Proceedings of the National Academy of Sciences of the United States of America最新文献_第6页

Biphasic mechanochemistry of single-chain polymerization.

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 : 2025-04-08 Epub Date: 2025-03-31 DOI: 10.1073/pnas.2418844122

Udit Kumar Chakraborty, Muwen Yang, Susil Baral, Chunming Liu, AnQi Chen, Peng Chen

{"title":"Biphasic mechanochemistry of single-chain polymerization.","authors":"Udit Kumar Chakraborty, Muwen Yang, Susil Baral, Chunming Liu, AnQi Chen, Peng Chen","doi":"10.1073/pnas.2418844122","DOIUrl":"https://doi.org/10.1073/pnas.2418844122","url":null,"abstract":"Mechanical forces can induce chemical reactions, produce chemical signals, and alter reaction kinetics. Here, using magnetic tweezers-based single-molecule force spectroscopy, we study the force effects on the ring-opening metathesis polymerization (ROMP) of single-polymer chains, during which nonequilibrium conformational entanglements can form and unravel stochastically. We find a surprising, biphasic force dependence of polymerization kinetics: The single-chain polymerization rate initially slows down with increasing stretching forces, reaching a minimum, and then accelerates at higher forces. Analysis of real-time single-chain growth trajectories allows for dissecting the polymerization process into two distinct regimes, one with and the other without entanglement formation, unveiling the biphasic force dependence in both regimes. Two different mechanisms likely operate for the biphasic dependence: a force-induced entanglement tightening and then splitting and a force-induced catalyst structural distortion that switches the reaction pathway between reactant states of different stability and reactivity. These findings and insights point to opportunities of using force to manipulate polymerization reactions and tune the physiochemical properties of synthetic polymers.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 14","pages":"e2418844122"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754154","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

Reply to Brown et al.: Significant sex differences in accelerated cortical thinning associated with the COVID-19 lockdowns.

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 : 2025-04-08 Epub Date: 2025-04-01 DOI: 10.1073/pnas.2426640122

Neva M Corrigan, Ariel Rokem, Patricia K Kuhl

引用次数: 0

Digital phenotyping using smartphones could help steer mental health treatment. 利用智能手机进行数字表型分析有助于指导心理健康治疗。

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 : 2025-04-08 Epub Date: 2025-04-02 DOI: 10.1073/pnas.2505700122

David Adam

引用次数: 0

RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa.

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 : 2025-04-08 Epub Date: 2025-04-03 DOI: 10.1073/pnas.2421978122

Laurel C Chandler, Apolonia Gardner, Constance L Cepko

{"title":"RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa.","authors":"Laurel C Chandler, Apolonia Gardner, Constance L Cepko","doi":"10.1073/pnas.2421978122","DOIUrl":"https://doi.org/10.1073/pnas.2421978122","url":null,"abstract":"Retinitis pigmentosa (RP) is the most common cause of inherited retinal degeneration worldwide. It is characterized by the sequential death of rod and cone photoreceptors, the cells responsible for night and daylight vision, respectively. Although the expression of most RP genes occurs only in rods, there is a secondary degeneration of cones. One possible mechanism of cone death is metabolic dysregulation. Photoreceptors are highly metabolically active, consuming large quantities of glucose and producing substantial amounts of lactate. The retinal pigment epithelium (RPE) mediates the transport of glucose from the blood to photoreceptors and, in turn, removes lactate, which can influence the rate of consumption of glucose by the RPE. One model for metabolic dysregulation in RP suggests that following the death of rods, lactate levels are substantially diminished causing the RPE to withhold glucose, resulting in nutrient deprivation for cones. Here, we present adeno-associated viral vector-mediated delivery of monocarboxylate transporter 2 (MCT2, Slc16a7) into the eye, with expression limited to RPE cells, with the aim of promoting lactate uptake from the blood and encouraging the passage of glucose to cones. We demonstrate prolonged survival and function of cones in rat and mouse RP models, revealing a possible gene-agnostic therapy for preserving vision in RP. We also present the use of fluorescence lifetime imaging-based biosensors for lactate and glucose within the eye. Using this technology, we show changes to lactate and glucose levels within MCT2-expressing RPE, suggesting that cone survival is impacted by changes in RPE metabolism.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 14","pages":"e2421978122"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773187","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

DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden. 下调 DDX54 可增强具有高肿瘤突变负荷的免疫凋亡肺癌的抗 PD1 治疗。

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 : 2025-04-08 Epub Date: 2025-04-02 DOI: 10.1073/pnas.2412310122

Jeong-Ryeol Gong, Jungeun Lee, Younghyun Han, Kwang-Hyun Cho

{"title":"DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden.","authors":"Jeong-Ryeol Gong, Jungeun Lee, Younghyun Han, Kwang-Hyun Cho","doi":"10.1073/pnas.2412310122","DOIUrl":"10.1073/pnas.2412310122","url":null,"abstract":"High tumor mutational burden (TMB-H) is a predictive biomarker for the responsiveness of cancer to immune checkpoint inhibitor (ICI) therapy that indicates whether immune cells can sufficiently recognize cancer cells as nonself. However, about 30% of all cancers from The Cancer Genome Atlas (TCGA) are classified as immune-desert tumors lacking T cell infiltration despite TMB-H. Since the underlying mechanism of these immune-desert tumors has yet to be unraveled, there is a pressing need to transform such immune-desert tumors into immune-inflamed tumors and thereby enhance their responsiveness to anti-PD1 therapy. Here, we present a systems framework for identifying immuno-oncotargets, based on analysis of gene regulatory networks, and validating the effect of these targets in transforming immune-desert into immune-inflamed tumors. In particular, we identify DEAD-box helicases 54 (DDX54) as a master regulator of immune escape in immune-desert lung cancer with TMB-H and show that knockdown of DDX54 can increase immune cell infiltration and lead to improved sensitivity to anti-PD1 therapy.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 14","pages":"e2412310122"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764656","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

microRNA-218-5p coordinates scaling of excitatory and inhibitory synapses during homeostatic synaptic plasticity.

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 : 2025-04-08 Epub Date: 2025-04-02 DOI: 10.1073/pnas.2500880122

David Colameo, Sara M Maley, Jochen Winterer, Waleed ElGrawani, Carlotta Gilardi, Simon Galkin, Roberto Fiore, Steven A Brown, Gerhard Schratt

{"title":"microRNA-218-5p coordinates scaling of excitatory and inhibitory synapses during homeostatic synaptic plasticity.","authors":"David Colameo, Sara M Maley, Jochen Winterer, Waleed ElGrawani, Carlotta Gilardi, Simon Galkin, Roberto Fiore, Steven A Brown, Gerhard Schratt","doi":"10.1073/pnas.2500880122","DOIUrl":"10.1073/pnas.2500880122","url":null,"abstract":"Homeostatic synaptic plasticity (HSP) is a neuronal mechanism that allows networks to compensate for prolonged changes in activity by adjusting synaptic strength. This process is crucial for maintaining stable brain function and has been implicated in memory consolidation during sleep. While scaling of both excitatory and inhibitory synapses plays an important role during homeostatic synaptic plasticity, molecules coordinating these processes are unknown. In this study, we investigate the role of miR-218-5p as a regulator of inhibitory and excitatory synapses in the context of picrotoxin (PTX)-induced homeostatic synaptic downscaling (HSD) in rat hippocampal neurons. Using enrichment analysis of microRNA-binding sites in genes changing upon PTX-induced HSD, we bioinformatically predict and experimentally validate increased miR-218-5p activity upon PTX treatment. By electrophysiological recordings and confocal microscopy, we demonstrate that inhibiting miR-218-5p activity exerts a dual effect during HSD: It occludes the downscaling of excitatory synapses and dendritic spines, while at the same time attenuating inhibitory synapse upscaling. Furthermore, we identify the Neuroligin2 interacting molecule Mdga1 as a direct miR-218-5p target which potentially mediates the effect of miR-218-5p on homeostatic upscaling of inhibitory synapses. By performing long-term electroencephalographic recordings, we further reveal that local inhibition of miR-218-5p in the somatosensory cortex reduces local slow-wave activity during non-rapid-eye-movement sleep. In summary, this study uncovers miR-218-5p as a key player in coordinating inhibitory and excitatory synapses during homeostatic plasticity and sleep. Our findings contribute to a deeper understanding of how neural circuits maintain stability in the face of activity-induced perturbations, with implications for pathophysiology.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 14","pages":"e2500880122"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764738","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 to Supporting Information for Ikeda et al., Seesaw protein: Design of a protein that adopts interconvertible alternative functional conformations and its dynamics. 更正 Ikeda 等人的佐证信息，Seesaw 蛋白质：设计一种可相互转换替代功能构象的蛋白质及其动力学。

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 : 2025-04-08 Epub Date: 2025-03-28 DOI: 10.1073/pnas.2504749122

引用次数: 0

Correction for Kuan et al., Behavioral nudges prevent loan delinquencies at scale: A 13-million-person field experiment.

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 : 2025-04-08 Epub Date: 2025-03-28 DOI: 10.1073/pnas.2504666122

引用次数: 0

Quirks of cognition explain why we dramatically overestimate the size of minority groups.

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 : 2025-04-08 Epub Date: 2025-03-31 DOI: 10.1073/pnas.2413064122

Brian Guay, Tyler Marghetis, Cara Wong, David Landy

{"title":"Quirks of cognition explain why we dramatically overestimate the size of minority groups.","authors":"Brian Guay, Tyler Marghetis, Cara Wong, David Landy","doi":"10.1073/pnas.2413064122","DOIUrl":"https://doi.org/10.1073/pnas.2413064122","url":null,"abstract":"Americans dramatically overestimate the size of African American, Latino, Muslim, Asian, Jewish, immigrant, and LGBTQ populations, leading to concerns about downstream racial attitudes and policy preferences. Such errors are common whenever the public is asked to estimate proportions relevant to political issues, from refugee crises and polarization to climate change and COVID-19. Researchers across the social sciences interpret these errors as evidence of widespread misinformation that is topic-specific and potentially harmful. Here, we show that researchers and journalists have misinterpreted the origins and meaning of these misestimates by overlooking systematic distortions introduced by the domain-general psychological processes involved in estimating proportions under uncertainty. In general, people systematically rescale estimates of proportions toward more central prior expectations, resulting in the consistent overestimation of smaller groups and underestimation of larger groups. We formalize this process and show that it explains much of the systematic error in estimates of demographic groups ([Formula: see text] estimates from 22 countries). This domain-general account far outperforms longstanding group-specific explanations (e.g., biases toward specific groups). We find, moreover, that people make the same errors when estimating the size of racial, nonracial, and entirely nonpolitical groups, such as the proportion of Americans who have a valid passport or own a washing machine. Our results call for researchers, journalists, and pundits alike to reconsider how to interpret misperceptions about the demographic structure of society.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 14","pages":"e2413064122"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754226","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

Unbalanced growth and land overvaluation.

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 : 2025-04-08 Epub Date: 2025-04-03 DOI: 10.1073/pnas.2423295122

Tomohiro Hirano, Alexis Akira Toda

{"title":"Unbalanced growth and land overvaluation.","authors":"Tomohiro Hirano, Alexis Akira Toda","doi":"10.1073/pnas.2423295122","DOIUrl":"https://doi.org/10.1073/pnas.2423295122","url":null,"abstract":"Historical trends suggest the decline in the importance of land as a production factor, as evidenced by the decline in the employment and gross domestic product (GDP) shares of land-intensive industries. However, land continues to be a prominent store of value, as over half of household wealth in major countries is real estate. To explain this apparent disconnection between land output and land value, in a plausible economic model with land and aggregate risk, we theoretically study the long-run behavior of land prices and identify economic conditions under which land becomes overvalued relative to the fundamentals defined by the present value of land rents. Unbalanced growth together with the elasticity of substitution between production factors plays a critical role. We establish the Land Overvaluation Theorem: When the elasticity of substitution between land and nonland factors exceeds 1 (which is natural because we can create more space by constructing taller buildings with fixed land) and technological progress is faster in nonland sectors, land overvaluation necessarily emerges. As applications of the Theorem, we present three examples: i) land overvaluation emerges along the long-run transition from the Malthusian agricultural economy to the modern knowledge- and service-based economy; ii) with aggregate uncertainty, land prices exhibit recurrent stochastic fluctuations around the trend, with expansions and contractions in the size of land overvaluation; and iii) in modern economies, land use is also changing and urban land has high value. We present a model of urban land prices and show that land overvaluation emerges in the process of urban formation characterized by unbalanced growth.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 14","pages":"e2423295122"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773204","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