Proceedings of the National Academy of Sciences of the United States of America最新文献_第9页

A binary trait model reveals the fitness effects of HIV-1 escape from T cell responses

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-19 DOI: 10.1073/pnas.2405379122

Yirui Gao, John P. Barton

{"title":"A binary trait model reveals the fitness effects of HIV-1 escape from T cell responses","authors":"Yirui Gao, John P. Barton","doi":"10.1073/pnas.2405379122","DOIUrl":"https://doi.org/10.1073/pnas.2405379122","url":null,"abstract":"Natural selection often acts on multiple traits simultaneously. For example, the virus HIV-1 faces pressure to evade host immunity while also preserving replicative fitness. While past work has studied selection during HIV-1 evolution, as in other examples where selection acts on multiple traits, it is challenging to quantitatively separate different contributions to fitness. This task is made more difficult because a single mutation can affect both immune escape and replication. Here, we develop an evolutionary model that disentangles the effects of escaping CD8 + T cell–mediated immunity, which we model as a binary trait, from other contributions to fitness. After validation in simulations, we applied this model to study within-host HIV-1 evolution in a clinical dataset. We observed strong selection for immune escape, sometimes greatly exceeding past estimates, especially early in infection. Conservative estimates suggest that roughly half of HIV-1 fitness gains during the first months to years of infection can be attributed to T cell escape. Our approach is not limited to HIV-1 or viruses and could be adapted to study the evolution of quantitative traits in other contexts.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"81 3 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451419","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}

引用次数: 0

Nongenetic adaptation by collective migration

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-19 DOI: 10.1073/pnas.2423774122

Lam Vo, Fotios Avgidis, Henry H. Mattingly, Karah Edmonds, Isabel Burger, Ravi Balasubramanian, Thomas S. Shimizu, Barbara I. Kazmierczak, Thierry Emonet

{"title":"Nongenetic adaptation by collective migration","authors":"Lam Vo, Fotios Avgidis, Henry H. Mattingly, Karah Edmonds, Isabel Burger, Ravi Balasubramanian, Thomas S. Shimizu, Barbara I. Kazmierczak, Thierry Emonet","doi":"10.1073/pnas.2423774122","DOIUrl":"https://doi.org/10.1073/pnas.2423774122","url":null,"abstract":"Cell populations must adjust their phenotypic composition to adapt to changing environments. One adaptation strategy is to maintain distinct phenotypic subsets within the population and to modulate their relative abundances via gene regulation. Another strategy involves genetic mutations, which can be augmented by stress-response pathways. Here, we studied how a migrating bacterial population regulates its phenotypic distribution to traverse diverse environments. We generated isogenic Escherichia coli populations with varying distributions of swimming behaviors and observed their phenotype distributions during migration in liquid and porous environments. We found that the migrating populations became enriched with high-performing swimming phenotypes in each environment, allowing the populations to adapt without requiring mutations or gene regulation. This adaptation is dynamic and rapid, reversing in a few doubling times when migration ceases. By measuring the chemoreceptor abundance distributions during migration toward different attractants, we demonstrated that adaptation acts on multiple chemotaxis-related traits simultaneously. These measurements are consistent with a general mechanism in which adaptation results from a balance between cell growth generating diversity and collective migration eliminating underperforming phenotypes. Thus, collective migration enables cell populations with continuous, multidimensional phenotypes to flexibly and rapidly adapt their phenotypic composition to diverse environmental conditions.","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":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451579","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}

引用次数: 0

Mussel-inspired cross-linking mechanisms enhance gelation and adhesion of multifunctional mucin-derived hydrogels

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-19 DOI: 10.1073/pnas.2415927122

George D. Degen, Corey A. Stevens, Gerardo Cárcamo-Oyarce, Jake Song, Raju Bej, Peng Tang, Katharina Ribbeck, Rainer Haag, Gareth H. McKinley

{"title":"Mussel-inspired cross-linking mechanisms enhance gelation and adhesion of multifunctional mucin-derived hydrogels","authors":"George D. Degen, Corey A. Stevens, Gerardo Cárcamo-Oyarce, Jake Song, Raju Bej, Peng Tang, Katharina Ribbeck, Rainer Haag, Gareth H. McKinley","doi":"10.1073/pnas.2415927122","DOIUrl":"https://doi.org/10.1073/pnas.2415927122","url":null,"abstract":"Mucus supports human health by hydrating, lubricating, and preventing infection of wet epithelial surfaces. The beneficial material properties and bioactivity of mucus stem from glycoproteins called mucins, motivating the development of mucin-derived hydrogels for wound dressings and antifouling coatings. However, these applications require robust gelation and adhesion to a wide range of substrates. Inspired by the chemical cross-linking and water-tolerant adhesion of marine mussel adhesive structures, we use catechol–thiol bonding to drive gelation of native mucin proteins and synthetic mucin-inspired polymers, forming soft, adhesive hydrogels that can be coated onto diverse surfaces. The gelation dynamics and adhesive properties can be systematically tuned by varying the hydrogel composition, polymer architecture, and thiol availability, with gelation timescales adjustable from seconds to hours, and values of elastic modulus, failure stress, and debonding work spanning orders of magnitude. We demonstrate the functionality of these gels in two applications: as tissue adhesives, using porcine skin as a proxy for human skin, and as bioactive surface coatings to prevent bacterial colonization. The results highlight the potential of catechol–thiol cross-linking as a versatile platform for engineering multifunctional glycoprotein hydrogels with applications in wound repair and antimicrobial surface engineering.","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":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451573","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}

引用次数: 0

Biophysical modeling of membrane curvature generation and curvature sensing by the glycocalyx

IF 11.1 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-19 DOI: 10.1073/pnas.2418357122

Ke Xiao, Sujeong Park, Jeanne C. Stachowiak, Padmini Rangamani

{"title":"Biophysical modeling of membrane curvature generation and curvature sensing by the glycocalyx","authors":"Ke Xiao, Sujeong Park, Jeanne C. Stachowiak, Padmini Rangamani","doi":"10.1073/pnas.2418357122","DOIUrl":"https://doi.org/10.1073/pnas.2418357122","url":null,"abstract":"Generation of membrane curvature is fundamental to cellular function. Recent studies have established that the glycocalyx, a sugar-rich polymer layer at the cell surface, can generate membrane curvature. While there have been some theoretical efforts to understand the interplay between the glycocalyx and membrane bending, there remain open questions about how the properties of the glycocalyx affect membrane bending. For example, the relationship between membrane curvature and the density of glycosylated proteins on its surface remains unclear. In this work, we use polymer brush theory to develop a detailed biophysical model of the energetic interactions of the glycocalyx with the membrane. Using this model, we identify the conditions under which the glycocalyx can both generate and sense curvature. Our model predicts that the extent of membrane curvature generated depends on the grafting density of the glycocalyx and the backbone length of the polymers constituting the glycocalyx. Furthermore, when coupled with the intrinsic membrane properties such as spontaneous curvature and a line tension along the membrane, the curvature generation properties of the glycocalyx are enhanced. These predictions were tested experimentally by examining the propensity of glycosylated transmembrane proteins to drive the assembly of highly curved filopodial protrusions at the plasma membrane of adherent mammalian cells. Our model also predicts that the glycocalyx has curvature-sensing capabilities, in agreement with the results of our experiments. Thus, our study develops a quantitative framework for mapping the properties of the glycocalyx to the curvature generation capability of the membrane.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"240 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451575","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}

引用次数: 0

Interrogating nucleotide sequences with AI to understand codon usage patterns.

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-18 Epub Date: 2025-02-10 DOI: 10.1073/pnas.2426326122

Assaf Elazar, Steve Mathew D A, M Madan Babu

引用次数: 0

Spatial profiling of the interplay between cell type- and vision-dependent transcriptomic programs in the visual cortex.

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-18 Epub Date: 2025-02-13 DOI: 10.1073/pnas.2421022122

Fangming Xie, Saumya Jain, Runzhe Xu, Salwan Butrus, Zhiqun Tan, Xiangmin Xu, Karthik Shekhar, S Lawrence Zipursky

{"title":"Spatial profiling of the interplay between cell type- and vision-dependent transcriptomic programs in the visual cortex.","authors":"Fangming Xie, Saumya Jain, Runzhe Xu, Salwan Butrus, Zhiqun Tan, Xiangmin Xu, Karthik Shekhar, S Lawrence Zipursky","doi":"10.1073/pnas.2421022122","DOIUrl":"10.1073/pnas.2421022122","url":null,"abstract":"How early sensory experience during \"critical periods\" of postnatal life affects the organization of the mammalian neocortex at the resolution of neuronal cell types is poorly understood. We previously reported that the functional and molecular profiles of layer 2/3 (L2/3) cell types in the primary visual cortex (V1) are vision-dependent [S. Cheng et al., Cell 185, 311-327.e24 (2022)]. Here, we characterize the spatial organization of L2/3 cell types with and without visual experience. Spatial transcriptomic profiling based on 500 genes recapitulates the zonation of L2/3 cell types along the pial-ventricular axis in V1. By applying multitasking theory, we suggest that the spatial zonation of L2/3 cell types is linked to the continuous nature of their gene expression profiles, which can be represented as a 2D manifold bounded by three archetypal cell types. By comparing normally reared and dark reared L2/3 cells, we show that visual deprivation-induced transcriptomic changes comprise two independent gene programs. The first, induced specifically in the visual cortex, includes immediate-early genes and genes associated with metabolic processes. It manifests as a change in cell state that is orthogonal to cell-type-specific gene expression programs. By contrast, the second program impacts L2/3 cell-type identity, regulating a subset of cell-type-specific genes and shifting the distribution of cells within the L2/3 cell-type manifold. Through an integrated analysis of spatial transcriptomics with single-nucleus RNA-seq data, we describe how vision patterns cortical L2/3 cell types during the critical period.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"e2421022122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415046","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}

引用次数: 0

Correction for Zhu et al., Bioinspired nanogels as cell-free DNA trapping and scavenging organelles for rheumatoid arthritis treatment.

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-18 Epub Date: 2025-01-24 DOI: 10.1073/pnas.2500091122

引用次数: 0

Correction to Supporting Information for Guo et al., Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex.

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-18 Epub Date: 2025-01-24 DOI: 10.1073/pnas.2426756122

引用次数: 0

Reply to Chen et al.: Coarse simulations overestimate the distance to recover NO-NO₂-O₃ photochemical steady state in fresh NO_x plumes.

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-18 Epub Date: 2025-02-10 DOI: 10.1073/pnas.2425976122

Daniel J Varon, Dylan Jervis, Sudhanshu Pandey, Sebastian L Gallardo, Nicholas Balasus, Laura Hyesung Yang, Daniel J Jacob

引用次数: 0

Photoreceptor-induced LHL4 protects the photosystem II monomer in Chlamydomonas reinhardtii.

IF 9.4 1区综合性期刊

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-02-18 Epub Date: 2025-02-13 DOI: 10.1073/pnas.2418687122

Marie Dannay, Chloé Bertin, Eva Cavallari, Pascal Albanese, Dimitri Tolleter, Cécile Giustini, Mathilde Menneteau, Sabine Brugière, Yohann Couté, Giovanni Finazzi, Emilie Demarsy, Roman Ulm, Guillaume Allorent

{"title":"Photoreceptor-induced LHL4 protects the photosystem II monomer in Chlamydomonas reinhardtii.","authors":"Marie Dannay, Chloé Bertin, Eva Cavallari, Pascal Albanese, Dimitri Tolleter, Cécile Giustini, Mathilde Menneteau, Sabine Brugière, Yohann Couté, Giovanni Finazzi, Emilie Demarsy, Roman Ulm, Guillaume Allorent","doi":"10.1073/pnas.2418687122","DOIUrl":"https://doi.org/10.1073/pnas.2418687122","url":null,"abstract":"Photosynthesis, the fundamental process using light energy to convert carbon dioxide to organic matter, is vital for life on Earth. It relies on capturing light through light-harvesting complexes (LHC) in photosystem I (PSI) and PSII and on the conversion of light energy into chemical energy. Composition and organization of PSI and PSII core complexes are well conserved across evolution. PSII is particularly sensitive to photodamage but benefits from a large diversity of photoprotective mechanisms, finely tuned to handle the dynamic and ever-changing light conditions. Light Harvesting Complex protein family members (LHC and LHC-like families) have acquired a dual function during evolution. Members of the LHC antenna complexes of PS capture light energy, whereas others dissipate excess energy that cannot be harnessed for photosynthesis. This process mainly occurs through nonphotochemical quenching (NPQ). In this work, we focus on the Light Harvesting complex-Like 4 (LHL4) protein, a LHC-like protein induced by ultraviolet-B (UV-B) and blue light through UV Resistance locus 8 (UVR8) and phototropin photoreceptor-activated signaling pathways in the model green microalgae Chlamydomonas reinhardtii. We demonstrate that alongside established NPQ effectors, LHL4 plays a key role in photoprotection, preventing singlet oxygen accumulation in PSII and promoting cell survival upon light stress. LHL4 protective function is distinct from that of NPQ-related proteins, as LHL4 specifically and uniquely binds to the transient monomeric form of the core PSII complex, safeguarding its integrity. LHL4 characterization expands our understanding of the interplay between light harvesting and photoprotection mechanisms upon light stress in photosynthetic microalgae.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 7","pages":"e2418687122"},"PeriodicalIF":9.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415083","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}

引用次数: 0