction. These findings present unique insights into the function of Arg1 in central nervous system injury and highlight an interaction between infiltrating macrophages and resident microglia in shaping the poststroke inflammatory milieu. Our study identifies Arg1 in macrophages as a potential therapeutic target for modulating poststroke inflammation and improving functional recovery.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"e2413484122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417034","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}
Noah Lupu-Gladstein, Ou Teen Arthur Pang, Hugo Ferretti, Weng-Kian Tham, Aephraim M Steinberg, Kent Bonsma-Fisher, Aharon Brodutch
{"title":"Variable-strength nonlocal measurements reveal quantum violations of classical counting principles.","authors":"Noah Lupu-Gladstein, Ou Teen Arthur Pang, Hugo Ferretti, Weng-Kian Tham, Aephraim M Steinberg, Kent Bonsma-Fisher, Aharon Brodutch","doi":"10.1073/pnas.2416331122","DOIUrl":"https://doi.org/10.1073/pnas.2416331122","url":null,"abstract":"<p><p>We implement a variant of the quantum pigeonhole paradox thought experiment to study whether classical counting principles survive in the quantum domain. We observe strong measurements significantly violate the pigeonhole principle (that among three pigeons in two holes, at least one pair must be in the same hole) and the sum rule (that the number of pigeon pairs in the same hole is the sum of the number of pairs across each of the holes) in an ensemble that is pre- and postselected into particular separable states. To investigate whether measurement disturbance is a viable explanation for these counterintuitive phenomena, we employ a we employ variable-strength nonlocal measurements. As we decrease the measurement strength, we find the violation of the sum rule decreases, yet the pigeonhole principle remains violated. In the weak limit, the sum rule is restored due to the cancellation between two weak values with equal and opposite imaginary parts. We observe the same kind of cancellation at higher measurement strengths, thus raising the question: do strong measurements have imaginary parts?</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"e2416331122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417060","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}
Darian T. Yang, Lillian T. Chong, Angela M. Gronenborn
{"title":"Illuminating an invisible state of the HIV-1 capsid protein CTD dimer using 19 F NMR and weighted ensemble simulations","authors":"Darian T. Yang, Lillian T. Chong, Angela M. Gronenborn","doi":"10.1073/pnas.2420371122","DOIUrl":"https://doi.org/10.1073/pnas.2420371122","url":null,"abstract":"The HIV-1 capsid protein (CA) assembles into a conical shell during viral maturation, encasing and protecting the viral RNA genome. The C-terminal domain (CTD) of the two-domain capsid protein dimerizes, and this dimer connects individual chains in the mature capsid lattice. Previous NMR studies have shown that different dimer arrangements can be formed by isolated capsid protein chains and in assembled capsid lattices; however, the dynamics and functional relevance of these alternate dimers are unknown. To explore the conformational landscape of the CA-CTD dimer, we carried out atomistic molecular dynamics simulations using the weighted ensemble path sampling strategy, generating an ensemble of conformations. Focusing on the two dimer forms previously observed via solution NMR, we refined the conformational ensemble to highlight two metastable states using a Markov state model. Experimentally, we measured the interconversion rates between the two alternate dimers using <jats:sup> 19 </jats:sup> F NMR, and these rates showed good agreement with the interconversion rates derived from the simulations. After identifying the key interactions that distinguish the dimer states, the alternate dimer was further experimentally verified through disulfide crosslinking. Our results demonstrate the advantages of pairing weighted ensemble path sampling with <jats:sup> 19 </jats:sup> F NMR to gain atomistic insights into the hidden dimer state of the HIV-1 capsid protein.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"16 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443162","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 MutRS quorum-sensing system controls lantibiotic mutacin production in the human pathogen <i>Streptococcus mutans</i>.","authors":"Ryan M Wyllie, Paul A Jensen","doi":"10.1073/pnas.2421164122","DOIUrl":"https://doi.org/10.1073/pnas.2421164122","url":null,"abstract":"<p><p>Microbes use quorum-sensing systems to respond to ecological and environmental changes. In the oral microbiome, the pathogenic bacterium <i>Streptococcus mutans</i> uses quorum-sensing to control the production of bacteriocins. These antimicrobial peptides kill off ecological competitors and allow <i>S. mutans</i> to dominate the microenvironment of dental plaques and form dental caries. One class of bacteriocins produced by <i>S. mutans</i>, the lantibiotic mutacins, are particularly effective at killing due to their broad spectrum of activity. Despite years of study, the regulatory mechanisms governing production of lantibiotic mutacins I, II, and III in <i>S. mutans</i> have never been elucidated. We identified a distinct class of quorum-sensing system, MutRS, that regulates mutacins and is widespread among the streptococci. We demonstrate that MutRS systems are activated by a short peptide pheromone (Mutacin Stimulating Peptide) and show that MutRS controls production of three separate lantibiotic mutacins in three different strains of <i>S. mutans</i>. Finally, we show that paralogous MutRS systems participate in inter- and intrastrain crosstalk, providing further evidence of the interplay between quorum-sensing systems in the oral streptococci.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"e2421164122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415048","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}